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HIV and AIDS
Human Immunodeficiency Virus and
Acquired Immunodeficiency Syndrome

FDA HIV/AIDS List Serve Archive 2003

12/29/2003

The FDA approved, on December 24, 2003, new dosing regimens for the two available formulations of saquinavir, INVIRASE and FORTOVASE. The newly approved dosing regimen for saquinavir (both INVIRASE and FORTOVASE) is 1000 mg BID (two times a day) co-administered with ritonavir 100 milligrams bid.

For INVIRASE, the new, ritonavir boosted regimen replaces the previously approved regimen. As stated in the revised label, INVIRASE should never be used without ritonavir.

For FORTOVASE, the ritonavir boosted regimen allows a reduced pill burden and ease of administration compared to the previously approved regimen. Unboosted FORTOVASE, however remains a dosage option for patients who are unable to tolerate ritonavir.

The approval of the new dosing regimens were based on pharmacokinetic and safety data. Both boosted regimens of saquinavir provide plasma concentrations exceeding that of unboosted FORTOVASE.

Important changes in the INVIRASE and FORTOVASE labels include drug interaction information relevant to the co-administration of ritonavir.

The revised labeling will be available in the coming weeks through the index at http://www.fda.gov/cder/approval/index.htm

Hoffmann-La Roche of Nutley, NJ is the manufacturer of INVIRASE and FORTOVASE .

Richard Klein
Office of Special Health Issues
Food and Drug Administration

Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration

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11/14/2003

The Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents were revised on November 10, 2003.

A "What's New in this Document?" page has been added to the guidelines to indicate and summarize the changes. The most current version of the guidelines are always available at http://aidsinfo.nih.gov/

Richard Klein
Office of Special Health Issues
Food and Drug Administration

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11/4/2003

Revisions were made recently to the product labeling for VIREAD (tenofovir disoproxil fumarate) 300mg Tablets marketed by Gilead Sciences. The main revisions are summarized below. The revised labeling can be viewed at http://www.accessdata.fda.gov/scripts/cder/drugsatfda/

The revised label contains the following changes:

Addition of one paragraph in the "Pharmacokinetics, Special Populations" section about the results of a pharmacokinetics study of tenofovir in non-HIV infected patients with moderate to severe hepatic impairment. The main results of the study are summarized below.

The pharmacokinetics of tenofovir following a 300 mg single dose of VIREAD have been studied in non-HIV infected patients with moderate to severe hepatic impairment. There were no substantial alterations in tenofovir pharmacokinetics in patients with hepatic (liver) impairment compared with unimpaired patients. No change in VIREAD dosing is required in patients with hepatic impairment.
2. Addition of emtricitabine (Emtriva) to the list of drugs that, in combination with VIREAD, have been studied in healthy volunteers. Addition of emtricitabine in Table 2: "Drug Interactions: Changes in Pharmacokinetic Parameters for Tenofovir in the Presence of the Co-administered Drug" and Table 3: "Drug Interactions: Changes in Pharmacokinetic Parameters for Co-administered Drug in the Presence of VIREAD" to reflect most current study data.

In a drug-drug interaction study with tenofovir and emtricitabine, no changes in plasma levels of either tenofovir or emtricitabine were seen.

Richard Klein
Office of Special Health Issues
Food and Drug Administration

Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration

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10/21/2003

The Food and Drug Administration (FDA) approved, on October 20, 2003, LEXIVA (Fosamprenavir calcium), manufactured by GlaxoSmithKline of Research Triangle Park, NC and Vertex Pharmaceuticals, Incorporated of Cambridge, MA.

LEXIVA is a prodrug of amprenavir, a protease inhibitor used to treat infection with the human immunodeficiency virus (HIV-1). LEXIVA is rapidly converted to amprenavir by cellular or serum phosphatases in the body.

LEXIVA is indicated in combination with other antiretroviral agents for the treatment of HIV infection in adults. The approval of LEXIVA was based on two studies in antiretroviral naïve patients and one study in protease inhibitor experienced patients.

Antiretroviral Naïve Studies:

In study APV30001, LEXIVA (1400 mg twice daily) was compared to nelfinavir (1250 mg twice daily) in 249 antiretroviral naïve patients. Both treatment groups also received abacavir (300 mg twice daily) and lamivudine (150 mg twice daily).

The proportions of patients who achieved and maintained confirmed HIV RNA < 400 copies/mL (< 50 copies/mL) through week 48 was 66% (57%) for the LEXIVA group and 52% (42%) for the nelfinavir group, respectively. Through 48 weeks of therapy, the median increases from baseline in CD4+ cell counts were 201 cells/mm3 in the group receiving LEXIVA and 216 cells/mm3 in the nelfinavir group.

In study APV30002, LEXIVA (1,400 mg once daily) plus ritonavir (200 mg once daily) was compared to nelfinavir (1,250 mg twice daily) in 649 treatment-naive patients. Both treatment groups also received abacavir (300 mg twice daily) and lamivudine (150 mg twice daily).

The proportions of patients who achieved and maintained confirmed HIV RNA < 400 copies/mL (< 50 copies/mL) through week 48 was 69% (58%) for the LEXIVA group and 68% (55%) for the nelfinavir group, respectively. Through 48 weeks of therapy, the median increases from baseline in CD4+ cell counts were 203 cells/mm3 in the group receiving LEXIVA and 207 cells/mm3 in the nelfinavir group

Protease Inhibitor Experienced Study

In study APV30003, two different regimens of LEXIVA plus ritonavir (LEXIVA 700 mg twice daily plus ritonavir 100 mg twice daily or LEXIVA 1,400 mg once daily plus ritonavir 200 mg once daily) was compared to lopinavir/ritonavir (400 mg/100 mg twice daily) in 315 patients who had experienced virologic failure to 1 or 2 prior protease inhibitor-containing regimens.

The time-averaged changes in plasma HIV-1 RNA from baseline (AAUCMB) at 48 weeks (the endpoint on which the study was powered) were -1.4 log10 copies/mL for twice-daily LEXIVA/ritonavir and -1.67 log10 copies/mL for the lopinavir/ritonavir group.

The proportions of patients who achieved and maintained confirmed HIV-1 RNA <400 copies/mL were 58% with twice-daily LEXIVA/ritonavir and 61% with lopinavir/ritonavir (95% CI for the difference -16.6, 10.1).

The proportions of patients with HIV-1 RNA <50 copies/mL with twice-daily LEXIVA/ritonavir and with lopinavir/ritonavir were 46% and 50%, respectively (95% CI for the difference -18.3, 8.9). Through 48 weeks of therapy, the median increases from baseline in CD4+ cell counts were 81 cells/mm3 with twice-daily LEXIVA/ritonavir and 91 cells/mm3 with lopinavir/ritonavir

The following points should be considered when initiating therapy with LEXIVA/ritonavir in protease inhibitor-experienced patients.

The protease inhibitor-experienced patient study was not large enough to reach a definitive conclusion that LEXIVA/ritonavir and lopinavir/ritonavir are clinically equivalent.
Once-daily administration of LEXIVA plus ritonavir is not recommended for protease inhibitor-experienced patients.

The most common treatment-emergent adverse events in clinical studies of LEXIVA were diarrhea, nausea, vomiting, headache, and rash and were generally mild to moderate in severity. Treatment discontinuation due to adverse events occurred in 6.4% of patients receiving LEXIVA and in 5.9% of patients receiving comparator treatments.

LEXIVA tablets are available for oral administration in a strength of 700 mg of fosamprenavir as fosamprenavir calcium (equivalent to approximately 600 mg of amprenavir).

LEXIVA Tablets may be taken with or without food.

The recommended oral dose of LEXIVA, alone or in combination with ritonavir, is as follows:

Therapy-Naive Patients:

LEXIVA 1,400 mg twice daily (without ritonavir)
LEXIVA 1,400 mg once daily plus ritonavir 200 mg once daily
LEXIVA 700 mg twice daily plus ritonavir 100 mg twice daily
The twice-daily plus ritonavir dose is supported by pharmacokinetic and safety data

Protease Inhibitor-Experienced Patients:

LEXIVA 700 mg twice daily plus ritonavir 100 mg twice daily
Once-daily administration of LEXIVA plus ritonavir is not recommended in protease inhibitor-experienced patients.

Ritonivir is used to increase the plasma concentration of LEXIVA.

Please see the attached label for additional details about product details, clinical trial data, and indications. (pdf format)

Richard Klein
Office of Special Health Issues
Food and Drug Administration

Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration

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10/16/2003

UCB Pharma, Inc. and FDA recently issued a "Dear Healthcare Professional" letter advising health care professionals of the risk of dispensing errors between KALETRA (lopinavir/ritonavir), an antiretroviral, and KEPPRA (levetiracetam), an antiepileptic drug.

Medication dispensing errors are a serious threat to quality healthcare and necessitate the combined efforts of all involved to minimize their occurrence. UCB Pharma, Inc. would like to advise you that dispensing errors may occur between KEPPRA (levetiracetam) tablets and oral solution and KALETRA (lopinavir/ritonavir) capsules and oral solution. Your assistance is requested in clearly communicating oral and written prescriptions for these two products to help avoid dispensing errors.

Patients erroneously receiving either medication would be unnecessarily subjected to the risk of adverse effects. In addition, patients with epilepsy who do not receive their antiepileptic drug due to a dispensing error would be inadequately treated and could experience serious consequences, including status epilepticus.
KEPPRA, an antiepileptic, is available as tablets and oral solution. KEPPRA tablets, 250 mg are blue, 500 mg are yellow, and 750 mg are orange, oblong-shaped, scored, film-coated tablets debossed with "ucb" and "strength" on one side. They are supplied in containers of 120 tablets. KEPPRA oral solution is a clear, colorless, grape-flavored liquid supplied in 16 fl oz white HDPE bottles containing 500 mg levetiracetam per 5 mL.

KALETRA, an antiretroviral, is available as capsules or oral solution. KALETRA 133.3 mg lopinavir/33.3 mg ritonavir capsules are orange soft gelatin capsules imprinted with the Abbott corporate logo and "PK". KALETRA is available in bottles of 180 capsules. KALETRA oral solution is a light yellow to orange colored liquid supplied in amber-colored 160 mL glass bottles containing 400 mg lopinavir/100 mg ritonavir per 5 mL.

Please take great care when writing a prescription for KEPPRA by making sure that KEPPRA can be easily read and understood by the person filling the prescription. Clearly communicating both written and verbal prescriptions is a vital step in the prevention of future dispensing errors. You might consider, when appropriate, including the intended use on prescriptions for these products. Please inform your patients that they should carefully check all medications they receive, and immediately bring any problems, questions, or concerns to the pharmacist's attention.
If you become aware of a prescription dispensing error involving KEPPRA, please contact UCB Pharma, Inc. immediately at 1-800-477-7877, option 9; the USP Medication Errors Reporting Program at 1-800-233-7767 or the FDA MEDWATCH program by telephone at 1-800-FDA-1088, by FAX at 1-800-FDA-0178, or by Internet http://www.fda.gov/medwatch.

Thank for your continued support in this very important matter.

Sincerely,
Leslie Magnus, MD
Vice President, Medical Affairs
UCB Pharma, Inc.

Before prescribing KEPPRA, please consult the enclosed full prescribing information.
KALETRA is a registered trademark of Abbott Laboratories. K1312-0403

A pdf version of the original letter is posted at: http://www.fda.gov/medwatch/SAFETY/2003/keppra_deardoc.pdf

Richard Klein
Office of Special Health Issues
Food and Drug Administration

Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration

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10/14/2003

Gilead Sciences today issued a "Dear Health Care Professional" letter (below) describing high rates of vriologic failure in patients treated with a once-daily triple NRTI regimen containing Didanosine (ddI, Videx EC), Lamivudine (3TC, Epivir), and Tenofovir (Viread).

October 14, 2003

IMPORTANT DRUG WARNING

RE: High Rate of Virologic Failure in Patients with HIV Infection Treated With a Once-
Daily Triple NRTI Regimen containing Didanosine, Lamivudine, and Tenofovir

Dear Health Care Professional,

Gilead Sciences, Inc (Gilead) is writing to inform you of a high rate of early virologic failure and
emergence of nucleoside reverse transcriptase inhibitor (NRTI) resistance associated mutations
observed in a clinical study of HIV-infected treatment-naïve patients receiving a once-daily triple
NRTI regimen containing didanosine enteric coated beadlets (Videx EC, Bristol-Myers
Squibb), lamivudine (Epivir, GlaxoSmithKline), and tenofovir disoproxil fumarate (Viread,
Gilead).

These new data are consistent with the high rates of virologic failure observed in several recent
clinical studies that have evaluated the use of triple NRTI regimens. Based on these results:

· Tenofovir DF in combination with didanosine and lamivudine is not recommended when
considering a new treatment regimen for therapy-naïve or experienced patients with HIVinfection.
Patients currently on this regimen should be considered for treatment
modification.

In a 24-week, single-site, pilot study (N=24) designed to evaluate the safety and efficacy of a
triple NRTI once-daily regimen of didanosine EC (250 mg), lamivudine (300 mg) and tenofovir
DF (300 mg) in HIV-infected treatment-naïve patients, Jemsek et al. (Oral Communication,
September 2003) have identified a high frequency of virologic failure (91%), which was defined
as < 2 log10 reduction in plasma HIV RNA level by Week 12. Resistance testing was performed
on 21 patients; 20 patients (95%) had M184I/V and 10 of these patients (50%) had K65R in
addition to M184V. As a result of this high early failure rate, study enrollment was stopped.

Sub-optimal virologic response has also been reported with the use of the triple NRTI regimen
abacavir/lamivudine/zidovudine (Trizivir) (Gulick 2003) and abacavir/didanosine/stavudine
(Gerstoft 2003), and similarly early virologic failure and high rates of resistance mutations have
been reported with abacavir/lamivudine/tenofovir DF (Farthing 2003, Gallant 2003). Overall,
these studies demonstrate a lower response rate in patients on a triple NRTI regimen.
Furthermore, they indicate that patients who achieve viral suppression on a triple NRTI regimen
have a higher rate of virologic failure.
Reporting of Adverse Events

Please report all adverse events, following or coincident with the use of Viread, to Gilead Global
Drug Safety at 1-800-GILEAD-5, option 3, or to the FDA MedWatch Program by phone (1-800-
FDA-1088), by fax (1-800-FDA-0178), by mail (using postage-paid form to MedWatch, FDA,
5600 Fishers Lane, Rockville, MD 20852-9787) or via the internet (www.accessdata.fda.gov/scripts/medwatch/).

We hope this information will be helpful to you in caring for your patients. Please consult the
enclosed Prescribing Information for complete product information. If you have any additional
questions, please contact Gilead Medical Information toll free at 1-800-GILEAD-5, option 2.

Sincerely,

Jay Toole, MD, Ph.D.
Senior Vice President
Clinical Research

References: Farthing C, Khanlou H, Yeh V, et al. Early virologic failure in a pilot study evaluating the
efficacy of once daily abacavir (ABC), lamivudine (3TC), and tenofovir DF (TDF) in treatment naïve
HIV-infected patients (oral presentation). Presented at the 2nd International AIDS Society Meeting, Paris,
France, July 13-16, 2003. Gallant JE, Rodriguez A, Weinberg W, et al. Early non-response to tenofovir
DF (TDF) + abacavir (ABC) and lamivudine (3TC) in a randomized trial compared to efavirenz (EFV) +
ABC and 3TC: ESS30009 unplanned interim analysis (oral presentation # H-1722a). Presented at the 43rd
Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, September 14-17,
2003. Gerstoft J, Kirk O, Obel N, et al. Low efficacy and high frequency of adverse events in a
randomized trial of the triple nucleoside regimen abacavir, stavudine and didanosine. AIDS 2003,
17:2045-2052. Gulick RM, Ribaudo HJ, Shikuma CM, et al. ACTG 5095: a comparative study of 3
protease inhibitor-sparing antiretroviral regimens for the initial treatment of HIV infection. 2nd IAS
Conference on HIV Pathogenesis and Treatment. July 13-16, 2003. Paris. Abstract 41.

Richard Klein
Office of Special Health Issues
Food and Drug Administration

Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration

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10/10/2003

AIDSinfo recently began a new service on their web site called Live Help. AIDSinfo is a web site sponsored by agencies within the Department of Health and Human Services. AIDSinfo presents federally approved information on HIV/AIDS treatment and prevention guidelines, a comprehensive database of both government and industry-supported HIV/AIDS clinical trials, and information about approved and experimental HIV/AIDS drugs, and vaccines.
Live Help provides confidential, one-on-one assistance via the Internet in an "instant message" like setting. AIDSinfo information specialists are available Monday - Friday, 12:00 p.m. (Noon) - 4:00 p.m. Eastern Time.

Live Help can help you navigate the AIDSinfo web site and/or answer your questions about HIV/AIDS research, clinical trials, and treatment.

AIDSinfo Live Help staff are trained health information specialists who are knowledgeable about HIV/AIDS hotlines, publications, web sites, and other information about HIV/AIDS-related resources.

Although AIDSinfo can offer assistance finding information, they do not provide medical advice. Always consult your health care provider for answers to your personal medical questions.

Live Help can be accessed by using the Live Help icon (http://aidsinfo.nih.gov/live_help/) on the AIDSinfo Web site (http://aidsinfo.nih.gov).

Richard Klein
Office of Special Health Issues
Food and Drug Administration

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10/9/2003

Revisions were recently made to the product labeling for Norvir (ritonavir) 100mg soft gelatin capsules and Norvir (ritonavir) 80mg/mL oral solution, marketed by Abbott Laboratories. The changes address a Phase IV commitment to develop appropriate labeling for patients with hepatic insufficiency. Changes were also made to the Drug Interaction tables, including new information on the co-administration of Warfarin. Other revisions include minor editorial changes such as renumbering of tables and consolidation of information into specific sections. The new information is summarized in the Portable Document Format (pdf) file linked below.

To view or print this document, use Adobe Acrobat Reader. Acrobat Reader is free and available directly from Adobe's Website, http://www.adobe.com/products/acrobat/readstep2.html.

Please refer to the complete revised package insert for further details.

The revised label is available at
www.fda.gov/cder/foi/label/2003/20659slr030,20945slr013_norvir_lbl.pdf

Richard Klein
Office of Special Health Issues
Food and Drug Administration

Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration

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8/15/2003

Viread labeling has been updated to include results from Gilead Sciences study 903 (antiretroviral naïve subjects). The revised label also includes new dose recommendations for patients with renal impairment, a new warning about HIV/HBV coinfection, dose recommendation for ddI when used with tenofovir, and updated information regarding bone effects.

In addition, the original label stated that Viread should be taken with a meal. New information indicates that Viread may be taken without regard to food. This information can be found in the Dosage and Administration section of the new label.

Below is a summary of the information that can be found in the updated labeling.

Description of Clinical Studies

Treatment-Naïve Patients

Study 903: VIREAD + Lamivudine +Efavirenz Compared to Stavudine + Lamivudine + Efavirenz
Data through 48-weeks are reported for Study 903, a double-blind, active-controlled multicenter study comparing VIREAD (300 mg QD) administered in combination with lamivudine and efavirenz versus stavudine, lamivudine, and efavirenz in 600 antiretroviral-naïve patients. Patients had a mean age of 36 years (range 18 to 64), 74% were male, 64% were Caucasian and 20% were Black. The mean baseline CD4 cell count was 279 cells/mm3 (range 3-956) and median baseline plasma HIV-1 RNA was 77,600 copies/mL (range 417-5,130,000). Patients were stratified by baseline HIV-1 RNA and CD4 count. Forty-three percent of patients had baseline viral loads > 100,000 copies/mL and 39% had CD4 cell counts <200 cells/mL. Treatment outcomes through 48 weeks are presented in Table 6 below.

Table 6. Outcomes of Randomized Treatment at Week 48 (Study 903)

1 Patients achieved and maintained confirmed HIV-1 RNA <400 copies/mL through Week 48

2 Includes confirmed viral rebound and failure to achieve confirmed <400 copies/mL through Week 48

3 Includes lost to follow-up, patient's withdrawal, noncompliance, protocol violation and other reasons

Achievement of plasma HIV-1 RNA concentrations of less than 400 copies/mL at week 48 was similar between the two treatment groups for the population stratified at baseline on the basis of HIV-1 RNA concentration (< or >100,000 copies/mL) and CD4 cell count (< or ³ 200 cells/mm3). Through 48 weeks of therapy, 76% and 79% of patients in the VIREAD and stavudine arms, respectively achieved HIV-1 RNA < 50 copies/mL. The mean increase from baseline in CD4 cell count was 169 cells/mm3 for the VIREAD arm and 167 cells/mm3 for the stavudine arm.

Through 48 weeks, eight patients in the VIREAD group and six patients in the stavudine group experienced a new CDC Class C event

Safety information in Treatment-Naïve Patients

Treatment-Emergent Adverse Events: The adverse reactions seen in a double-blind comparative controlled study in which 600 treatment-naïve patients received VIREAD (N=299) or stavudine (N=301) in combination with lamivudine and efavirenz for 48 weeks (Study 903) were generally consistent, with the addition of dizziness, with those seen in treatment-experienced patients. Mild adverse events (Grade 1) were common with a similar incidence in both arms, and included dizziness, diarrhea and nausea.

Laboratory Abnormalities: With the exception of triglyceride elevations that were more common in the stavudine group (8%) compared with VIREAD (2%), laboratory abnormalities observed in this study occurred with similar frequency in the VIREAD and stavudine treatment arms.

WARNINGS

Renal Impairment
Tenofovir is principally eliminated by the kidney. Dosing interval adjustment is recommended in all patients with creatinine clearance < 50 mL/min (see dosing information below). No safety data are available in patients with renal dysfunction who received VIREAD using these dosing guidelines.

Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported in association with the use of VIREAD. The majority of these cases occurred in patients with underlying systemic or renal disease, or in patients taking nephrotoxic agents, however, some cases occurred in patients without identified risk factors.

VIREAD should be avoided with concurrent or recent use of a nephrotoxic agent. Patients at risk for, or with a history of, renal dysfunction and patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.

Dose Adjustment for Renal Impairment:
Significantly increased drug exposures occurred when VIREAD was administered to patients with moderate to severe renal impairment. The dosing interval of VIREAD should be adjusted in patients with baseline creatinine clearance < 50 mL/min using the recommendations below. The safety and effectiveness of these dosing interval adjustment recommendations have not been clinically evaluated, therefore, clinical response to treatment and renal function should be closely monitored in these patients.

The recommended dosing for subjects with Creatinine Clearance > 50 (mL/min)3 is 300 mg every 24 hours
The recommended dosing for subjects with Creatinine Clearance 30 - 49 (mL/min)3 is 300 mg every 48 hours
The recommended dosing for subjects with Creatinine Clearance 10 - 29 (mL/min)3 is 300 mg twice a week
For hemodialysis patients the recommended dose is 300 mg every 7 days or after a total of approximately 12 hours of dialysis (Generally once weekly assuming three hemodialysis sessions a week of approximately 4 hours duration. VIREAD should be administered following completion of dialysis)
The pharmacokinetics of tenofovir have not been evaluated in non-hemodialysis patients with creatinine clearance < 10 mL/min; therefore, no dosing recommendation is available for these patients.

Patients with HIV and Hepatitis B Virus Coinfection
It is recommended that all patients with HIV be tested for the presence of hepatitis B virus (HBV) before initiating antiretroviral therapy. VIREAD is not indicated for the treatment of chronic HBV infection and the safety and efficacy of VIREAD have not been established in patients co-infected with HBV and HIV. Exacerbations of HBV have been reported in patients after the discontinuation of VIREAD. Patients co-infected with HIV and HBV should be closely monitored with both clinical and laboratory follow up for at least several months after stopping VIREAD treatment.

PRECAUTIONS

Drug Interactions
When administered with VIREAD, Cmax and AUC of didanosine administered as either the buffered or enteric-coated formulation increased significantly. The mechanism of this interaction is unknown. Higher didanosine concentrations could potentiate didanosine-associated adverse events, including pancreatitis and neuropathy. In adults weighing >60kg, the didanosine dose should be reduced to 250mg when it is co-administered with VIREAD. Data are not available to recommend a dose adjustment of didanosine for patients weighing < 60 kg. When co-administered, VIREAD and didanosine EC may be taken under fasted conditions or with a light meal <400 kcal, =20% fat). Co-administration of didanosine buffered tablet formulation with VIREAD should be under fasted conditions. Co-administration of VIREAD and didanosine should be undertaken with caution and patients receiving this combination should be monitored closely for didanosine-associated adverse events. Didanosine should be discontinued in patients who develop didanosine-associated adverse events.

Bone Effects
In study 903 through 48 weeks, decreases from baseline in bone mineral density (BMD) were seen at the lumbar spine and hip in both arms of the study. At 48 weeks, percent decreases in BMD from baseline (mean ± SD) were greater in patients receiving VIREAD + lamivudine + efavirenz (spine, -3.3% ± 3.9 ; hip, -3.2% ± 3.6) compared with patients receiving stavudine + lamivudine + efavirenz (spine, -2.0 ± 3.5; hip. -1.8% ± 3.3). The proportion of patients who met a protocol defined value of BMD loss (5% decrease in spine or 7% decrease in hip) was higher in the VIREAD group than the stavudine group. In addition, there were significant increases in levels of four biochemical markers of bone metabolism (serum bone -specific alkaline phosphatase, serum osteocalcin, serum C-telopeptide and urinary N-telopeptide) in the VIREAD group relative to the stavudine group, suggesting increased bone turnover. Serum parathyroid hormone levels were also higher in the VIREAD group. Except for bone specific alkaline phosphatase, these changes resulted in values that remained within the normal range. There was one bone fracture reported in the VIREAD group compared with four in the stavudine group; no pathologic fractures were identified over 48 weeks of study treatment. The clinical significance of the changes in BMD and biochemical markers is unknown and follow-up is continuing to assess long-term impact.

Bone monitoring should be considered for HIV infected patients who have a history of pathologic bone fracture or are at substantial risk for osteopenia. Although the effect of supplementation with calcium and vitamin D was not studied, such supplementation may be considered for HIV-associated osteopenia or osteoporosis. If bone abnormalities are suspected then appropriate consultation should be obtained.

Richard Klein
Office of Special Health Issues
Food and Drug Administration

Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration

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8/14/2003

The following information, related to the August 20, 2003 FDA Antiviral Drugs Advisory Committee meeting to discuss clinical trial design issues for the development of topical microbicides to to reduce HIV transmission has been posted on the FDA website:

Notice of Meeting
August 20, 2003 Draft Agenda
August 20, 2003 Draft Questions
August 20, 2003 Briefing Information

You can access the information from the links above, or find the posting at http://www.fda.gov/ohrms/dockets/ac/cder03.html#AntiviralDrugs


Richard Klein
Office of Special Health Issues
Food and Drug Administration

Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration

Return to Index

8/8/2003

August 8, 2003

Re: Important New Pharmacokinetic Data for REYATAZ™ (atazanavir sulfate) in combination with Viread® (tenofovir disoproxil fumarate)

Dear Health Care Provider,

Bristol-Myers Squibb Company would like to make clinicians caring for HIV-infected patients aware of important new pharmacokinetic (PK) data concerning the coadministration of REYATAZ™ (atazanavir sulfate) and Viread® (tenofovir disoproxil fumarate, Gilead Sciences, Inc.). Two studies have been conducted to evaluate the potential PK interaction between REYATAZ and tenofovir disoproxil fumarate (tenofovir DF), and an additional ongoing clinical study has provided preliminary data on the safety profile of this combination. Data from these trials are currently under review by the Food and Drug Administration. For more details on these studies please refer to the STUDY INFORMATION section below.

The following observations were made from these three trials:

Study AI454-181: In healthy volunteers atazanavir AUC and Cmin were decreased by approximately 25% and 40%, respectively, when unboosted REYATAZ 400 mg was coadministered with tenofovir DF 300 mg once daily (QD) as compared to REYATAZ alone. In addition, an increase of approximately 24% in tenofovir AUC was observed.

Study PUZZLE 2 (ANRS 107): Atazanavir AUC and Cmin were decreased by approximately 25% and 23%, respectively, when REYATAZ 300 mg and ritonavir 100 mg (boosted REYATAZ) were coadministered with tenofovir DF 300 mg QD, as compared to REYATAZ 300 mg and ritonavir 100 mg administered without tenofovir DF to HIV-infected patients.

For the combination of boosted REYATAZ with tenofovir DF, the atazanavir AUC and Cmin observed in the Puzzle 2 study were approximately 1.2 and 4 fold higher than the respective values observed for unboosted REYATAZ, 400 mg given alone, to healthy volunteers in Study AI424-181.

Study AI424-045: Interim safety data from an ongoing clinical trial suggest that the treatment emergent adverse events of moderate or severe intensity are comparable for boosted REYATAZ in treatment experienced patients and for unboosted REYATAZ treated patients in other clinical trials .

Based on these results:

Clinicians should use caution when administering unboosted REYATAZ with tenofovir DF. Unboosted REYATAZ may be less effective due to decreased atazanavir concentrations in patients taking REYATAZ and tenofovir DF. As a result the coadministration of unboosted REYATAZ with tenofovir DF may lead to loss or lack of virologic response and possible resistance to REYATAZ.

If REYATAZ is coadministered with tenofovir DF, consideration should be given to administering REYATAZ 300 mg with ritonavir 100 mg and tenofovir DF 300 mg (all as a single daily dose with food), until additional data are obtained. Coadministration of REYATAZ 300 mg and ritonavir 100 mg QD is currently under clinical investigation.

The increase in tenofovir AUC does not appear to be associated with increased toxicity over 24 weeks.

STUDY INFORMATION:

Study AI454-181 conducted by Bristol-Myers Squibb (BMS) Pharmaceutical Research Institute

Design: Phase I, open-label study in healthy subjects to evaluate whether the PK parameters of either unboosted REYATAZ 400 mg QD or tenofovir DF 300 mg QD were affected by their coadministration. The PK parameters of REYATAZ 400 mg QD administered with food were compared to those of REYATAZ 400 mg QD when coadministered with tenofovir 300 mg QD and food.

Puzzle 2 (ANRS 107) Trial - PK Sub-study conducted by Taburet et al.

Design: An ongoing efficacy study and PK sub-study in highly treatment-experienced HIV-infected subjects. HIV-infected subjects experiencing failure on a protease inhibitor (PI)-containing regimen were treated for the initial two weeks of the study with REYATAZ 300 mg QD plus ritonavir 100 mg QD substituted for the failing PI. Current nucleoside reverse transcriptase inhibitors (NRTIs) were continued for the initial two-week period after which time they were replaced with tenofovir DF 300 mg QD and a second NRTI chosen by genotypic testing. Atazanavir pharmacokinetics were determined at Week 2 before the introduction of tenofovir DF and again at Week 6.

Study AI424-045 conducted by Bristol-Myers Squibb (BMS) Pharmaceutical Research Institute

Design: An ongoing 48-week, Phase III, randomized, multinational, open-label three-arm trial of 358 highly treatment-experienced HIV-infected subjects. One arm of this study is evaluating the efficacy, safety and tolerability of the combination of REYATAZ 300 mg and ritonavir 100 mg QD coadministered with tenofovir DF 300 mg QD and one NRTI.

BMS is committed to providing you with current product information for the management of your patients with HIV infection. You can assist us in monitoring the safety of our products by reporting adverse reactions to BMS at 1-800-426-7644 (select option 2) or to FDA's MedWatch program by telephone at 1-800-332-1088, by fax at 1-800-332-0178, via www.FDA.gov/medwatch, or by mail to MedWatch, HF-2, FDA, 5600 Fishers Lane, Rockville, MD 20857.

If you have questions about the new information or want additional medical information, please contact the Virology Medical Services Department at Bristol-Myers Squibb Company at 1-800-426-7644 (select option 3).

Sincerely,

Sally Hodder, MD
Vice President, Virology Medical Affairs
Bristol-Myers Squibb Company

REYATAZ™ is a trademark of Bristol-Myers Squibb Company.
Viread® is a registered trademark of Gilead Sciences, Inc.

Richard Klein
Office of Special Health Issues
Food and Drug Administration

Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration

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8/8/2003

The Centers for Disease Control and Prevention (CDC), the American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA) have worked together to develop the attached revisions in recommendations for the treatment of latent TB infection because of unacceptable toxicity experienced with the use of two months of rifampin plus pyrazinamide. (See attached letter from Dr. Kenneth Castro and summary from CDC at http://www.cdc.gov/nchstp/tb/pubs/tbfactsheets/250110.htm

James B. McAuley, MD, MPH

Chair, IDSA Tuberculosis Committee

------------------------------------------------------------------------------------------------------------------

August 7, 2003

Dear Colleague:

The August 8, 2003 issue of the Morbidity and Mortality Weekly Report (MMWR) contains an article entitled Adverse Event Data and Revised American Thoracic Society/CDC Recommendations Against the Use of Rifampin and Pyrazinamide for Treatment of Latent Tuberculosis Infection. The article revises the Centers for Disease Control and Prevention (CDC) and the American Thoracic Society (ATS) treatment recommendations for latent tuberculosis infection (LTBI) to indicate that the 2-month regimen of rifampin plus pyrazinamide (RZ) should generally not be offered.

The following is key background information:

Studies in HIV-infected persons documenting the safety and efficacy of the RZ regimen for the treatment of LTBI led the ATS and CDC, in April 2000, to recommend this regimen for the treatment of LTBI. However, in October 2000, CDC received a report of a patient who died while receiving RZ. To investigate this event, CDC initiated surveillance for such adverse events and undertook a study to estimate their frequency.

From October 2000 to June 2003, a total of 48 cases of confirmed RZ-associated severe liver injury were reported to CDC; 11 were fatal, including two known to be HIV-infected.

To estimate the incidence of RZ-associated severe liver injury and provide more precise data to guide treatment for LTBI, CDC collected data from cohorts of patients in the United States who received RZ for the treatment of LTBI during January 2000-June 2002. This survey found high rates of hospitalization and death from liver injury associated with the use of RZ.

In May, June, and July 2003, CDC presented the surveillance data, survey results, and recent published studies of RZ-associated liver injury, and hospitalization to several groups of national experts, including the ATS, Infectious Diseases Society of America (IDSA), the American College of Chest Physicians, and the Food and Drug Administration (FDA). After reviewing all these data and the experts' opinions, ATS and CDC (with IDSA endorsement) revised their original recommendation to advise that the RZ regimen should generally not be offered.

The response of CDC in identifying patients with adverse effects and issuing alerts to the medical community led to a rapid decline in reports of serious adverse effects; however, such events have continued to occur. Although we are recommending against the use of the RZ regimen, we continue to strongly support the treatment of LTBI as a key component of CDC's efforts to eliminate tuberculosis. Fortunately, other regimens for the treatment of LTBI are safe and effective. The preferred regimen is isoniazid (INH) for 9 months; alternatives are INH for 6 months or rifampin for 4 months. It is important to note that the recommendation against the use of RZ for treatment of LTBI does not apply to the appropriate use of rifampin and pyrazinamide in multidrug regimens for the treatment of persons with active TB disease.

Copies of this report may be viewed on the internet at http://www.cdc.gov/mmwr/

If you have any questions or need additional information, please contact the National Center for HIV, STD, and TB Prevention's Office of Communications at 404-639-8890.

Sincerely,

Kenneth G. Castro, M.D.
Assistant Surgeon General, USPHS
Director
Division of Tuberculosis Elimination
National Center for HIV, STD, and TB Prevention
________________________________________

Richard Klein
Office of Special Health Issues
Food and Drug Administration

Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration

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8/6/2003

The FDA Drug Review Package for Fuzeon (enfuvirtide), manufactured by Hoffman-LaRoche, Inc., for injection to treat HIV is available on the FDA website.

The following information is available at /cder/approval/index.htm
Choose "F" from the Index, and scroll down to "Fuzeon" at the end of the list.

Approval Letter
Printed Labeling
Medical Review
Chemistry Review
Clinical Review
Pharmacology Review
Statistical Review
Microbiology Review
Clinical Pharmacology Biopharmaceutics Review
Administrative Document(s) & Correspondence

Richard Klein
Office of Special Health Issues
Food and Drug Administration

Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration

Return to Index

7/25/2003

GalxoSmith Kline has issued the following Dear Health Care Provider Letter regarding Early Virologic Non-Response in Patients wtih HIV infection treated with lamivudine, abacavir and tenofovir. Below is a copy of the letter.

July 2003

IMPORTANT DRUG WARNING

RE: Early Virologic Non-Response in Patients with HIV Infection Treated
With Lamivudine, Abacavir and Tenofovir

Dear Health Care Provider,

GlaxoSmithKline (GSK) is writing to inform you of a high rate of early virologic non-response observed in a GSK-sponsored clinical study (ESS30009) of therapy-naive adults receiving once-daily three-drug combination therapy with lamivudine (Epivir®, GlaxoSmithKline), abacavir (Ziagen®,
GlaxoSmithKline) and tenofovir (Viread(tm), TDF, Gilead Sciences). Based on these results:

* Abacavir and lamivudine in combination with tenofovir should not be
used as a triple antiretroviral therapy when considering a new treatment regimen for naive or pre-treated patients.
* Any patient currently controlled on therapy with this combination
should be closely monitored and considered for modification of therapy.
* Any usage of this triple combination with other antiretroviral
agents should be closely monitored for signs of treatment failure.

Study ESS30009 is a randomized, open-label, multi-center study of the safety and efficacy of efavirenz (EFV 600mg daily, Sustiva®, Bristol-Myers Squibb
Co.) versus tenofovir (TDF 300mg daily) when administered in combination with an investigational abacavir/lamivudine (ABC 600mg daily plus 3TC 300mg
daily) fixed-dose combination tablet as a once-daily regimen in antiretroviral-naïve HIV-1 infected adults. Shortly after initiation of this study, GlaxoSmithKline received reports from investigators of poor efficacy in patients receiving TDF+3TC+ABC. An urgent, unplanned interim analysis was conducted to assess virologic non-response, defined as either
(a) failure to achieve a 2 log decrease from baseline by treatment week 8 or
(b) a 1 log increase above nadir on any subsequent treatment visit. Results are shown in the following table:

Number (%) of Patients Meeting the Definition of Virologic Non-Response
TDF + 3TC + ABC EFV +3TC+ ABC
HIV-1 RNA data for subjects on therapy 50 / 102 (49%) 5 / 92 (5%) for > 8 weeks
HIV-1 RNA data for subjects on therapy 30 / 63 (48%) 3 / 62 (5%)
for > 12 weeks

The precise nature of any interaction leading to non-response in this study is not known. Preliminary genotypes of viral isolates from 14 patients with non-response taking the TDF+3TC+ABC regimen have shown all 14 isolates had the M184V mutation in HIV reverse transcriptase. In addition, 8 of the 14
(57%) isolates also had the K65R mutation.

On review of these results, GSK promptly informed all participating clinical investigators and terminated the TDF+3TC+ABC arm in this study. Clinical investigators are working with patients to change therapy based on genotype and clinical judgement. The once daily EFV+3TC+ABC arm performed well and continues unchanged in this clinical study.

In addition to study ESS30009, a pilot study by Farthing et al. (2nd annual meeting of the International AIDS Society, July, 2003, Paris, France) provided data in 20 patients receiving TDF+3TC+ABC once daily for initial therapy. As in ESS30009, a high rate of virologic non-response was documented.

GlaxoSmithKline is committed to providing you with current product information for the management of your patients with HIV infection. You can assist us in monitoring the safety of our products by reporting adverse reactions to GlaxoSmithKline's Product Surveillance Department at 1-888-825-5249 or to FDA's MedWatch program by telephone at 1-800-332-1088, by fax at 1-800-332-0178, via www.FDA.gov/medwatch, or by mail to MedWatch, HF-2, FDA, 5600 Fishers Lane, Rockville, MD 20857.

If you have questions about the new information or want additional medical information, please contact the GlaxoSmithKline Customer Response Center at 1-888-825-5249. Thank you.

Sincerely,

Douglas J. Manion, M.D.
Vice President, Clinical Development and Medical Affairs
___________________________________________________

Richard Klein
Office of Special Health Issues
Food and Drug Administration

Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration

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7/2/2003

The Food and Drug Administration (FDA) announced on Wednesday, July 2, 2003, the approval of Emtriva (FTC, emtricitabine), a new nucleoside reverse transcriptase inhibitor (NRTI) to be used in combination with other anti-retroviral agents for the treatment of patients with HIV infection. As with other anti-retroviral agents, Emtriva does not cure and does not prevent transmission of HIV infection or AIDS.

Emtriva is indicated for adults age 18 and older. Safety and effectiveness in pediatric patients have not been established. In antiretroviral-treatment-experienced patients, the use of Emtriva may be considered for adults with HIV strains that are expected to be susceptible to Emtriva as assessed by genotypic or phenotypic testing. The recommended dose of Emtriva is one 200 mg capsule daily, with or without food.

FDA based its approval on data from two 48 week clinical trials. The first trial was a double-blind, active-controlled multicenter study comparing Emtriva (200 mg once daily) administered in combination with didanosine and efavirenz versus stavudine, didanosine and efavirenz in 571 antiretroviral naïve patients. The proportion of patients who achieved and maintained confirmed HIV RNA < 400 copies/mL (< 50 copies/mL) through week 48 was 81% (78%) for the Emtriva, didanosine and efavirenz group vs 61% (59%) for the stavudine, didanosine and efavirenz group, respectively. The mean increase from baseline in CD4 cell count was 168 cells/mm3 for the Emtriva arm compared to 134 cells/mm3 for the control arm.

The second trial was an open-label, active-controlled multicenter study comparing Emtriva to lamivudine, in combination with stavudine or zidovudine and a protease inhibitor or NNRTI in 440 treatment experienced patients who were on lamivudine-containing triple-antiretroviral drug regimen for at least 12 weeks prior to study entry, and had HIV-1 RNA £ 400 copies/mL. The proportion of patients who achieved confirmed HIV RNA < 400 copies/mL (< 50 copies/mL) through week 48 was 77% (67%) for the Emtriva group vs 82% (72%) for the lamivudine group. The mean increase from baseline in CD4 cell count was 29 cells/mm3 for the Emtriva arm compared to 61 cells/mm3 for the lamivudine arm.

The most common adverse events that occurred in patients receiving Emtriva with other antiretroviral agents in clinical trials were headache, diarrhea, nausea, and rash, which were generally of mild to moderate severity. Approximately 1% of patients discontinued participation in the clinical studies due to these events. With the exception of skin discoloration, which was reported with higher frequency in the Emtriva treated group all other adverse events were reported with similar frequency in Emtriva and control treatment groups.

Skin discoloration, manifested by hyperpigmentation (excess pigmentation) on the palms and/or soles, was predominantly observed in non-Caucasian patients. The mechanism and clinical significance are unknown.

It is recommended that all patients with HIV be tested for the presence of chronic hepatitis B virus (HBV) before initiating antiretroviral therapy. Emtriva is not indicated for the treatment of chronic HBV infection and the safety and efficacy of Emtriva have not been established in patients co-infected with HBV and HIV. "Flare-ups" of hepatitis B, where the illness can return in a worse way than before, have been reported in patients after the discontinuation of Emtriva. Patients co-infected with HIV and HBV should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment.

As with other NRTIs, Emtriva may cause lactic acidosis (buildup of an acid in the blood), serious liver problems called hepatotoxicity, with liver enlargement (hepatomegaly) and fat in the liver (steatosis).

Emtriva is a product of Gilead Sciences, Foster City, CA, USA.

Richard Klein
Office of Special Health Issues
Food and Drug Administration

Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration

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6/23/2003

The Food and Drug Administration (FDA) announced on Friday, June 20, 2003, the approval of Reyataz (atazanavir sulfate), a protease inhibitor to be used in combination with other anti-retroviral agents for the treatment of patients with HIV infection. As with other anti-retroviral agents, Reyataz does not cure and does not prevent transmission of HIV infection or AIDS.

Approval of this drug permits patients access to a once-a-day protease inhibitor. The recommended dose of Reyataz is 400 mg (two 200 mg capsules) once daily, with food.

FDA based its approval of Reyataz on data from two Phase 2 48-week trials and from 24-48 week data from Phase 3 studies. Results from these trials showed a decrease in viral load (the amount of HIV-1 virus circulating in plasma) and an increase in CD4 cell counts (a measure of immune cells created by the body) in patients taking Reyataz in combination with other anti-retroviral agents. These treatment benefits were observed both in patients who had not been previously treated and in patients who had previously received other anti-retroviral therapy.

A significant safety concern commonly observed with the use of protease inhibitors is hyperlipidemia. Reyataz appears to have minimal impact on lipid parameters such as triglycerides and cholesterol.

The most common laboratory abnormality observed with the use of Reyataz is hyperbilirubinemia (abnormally high amounts of bilirubin, an orange-yellow pigment in the bile that forms as a product of hemoglobin; excess amounts in the blood produce the yellow appearance observed in jaundice) in the blood. This laboratory abnormality resulted in the clinical adverse event of jaundice (yellowing of the skin) or scleral icterus (yellowing of the eyes) in 15-24% of subjects taking Reyataz. This abnormality was shown to be reversible upon discontinuation of the drug. Hyperbilirubinemia with Reyataz did not appear to be associated with an increased risk of liver injury.

The most frequently reported adverse events among patients in the clinical trials were nausea, infection, headache, vomiting, diarrhea, abdominal pain, somnolence (drowsiness), insomnia, and fever.

Currently there are six other protease inhibitors approved by FDA for the treatment of HIV infection. These medications work at the final stages of viral replication and attempt to prevent HIV from making new copies of itself by interfering with the HIV protease enzyme. As a result, the new copies of HIV are not able to infect new cells.

Reyataz is manufactured by Bristol-Myers Squibb Company of Princeton, NJ.

Richard Klein
Office of Special Health Issues
Food and Drug Administration

Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration

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6/12/2003

The Food and Drug Administration (FDA) will hold a meeting of its Antiviral Drugs Advisory Committee on on August 20, 2003, from 8 a.m. to 5 p.m. at the Holiday Inn, Versailles Ballroom, 8120 Wisconsin Avenue, Bethesda, MD, 20814.

The committee will discuss clinical trial design issues in the development of topical microbicides for the reduction of HIV transmission.

The meeting will be open to the public. No registration is necessary. If you need directions or accommodations, please contact the hotel directly at 301.652.2000

Interested persons may present data, information, or views, orally or in writing, on issues pending before the committee.

Written submissions may be made to Tara P. Turner, Pharm.D (see contact information below) by August 13, 2003. Oral presentations from the public will be scheduled between approximately 1 p.m. and 2 p.m. Time allotted for each presentation may be limited depending on number of speakers.

Those desiring to make formal oral presentations should notify the contact person before August 13, 2003, and submit a brief statement of the general nature of the evidence or arguments they wish to present, the names and addresses of proposed participants, and an indication of the approximate time requested to make their presentation.

Persons attending FDA's advisory committee meetings are advised that the agency is not responsible for providing access to electrical outlets.

FDA welcomes the attendance of the public at its advisory committee meetings and will make every effort to accommodate persons with physical disabilities or special needs. If you require special accommodations due to a disability, please contact Tara Turner at least 7 days in advance of the meeting.

Contact Information: Tara P. Turner, Pharm.D., Center for Drug Evaluation and Research (HFD-21), Food and Drug Administration, 5600 Fishers Lane (for express delivery, 5630 Fishers Lane, Rm. 1093), Rockville, MD 20857, 301-827-7001, FAX 301.827.6776, e-mail: TurnerT@cder.fda.gov

Please call the FDA Advisory Committee Information Line, 1-800-741-8138 (301-443-0572 in the Washington, DC area), and enter code 12531 for up-to-date information about this meeting.

Richard Klein
Office of Special Health Issues
Food and Drug Administration

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4/30/2003

Today, April 30, 2003, the Food and Drug Administration approved a new alternate dosing formulation of Viracept (nelfinavir mesylate). Viracept has been available in 50 mg oral powder and 250 mg tablets. The new formulation of 625 mg reduces the pill burden from five-250 mg tablets twice a day to two-625 mg tablets twice a day, potentially facilitating adherence to treatment regimens.

Viracept is a protease inhibitor indicated for the treatment of HIV-1 infection in combination with other antiretroviral agents. The 250-mg tablet and oral powder received marketing approval in 1997 based on substantive evidence of efficacy and safety. Results of the bioequivalence study of the 250-mg tablet and the 625-mg tablet revealed increased bioavailability with the 625-mg formulation.

The sponsor, Agouron Pharmaceuticals, has submitted clinical safety and pharmacokinetic data to FDA providing evidence that the higher exposures do not pose a safety risk. However, diarrhea may be more common in patients receiving the 625 mg formulation. No efficacy information is contained in this submission because it is unlikely that a more bioavailable formulation would be less efficacious.

The efficacy of Viracept was previously demonstrated and reviewed in NDAs 20778/9.

Richard Klein
Office of Special Health Issues
Food and Drug Administration

Return to Index

4/28/2003

Available on the FDA web site:
A Catalog of FDA Approved Drug Products
FDA announces Drugs@FDA: A Catalog of FDA Approved Drug Products, a pilot project that provides a single, searchable internet source where you can search for official, up-to-date information about FDA approved brand name and generic drugs(including those for the treatment of HIV/AIDS and related conditions).

Prescription, over-the-counter, and discontinued drugs are included in the database. Links are provided to access approval letters, labels, and scientific reviews. The majority of labels, approval letters, reviews, and other information are available for drug products approved from 1998 to the present.

Drugs@FDA does not include:

Dietary supplements.
Drugs for animals. Drugs withdrawn for reasons of safety or effectiveness.
Over-the-counter products that are approved for marketing though a process other than submitting a New Drug Application.
Prescription drugs sold in countries other than the United States.
Prescription drugs sold (illegally) in the United States without FDA approval.
Drugs that are under review at FDA for which no action regarding approval has occurred.
Biological products including bacterial and viral vaccines; human blood products; certain products produced by biotechnology, such as interferons and erythropoietins; and gene therapy. You can access the site at
http://www.accessdata.fda.gov/scripts/cder/drugcat/
[Note, 8-1-2005: The URL for Drugs@FDA is now http://www.accessdata.fda.gov/scripts/cder/drugsatfda/

Search results for all drug products include:

drug name (brand name or generic name)
active ingredient
form and route of administration
strength
marketing status (prescription, over-the-counter, or discontinued)
company that sponsored an application for approval
FDA action date
Product numbers
Supplement type (type of regulatory action)

This is a pilot project of FDA. Your comments, which can be submitted at the website, are encouraged.

Richard Klein
Office of Special Health Issues
Food and Drug Administration

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4/4/2003

The Food and Drug Administration (FDA) will hold a meeting of its Antiviral Drugs Advisory Committee on on May 13 and 14, 2003, from 8 a.m. to 5 p.m. at the Holiday Inn, 2 Montgomery Village Avenue, Gaithersburg, MD.

On May 13, 2003, the committee will discuss new drug applications (NDA) 21-567 and 21-568, Reyataz™ (atazanavir sulfate) capsules and powder for oral use, Bristol-Myers Squibb Company, proposed for the treatment of HIV infection in combination with other antiretroviral agents.

On May 14, 2003, the committee will discuss supplemental new drug application (sNDA) 20-550/S-019, Valtrex® (valacyclovir hydrochloride) caplets, GlaxoSmithKline, proposed for reduction of the risk of transmission of genital herpes with the use of suppressive therapy.

The meeting will be open to the public. No registration is necessary. If you need directions or accommodations, please contact the hotel directly at 301.948-8900

Interested persons may present data, information, or views, orally or in writing, on issues pending before the committee. Written submissions may be made to Tara P. Turner, Pharm.D (see contact information below) by May 6, 2003. Oral presentations from the public will be scheduled between approximately 1 p.m. and 2 p.m. on May 13, 2003, and between approximately 11 a.m. and 12 noon on May 14, 2003. Time allotted for each presentation may be limited depending on number of speakers. Those desiring to make formal oral presentations should notify the contact person before May 6, 2003, and submit a brief statement of the general nature of the evidence or arguments they wish to present, the names and addresses of proposed participants, and an indication of the approximate time requested to make their presentation.

Persons attending FDA's advisory committee meetings are advised that the agency is not responsible for providing access to electrical outlets.

FDA welcomes the attendance of the public at its advisory committee meetings and will make every effort to accommodate persons with physical disabilities or special needs. If you require special accommodations due to a disability, please contact Tara Turner at least 7 days in advance of the meeting.

Contact Person: Tara P. Turner, Pharm.D., Center for Drug Evaluation and Research (HFD-21), Food and Drug Administration, 5600 Fishers Lane (for express delivery, 5630 Fishers Lane, Rm. 1093), Rockville, MD 20857, 301-827-7001, e-mail: TurnerT@cder.fda.gov

Please call the FDA Advisory Committee Information Line for up-to-date information about this meeting.
FDA Advisory Committee Information Line, 1-800-741-8138 (301-443-0572 in the Washington, DC area), and enter code 12531.

Richard Klein
Office of Special Health Issues
Food and Drug Administration

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4/1/2003

A special supplement to Clinical Infectious Diseases, a journal of The Infectious Diseases Society of America , was published today, April 1, 2003 (Clinical Infectious Diseases, Volume 36, Supplement 2). It contains a special report on current issues related to nutrition management and HIV infection.

The supplement is a collaborative work of more than 50 authorities representing a wide range of expertise in conjunction with 5 federal agencies: the Health Resources and Services Administration, the Food and Drug Administration, the Centers for Disease Control and Prevention, the National Institutes of Health, and the Department of Veterans Affairs.

Nutrition is an important, but often overlooked aspect of HIV disease management. John Bartlett, of the Johns Hopkins University School of Medicine, states in the supplement's introduction: "...modern management of HIV infection now requires substantial expertise in dealing with nutritional issues and access to this expertise, despite the fact that there have been virtually no guidelines that specifically target the nutritional care of the HIV-infected population. This report on the nutrition management and concerns of HIV infection is consequently most welcome as timely, authoritative, and greatly needed."


INTEGRATING NUTRITION THERAPY INTO MEDICAL MANAGEMENT OF HUMAN
IMMUNODEFICIENCY VIRUS
is now available at http://www.journals.uchicago.edu/cgi-bin/contents?CID+v36nS2
(Available to IDSA subscribers)

The topics covered in this special supplement are:

Introduction: Integrating Nutrition Therapy into Medical Management of Human Immunodeficiency Virus
John G. Bartlett

General Nutrition Management in Patients Infected with Human Immunodeficiency Virus
Judith Nerad, Mary Romeyn, Ellyn Silverman, Jackie Allen-Reid, Doug
Dieterich, Jill Merchant, Veronique A. Pelletier, Donna Tinnerello, and
Marcy Fenton

Assessment of Nutritional Status, Body Composition, and Human
Immunodeficiency Virus-Associated Morphologic Changes
Tamsin A. Knox, Melissa Zafonte-Sanders, Cade Fields-Gardner, Karol Moen,
Diana Johansen, and Nicholas Paton

Weight Loss and Wasting in Patients Infected with Human Immunodeficiency Virus
Steven Grinspoon, and Kathleen Mulligan, for the Department of Health and
Human Services Working Group on the Prevention and Treatment of Wasting and
Weight Loss

Lipid Abnormalities
Michael Dube and Marcy Fenton

Body Habitus Changes Related to Lipodystrophy
Fred Sattler

Insulin and Carbohydrate Dysregulation
Marie C. Gelato

Lactic Acidemia in Infection with Human Immunodeficiency Virus
Andrew Carr

Emerging Bone Problems in Patients Infected with Human Immunodeficiency Virus
Kristin Mondy and Pablo Tebas

Food and Water Safety for Persons Infected with Human Immunodeficiency Virus
Celia Hayes, Elisa Elliot, Edwin Krales, and Goulda Downer

To subscribe to CID or to order single copies of the supplement, see http://www.journals.uchicago.edu/CID/order1.html

Richard Klein
Office of Special Health Issues
Food and Drug Administration

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3/13/2003

First drug in a new class of HIV/AIDS treatments for HIV-infected adults and children with advanced HIV infection

The Food and Drug Administration (FDA) approved FUZEON (enfuvirtide, also known as T-20) on Thursday, March 15, 2003, for use in combination with other anti-HIV medications to treat advanced HIV-1 infection in adults and children ages 6 years and older.

FDA's approval of FUZEON is the first, worldwide, of a new class of drugs known as "fusion inhibitors." Fusion inhibitors interfere with the entry of HIV-1 into cells by inhibiting the merging of the virus with the cellular membrane, the first step in viral infiltration. This inhibition blocks HIV before it enters the human immune cell.

Combination therapy using multiple medications is used to effectively treat HIV infection. However, a significant percentage of patients with chronic HIV have developed infection resistant to many existing medications. Because of its unique mode of action, FUZEON may be active against HIV that is resistant to currently available classes of anti-HIV drugs.

FUZEON, administered twice daily as a subcutaneous injection (under the skin), can be used as part of a treatment regimen in patients for whom there are limited options. It should only be used in patients who have used other anti-HIV medications and show evidence of ongoing viral replication.

FDA based its approval on an analysis of six months of data from two ongoing clinical studies of FUZEON involving approximately 1,000 patients. The data from this analysis showed that the addition of FUZEON to a combination of other antiretroviral medications reduced viral load in the blood, a measure of HIV infection, more than the use of the combination of medications alone.

FUZEON was studied in 35 pediatric patients from the age of 6 years to 16 with pharmacokinetic data from 18 of these patients.

The long-term effects of FUZEON are not known at this time, but are being evaluated by ongoing clinical studies.

The approved labeling for FUZEON warns physicians to carefully monitor patients for signs and symptoms of pneumonia. Although bacterial pneumonia was not common in clinical study participants, more patients treated with FUZEON developed bacterial pneumonia than did patients who did not receive FUZEON. Patients receiving FUZEON are advised to seek medical evaluation immediately if they develop signs or symptoms suggestive of pneumonia, such as cough with fever, rapid breathing and shortness of breath.

In addition, FUZEON can cause serious allergic reactions, and local skin reactions at the site of injection.

Symptoms of a serious allergic reaction with FUZEON can include: trouble breathing, fever with vomiting and a skin rash, blood in urine, and swelling of the feet. Patients taking FUZEON should contact their healthcare provider right away if they experience any of these symptoms.

Local skin reactions from FUZEON injections are common, occurring in almost all patients, and may be painful. Patients must be careful that their skin does not become infected at the site of injection. It is important to follow the injection Instructions that come with the medication to lower the chances of getting an injection site infection.

Patients should call their health care provider if there are signs of infection at the injection site such as drainage, increasing heat, swelling, redness or pain.

Because of the molecular complexity, and difficulty of manufacture, it is possible that demand for FUZEON may exceed supply at launch. The sponsor is working with HIV physician and patient groups to develop a progressive launch plan, and will carefully manage allocation of FUZEON.

Roche Pharmaceuticals of Nutley, N.J., has licensed the product from Trimeris Inc. of Durham, N.C., and will distribute FUZEON.

Richard Klein
Office of Special Health Issues
Food and Drug Administration

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3/12/2003

Counterfeit Procrit

As part of the Food and Drug Administration's (FDA) ongoing efforts to investigate and address unscrupulous counterfeiting activities, FDA's Office of Criminal Investigation has uncovered the existence of contaminated counterfeit Procrit, also known as epoetin alfa. Procrit is used to stimulate the production of red blood cells in humans to treat severe anemia, and is indicated for some people with anemia related to treatment for HIV/AIDS.

As a result of investigative review and laboratory testing performed by FDA, and in cooperation with Ortho Biotech Products, L.P., Bridgewater, N.J., healthcare providers and consumers are being alerted to the existence of three lots of counterfeit product labeled as Procrit (epoetin alfa):

P007645 - 40,000 units/mL, Expiration 10-2004
P004677 - 40,000 units/mL, Expiration 02-2004
P004839 - 40,000 units/mL, Expiration 02-2004

The firm is issuing the warning to healthcare providers and others today in a letter (also posted on its website - see below) because counterfeit Procrit has been found to be contaminated with bacteria and therefore represents a significant potential hazard to consumers. In addition, FDA testing has demonstrated that some counterfeit product contains no active ingredient.

FDA urges health care providers and patients alike to check the packaging and vials very carefully before using this product. Anyone finding counterfeit product should not use it, should quarantine it, and should immediately contact FDA's Center for Biologics Evaluation and Research at 1-800-835-4709, prompt #1, then prompt #5, and Ortho Biotech at 1-800-325-7504, prompt #2.

In the performance of its responsibilities to assure the safety of products it regulates, FDA regularly conducts investigations and testing to identify and remove from the market counterfeit, tampered, or otherwise unsuitable products. FDA supports the activities of legitimate manufacturers, in cooperation with FDA, to inform the public about counterfeit products and how to identify them. FDA is committed to continued vigilance in rooting out counterfeiting activity and alerting the public to the existence of counterfeit product.

Physicians, pharmacists, nurses and patients should carefully examine all PROCRIT packaging and vials before use. Additional details concerning the counterfeit product, including identifying characteristics and photographs to help identify possible counterfeit product are available on Ortho's website.

FDA's investigation into this matter is continuing.

Richard Klein
Office of Special Health Issues
Food and Drug Administration

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3/11/2003

Although this issue is not specifically related to HIV/AIDS, it may be of interest to patients, caregivers, and others involved in HIV issues, as well as other consumers, because of the widespread use and popularity of dietary supplements.

FDA is soliciting comments from the public and industry on how this proposed regulation can best achieve the goals of promoting accurate labeling information and preventing adulteration of dietary supplements without imposing unnecessary regulatory burdens.
FDA Proposes Labeling and Manufacturing Standards For All Dietary Supplements
The Food and Drug Administration took action late last week to help consumers get accurately labeled and unadulterated dietary supplements by proposing a new regulation to require current good manufacturing practices (CGMPs) in their manufacturing, packing, and holding. The proposed rule would, for the first time, establish standards to ensure that dietary supplements and dietary ingredients are not adulterated with contaminants or impurities, and are labeled to accurately to reflect the active ingredients and other ingredients in the product.

This proposed rule includes requirements for designing and constructing physical plants, establishing quality control procedures, and testing manufactured dietary ingredients and dietary supplements. It also includes proposed requirements for maintaining records and for handling consumer complaints related to CGMPs.

"Americans must have confidence that the dietary supplements they purchase are not contaminated and that they contain the dietary ingredients and the amounts claimed on the labels," said HHS Secretary Tommy G. Thompson. "Millions of Americans use dietary supplements, and we owe it to them to ensure that they are getting the products they're paying for."

In recent years, analyses of dietary supplements by a private sector laboratory suggest that a substantial number of dietary supplement products analyzed may not contain the amounts of dietary ingredients that would be expected to be found based on their product labels. For example:

Five of 18 soy and/or red clover-containing products were found to contain only 50 percent to 80 percent of the declared amounts of isoflavones.
Of 25 probiotic products tested, 8 contained less than 1 percent of the claimed number of live bacteria or the number of bacteria that would be expected to be found in such a product.
FDA has also encountered products being marketed that are not accurately labeled or contain contaminants that should not be present or may be harmful. For example:

One firm recalled its dietary supplements that were contaminated with excessive amounts of lead, which may have posed a health risk to many consumers, especially children and women of childbearing age.
Another firm recalled a niacin product after it received reports of nausea, vomiting, liver damage, and heart attack associated with the use of its product. A dietary ingredient manufacturing firm had mislabeled a bulk ingredient container that subsequently was used by another firm in making a product that contained almost ten times more niacin than the amount that may be safe.
Another firm recalled its product after it was found that a dietary supplement containing folic acid, which is often taken by women to reduce the risk of having a baby with neural tube defects, contained only 35 percent of the amount of folic acid claimed on the label.
"This proposed regulation is another major step in our efforts to help Americans take more control over their own health. Too often, consumers purchase dietary supplements based on inaccurate or incomplete information on what they are getting. This proposed regulation would require that dietary supplements provide accurate information on the type and amount of ingredients they contain and that dietary supplements are produced using safe methods, " said Mark B. McClellan, M.D., Ph.D., Commissioner of Food and Drugs. "Consumers should have access to dietary supplements that are accurately labeled and are free from contaminants."

FDA's action will also permit more informative research on dietary supplements, to improve the science available on their safety and effectiveness. "We commend FDA for proposing good manufacturing practices that will help ensure that all dietary supplements are of the quality that the public deserves. Since credible research studies cannot be performed using many of the current, highly variable products, these practices will also speed our ability to provide the public with more definitive data about the safety and effectiveness of popular dietary supplements," said Dr. Stephen Straus, Director, National Center for Complementary and Alternative Medicine at the National Institutes of Health.

This proposed regulation follows the agency's consumer initiative announced last December intended to improve FDA's policies on providing information about health consequences of food and dietary supplements and to increase enforcement efforts to prevent misleading health claims made by certain dietary supplement manufacturers. By putting in place requirements that will ensure universal good manufacturing practices, the proposed regulation should serve to eliminate the guesswork for consumers about which dietary supplements may or may not be of high quality. In turn, manufacturers of dietary supplements will have to compete based on the quantity of their product, not through potentially misleading labels or inexpensive but less safe manufacturing processes.

Under the CGMP proposal, manufacturers would be required to evaluate the identity, purity, quality, strength, and composition of their dietary ingredients and dietary supplements. If dietary supplements contain contaminants or do not contain the dietary ingredient they are represented to contain, FDA would consider those products to be adulterated. Some product quality problems the CGMPs would help prevent include products that are superpotent or subpotent; that contain the wrong ingredient, a drug contaminant, or other contaminants (e.g., bacteria, pesticide, glass, lead); that contain foreign material; and that are improperly packaged and mislabeled.

This proposal is intended to cover all types of dietary supplements. However, to limit any disruption for dietary supplements produced by small businesses, FDA is proposing a three-year phase-in of a final rule for small businesses. The proposal includes flexible standards that can evolve with improvements in the state of science, such as in validating tests for identity, purity, quality, strength, and composition of dietary ingredients.

FDA is soliciting comments from the public and industry on how this proposed regulation can best achieve the goals of promoting accurate labeling information and preventing adulteration without imposing unnecessary regulatory burdens. Written comments will be received until 90 days after the date of publication in the Federal Register and may be addressed to Dockets Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Room 1061, Rockville, MD 20852.

Additional information, including the proposed rule, may be found on FDA's Website at the following addresses:

Fact Sheet
http://www.fda.gov/bbs/topics/NEWS/dietarysupp/factsheet.html

Backgrounder
http://www.fda.gov/bbs/topics/NEWS/dietarysupp/background.html

Proposed Rule (PDF 89.5 MB)
http://www.fda.gov/OHRMS/DOCKETS/98fr/96n-0417-npr0001-01.pdf

Richard Klein
Office of Special Health Issues
Food and Drug Administration

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2/24/2003

FDA will hold a meeting of its Pediatric Subcommittee of the Anti-Infective Drugs Advisory Committee on March 3, 2003, beginning at 8:30 a.m. at the CDER Advisory Committee Conference Room (Rm. 1066), 5630 Fishers Lane, Rockville, MD, to seek public discussion and advice on issues related to the development of antiretroviral drugs in human immunodeficiency virus (HIV)-infected and HIV-exposed neonates younger than 4 weeks of age.

While there have been other public discussions regarding HIV drug development and perinatal transmission, FDA believes that it is appropriate to re-visit some specific questions regarding pediatric drug development in this age group.

The Division of Antiviral Drug Products (DAVDP) routinely encourages sponsors to study drugs for treatment of HIV in children, requesting pharmacokinetic (PK), safety, and activity data for HIV drugs in studies that include HIV-infected children from 1 month to adolescence, as well as PK and safety data in HIV-exposed neonates (infants born to HIV-infected women). Over the last year, companies have questioned the feasibility of conducting studies of antiretrovirals in HIV-exposed neonates. They note, for example, that the current success of maternal treatment and perinatal prophylaxis has reduced the rate of perinatal transmission in the U.S. to very low levels, significantly decreasing the number of infected neonates available for study. They also cite current guidelines endorsed by the American Academy of Pediatrics, NIH and FDA stating that infants who are unlikely to directly benefit from research should not be exposed to greater than "minimal risk," and suggest that exposure of uninfected infants to antiretroviral drugs constitutes a greater than minimal risk. They also express concern for parents who are trying to assimilate information about HIV transmission in their newborn and suggest that they may be poor candidates for providing informed consent during that time.

Questions to be addressed at the upcoming Advisory Committee meeting include: (1) Is it feasible and ethical to conduct studies of antiretroviral drugs in HIV-infected or exposed neonates in the United States? (2) Should we continue to request pharmacokinetic and safety studies in HIV infected neonates for every drug under development or should we develop criteria for deciding which drugs should be studied. (3) If studies are conducted in resource poor countries, where perinatal transmission rates are still unacceptably high, can the results be extrapolated to pertain to the U.S. population?

Interested persons may present data, information, or views, orally or in writing, on issues pending before the subcommittee. Oral presentations from the public will be scheduled between approximately 9:50 a.m. and 10:50 a.m. Time allotted for each presentation may be limited. Those desiring to make formal oral presentations should notify the contact person (see below) as soon as possible, and submit a brief statement of the general nature of the evidence or arguments they wish to present, the names and addresses of proposed participants, and an indication of the approximate time requested to make their presentation.

If it is not possible to send a representative to the meeting, you may also send a brief email correspondence to DAVDP at DAVDPSPECIAL@cder.fda.gov to submit comments.

The contact person for this meeting is Thomas H. Perez, Center for Drug Evaluation and Research (HFD-21), Food and Drug Administration, 5600 Fishers Lane, (for express delivery, 5630 Fishers Lane, Rm. 1093) Rockville, MD 20857, 301-827-7001, or by e-mail: perezt@cder.fda.gov

You can access the Federal Register Notice announcing this meeting at http://www.fda.gov/OHRMS/DOCKETS/98fr/021903e.htm

You may call the FDA Advisory Information Line, 1-800-741-8138 (301-443-0572 in the Washington, DC area), and enter code 12530. for up-to-date information on this meeting.

Richard Klein
Office of Special Health Issues
Food and Drug Administration

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2/4/2003

The Food and Drug Administration (FDA) Division of Antiviral Drug Products is seeking nominations of qualified experts to serve as voting members on the agency's Antiviral Drug Products Advisory Committee. FDA advisory committees advise the agency on issues related to therapeutic agents, diagnostic tests, or regulatory policy related to viral conditions, including, but not limited to HIV/AIDS, AIDS related opportunistic infections, hepatitis B and C, influenza and other respiratory viruses, and herpes viruses.

FDA depends on scientific technical committees, such as the Antiviral Drug Products Advisory Committee, to provide independent, outside expert scientific advice to the agency in its evaluation of regulated products, and to help the agency make sound decisions grounded in the application of scientific principle.

Advisory committees weigh available evidence and provide scientific and medical advice on the safety, effectiveness and appropriate use of products under FDA jurisdiction. Sometimes advisory committees advise the agency on general criteria for evaluation of regulated products, and broad regulatory and scientific issues that are not related to a specific product.

Nominees should have degrees in medicine and have notable clinical and research expertise in the study or treatment of one or more viral illnesses. The committee typically meets 2-4 times per year for one or two days in the Washington DC area. Appointments last from two to four years.

Travel expenses, per diem, and a modest honorarium are paid by FDA to committee members for each meeting attended.

Potential members will be asked to disclose financial and other interests that might represent a potential conflict of interest with issues being considered by the advisory committee. This includes the interests of the organization where they are employed.

Individuals interested in serving as a member of the FDA Antiviral Drug Products Advisory Committee should submit their name, affiliation, address, telephone number, e-mail address, and a current curriculum vitae to DAVDPSpecial@cder.fda.gov

Patient Representatives

The Division is also seeking nominations for patient representatives or patient advocates, to serve on the committee on an intermittent basis.

FDA believes that community/patient representatives bring an important and unique perspective to the committee's decision making process. The patient representative serves as an ad hoc participant on the committee, contributing views or opinions about questions and issues pertinent to the patient perspective.

Although strict scientific training is not required, patient representatives should possess an understanding of scientific data and research design, risk and benefit analysis, and be able to contribute to discussions based principally on technical and clinical considerations. The patient representative should be able to represent the community as broadly as possible (including issues related to women, communities of color, and children), and relay information back to the community.

Patient representatives will also be asked to disclose financial and other interests that might represent a potential conflict of interest with issues being considered by the advisory committee, including the interests of the organization where they are employed.

As with regular members, patient representatives will have travel and per diem expenses reimbursed for meeting attendance, and will receive a small honorarium for their service on the committee.

Individuals interested in serving as patient representatives on the FDA Antiviral Drug Products Advisory Committee should submit their name, affiliation, address, telephone number, e-mail address, and a current curriculum vitae to DAVDPSpecial@cder.fda.gov

Richard Klein
Office of Special Health Issues
Food and Drug Administration

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2/3/2003

HHS EXTENDS USE OF RAPID HIV TEST TO NEW SITES NATIONWIDE
HHS Secretary Tommy G. Thompson today announced that HHS has extended the availability of a recently approved rapid HIV test from the current 38,000 laboratories to more than 100,000 sites, including physician offices and HIV counseling centers.

"Ensuring the widespread availability of a rapid HIV test to outreach services in communities where people are at high risk of HIV is vital to the public health," Secretary Thompson said. "Without today's action, this test would be limited to use in laboratory settings where many high-risk people do not go for testing."

The OraQuick Rapid HIV-1 Antibody Test, manufactured by OraSure Technologies, Inc., of Bethlehem, Pa., provides results in as little as 20 minutes. It is performed on a fingerstick sample of blood. Studies show that the test has an accuracy of 99.6 percent. Unlike other antibody tests for HIV, this test can be stored at room temperature, requires no specialized equipment and can be used outside of traditional laboratory or clinical settings.

HHS' Food and Drug Administration (FDA) approved OraQuick last November for use in laboratories that perform moderate complexity testing. The expanded use to additional sites was granted by HHS under a Clinical Laboratory Improvement Amendments (CLIA) waiver.

Each year, 8,000 HIV-infected people who come to public clinics for HIV testing do not return a week later to receive their test results. With the new rapid HIV test, results are available on the spot in about 20 minutes. As with all screening tests for HIV, if the OraQuick gives a reactive test result, that result must be confirmed with an additional specific test.

Widespread availability of the rapid HIV test is likely to increase overall HIV testing and decrease the number of people -- an estimated 225,000 Americans -- who are unaware they are infected with the HIV virus. Early testing enables infected individuals to obtain medical care earlier in the course of their infection, potentially saving lives and limiting the spread of this deadly virus.

FDA approved the OraQuick test in November as a moderate complexity test. Moderate complexity tests must be performed in a CLIA-approved laboratory by CLIA-certified laboratory staff.

Manufacturers can request a CLIA waiver that allows the test to be used under less stringent controls. CLIA-waived tests can be performed and interpreted in a physician's office or other settings without having to be sent out to a CLIA-certified laboratory. To qualify for a waiver, a test must be simple, accurate and present no reasonable risk of harm.

OraSure Technologies tested the accuracy and ease of the test by having 102 untrained users administer the test at four sites in the United States, including a local AIDS foundation, a program for homeless and low income and community-based HIV organization. These users were able to obtain results similar to those obtained in the firm's original studies done in laboratories.

Richard Klein
Office of Special Health Issues
Food and Drug Administration

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1/16/2003

The Food and Drug Administration (FDA) is proposing new labeling warning statements for all over-the-counter (OTC) vaginal contraceptive drug products containing nonoxynol 9. These warning
statements will advise consumers that vaginal contraceptives containing nonoxynol 9 do not protect against infection from the human immunodeficiency virus (HIV), the virus that causes acquired
immunodeficiency syndrome (AIDS), or against getting other sexually transmitted diseases (STDs). The warnings will also advise consumers that frequent use of vaginal contraceptives containing nonoxynol 9 can increase vaginal irritation. Increased vaginal irritation from use of nonoxynol 9 may increase the possibility of transmission of the AIDS virus (HIV) and STDs from infected partners. The agency is requesting public comment on the proposed labeling statements and how such information could best be presented in labeling. This proposal is part of FDA's ongoing review of OTC drug products.

FDA invites written or electronic comments from the public on this proposal by April 16, 2003.

Full text of the Federal Register Notice, and details for submitting comments may be found on the web at:
http://a257.g.akamaitech.net/7/257/2422/14mar20010800/edocket.access.gpo.gov/2003/03-902.htm

Richard Klein
Office of Special Health Issues
Food and Drug Administration

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