HIV and AIDS
Human Immunodeficiency Virus and
Acquired Immunodeficiency Syndrome

HIV/AIDS Historical Time Line

2000 - 2007

2000 | 2001 | 2002 | 2003 | 2004 | 2005 | 2006 | 2007

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2000

On June 19, 2000 FDA and Cal-Test Diagnostics, Chino, California signed a consent decree to stop manufacturing and selling its HIV in-vitro diagnostic test kits until long-standing manufacturing problems are corrected.
On September 15, 2000 FDA approved Kaletra (lopinavir and ritonavir, Abbott Laboratories) for combination use with other antiretroviral agents for the treatment of HV-1 infection in adults and pediatric patients age six months and older.
On October 31, 2000, FDA approved the new formulation Videx EC, enteric coated capsule (ddI, Dideoxyinosine, Bristol Myers-Squibb) for combination use with other antiretroviral agents, as indicated for the treatment of HIV-1 infection in adults whose management requires once-daily administration of didanosine or an alternative didanosine formulation.
On November 14, 2000 FDA approved Trizivir (fixed-dose combination of Ziagen (abacavir/ABC), Retrovir (zidovudine/AZT), and Epivir (lamivudine/3TC) , made by Glaxo Wellcome, for the treatment of HIV in adults and adolescents. Trizivir is not recommended for treatment in adults or adolescents who weigh less than 40 kilograms because it is a fixed-dose tablet.
On December 22, 2000, FDA issued a Safety Alert on Unapproved Goat Serum Treatment for HIV/AIDS, alerting health care providers and patients of a potential safety concern involving unapproved experimental product for HIV/AIDS, goat antiserum, which was allegedly stolen from a "storage facility".

2001

On January 5, 2001, FDA and Bristol Myers Squibb Issued Caution for HIV Combination Therapy with Zerit and Videx in Pregnant Women
On July 20, 2001, a scientific review panel confirms Condoms Are Effective Against HIV/AIDS, but epidemiological studies are insufficient for other STDs
On July 26, 2001, FDA approved the Stand-Alone (Unbundled) Package for Rebetol Capsules for use with Intron A for the treatment of chronic hepatitis C infection,
On September 21, 2001, FDA licensed the First Nucleic Acid Test (NAT) systems to Screen Plasma for Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV). Nucleic acid test (NAT) systems intended for screening of plasma donors. These test systems are expected to further ensure the safety of plasma-derived products by permitting earlier detection of HIV and HCV infections in donors
On September 26, 2001 FDA approved Visible Genetics, Inc., TrueGene HIV-1 Genotyping Kit and Open Gene DNA Sequencing System to be used to identify drug resistance in HIV patients. (Approval Information)
On October 26, 2001 Viread (tenofovir disoproxil fumarate) received accelerated approval on for treatment of HIV-1 infection in combination with other antiretroviral medicines. Viread is the first nucleotide analog approved for HIV-1 treatment. Nucleotides are similar to nucleoside analogs, and block HIV replication in the same manner. Viread is manufactured by Gilead Sciences.
Approval Letter [PDF format] | Package Insert [PDF format]
On November 19, 2001, FDA approved NucliSens HIV-1 QT, made by bioMerieux, Inc., Durham, NC, PMA number: BP010001/0. The Indication for Use is: in conjunction with clinical presentation and other laboratory markers of disease progression for prognostic assessment of HIV-1 infected patients, and for monitoring the effects of anti-retroviral therapy by serial measurements of plasma HIV-1 RNA for pediatric and adult patients with baseline viral loads greater than 93,000 and 28,000 copies of HIV-1 viral RNA/mL respectively.

2002

On February 1, 2002, FDA approved a new 600 mg formulation of Sustiva (efavirenz) [PDF] to be taken once daily, in combination with a protease inhibitor and/or nucleoside analogue reverse transcriptase inhibitors (NRTIs), for the treatment of HIV infection.
On February 5, 2002, FDA approved a new dosing regimen for Agenerase (amprenavir) and Norvir (ritonavir) used in combination. [PDF]
In February 2002, Changes in the WARNINGS, PRECAUTIONS, ADVERSE REACTIONS, and PATIENT INFORMATION sections of the ZERIT( (stavudine, d4T) label were made to describe the occurrence of lactic acidosis and neuromuscular toxicity in patients using stavudine.
On June 26, 2002, a supplemental new drug application from GlaxoSmithKline was approved, expanding the labeled indication to provide for the use of Epivir (lamivudine) once daily for the treatment of HIV infection in combination with other antiretroviral agents, and a new 300 mg tablet. The product label was modified to reflect these changes. Epivir Label
FDA announced in July 2002 the analysis of findings from a 2001 study designed to assess the extent and usefulness of private sector prescription information patients receive when filling their prescriptions. Study results show approximately 89 percent of patients received written information about the drugs prescribed for them.
In August, 2002 Product labeling changed for AGENERASE (amprenavir) Capsules and AGENERASE (amprenavir) Oral Solution to reflect new precautions related to use of Agenerase with Methadone, and with oral (hormonal) contraceptives.
On September 11, 2002, FDA approved the VERSANT HIV-1 RNA 3.0 Assay (bDNA), manufactured by Bayer Corporation of Berkeley, CA. The test is indicated for the direct quantitation of Human Immunodeficiency Virus Type 1 (HIV-1) in plasma of HIV-infected individuals. This test is intended for use in conjunction with clinical presentation and other laboratory markers of disease status as an aid in management of individuals infected with HIV-1. HIV-1 RNA results from the assay can be used to assess prognosis of disease progression and to monitor the effects of antiretroviral therapy by measuring changes in HIV-1 RNA levels during the course of therapy. Monitoring the effects of antiretroviral therapy by serial measurements of plasma HIV-1 RNA has been validated for patients with viral loads ³ 25,000 copies/mL. The VERSANT HIV-1 RNA 3.0 Assay (bDNA) is not intended for use as a screening assay for HIV infection or as a diagnostic test to confirm the diagnosis of HIV infection.
In September 2002 The VIDEX (Didanosine, ddI) label was revised to include new, precautionary information about co-administration of VIDEX and ribavirin (RBV) in HIV/HCV co-infected patients. In vitro data demonstrating that RBV increases the levels of the active Didanosine metabolite, dideoxyadenosine 5'-triphosphate (ddATP), and clinical reports suggesting the potential for didanosine-related toxicities led to the addition of new precautionary language in the VIDEX label. The following has been added to the "Precautions" section of the label: Exposure to didanosine or its active metabolite (dideoxyadenosine 5'-triphosphate) is increased when didanosine is co-administered with ribavirin. Increased exposure may cause or worsen didanosine-related clinical toxicities, including pancreatitis, symptomatic hyperlactatemia/lactic acidosis, and peripheral neuropathy. Co-administration of ribavirin with VIDEX should be undertaken with caution, and patients should be monitored closely for didanosine-related toxicities. VIDEX should be suspended if signs or symptoms of pancreatitis, symptomatic hyperlactatemia, or lactic acidosis develop.
On September 25, 2002, FDA Announced that pharmacokinetic data demonstrated that co-administration of VIREAD (tenofovir disoproxil fumarate) and VIDEX (Didanosine, ddI) resulted in significant increases in didanosine exposures; this information was included in the VIREAD label at the time it was initially approved. Subsequent results of an interaction study of VIREAD and VIDEX EC were submitted and reviewed. Based on this later study, it was concluded that the magnitude of the interaction between VIREAD and VIDEX was significant enough to warrant additional precautionary language to be included in both products' labeling. The following precautionary language was added: Exposure to didanosine or its active metabolite (dideoxyadenosine 5'-triphosphate) is increased when didanosine is co-administered with VIREAD. Increased exposure may cause or worsen didanosine-related clinical toxicities, including pancreatitis, symptomatic hyperlactatemia/lactic acidosis, and peripheral neuropathy. Co-administration of VIREAD with VIDEX should be undertaken with caution, and patients should be monitored closely for didanosine-related toxicities. VIDEX should be suspended if signs or symptoms of pancreatitis, symptomatic hyperlactatemia, or lactic acidosis develop.
In November 2002 FDA issued new guidance on clinical trial design in developing treatment for HIV infection [PDF]. The guidance is intended to assist sponsors in the clinical development of drugs for the treatment of human immunodeficiency virus (HIV) infection. Specifically, this guidance addresses the Agency's current thinking regarding designs of clinical trials that use HIV ribonucleic acid (RNA) measurements to support accelerated and traditional approvals of antiretroviral drug products. It is also intended to serve as a focus for continued discussions among the Division of Antiviral Drug Products (DAVDP), pharmaceutical sponsors, the academic community, and the public.
On November 7, 2002 FDA approved the first rapid HIV diagnostic test kit for use in the United States that provides results with 99.6 percent accuracy in as little as 20 minutes. Using less than a drop of blood collected, the OraQuick Rapid HIV-1 Antibody Test, manufactured by OraSure Technologies, Inc., Bethlehem, Pennsylvania, can quickly and reliably detect antibodies to HIV-1, the HIV virus that causes infection in most cases in the U.S. Unlike other antibody tests for HIV, this test can be stored at room temperature, requires no specialized equipment, and may be considered for use outside of traditional laboratory or clinical settings. Although the results of rapid screenings are reported in point-of-care settings, as with all screening tests for HIV, if the OraQuick test gives a reactive test result, that result must be confirmed with an additional specific test. The OraQuick test has not been approved to screen blood donors.
On December 31, 2002, FDA approved a new, extended release formulation of ZERIT® (stavudine, d4T) called ZERIT® XR, a product of the Bristol-Myers Squibb Company. This extended-release formulation has been demonstrated to maintain measurable plasma concentrations for 24 hours after once-daily dosing. ZERIT® XR is indicated for the treatment of HIV in combination with other antiretrovirals. The recommended dose of ZERIT® XR is 100 mg once daily for individuals weighing at least 60 kg and 75 mg once daily for individuals weighing less than 60 kg.

2003

In January 2003 FDA proposed a 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.
On February 3, 2003 the Department of Health and Human Services (HHS) expanded availability of the rapid HIV test from the current 38,000 laboratories to more than 100,000 sites, including physician offices and HIV counseling centers. The expanded use to additional sites was granted by HHS under a Clinical Laboratory Improvement Amendments (CLIA) waiver. 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.
On March 3, 2003, FDA held a meeting of its Pediatric Subcommittee of the Anti-Infective Drugs Advisory Committee 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. Questions addressed included: (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?
Briefing Information | Slides | Minutes | Complete Transcript
On March 15, 2003 FDA approved FUZEON (enfuvirtide, also known as T-20), for use in combination with other anti-HIV medications to treat advanced HIV-1 infection in adults and children ages 6 years and older. This marked the first approval, worldwide, of a new class of drugs known as "fusion inhibitors," which interfere with the entry of HIV-1 into cells by inhibiting the merging of the virus with the cellular membrane. This inhibition blocks HIV before it enters the human immune cell. Roche Pharmaceuticals of Nutley, N.J., has licensed the product from Trimeris Inc. of Durham, NC, and will distribute FUZEON. Additional Information on FUZEON: Choose "F" from the Index, and scroll down to "Fuzeon" at the end of the list.
On April 1, 2003 a special nutrition management and HIV infection supplement to Clinical Infectious Diseases, a journal of The Infectious Diseases Society of America, was published (Clinical Infectious Diseases, Volume 36, Supplement 2), stressing the importance of nutrition as part of the medical treatment of HIV. It contains a special report on current issues related to 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.
On April 30, 2003, the Food and Drug Administration approved a new dosing formulation of Viracept (nelfinavir mesylate) a protease inhibitor indicated for the treatment of HIV-1 infection in combination with other antiretroviral agents. 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.
On May 13, 2003, FDA held a meeting of its Antiviral Drugs Advisory Committee to discuss the 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.
Briefing Information | Transcript | Slides
On June 20, 2003, FDA approved Reyataz (atazanavir sulfate) [PDF], a protease inhibitor, manufactured by Bristol-Myers Squibb Company of Princeton, NJ, to be used in combination with other anti-retroviral agents for the treatment of patients with HIV infection. Approval of this drug permits patients access to a once-a-day protease inhibitor. Reyataz appears to have minimal impact on lipid parameters such as triglycerides and cholesterol. Product Label
On July 2, 2003, FDA approved Emtriva (FTC, emtricitabine) [PDF], a new nucleoside reverse transcriptase inhibitor (NRTI) manufactured by Gilead Sciences, Foster City, CA, USA, for use in combination with other anti-retroviral agents for the treatment of patients with HIV infection. Product Label
In July 2003 an important drug warning was issued regarding Early Virologic Non-Response in Patients with HIV Infection Treated With Lamivudine, Abacavir and Tenofovir.
On August 8, 2003, an important drug warning was issued regarding Important New Pharmacokinetic Data for REYATAZ™ (atazanavir sulfate) in combination with Viread® (tenofovir disoproxil fumarate)
On August 15, 2003, Viread labeling was 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.
On August 20, 2003, FDA held a meeting of its Antiviral Drugs Advisory Committee to discuss clinical trial design issues in the development of topical microbicides for the reduction of HIV transmission.
Agenda | Briefing Information | Slides

2004

On January 12, 2004 FDA approved a labeling supplement for Crixivan (Indinavir Sulfate) Capsules summarizing tubulointerstitial nephritis with medullary calcification and cortical atrophy observed in patients with asymptomatic severe leukocyturia (>100 cells/high power field) and reports of Immune reconstitution syndrome in patients treated with combination antiretroviral therapy (CART), including CRIXIVAN. During the initial phase of treatment, patients responding to antiretroviral therapy whose immune system responds to CART may develop an inflammatory response to indolent or residual opportunistic infections (such as MAI, CMV, PCP, or TB), which may necessitate further evaluation and treatment." Additionally, information was added about Reyataz (atazanavir):
"Both CRIXIVAN and atazanavir are associated with indirect (unconjugated) hyperbilirubinemia. Combinations of these drugs have not been studied and coadministration of CRIXIVAN and atazanavir is not recommended." Changes were also made to the Patient Package Insert (PPI) indicating that "In some patients with advanced HIV infection (AIDS), signs and symptoms of inflammation from opportunistic infections may occur when combination antiretroviral treatment is started.
In March 2004, new drug interaction information led to changes in the REYATAZ (atazanavir sulfate) label based on drug-drug interactions. Tenofovir decreases the AUC (area under the curve) and Cmin (minimum concentration) of REYATAZ. When coadministered with tenofovir, it is recommended that REYATAZ 300 mg is given with ritonavir 100 mg and tenofovir 300 mg (all as a single daily dose with food). REYATAZ without ritonavir should not be coadministered with tenofovir.
In March, 2004, FDA has approved new dosing recommendations for VIRACEPT (nelfinavir) in patients 2 years of age or older, based on clinical and pharmacokinetic data from 5 pediatric studies.
On March 19, 2004, FDA approved the OraSure rapid test for detection of HIV-2 when used with a whole blood sample. The rapid test kit is identical to the earlier approved version, however, subsequent data submitted to the agency has demonstrated its ability to detect HIV-2.
On March 26, 2004, FDA approved the use of oral fluid samples with a rapid HIV diagnostic test kit that correctly identified 99.3 of specimens from infected people (sensitivity) and 99.8% of specimens from uninfected people (specificity) in limited studies provided by the manufacturer in support of this approval. The test provides the result in approximately 20 minutes.
On March 26, 2004, the OraQuick Rapid HIV-1 Antibody Test was approved for testing plasma for HIV-1 and HIV-2 (a variant of HIV that is prevalent in parts of Africa but rarely found in the United States).
In May, 2004, FDA approved changes in the label for Voriconazole (VFEND) triazole antifungal agent to include drug interaction information when coadministered with efavirenz or ritonavir.
In May, 2004, revisions were made to the Crixivan product label to reflect data about drug-drug interactions, including those related to VIAGRA (sildenafil), CIALIS (tadalafil), or LEVITRA (vardenafil), and REYATAZ (atazanavir).
On May 17, 2004, FDA issued a guidance document that describes a process to expedite approval of low cost, safe and effective co-packaged and fixed dose combination (FDC) HIV therapies so that high quality drugs can be made available in Africa and developing countries around the world under the President's Emergency Plan for AIDS Relief.
On May 20, 2004, FDA published a new Final Rule on Donor Eligibility for Human Tissues and Cells (Eligibility Determination for Donors of human Cells, Tissues, and Cellular and Tissue-Based Products), and draft guidance (Guidance for Industry Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products) related to donor screening and eligibility. These documents include HIV, among a variety of conditions for which cell and tissue donor screening would be required. Federal Register Notice (PDF 363 MB); Draft Guidance Document (PDF 143 MB); Questions and Answers
In May, 2004, FDA and Bristol-Myers Squibb notified healthcare professionals of revisions to the CLINICAL PHARMACOLOGY and PRECAUTIONS sections of the product labeling for DESYREL (trazodone hydrochloride) Tablets, indicated for the treatment of depression, citing a potential for drug interactions when trazodone is given with the CYP3A4 inhibitors ketoconazole, ritonavir, and indinavir. Dear Health Care Provider Letter
On June 25, 2004, FDA granted a CLIA (Clinical Laboratory Improvements Amendments of 1988] waiver to the OraQuick ADVANCE Rapid HIV-1/2 Antibody Test for use with oral fluid, a fast and non-invasive test approved on March 26, 2004, to detect antibodies to HIV-1 in oral fluid. The oral fluid indication was extended by FDA to include detection of antibodies to HIV-2 in oral fluid on June 22, 2004. The CLIA waiver allows the rapid oral fluid test to be used in more health care settings, such as doctors' offices, clinics, and some mobile labs that can offer testing in high-risk areas. Through these venues, testing are accessible to many more people, particularly to those individuals who are reluctant to be tested due to the need to draw blood.
On July 1, 2004, the VIREAD (tenofovir disoproxil fumerate) label was updated to recommend against use in patients with chronic hepatitis B infection, because of severe, acute exacerbations of Hepatitis B may occur in patients who are coinfected with hepatitis B and HIV and have discontinued Viread.
On July 6, 2004, FDA approved a new dosing regimen for REYATAZ of 300 mg (two 150 mg capsules) once daily plus ritonavir 100 mg once daily taken taken with food in antiretroviral-experienced patients. For antiretroviral-naïve patients the recommended dose remains as REYATAZ 400 mg (two 200 mg capsules) once daily with food.
On July 27, 2004, FDA launched a new web page to consolidate records of advisory committee meetings related to HIV/AIDS and associated conditions, making them easier to access. The new page, which lists HIV/AIDS-related advisory committee meetings held since 1996, indexed by topic and by year. It is the first consolidation of advisory committee records by topic, and includes records of meeting held by advisory committees related to drugs, biologics, and medical devices, with links to a variety of documents, such as meeting announcements, committee rosters, briefing materials - which often contain background materials and slides - and meeting transcripts. Topics include consideration of new drug applications, regulatory policy issues, and trial design topics. FDA Advisory Committees Page.
On August 2, 2004, FDA approved two fixed-dose combination (FDC) antiretroviral drug products for use with other antiretroviral agents for the treatment of HIV-1 infection. The FDCs are GlaxoSmithKline's EPZICOM (abacavir/lamivudine) and Gilead Sciences, Inc.'s TRUVADA (tenofovir disoproxil/emtricitabine). These FDC approvals are important because they provide simplified dosing regimens - one pill, once daily, for the component of multi-drug therapy represented by these FDCs.
On August 3, 2004, FDA approved Sculptra to correct facial fat loss in people with human immunodeficiency virus (HIV). Sculptra, a medical device, is a product of Dermik Laboratories, of Berwyn, PA. It is an injectable form of poly-L-lactic acid, a biodegradable, biocompatible synthetic polymer from the alpha-hydroxy-acid family that has been widely used for many years in dissolvable stitches, bone screws and facial implants. It is the first such treatment approved for the condition known as lipoatrophy, or facial wasting. FDA expedited review of the product because of its importance in treating people living with AIDS.
In August 2004, Sustiva labeling was revised to include safety and efficacy data representing 168 weeks of treatment from Study 006 ( efavirenz + lamivudine + zidovudine vs indinavir + lamivudine + zidovudine vs efavirenz + indinavir) and other available data.
On September 23, 2004, FDA held a meeting of its Vaccines and Related Biological Products Advisory Committee (VRBPAC) to update the Committee on the phase 3 Thai trial of ALVAC vCP 1521 [Aventis Pasteur, Inc.] with AIDSVAX B/E [VaxGen, Inc.] (HIV-1 Recombinant Canarypox-Vectored Vaccine with Recombinant gp 120 B/E) for the prevention of HIV-1 infection.
On October 7, 2004, FDA held a public workshop entitled "From Concept to Consumer: Center for Biologics Evaluation and Research (CBER) Working with Stakeholders on Scientific Opportunities for Facilitating Development of Vaccines, Blood and Blood Products, and Cellular, Tissue, and Gene Therapies" to provide stakeholders a forum for the development of innovative scientific knowledge and tools to facilitate the development and availability of new biological products including vaccines, blood and blood products, and cellular, tissue, and gene therapies.
In October 2004, Kaletra (lopinavir and ritonavir) Soft Gel Capsules and Oral Solution labeling was revised to include long-term (week 144-204) efficacy and safety results from two phase II trials. These were the Week 204 efficacy results from study M97-720 in antiretroviral-naïve subjects and the Week 144 results from study M97-765 in antiretroviral-experienced subjects were included in the label. In addition, results of a multiple dose study in HIV and HCV co-infected subjects with mild to moderate hepatic impairment and Week 104 mice and rat data were submitted to update the respective sections of the package insert.
On October 15, 2004, FDA granted" traditional approval" for Fuzeon (enfuvirtide, also known as T-20) injection, in combination with other antiretroviral agents, for the treatment of HIV-1 infection in treatment experienced patients with ongoing viremia. FDA originally approved Fuzeon on March 13, 2003 under the regulations at 21 CFR 314, Subpart H, for accelerated approval of new drugs for serious or life-threatening illnesses.
On November 12, 2004 Bristol-Myers Squibb (BMS) issued a "Dear Healthcare Provider" letter regarding is important new clinical data regarding coadministration of Viread (tenofovir disoproxil fumarate [TDF]), Videx EC (didanosine delayed-release capsules enteric-coated beadlets [ddI EC]), and either Sustiva (efavirenz [EFV]) or Viramune (nevirapine [NVP]).
In November, 2004, FDA issued final guidance on the "Use of Nucleic Acid Tests on Pooled and Individual Samples from Donors of Whole Blood and Blood Components (including Source Plasma and Source Leukocytes) to Adequately and Appropriately Reduce the Risk of Transmission of HIV-1 and HCV."
On November 26, 2004 FDA issued draft guidance for industry entitled "Role of HIV Drug Resistance Testing in antiretroviral Drug Development," addressing the role of HIV resistance testing during antiretroviral drug development and postmarketing. The draft guidance discusses the nonclinical studies (mechanism of action; antiviral activity in vitro; cytotoxicity/therapeutic index; and the effects of serum protein binding on antiviral activity) recommended be completed prior to the initiation of phase 1 clinical studies in HIV-infected patients, as well as the use of resistance testing in the clinical phases of drug development and recommends the type of information that should be collected, and the types of analyses that should be conducted to characterize an antiretroviral's resistance profile. It also reviews the role of resistance testing in initial activity and dose-finding, for study enrollment criteria, for background regimen selection, and to establish an indication.
On December 3, 2004, FDA approved a generic formulation of Didanosine (ddI) Delayed Release capsules, 200 mg, 250 mg, and 400 mg for use in combination with other antiretroviral agents in the treatment of HIV-1 infection in adults. The product, manufactured by Barr Laboratories, Inc. of Pomona, NY, is the first approval in the United States of a generic antiretroviral therapeutic formulation to treat HIV/AIDS.
On December 17, 2004, FDA approved a new 500 mg tablet formulation of the HIV protease inhibitor, INVIRASE (saquinavir mesylate). The dosage and administration for INVIRASE in adults (over the age of 16 years) is 1000 mg twice a day (taken as either two 500 mg tablets or five 200 mg capsules) in combination with ritonavir 100 mg twice a day, after a meal. The new tablet formulation reduces the pill burden compared to the capsule formulation.
On December 30, 2004, FDA approved the Multispot HIV-1/HIV-2 Rapid Test. This device, manufactured by Bio-Rad Laboratories, Redmond, WA, is indicated for the detection and differentiation of circulating antibodies associated with HIV-1 and HIV-2 in human plasma and serum, as an aid in the diagnosis of infection with HIV-1 and/or HIV-2.

2005

On 1/26/2005, FDA announced the first tentative approval under a new FDA review process designed to expedite the availability of generic products under the President's Emergency Plan for AIDS Relief (PEPFAR). The product was a new copackaged antiretroviral drug regimen, consisting of both lamivudine/zidovudine fixed dose tablets (a version of Combivir tablets manufactured by GlaxoSmithKline) and nevirapine tablets(a version of Viramune tablets manufactured by Boehringer-Ingelheim), one of each tablet to be taken twice daily, after the initial two week initiation phase of this nevirapine regimen. The product was manufactured by Aspen Pharmacare of South Africa. Tentative Approval means that FDA concluded the drug product met all of the required quality, safety and efficacy standards, even though it may not yet be marketed in the U.S. due to existing patents and/or exclusivity. It did, however, make the product eligible for use under PEPFAR, and the first tentative approval of an HIV drug regimen manufactured by a non-U.S.-based generic pharmaceutical company.
On 2/8/2005, FDA Roche Laboratories Inc. issued a "Dear Health Care Provider" letter, created in collaboration with FDA, to communicate an important drug interaction warning for saquinavir/ritonavir, and rifampin, an antibacterial agent: drug-induced hepatitis with marked transaminase elevations has been observed in healthy volunteers receiving rifampin 600 mg once daily in combination with ritonavir 100 mg/saquinavir 1000 mg twice daily (ritonavir boosted saquinavir). As a result of high incidence of hepatotoxicity in a Phase I, randomized, open-label, multiple-dose clinical pharmacology study in healthy volunteers, the letter advised prescribers that: Rifampin SHOULD NOT be administered to patients also receiving saquinavir/ritonavir (ritonavir boosted saquinavir) as part of combination antiretroviral therapy (ART) for HIV infection.
FDA approved, on February 25, 2005, efficacy supplements for Pegasys (peginterferon alfa-2a) and Copegus (ribavirin), making them the first approved therapies for treatment of Hepatitis C in patients coinfected with HIV. The approvals expand the therapeutic indications to include Peg-interferon alone, or in combination with ribavirin, for the treatment of adult chronic hepatitis C in patients coinfected with HIV, who have clinically stable HIV disease (patients either on stable HIV antiretroviral therapy, or those who have not met the criteria to begin therapy).
In March of 2005, the Norvir (ritonavir) and Kaletra (lopinavir/ritonavir) package inserts (product labeling) were updated to include information regarding interactions with fluticasone (a synthetic corticosteroid, the active component of Flonase nasal Spray) and trazodone (Desyrel, a non-tricyclic antidepressant). In addition, alfuzosin (an alpha-blocker used to increase the flow of urine in people with benign prostatic hypertrophy (BPH)) was added to the Contraindications section of the Norvir package insert.
On March 31, 2005, Bristol-Myers Squibb Company has issued a Dear Health Care Provider Letter, developed in collaboration with FDA, highlighting the important change in Sustiva (efavirenz) from Pregnancy Category C to D (Risk of Fetal Harm Cannot Be Ruled Out) to Category D (Positive Evidence of Fetal Risk). The change came as a result of four retrospective reports of neural tube defects in infants born to women with first trimester exposure to Sustiva including three cases of meningomyelocele and one Dandy Walker Syndrome. Because of the potential for fetal harm when administered during the first trimester to a pregnant woman, pregnancy should be avoided in women receiving SUSTIVA.
On April 29, 2005, FDA approved the use of KALETRA 800/200mg once-daily administration for the treatment of HIV-infection in therapy-naïve adult patients, based on review and analysis of two clinical trials comparing safety and efficacy of lopinavir (LPV)/ritonavir (RTV) 800/200 mg once daily (qd) and LPV/RTV 400/100 mg twice daily (bid), for a duration of at least 48 weeks in antiretroviral-naïve HIV-1 infected subjects.
On May 12, 2005, the FDA approved a new 30-count bottle for Norvir (ritonavir) Soft Gelatin Capsules, 100 mg. Previously only 120-count bottles were available. The new 30-count bottle is more convenient for pharmacy dispensing, and for patients who use Norvir 100 mg once or twice daily in combination with other protease inhibitors.
On May 12, 2005, FDA approved new labeling for Viread (tenofovir disoproxil fumarate). The label was updated to include results from a 144 week efficacy and safety data in treatment-naïve patients that fulfilled part of the requirement for traditional approval by confirming long-term efficacy in treatment-naïve patients, and by providing long-term safety information with respect to bone effects.
On May 19, 2005, FDA held a meeting of its Antiviral Drugs Advisory Committee to consider data relative to Aptivus (Tipranavir), 250 milligrams (mg) capsules, new drug application (NDA) 021-814 (Boehringer Ingelheim Pharmaceuticals, Inc.), indicated for the treatment of patients with HIV.
On May 25, 2005 the Food and Drug Administration issued draft guidance to assist product sponsors in the development of antiviral drug products and to serve as a starting point for understanding the nonclinical and clinical virology data important to support clinical trials of antiviral agents. This guidance focuses on nonclinical and clinical virology reports, which are essential components in the review of investigational antiviral drugs. Because of the experience, history, and lessons learned with HIV-1 studies, the guidance focuses on studies commonly used to evaluate HIV-1 drugs and uses them as a model for future studies of drugs to treat other viruses.
On May 27, 2005FDA granted "tentative approval" for a generic formulation of lamivudine tablets, 150 mg, manufactured by Ranbaxy Laboratories Limited (India), for use in combination with other antiretroviral agents in the treatment of HIV-1 infection in adults. A Tentative Approval means that FDA had reviewed an Abbreviated New Drug Application (ANDA), and concluded that a drug product had met all of the required quality, safety and efficacy standards, even though it may not yet be marketed in the U.S. due to existing patents and/or exclusivity. It did, however, make the product eligible for use under the President's Emergency Plan for AIDS Relief (PEPFAR) program outside the United States. The lamivudine tablets are a generic version of Epivir (lamivudine) Tablets, 150 mg, manufactured by Glaxo Smith Kline. A second generic formulation was granted a tentative approval on June 15, 2005 for generic lamivudine tablets, 150 mg and 300 mg, manufactured by Aurobindo Pharma Ltd., Hyderabad, India. Lamivudine tablets are indicated for use in combination with other antiretroviral agents for the treatment of HIV-l infection.
On May 31, 2005 FDA approved a generic formulation of foscarnet sodium injection, 24 mg/mL, 250 mL and 500 mL single-dose containers, manufactured by Pharmaforce, Inc., of Columbus, Ohio. The product is indicated for the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS), making a generic alternative formulation of Foscavir (foscarnet sodium Injection) 24 mg/mL, 250 mL and 500 mL single-dose containers, manufactured by Astra Zeneca, originally approved in 1991,available in the United States.
On June 20, 2005, FDA announced the tentative approval of two applications for nevirapine tablets manufactured by Ranbaxy Laboratories Limited, Guragon, India and Aurobindo Pharma Limited, Hyderabad, India. Although existing patents and/or exclusivity prevent the marketing of Aurobindo's and Ranbaxy's products in the United States, the products, tentative approval allows consideration of these products for purchase under the President's Emergency Plan for AIDS Relief (PEPFAR).
On June 22, 2005, FDA granted accelerated approval of APTIVUS (tipranavir), a protease inhibitor. APTIVUS, co-administered with 200 mg of ritonavir, is indicated for use as part of combination antiretroviral treatment of HIV-1 infected adult patients with evidence of viral replication, who are highly treatment-experienced or have HIV-1 strains resistant to multiple protease inhibitors. FDA reviewed and approved APTIVUS in a six month time frame.
On June 24, 2005 FDA granted tentative approval for generic efavirenz tablets manufactured by Aurobindo Pharma LTD. of Hyderabad, India, the first tentatively approved generic version of Sustiva tablets (manufactured by Bristol-Myers Squibb). Efavirenz is a member of the non-nucleoside reverse transcriptase inhibitors (NNRTIs) Tentative approval means that although existing patents and/or exclusivity prevent marketing of a particular product in the United States, it meets all of FDA's quality, safety and efficacy standards required for marketing in the United States which allows this product to be considered for purchase under the President's Emergency Plan for AIDS Relief (PEPFAR).
On July 1, 2005 FDA announced the tentative approval for generic stavudine capsules manufactured by Aurobindo Pharma LTD., Hyderabad, India, a generic version of the approved drug, Zerit, a Nucleoside Reverse Transcripts Inhibitors (NRTIs)manufactured by Bristol-Myers Squibb. Tentative approval means that although existing patents and/or exclusivity prevent marketing the particular product in the U.S. at this time, the product meets all FDA's quality, safety and efficacy standards. The tentative approval allows this product to be considered for purchase under the President's Emergency Plan for AIDS Relief (PEPFAR).
On July 7, 2005, granted tentative approval for a generic combination drug product consisting of lamivudine and zidovudine, manufactured by Aurobindo Pharma LTD. Hyderabad, India.FDA tentative approval means that the product meets all of FDA's quality, safety and efficacy standards, but existing patents and/or exclusivity prevent marketing of the product in the U.S. Tentative approval by FDA, however, makes this Aurobindo generic product available for consideration for purchase and use outside the United States under the President's Emergency Plan for AIDS Relief (PEPFAR).The Aurobindo lamivudine/zidovudine combination product is a generic version of the U.S. approved Combivir lamivudine/zidovudine combination manufactured by GlaxoSmithKline.
On July 13, 2005 FDA announced the tentative approval of generic zidovudine tablets manufactured by Ranbaxy Laboratories Limited of Guragon, India. The product contains 300 mg of zidovudine in each tablet. It is a generic version of the already-approved Retrovir brand of the product manufactured by GlaxoSmithKline. Tentative approval means that although existing patents and/or exclusivity prevent marketing of this product in the United States, it meets the quality, safety and efficacy standards for U.S. marketing. Tentative approval by FDA makes the generic product eligible for purchase and use outside the United States under the President's Emergency Plan for AIDS Relief.
On September 7, 2005 FDA granted tentative approval for a generic zidovudine oral solution manufactured by Aurobindo Pharma LTD. Hyderabad, India. This product is the first tentatively approved generic version of Retrovir brand of the zidovudine oral solution (manufactured by GlaxoSmithKline). This oral dosage form of the drug is the first pediatric-friendly oral solution available for consideration for purchase under the President's Emergency Plan for AIDS Relief (PEPFAR). This product contains 50 mg/5mL of zidovudine in an oral solution. Tentative approval means that although existing patents and/or exclusivity prevent marketing of this product in the United States, it meets all of FDA's quality, safety and efficacy standards for U.S. marketing.
On September 19, 2005, FDA approved three generic formulations of Zidovudine for the U.S. market. Previously, the products had been only tentatively approved and were not available in the United States because patent or market exclusivity blocked their approval for domestic marketing. With the expiration of those patents, the following products have received full marketing authorization for the United States:
(1) zidovudine tablets, 300 mg , manufactured by Ranbaxy Laboratories Limited of Guragon, India;
(2) zidovudine tablets, 300 mg and oral solution, 50 mg/5mL, manufactured by Aurobindo Pharma LTD. Hyderabad, India; and
(3) zidovudine tablets, 300 mg, manufactured by Roxane Laboratories of Columbus, Ohio, U.S.A. These are generic versions of Retrovir brand manufactured by GlaxoSmithKline.
On September 28, 2005 the Food and Drug Administration approved EMTRIVA (emtricitabine) Oral Solution 10 mg/mL. The approval of this Oral Solution formulation allows for dosing recommendations in pediatric patients. EMTRIVA is now indicated in combination with other antiretroviral agents, for the treatment of HIV-1 infection in patients over three months of age.
On October 6, 2005, FDA approved dosing recommendations for NORVIR (ritonavir) in pediatric patients one month to two years of age.
On October 28, 2005 the Food and Drug Administration approved a new formulation of Kaletra. Kaletra (lopinavir/ritonavir) became available as a film coated tablet (200mg/50mg) that provides advantages over the currently marketed capsule formulation for HIV-1 infected patients. Specifically, the tablet formulation does not require refrigeration, can be administered without regard to meals, does not require dose adjustments for concomitant use with certain NNRTIs and PIs in treatment-naïve patients and has a decreased pill burden compared to the capsule formulation (2 tablets twice daily or 4 tablets once daily in treatment-naïve patients only vs 3 capsules twice daily or 6 capsules once daily in treatment-naïve patients only).
On November 3, 2005 the Food and Drug Administration held a meeting of its Blood Products Advisory Committee (BPAC) to discuss important issues related to home-use rapid HIV test kits. The Committee heard a proposal by OraSure Technologies, Inc. for over-the-counter (OTC) availability of the OraQuick ADVANCE Rapid HIV-1/2 Antibody Test for use with oral fluid specimens, and discussed issues related to proposed studies to validate adequate performance in the hands of intended users, and the ability of informational materials to provide counseling and other information regarding accuracy of testing, correct test interpretation, management of psychological and social issues, and medical referral. The committee also considered the role of rapid HIV tests in CDC's Advancing HIV Prevention initiative and CDC's current HIV test counseling recommendations, the role of quality systems in diagnostic testing, psychological and social issues associated with HIV testing, and prior experience with approved home-use test kits.
On November 4, 2005 FDA announced the tentative approval of Lamivudine Oral Solution, 10 mg/mL manufactured by Aurobindo Pharma LTD. of Hyderabad , India. Lamivudine Oral Solution was the first generic version of the already approved Epivir Oral Solution, 10 mg/mL, manufactured by GlaxoSmithKline. This child-friendly-product is indicated for use in pediatric patients with HIV from three months to 16 years. FDA's tentative approval of this product means that although existing patents and/or exclusivity prevent marketing of this product in the United States, the product meet all of FDA's safety, efficacy, and manufacturing quality standards required for marketing in the U.S. and becomes eligible for consideration for purchase under the President's Emergency Plan for AIDS Relief (PEPFAR).
On November 14, 2005 FDA published information about proposed changes in the way condoms are to be regulated, and draft guidelines for condom labeling. The agency solicited input to help finalize the guidance. FDA proposed to amend the classification regulations to designate a special control for natural rubber latex (latex) condoms, with and without spermicidal lubricant, and proposed new guidelines to specify the kind of labeling that will be considered sufficient and appropriate for the products.

Three separate documents were published on November 14, 2005 to support these proposed changes:
1. Proposed Rule - Obstetrical and Gynecological Devices; Designation of Special Control for Condom and Condom With Spermicidal Lubricant
2. Class II Special Controls Guidance Document: Labeling for Male Condoms Made of Natural Rubber Latex
3. Draft Guidance - Class II Special Controls Guidance Document: Labeling for Male Condoms Made of Natural Rubber Latex.
On December 21, FDA granted tentative approval for generic stavudine for Oral Solution, 1 mg/mL manufactured by Aurobindo Pharma LTD., of Hyderabad, India. This was the first generic version of the approved product, Zerit for oral solution, manufactured by Bristol-Myers Squibb. This child-friendly product is indicated for use in pediatric patients with HIV from birth through adolescence. FDA's tentative approval of this product means that although existing patents and/or exclusivity prevent marketing of this product in the United States, the product meet all of FDA's safety, efficacy, and manufacturing quality standards required for marketing in the U.S. and becomes eligible for consideration for purchase under the President's Emergency Plan for AIDS Relief (PEPFAR).
FDA, on December 27, 2005, granted tentative approval, through an expedited procedure, to generic Nevirapine Oral Suspension, 50 mg/5 mL, manufactured by Aurobindo Pharma LTD., of Hyderabad, India. This was a generic version of the approved product, Viramune Oral Suspension, 50 mg/5 mL, manufactured by Boehringer Ingelheim Pharmaceuticals indicated for use in pediatric patients with HIV. FDA's tentative approval of this product means that although existing patents and/or exclusivity prevent marketing of this product in the United States, the product meet all of FDA's safety, efficacy, and manufacturing quality standards required for marketing in the U.S. and becomes eligible for consideration for purchase under the President's Emergency Plan for AIDS Relief (PEPFAR).

2006

FDA approved updates to the REYATAZ (atazanavir sulfate) package insert on January 25, 2006, to reflect new in vitro inhibition data and clinical drug-drug interaction information regarding coadministration of atazanavir and/or atazanavir/ritonavir with proton pump inhibitors, H2 receptor antagonists, methadone, rifampin, enteric-coated didanosine and tenofovir. The complete revised label is available at http://www.fda.gov/cder/foi/label/2006/021567s007lbl.pdf
FDA held a public workshop on March 8, 2006, entitled "Behavior-Based Blood Donor Deferrals in the Era of Nucleic Acid Testing [NAT)." The workshop provided an opportunity for public discussion on the scientific basis for behavior-based donor deferral criteria, and the value of their continued use now that nucleic acid based tests (NAT) are available for certain transfusion-transmissible agents. Meeting transcript.
On March 10, 2006, FDA held a meeting of its Blood Products Advisory Committee to discuss the design of proposed studies to support the approval of over-the-counter (OTC) home-use human immunodeficiency virus (HIV) test kits. The agency sought the advice of the Committee on proposed studies that would be needed to validate a home-use HIV test kit with regard to test accuracy, test interpretation, and medical follow-up based on the provision of informational material in place of a trained test operator and counselor. Meeting transcript.
On March 6, 2006 FDA granted tentative approval for a copackaged antiretroviral drug regimen, consisting of lamivudine/zidovudine fixed dose combination tablets and efavirenz tablets, for the treatment of HIV-1 infection in adults. It was manufactured by Aurobindo Pharma Ltd., Hyderabad, India. There was no predicate version of this co-packaged product approved in the United States. A Tentative Approval means that FDA has concluded that a drug product has met all required quality, safety and efficacy standards, though it may not yet be marketed in the U.S. due to existing patents and/or exclusivity rights. Tentative approval, however, does make the product eligible for consideration for purchase under the President's Emergency Plan for AIDS Relief (PEPFAR) program.
On March 8, 2006, FDA granted traditional approval to two tenofovir DF containing products manufactured by Gilead Sciences, VIREAD (tenofovir disoproxil fumarate) and TRUVADA (fixed dose combination of tenofovir DF and emtricitabine). Both products are indicated for the treatment of HIV in combination with other antiretroviral drugs. VIREAD and TRUVADA had received accelerated approval on Oct. 26, 2001 and August 2, 2004, respectively. Traditional approval is supported by previously submitted studies and the recently submitted Study 934, which compared the antiviral activity of tenofovir DF, emtricitabine, and efavirenz to zidovudine, lamivudine and efavirenz in treatment naïve HIV-infected individuals receiving these regimens through 48 weeks.
The FDA, on March 27, 2006, granted approval for generic zidovudine 100 mg capsules manufactured by Aurobindo Pharma Limited Inc., of Hyderabad, India. This was a generic version of the already-approved Retrovir brand of the product manufactured by GlaxoSmithKline.The tablet and oral solution dosage forms of zidovudine were previously approved for sale in the United States when the patent on those dosage forms expired in September 2005. The approval for the capsule formulation followed expiration of GlaxoSmithKline's patent on its capsule form of the product marketed under the trade name Retrovir and means that the capsules are available in the United States, and eligible for consideration for purchase under the President's Emergency Plan for AIDS Relief (PEPFAR) program.
On May 4, 2006 FDA is issued guidance regarding data to support the: 1) Initiation of pediatric studies of a preventive HIV vaccine under a United States (U.S.) investigational new drug application (IND); and 2) licensure of a preventive HIV vaccine for pediatric use. The guidance also provides recommendations to investigators and institutional review boards (IRBs) who are involved with these pediatric studies. The guidance is available on the FDA web site.
On May 18, 2006 FDA granted tentative approval for a generic version of abacavir sulfate tablets, 300 mg, manufactured by Aurobindo Pharma LTD. of Hyderabad, India. Abacavir sulfate tablets was the first generic version of FDA approved Ziagen Tablets manufactured by GlaxoSmithKline. The agency's tentative approval meant that Aurobindo's product met all of FDA's manufacturing quality and clinical safety and efficacy standards, but existing patents and/or exclusivity prevent its marketing in the United States at this time. Tentative approval made this product available for consideration for purchase under the President's Emergency Plan for AIDS Relief (PEPFAR).
On May 31, 2006, FDA cosponsored an open public meeting to discuss issues regarding the development of CCR5 co-receptor antagonists for the treatment of HIV infection with the Forum for Collaborative HIV Research. To help improve the development of this complex class of HIV therapy, issues for discussion included mechanisms for long-term follow-up to monitor safety of patients enrolled in CCR5 antagonist clinical trials, potential consequences of viral tropism changes, and characterization of resistance to these investigational agents.
On June 8, 2006 FDA published a final Guidance for Industry on Antiviral Product Development--Conducting and Submitting Virology Studies to the Agency to assist sponsors in the development of antiviral drugs and biological products (i.e., therapeutic proteins and monoclonal antibodies) from the initial pre-IND through the new drug application (NDA) and postmarketing stages. The guidance describes what nonclinical and clinical virology data are important to support the submission of an Investigational New Drug Application (IND), New Drug Application (NDA), or Biologics License Application (BLA) for approval of an antiviral product. Focusing on nonclinical and clinical virology study reports, the guidance provides recommendations for collecting and submitting resistance data to the Food and Drug Administration (FDA). Nonclinical and clinical virology study reports, based on collected data, are essential for FDA's review of antiviral drug investigational and marketing applications. Specific topics discussed in the guidance include:
- Defining the mechanism of action
- Establishing specific antiviral activity of the investigational product
- Assessing the potential for antagonism of other antiviral products that might be used in combination with the investigational product
- Providing data on the development of viral resistance to the investigational product
- Providing data that identify cross-resistance to approved antiviral products having the same target
You can view the guidance and its various attachments on the FDA web site:
- View The Guidance
- The Guidance Attachment- Submitting HIV Resistance Data
- The Guidance Attachment- Submitting Influenza Resistance Data
- The Guidance Attachment- Submitting HBV Resistance Data
- The Guidance Attachment- Submitting HCV Resistance Data
On June 22, 2006 FDA granted tentative approval to generic lamivudine, oral solution, 10 mg/mL manufactured by Cipla Limited, Mumbai, India, for purchase under the President's Emergency Plan for AIDS Relief (PEPFAR).
Prezista (darunavir), was granted accelerated approval by FDA on June 23, 2006. Prezista, a protease inhibitor, manufactured for Tibotec, Inc., Division of Ortho Biotech Products, L.P., Raritan, N.J., by JOLL, Gurabo, Puerto Rico, co-administered with a low-dose of ritonavir, in combination with other active anti-HIV agents was approved for treatment experienced adults whose infection with HIV does not respond to treatment with other antiretroviral drugs.
FDA, on June 27, 2006, granted tentative approval for stavudine 15 and 20 mg capsules manufactured by Aurobindo Pharma Limited Inc., of Hyderabad, India. A generic version of the approved Zerit brand of the product manufactured by Bristol Myers-Squibb, tentative approval made the generic formulation available for purchase under the President's Emergency Plan for AIDS Relief program for use outside the U.S.
On June 27, 2006, FDA granted tentative approval for Abacavir Sulfate Oral Solution, 20 mg/mL, manufactured by Aurobindo Pharma Limited Inc., of Hyderabad, India. A generic version of the approved Ziagen brand of the product manufactured by GlaxoSmithKline, the application was reviewed under expedited review provisions for the President's Emergency Plan for AIDS Relief (PEPFAR).
On June 30, 2006, FDA issued the first tentative approval for a fixed-dose, three-ingredient tablet for use as a complete anti-viral treatment of human immunodeficiency virus (HIV-1) infection in adults. The product, (lamivudine-zidovudine-nevirapine tablet), contains the active ingredients in the widely used antiretroviral drugs Epivir (lamivudine), Retrovir (zidovudine) and Viramune (nevirapine). The combination tablet is manufactured by Aurobindo Pharma Ltd. in Hyderabad, India for purchase by the PEPFAR program. The recommended regimen for the lamivudine-zidovudine-nevirapine tablet is one pill twice a day following an initial two week treatment with the individual components taken individually.
On July 10, 2006, FDA granted tentative approval for generic didanosine tablets (chewable, dispersible, buffered), 100 mg, 150 mg and 200 mg, manufactured by Aurobindo Pharma Limited Inc., of Hyderabad, India. This is a generic version of the approved Videx Chewable Tablets manufactured by Bristol Myers Squibb. The application for the generic version for use outside the U.S. was reviewed under expedited review provisions for the President's Emergency Plan for AIDS Relief (PEPFAR).
On July 12, 2006 FDA approved Atripla Tablets, a new fixed-dose combination of three widely used antiretroviral drugs, to be taken in a single tablet once a day, alone or in combination with other antiretroviral products for the treatment of HIV-1 infection in adults. Atripla is the first fixed dose combination available in the United States to combine two different classes of antiviral drugs in a single pill. This "one-pill-once-a-day" product to treat HIV/AIDS combines the active ingredients of Sustiva (efavirenz) a Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI), with Emtriva (emtricitabine) and Viread (tenofovir disoproxil fumarate), two Nucleoside Reverse Transcriptase Inhibitors (NRTIs). Emtriva and Viread are also available in a fixed dose combination known as Truvada. Atripla was the result of an unprecedented inter-company cooperative effort between Gilead Sciences, the manufacturer of Emtriva and Viread, with Bristol-Myers Squibb, the manufacturer of Sustiva. Merck controls the marketing of Sustiva outside the United States. The approval of Atripla not only makes the new fixed dose combination available in the U.S., but also permits its purchase under the President's Emergency Plan for AIDS Relief (PEPFAR) program.
The Food and Drug Administration granted tentative approval on July 26, 2006 for lamivudine/zidovudine tablets, co-packaged with abacavir sulfate tablets, manufactured by Aurobindo Pharma Limited Inc., of Hyderabad, India, for treatment of HIV, . The lamivudine/zidovudine combination is a generic formulation of the approved combination product, Combivir, manufactured by GlaxoSmithKline, which combines the two Nucleoside Reverse Transcriptase Inhibitors (NRTIs) in a single tablet. Abacavir sulfate, which is also an NRTI, is a generic formulation of the approved product, Ziagen, also manufactured by GlaxoSmithKline. The application was reviewed under expedited review provisions for the President's Emergency Plan for AIDS Relief (PEPFAR). The generic products can be used in countries which fall under the PEPFAR program.
On August 11, 2006, FDA granted tentative approval, for generic nevirapine tablets, 200 mg, manufactured by Strides Acrolab Ltd., Bangalore, India, under the expedited review provisions created for the President's Emergency Plan for AIDS Relief (PEPFAR) for availability in PEPFAR-affected countries.
The Food and Drug Administration, on August 23, 2006, granted tentative approval for a fixed dose tablet containing generic lamivudine/zidovudine 150 mg/300 mg, manufactured by Pharmacare Limited of South Africa. The tablets are indicated for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults. Tentative approval means that FDA has concluded that a drug product has met all of the required quality, safety and efficacy standards, though it may not be marketed in the U.S. due to existing patents and/or exclusivity rights. However, tentative approval makes the product eligible to be considered for purchase under the President's Emergency Plan for AIDS Relief (PEPFAR) program. The lamivudine/zidovudine fixed dose combination tablets are a version of the FDA approved Combivir tablets manufactured by GlaxoSmithKline.
On August 28, 2006, FDA granted tentative approval for stavudine capsules, 30 mg and 40 mg, manufactured by Strides Acrolab Ltd., Bangalore, India, under the expedited review provisions created for the President's Emergency Plan for AIDS Relief (PEPFAR). Tentative approval qualifies the product for consideration for purchase under the PEPFAR program. The tentative approval covers a generic version of Zerit Capsules, 30 mg and 40 mg, a nucleoside reverse transcriptase inhibitor (NRTI) used in combination with other antiretroviral agents for the treatment of HIV-1 infection, manufactured by Bristol-Myers Squibb.
On September 13, 2006, FDA granted tentative approval for a fixed dose tablet containing lamivudine/zidovudine 150 mg/300 mg manufactured by Cipla Limited of Mumbai, India. The tablets are indicated for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults. Tentative approval makes the product eligible to be considered for purchase under the President's Emergency Plan for AIDS Relief program, even though patent exclusivity makes them ineligible for sale in the U.S. The lamivudine/zidovudine fixed dose combination tablets are a version of the approved Combivir tablets manufactured by GlaxoSmithKline.
The Food and Drug Administration, on October 5, 2006, announced approval of the APTIMA(r) HIV-1 RNA Qualitative Assay, manufactured by Gen-Probe Incorporated of San Diego, California, for use in clinical laboratories and public health facilities to detect primary (early) HIV-1 infection. The APTIMA® HIV-I RNA Qualitative Assay is an in vitro nucleic acid test (NAT) for the detection of human immunodeficiency virus (HIV-1) in human plasma intended for use as an aid in the diagnosis of HIV-I infection, including acute or primary infection, before the appearance of antibodies to HIV-1. The newly approved test may provide earlier diagnosis of infection than traditional detection and diagnosis of HIV-I infection by enzyme immunoassay (EIA) because it detects nucleic acid of the human immunodeficiency virus (HIV-1) in human plasma, rather than the body's antibody response to the virus. The APTIMA test can also be used instead of the traditional Western blot test or IFA for confirmation of HIV-1 infection when the screening test result for HIV-1 antibodies is positive.
FDA, on October 5, 2006, granted tentative approval for didanosine for Oral Solution (Pediatric Powder), 10 mg/mL, manufactured by Aurobindo Pharma Limited Inc., of Hyderabad, India. A generic version of the approved Videx Pediatric Powder for Oral Solution, 10 mg/mL, manufactured by Bristol Myers Squibb, the application was reviewed under expedited review provisions for the President's Emergency Plan for AIDS Relief (PEPFAR).
On October 16, 2006, the Food and Drug Administration approved a new 300 mg capsule form of Reyataz (atazanavir) adding to the available 100mg, 150 mg, and 200 mg capsules. The new 300 mg capsules give treatment-experienced patients the option to take either one 300 mg capsule, or two 150 mg capsules of Reyataz, once daily plus ritonavir 100 mg once daily, with food. The recommended dose for treatment-naïve patients remains unchanged and is Reyataz 400 mg (two 200mg capsules) once daily with food. Reyataz is a product of Bristol-Myers Squibb.
FDA announced, on October 18, 2006, the availability of guidance for industry entitled "Fixed Dose Combinations (FDC), Co-Packaged Drug Products and Single Entity Versions of Previously Approved Antiretrovirals for the Treatment of HIV." The guidance encourages sponsors to develop various drug product versions of previously approved antiretroviral drugs and to submit drug applications for these products to FDA for review. The availability of a wide range of safe and effective antiretroviral drug products is hoped to facilitate a wider distribution of anti-HIV drugs to better meet the demands of the global HIV/AIDS pandemic. The draft version of this guidance entitled "Fixed Dose Combination and Co-Packaged Drug Products for Treatment of HIV," was first posted on May 2004. The guidance was updated to address public comments to the draft version. Significant changes to the draft include: 1) the inclusion of single entity versions, in addition to combination products, in the expedited FDA review pathway for these products 2) the addition of tables that supply references supporting the clinical efficacy and safety of antiretroviral combinations 3) the inclusion of more details and clarification on the amount and type of data that should be submitted in a drug application to support a potential approval or tentative approval. You can read the guidance on the FDA web site (PDF 343 KB).
On November 6, 2006, FDA granted tentative approval for a generic formulation of abacavir sulfate tablets, 300 mg, manufactured by Cipla Limited of Mumbai, India. The application was reviewed under the expedited review provisions of the President's Emergency Plan for AIDS Relief (PEPFAR). Although existing patents and/or exclusivity prevent marketing of this product in the United States, the product met all of the safety, efficacy, and manufacturing quality standards required for marketing in the U.S., and can thus be considered for purchase under PEPFAR.
On November 17, 2006, FDA granted tentative approval for a new fixed drug combination of stavudine/lamivudine/nevirapine tablets manufactured by Cipla Limited, of Mumbai, India. This product was reviewed under expedited procedures for the President's Emergency Plan for AIDS Relief (PEPFAR) program, although it cannot be marketed in the U.S. because of existing patents and exclusivities. Stavudine, lamivudine, and nevirapine are anti-viral drugs for the treatment of HIV-1 infection. This new combination can significantly decrease pill burden and could result in improved compliance for HIV infected individuals.

2007

On January 20, 2007, the Food and Drug Administration (FDA) granted tentative approval for a new fixed drug combination of lamivudine/stavudine (150mg/ 30mg or 150mg/40mg) tablets manufactured by Cipla Limited, of Mumbai, India. This product was reviewed under expedited procedures for the President's Emergency Plan for AIDS Relief (PEPFAR) program.
In January, the Sustiva (efavirenz) package insert was updated to include drug-drug interaction information regarding coadministration of efavirenz with rifampin, diltiazem, itraconazole, voriconazole, atorvastatin, pravastatin, simvastatin, pimozide and bepredil.
In January, additions were made to the Fuzeon (enfuvirtide) for injection product label to include important information about nerve bundle pain, hematoma, and cautionary wording regarding Biojector use in patients with coagulopathy.
On January 31, 2007, FDA granted tentative approval for a fixed-dose, three-drug tablet for use as a complete anti-viral treatment of HIV-1 infection in adults. The tablet contains lamivudine-zidovudine-nevirapine, the active ingredients in the widely used antiretroviral drugs Epivir (lamivudine), Retrovir (zidovudine) and Viramune (nevirapine). The new combination tablet is manufactured by Cipla Limited, of Mumbai, India.
FDA and Bristol-Myers Squibb notified healthcare professionals in February of revisions to the MICROBIOLOGY/Antiviral Activity and INDICATIONS AND USAGE/Description of Clinical Studies/Special Populations sections of the prescribing information for Baraclude (entecavir), a nucleoside analog used in the treatment of chronic hepatitis B virus (HBV), reflecting a case report in which a human immunodeficiency virus (HIV) variant containing the M184V resistance substitution was documented during Baraclude treatment for HBV infection in an HIV/HBV co-infected patient who was not simultaneously receiving highly active antiretroviral therapy (HAART).
On March 2, 2007, FDA granted tentative approval for a fixed dose tablet containing lamivudine/zidovudine(150 mg/300 mg) tablets, co-packaged with Nevirapine(200 mg tablets for the treatment of HIV-1 infection, manufactured by Strides Arcolab Ltd, Bangalore, India, for use by the PEPFAR Program.
In March, FDA issued final guidance, entitled "Guidance for Industry: Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps)," to assist establishments making donor eligibility determinations to comply with the requirements for determining donor-eligibility, including donor screening and testing for donors of human cells, tissues, and cellular and tissue-based products. (for background, The document provides guidance on donor-eligibility determination, donor screenings, donor testing requirements (including HIV), additional screening and testing requirements for reproductive cells and tissues, and exceptions from the requirements for determining donor-eligibility, and special circumstances.
On March 8, 2007, FDA granted approval for generic didanosine for oral solution (Pediatric Powder), 10 mg/mL, a generic version of the already FDA approved Videx Pediatric Powder for Oral Solution, 10 mg/mL, manufactured by Bristol Myers Squibb, packaged in 2 gram and 4 gram containers, manufactured by Aurobindo Pharma Limited, of Hyderabad, India, allowing marketing of the generic in United States.
On March 9, 2007, FDA issued a public health advisory outlining new safety information, including revised product labeling about erythropoiesis-stimulating agents (ESAs), widely-used drugs for the treatment of anemia in a variety of conditions, anemia due to zidovudine therapy in HIV patients.
On March 13, 2007, FDA granted tentative approval for two applications for antiretroviral drugs products made by Strides Acrolab Ltd., Bangalore, India, under the expedited review provisions created by FDA for the President's Emergency Plan for AIDS Relief (PEPFAR). The first was a fixed dose combination of stavudine/lamivudine (40mg/150mg) tablets, co-packaged with nevirapine tablets (200mg) for use in HIV-1 treatment of HIV-1. The second was a fixed dose combination of Stavudine/Lamivudine (40mg/150mg) Tablets for use in HIV-1 treatment in combination with other antiretroviral drugs. These drug combinations can significantly decrease pill burden and could result in improved compliance for HIV infected individuals.
FDA granted tentative approval on March 19, 2007 for lamivudine tablets (150 mg), manufactured by Matrix Laboratories, Inc., of Hyderabad, India, under expedited review provisions developed for the President's Emergency Plan for AIDS Relief (PEPFAR).
On March 26, 2007, FDA granted tentative approval for a generic drug formulation of efavirenz tablets (600 mg), manufactured by Strides Acrolab Ltd., Bangalore, India, under the expedited review provisions created by FDA for the President's Emergency Plan for AIDS Relief, for purchase under the PEPFAR Program.
On April 5, 2007, FDA granted tentative approval for abacavir sulfate tablets, 300 mg, manufactured by Matrix Laboratories, Inc., of Hyderabad, India, under expedited review provisions developed to permit the tentatively approved drug's use under the President's Emergency Plan for AIDS Relief
In April, Product labeling for KALETRA lopinavir/ritonavir) was been updated to reflect safety and efficacy data from study M97-720 in treatment-naïve patients out to 360 weeks.
FDA granted tentative approval on April 23, 2007 for a generic formulation for stavudine capsules, 30 mg and 40 mg, manufactured by Matrix Laboratories Limited of Hyderabad, India, under expedited review provisions developed for to permit use of the lower priced generic formulation by the President's Emergency Plan for AIDS Relief.
FDA granted approval, on May 23, 2007, to a generic formulation of zidovudine capsules, 100 mg, manufactured by Cipla Limited, of Mumbai, India, making this generic zidovudine capsules formulation available for marketing in the United States.
On May 11/2007, FDA granted marketing approval for the Abbott RealTime HIV-1 Assay, made by ABBOTT Molecular, Inc., an in vitro reverse transcription-polymerase chain reaction (RT-PCR) assay for the quantitation of Human Immunodeficiency Virus type 1 (HIV-1) on the automated m2000 System in human plasma from HIV-1 infected individuals over the range of 40 to 10,000,000 copies/mL, for use in managing the treatment of HIV infection. The Abbott RealTime HIV-1 assay is intended for use in conjunction with clinical presentation and other laboratory markers for disease prognosis and for use as an aid in assessing viral response to antiretroviral treatment as measured by changes in plasma HIV-1 RNA levels.
On May 11/2007, FDA granted marketing approval for the COBAS AmpliPrep/COBAS TaqMan HIV-1 Test, made by Roche Diagnostics. The automated PCR test, indicated for the quantitation of Human Immunodeficiency Virus Type 1 (HIV-1) nucleic acid in human plasma (viral load) for use in conjunction with clinical presentation and other laboratory markers for the clinical management of HIV-1 infected patients. It can be used to assess patient prognosis by measuring the baseline HIV-1 RNA level or to monitor the effects of antiretroviral therapy by measuring changes in plasma HIV-1 RNA levels during the course of antiretroviral treatment.
On May 23, 2007, FDA approved the Procleix Ultrio Assay on the fully automated Procleix TIGRIS system manufactured by Gen-Probe Inc., of San Diego, California, and marketed by Chiron Corporation, a fully automated qualitative in vitro nucleic acid test (NAT) to screen for human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) RNA in donated blood from donors of whole blood, blood components, or source plasma. It is also licensed to screen individual organ donations from living donors, heart-beating organ donors, and cadaveric (non-heart-beating) organ donors. The capability of full automation will reduce human error and accelerate blood screening, enhancing blood safety.
On June 14, 2007, the Food and Drug Administration approved a new formulation of Lexiva (fosamprenavir calcium), available as an oral suspension (50-mg/mL). The package insert was updated to include information on the new formulation and to provide dosing information for pediatric patients and patients with hepatic impairment
FDA granted tentative approval on July 10, 2007 for a generic formulation of nevirapine tablets, 200 mg, manufactured by Zhejiang Huahai Pharmaceutical Co. Ltd. of Zhejiang China, under expedited review provisions developed for the President's Emergency Plan for AIDS Relief for us of the generic formulation by that international relief program.
On July 12, 2007 FDA granted tentative approval for a generic formulation of efavirenz tablets, 600 mg, manufactured by Matrix Laboratories Limited, of Hyderabad, India, under expedited review provisions developed to allow purchase of this generic formulation by the President's Emergency Plan for AIDS Relief.
FDA approved revised labeling on July 24, 2007 for BARACLUDE (entecavir) 0.5 mg and 1.0 mg Film-Coated Tablets, and BARACLUDE (entecavir) 0.05 mg/mL Oral Solution for the treatment of chronic hepatitis B virus infection in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. The amended label includes safety information related to the use of entecavir (ETV) in patients with human immunodeficiency virus (HIV)/hepatitis B virus (HBV) coinfection who are not receiving simultaneous highly active antiretroviral therapy (HAART).
On August 6, 2007, the Food and Drug Administration (FDA) approved Selzentry (maraviroc) 150 mg and 300 mg tablets, the first drug in the new class of anti-HIV medications called CCR-5 co-receptor antagonists, under a priority review. CCR-5 co-receptor antagonist are used in combination with other antiretroviral products for the treatment of adults infected with CCR5-tropic HIV-1.
FDA granted tentative approval on August 8, 2007 for a generic formulation of a combination product consisting of lamivudine and zidovudine tablets,150 mg/300 mg, manufactured by Emcure Pharmaceuticals Inc. of Pune, India under expedited review provisions developed to permit purchase of this generic product by the President's Emergency Plan for AIDS Relief overseas.
FDA granted tentative approval on August 8, 2007 for a generic formulation of a combination product, lamivudine and zidovudine tablets,150 mg/300 mg, manufactured by Emcure Pharmaceuticals Inc. of Pune, India under expedited review provisions developed to allow purchase by the President's Emergency Plan for AIDS Relief for treatment use in the countries covered by the AIDS relief program.
FDA, on August 13, 2007, granted tentative approval for a new fixed dose three-drug combination pill containing generic lamivudine, stavudine and nevirapine, to treat human immunodeficiency virus (HIV-1) infection in children outside the United States. This was the first combination of its kind available to meet the needs of children less than 12 years of age, and represents a major advance in global AIDS treatment efforts. The generic combination drug tablet is manufactured by Cipla Limited, of Mumbai, India.
On October 4, 2007, FDA granted traditional approval to Aptivus (tipranavir), for combination antiretroviral treatment of HIV-1 infected adults with evidence of viral replication, who are treatment-experienced and infected with HIV-1 strains resistant to more than one protease inhibitor. Aptivus, a product of Boehringer Ingelheim, was granted accelerated approval on June 22, 2005, based on analysis of plasma HIV-1 RNA levels in two controlled phase 3 studies of 24 weeks duration of Aptivus/ritonavir. The traditional approval was based on continuation of the RESIST trials through 48 weeks and beyond, confirming durability of the virologic response.
On, October 12, 2007, FDA granted accelerated approval for raltegravir tablets (400 mg) to treat Human Immunodeficiency Virus (HIV)-1 infection in combination with other antiretroviral agents. Raltegravir, with the trade name Isentress, was the first approved product in the pharmacological class of antiretroviral agents known as HIV integrase strand transfer inhibitors, commonly referred to as integrase inhibitors. They are designed to slow the advancement of HIV-1 infection by blocking the HIV integrase enzyme that the virus needs in order to multiply. Raltegravir received a priority review by the FDA. The review and approval of the New Drug Application was completed in within six months.
On October 12, 2007, FDA approved a supplemental new drug application for Lexiva (fosamprenavir calcium; FPV) Oral Tablets, adding a new indication for once-daily dosing of 1400 mg of Lexiva with 100 mg ritonavir for the treatment of HIV infection in therapy-naïve adults.

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