INCLUSION CRITERIA: VIRAL SURVEY COHORT
-HIV-1 infection documented by HIV ELISA and WB
-Age greater than or equal to 18 years old
-Hemoglobin greater than or equal to 12 mg/dl within the last six weeks
-On HAART according to current DHHS guidelines.
-Most recent viral load (within the last 12 INCLUSION CRITERIA: VIRAL SURVEY COHORT
-HIV-1 infection documented by HIV ELISA and WB
-Age greater than or equal to 18 years old
-Hemoglobin greater than or equal to 12 mg/dl within the last six weeks
-On HAART according to current DHHS guidelines.
-Most recent viral load (within the last 12 weeks):
--less than 50 by bDNA or RT-PCR (65 patients)
--50-500 by bDNA or RT-PCR (3 patients)
--501 - 10,000 by bDNA or RT-PCR (2 patients)
EXCLUSION CRITERIA:
-Any febrile illness (T greater than 38.0 degrees C) in the 3 weeks prior to blood draw.
VIRAL SURVEY COHORT- M98-863, M97-720, AACTG 5201 SAMPLES (no inclusion/exclusion):
-Samples from patients enrolled in the completed M98-863, M97-720 or AACTG 5201 study.
INCLUSION CRITERIA: PILOT INTENSIFICATION COHORT:
-HIV-1 infection documented by HIV ELISA and WB
-Age greater than or equal to 18 years old
-Hgb greater than or equal to 12 mg/dl
-CD4 greater than 200 cells/ micro liter and CD4% greater than 14% and not requiring prophylaxis for opportunistic infections
-Therapy with accept HAART regimen for greater than or equal to 6 months
-Viral load less than 50 copies RNA/ml plasma by RT-PCR for at least four months
-Viral load greater than 0.38 copies RNA/ml plasma by SCA assay or positive in the adapted Amplicor assay
-Current HAART with DHHS-approved regimen NRTI+PI, NRTI alone, NRTI+NNRTI.
-Willingness to take an additional antiretroviral to current regimen for 30 days.
-For patients to start lopinavir/ritonavir, willingness to reduce the dose of sildenafil and other co-administered medicines that may be affected by the addition of lopinavir/ritonavir during the course of therapy with lopinavir/ritonavir
-For patients to start efavirenz arm, willingness to take efavirenz and adjust other medications or supplements as necessary, and to be aware that efavirenz is contraindicated in pregnancy and that may result in false positive urine tests for THC
-Patient must have primary care outside this protocol.
-Patients must practice accepted barrier methods to prevent pregnancy.
INCLUSION CRITERIA: RANDOMIZED INTENSIFICATION COHORT (NIH, University of Pittsburgh):
-HIV-1 infection documented by HIV ELISA and WB
-Age greater than or equal to 18 years old
-Hgb greater than or equal to 12 mg/dl
-CD4 greater than 200 cells/ micro liter and CD4% greater than 14% and not requiring prophylaxis for opportunistic infections
-Therapy with accepted HAART regimen for greater than or equal to 6 months.
-Viral load less than 50 copies RNA /ml plasma by RT-PCR for at least four months.
-Viral load greater than or equal to 0.38 copies RNA/ml plasma by SCA assay or positive in the adapted Amplicor assay
-Current HAART with DHHS-approved regimen NRTI+PI, NRTI alone, NRTI+NNRTI.
-Willingness to take an additional antiretroviral to current regimen for 30 days.
-For patients to start lopinavir/ritonavir, willingness to reduce the dose of sildenafil and other co-administered medicines that may be affected by the addition of lopinavir/ritonavir during the course of therapy with lopinavir/ritonavir
-For patients to start efavirenz arm, willingness to take efavirenz and adjust other medications or supplements as necessary, and to be aware that efavirenz is contraindicated in pregnancy and that may result in false positive urine tests for THC
-Patient must have primary care outside this protocol.
-Patients must practice accepted barrier methods to prevent pregnancy.
EXCLUSION CRITERIA:
-Requirement for cytotoxic agents including hydroxyurea or vaccinations during the study period
-Chronic corticosteroid therapy
-Concurrent therapy with investigational cytokines including IL-2 or IL-12 during the course of the study. Prior administration of cytokines is not an exclusion criteria; at least 4 months from most recent cycle of IL-2 or IL-12. GCSF and erythropoietin therapy will be permitted
-History of taking a salvage regimen; i.e., patient has had clinical resistance to antiretrovirals. Changing antiviral therapy because of adverse effects is permitted
-Prior PI therapy or NNRTI therapy is not permitted unless the previous PI-containing therapy was switched because of patient preference. If the patient has a documented history of lipid elevations (fasting triglycerides greater than 750 mg/dl), the patient will not be eligible for PI addition.
-Any febrile illness (T greater than 38.0 degrees C) in the 3 weeks prior to enrollment
-Any vaccination in the 6 weeks prior to enrollment
-Current pregnancy or lactation, history of pregnancy in the last 4 months
-Prior history of intolerance to the added antiretroviral
-For lopinavir/ritonavir addition, baseline elevated triglycerides greater than 400 mg/dl without lipid lowering agents
-Elevated baseline ALT liver function assays greater than 2 fold greater than upper limit of normal
-Known history of liver disease or Child-Pugh score greater than 5.
-History of pancreatitis requiring hospitalization
-Concomitant use with drugs that are highly dependent on cytochrome P450 for clearance, which, in the opinion of the investigators, may lead to the unexpected changes in their concentrations occurring after the addition of lopinavir/ritonavir or efavirenz. Examples include but are not limited to: wafarin-like anticoagulation , amiodarone, astemizole, cisapride, statin class of drugs, gemfibrozil, cyclosporine, ergonavine, ergotamine, methylergonavine, dihydroergotamine, dofetilide, flecanide, quinidine, fusidic acid, methadone, demerol, midazolam, triazolam, phenytoin, dilantin, pimozide, sirolimus, tacrolimus, propafenone, quinupristin, terfenadine, theophylline, rifampin, rifapentene, or rifabutin and illicit substances, including the recreational substance (ecstasy) methylenedioxymethamphetamine.
-History of chronic diarrhea or inflammatory bowel disease
-History of hemophilia
-Inability to comply with the protocol
For those starting efavirenz, significant depression, which, in the opinion of the investigators, would be significantly worsened by efavirenz.
INCLUSION CRITERIA - DRUG OVERLAP COHORT:
- HIV-1 infection documented by HIV ELISA and WB
- Age greater than or equal to18 years old
- Hgb greater than or equal to 12 mg/dl
- CD4 greater than 200 cells/ micro liter and CD4% greater than 14% and not requiring prophylaxis for opportunistic infections
- Therapy with accepted HAART regimen for greater than or equal to 6 months
- Viral load less than 50 copies RNA/ml plasma by RT-PCR for at least four months
- Viral load greater than 0.38 copies RNA/ml plasma by SCA assay or positive in the adapted Amplicor assay
- Current HAART with DHHS-approved regimen NRTI+PI, NRTI alone, NRTI+NNRTI
- Willingness to take an additional antiretroviral to current regimen for 30 days
- For patients planning to start lopinavir/ritonavir, or other ritonavir containing regimen willingness to reduce the dose of sildenafil and other co-administered medicines that may be affected by the addition of ritonavir during the course of therapy with lopinavir/ritonavir
- For patients to start efavirenz, willingness to take efavirenz and adjust other medications or supplements as necessary, and to be aware that efavirenz is contraindicated in pregnancy and that may result in false positive urine tests for THC
- Patient must have primary care outside this protocol
- Patients must practice accepted barrier methods to prevent pregnancy.
EXCLUSION CRITERIA:
- Requirement for cytotoxic agents including hydroxyurea or vaccinations during the study period
- Chronic corticosteroid therapy
- Concurrent therapy with investigational cytokines including IL-2 or IL-12 during the course of the study. Prior administration of cytokines is not an exclusion criteria; at least 4 months from most recent cycle of IL-2 or IL-12. GCSF and erythropoietin therapy will be permitted
- History of taking a salvage regimen; i.e., patient has had clinical resistance to antiretrovirals. Changing antiviral therapy because of adverse effects is permitted
- History of taking a salvage regimen; i.e., patient has had clinical resistance to antiretrovirals. Changing antiviral therapy because of adverse effects is permitted.
- Prior PI therapy or NNRTI therapy is not permitted unless the previous PI-containing therapy was switched because of patient preference. If the patient has a documented history of lipid elevations (fasting triglycerides greater than 750 mg/dl) the patient will not be eligible for PI addition.
- Any febrile illness (T greater than 38 degrees C) in the 3 weeks prior to enrollment
- Any vaccination in the 6 weeks prior to enrollment
- Current Pregnancy or lactation, history of pregnancy in the last 4 months
- Prior history of intolerance to the added antiretroviral
- For protease addition, baseline elevated triglycerides greater than 400 mg/dl without lipid lowering agents
- Elevated baseline ALT liver function assays greater than 2 fold greater than upper limit of normal
- Known history of liver disease or Child-Pugh score greater than 5.
- History of pancreatitis requiring hospitalization
- For patients who are adding ritonavir or efavirenz, concomitant use with drugs that are highly dependent on cytochrome P 450 for clearance, which, in the opinion of the investigators, may lead to the unexpected changes in their concentrations occurring after the new drug is added. Examples include but are not limited to: wafarin-like anticoagulation , amiodarone, astemizole, cisapride, statin class of drugs, gemfibrozil, cyclosporine, ergonavine, ergotamine, methylergonavine, dihydroergotamine, dofetilide, flecanide, quinidine, fusidic acid, methadone, demerol, midazolam, triazolam, phenytoin, dilantin, pimozide, sirolimus, tacrolimus, propafenone, quinupristin, terfenadine, theophylline, rifampin, rifapentene, or rifabutin and illicit substances, including the recreational substance (ecstasy) methylenedioxymethamphetamine
- History of chronic diarrhea or inflammatory bowel disease
- History of hemophilia
- Inability to comply with the protocol
- For those starting efavirenz, significant depression, which, in the opinion of the investigators, would be significantly worsened by efavirenz weeks):
--less than 50 by bDNA or RT-PCR (65 patients)
--50-500 by bDNA or RT-PCR (3 patients)
--501 - 10,000 by bDNA or RT-PCR (2 patients)
EXCLUSION CRITERIA:
-Any febrile illness (T greater than 38.0 degrees C) in the 3 weeks prior to blood draw.
VIRAL SURVEY COHORT- M98-863, M97-720, AACTG 5201 SAMPLES (no inclusion/exclusion):
-Samples from patients enrolled in the completed M98-863, M97-720 or AACTG 5201 study.
INCLUSION CRITERIA: PILOT INTENSIFICATION COHORT:
-HIV-1 infection documented by HIV ELISA and WB
-Age greater than or equal to 18 years old
-Hgb greater than or equal to 12 mg/dl
-CD4 greater than 200 cells/ micro liter and CD4% greater than 14% and not requiring prophylaxis for opportunistic infections
-Therapy with accept HAART regimen for greater than or equal to 6 months
-Viral load less than 50 copies RNA/ml plasma by RT-PCR for at least four months
-Viral load greater than 0.38 copies RNA/ml plasma by SCA assay or positive in the adapted Amplicor assay
-Current HAART with DHHS-approved regimen NRTI+PI, NRTI alone, NRTI+NNRTI.
-Willingness to take an additional antiretroviral to current regimen for 30 days.
-For patients to start lopinavir/ritonavir, willingness to reduce the dose of sildenafil and other co-administered medicines that may be affected by the addition of lopinavir/ritonavir during the course of therapy with lopinavir/ritonavir
-For patients to start efavirenz arm, willingness to take efavirenz and adjust other medications or supplements as necessary, and to be aware that efavirenz is contraindicated in pregnancy and that may result in false positive urine tests for THC
-Patient must have primary care outside this protocol.
-Patients must practice accepted barrier methods to prevent pregnancy.
INCLUSION CRITERIA: RANDOMIZED INTENSIFICATION COHORT (NIH, University of Pittsburgh):
-HIV-1 infection documented by HIV ELISA and WB
-Age greater than or equal to 18 years old
-Hgb greater than or equal to 12 mg/dl
-CD4 greater than 200 cells/ micro liter and CD4% greater than 14% and not requiring prophylaxis for opportunistic infections
-Therapy with accepted HAART regimen for greater than or equal to 6 months.
-Viral load less than 50 copies RNA /ml plasma by RT-PCR for at least four months.
-Viral load greater than or equal to 0.38 copies RNA/ml plasma by SCA assay or positive in the adapted Amplicor assay
-Current HAART with DHHS-approved regimen NRTI+PI, NRTI alone, NRTI+NNRTI.
-Willingness to take an additional antiretroviral to current regimen for 30 days.
-For patients to start lopinavir/ritonavir, willingness to reduce the dose of sildenafil and other co-administered medicines that may be affected by the addition of lopinavir/ritonavir during the course of therapy with lopinavir/ritonavir
-For patients to start efavirenz arm, willingness to take efavirenz and adjust other medications or supplements as necessary, and to be aware that efavirenz is contraindicated in pregnancy and that may result in false positive urine tests for THC
-Patient must have primary care outside this protocol.
-Patients must practice accepted barrier methods to prevent pregnancy.
EXCLUSION CRITERIA:
-Requirement for cytotoxic agents including hydroxyurea or vaccinations during the study period
-Chronic corticosteroid therapy
-Concurrent therapy with investigational cytokines including IL-2 or IL-12 during the course of the study. Prior administration of cytokines is not an exclusion criteria; at least 4 months from most recent cycle of IL-2 or IL-12. GCSF and erythropoietin therapy will be permitted
-History of taking a salvage regimen; i.e., patient has had clinical resistance to antiretrovirals. Changing antiviral therapy because of adverse effects is permitted
-Prior PI therapy or NNRTI therapy is not permitted unless the previous PI-containing therapy was switched because of patient preference. If the patient has a documented history of lipid elevations (fasting triglycerides greater than 750 mg/dl), the patient will not be eligible for PI addition.
-Any febrile illness (T greater than 38.0 degrees C) in the 3 weeks prior to enrollment
-Any vaccination in the 6 weeks prior to enrollment
-Current pregnancy or lactation, history of pregnancy in the last 4 months
-Prior history of intolerance to the added antiretroviral
-For lopinavir/ritonavir addition, baseline elevated triglycerides greater than 400 mg/dl without lipid lowering agents
-Elevated baseline ALT liver function assays greater than 2 fold greater than upper limit of normal
-Known history of liver disease or Child-Pugh score greater than 5.
-History of pancreatitis requiring hospitalization
-Concomitant use with drugs that are highly dependent on cytochrome P450 for clearance, which, in the opinion of the investigators, may lead to the unexpected changes in their concentrations occurring after the addition of lopinavir/ritonavir or efavirenz. Examples include but are not limited to: wafarin-like anticoagulation , amiodarone, astemizole, cisapride, statin class of drugs, gemfibrozil, cyclosporine, ergonavine, ergotamine, methylergonavine, dihydroergotamine, dofetilide, flecanide, quinidine, fusidic acid, methadone, demerol, midazolam, triazolam, phenytoin, dilantin, pimozide, sirolimus, tacrolimus, propafenone, quinupristin, terfenadine, theophylline, rifampin, rifapentene, or rifabutin and illicit substances, including the recreational substance (ecstasy) methylenedioxymethamphetamine.
-History of chronic diarrhea or inflammatory bowel disease
-History of hemophilia
-Inability to comply with the protocol
For those starting efavirenz, significant depression, which, in the opinion of the investigators, would be significantly worsened by efavirenz.
INCLUSION CRITERIA - DRUG OVERLAP COHORT:
- HIV-1 infection documented by HIV ELISA and WB
- Age greater than or equal to18 years old
- Hgb greater than or equal to 12 mg/dl
- CD4 greater than 200 cells/ micro liter and CD4% greater than 14% and not requiring prophylaxis for opportunistic infections
- Therapy with accepted HAART regimen for greater than or equal to 6 months
- Viral load less than 50 copies RNA/ml plasma by RT-PCR for at least four months
- Viral load greater than 0.38 copies RNA/ml plasma by SCA assay or positive in the adapted Amplicor assay
- Current HAART with DHHS-approved regimen NRTI+PI, NRTI alone, NRTI+NNRTI
- Willingness to take an additional antiretroviral to current regimen for 30 days
- For patients planning to start lopinavir/ritonavir, or other ritonavir containing regimen willingness to reduce the dose of sildenafil and other co-administered medicines that may be affected by the addition of ritonavir during the course of therapy with lopinavir/ritonavir
- For patients to start efavirenz, willingness to take efavirenz and adjust other medications or supplements as necessary, and to be aware that efavirenz is contraindicated in pregnancy and that may result in false positive urine tests for THC
- Patient must have primary care outside this protocol
- Patients must practice accepted barrier methods to prevent pregnancy.
EXCLUSION CRITERIA:
- Requirement for cytotoxic agents including hydroxyurea or vaccinations during the study period
- Chronic corticosteroid therapy
- Concurrent therapy with investigational cytokines including IL-2 or IL-12 during the course of the study. Prior administration of cytokines is not an exclusion criteria; at least 4 months from most recent cycle of IL-2 or IL-12. GCSF and erythropoietin therapy will be permitted
- History of taking a salvage regimen; i.e., patient has had clinical resistance to antiretrovirals. Changing antiviral therapy because of adverse effects is permitted
- History of taking a salvage regimen; i.e., patient has had clinical resistance to antiretrovirals. Changing antiviral therapy because of adverse effects is permitted.
- Prior PI therapy or NNRTI therapy is not permitted unless the previous PI-containing therapy was switched because of patient preference. If the patient has a documented history of lipid elevations (fasting triglycerides greater than 750 mg/dl) the patient will not be eligible for PI addition.
- Any febrile illness (T greater than 38 degrees C) in the 3 weeks prior to enrollment
- Any vaccination in the 6 weeks prior to enrollment
- Current Pregnancy or lactation, history of pregnancy in the last 4 months
- Prior history of intolerance to the added antiretroviral
- For protease addition, baseline elevated triglycerides greater than 400 mg/dl without lipid lowering agents
- Elevated baseline ALT liver function assays greater than 2 fold greater than upper limit of normal
- Known history of liver disease or Child-Pugh score greater than 5.
- History of pancreatitis requiring hospitalization
- For patients who are adding ritonavir or efavirenz, concomitant use with drugs that are highly dependent on cytochrome P 450 for clearance, which, in the opinion of the investigators, may lead to the unexpected changes in their concentrations occurring after the new drug is added. Examples include but are not limited to: wafarin-like anticoagulation , amiodarone, astemizole, cisapride, statin class of drugs, gemfibrozil, cyclosporine, ergonavine, ergotamine, methylergonavine, dihydroergotamine, dofetilide, flecanide, quinidine, fusidic acid, methadone, demerol, midazolam, triazolam, phenytoin, dilantin, pimozide, sirolimus, tacrolimus, propafenone, quinupristin, terfenadine, theophylline, rifampin, rifapentene, or rifabutin and illicit substances, including the recreational substance (ecstasy) methylenedioxymethamphetamine
- History of chronic diarrhea or inflammatory bowel disease
- History of hemophilia
- Inability to comply with the protocol
- For those starting efavirenz, significant depression, which, in the opinion of the investigators, would be significantly worsened by efavirenz