Antiretroviral Therapy

Early Infection: AZT/3TC (Combivir), Abacavir (Ziagen), Amprenavir (Agenerase)

This study will determine whether a four-drug combination of antiretroviral medications during the early stage of HIV infection causes undetectable levels of virus in the blood and body tissues, and whether the virus remains undetectable after these drugs are discontinued. All participants will take AZT(Retrovir)/3TC(Epivir), amprenavir, and abacavir twice a day for a year (the induction phase). If subjects have a viral load below 200 copies/mL and are still taking abacavir after 52 weeks, they will begin the maintenance phase at week 52. Subjects are then randomized to one of three groups: 1) AZT/3TC/amprenavir/abacavir, 2) AZT/3TC/amprenavir plus abacavir placebo, or 3) abacavir/amprenavir plus AZT/3TC placebo. Participants will know they are taking amprenavir but will not know if the other drugs are genuine or placebo until the study is completed. At week 88, subjects with a viral load of fewer than 50 copies/mL and no signs of virus in their blood will discontinue study medications. Subjects with a viral load between 50 and 199 copies/mL and those with a viral load below 50 copies/mL but with detectable virus in their plasma will continue study medications. The study will last a little over two years. There is no CD4 cell requirement, but participants must have a viral load of at least 2,000 copies/mL and one of the following: a negative ELISA result within seven days of study entry or a positive ELISA but negative or indeterminate Western blot result within seven days of study entry or positive ELISA and Western blot results within seven days of study entry but with a documented negative ELISA result or viral load below 2,000 copies/mL within 30 days prior to study entry. Prior use of any antiretroviral medications, hepatitis within 30 days, pancreatitis within 120 days, and use of vaccines or investigational drugs within 30 days of study entry are not allowed. The study is being offered in Boston (617-726-3819), Honolulu (808-737-2751), New York (212-241-0433 or 212-420-4519), Philadelphia (215-349-8092), San Francisco (415-514-0550 ext. 362), and San Juan (787-767-9193). (ACTG 371)

Indinavir (Crixivan), Ritonavir (Norvir), d4T (Zerit), 3TC

This study will evaluate the safety and efficacy of adding indinavir to ritonavir in addition to d4T and 3TC. All subjects will take all four drugs. All medications are pills taken orally twice a day. Study visits will take place once a month; the study will last 24 weeks. Participants must have a CD4 cell count of at least 75 cells/mm3 and at least 5,000 copies/mL of HIV RNA (viral load). Participants may not have active opportunistic infections (OIs) or cancers requiring chemotherapy. Prior use of 3TC, abacavir, or any protease inhibitors (PIs) is not allowed. Study locations include Boston (888-253-2712 ext. 242), Houston (713-500-6751), Miami (305-243-3838), New Orleans (504-584-3608), and San Francisco (415-476-9296 ext. 312 or 415-600-6660). (Merck 094)

Tenofovir Disoproxil Fumarate (Tenofovir DF)

This study will evaluate the antiviral activity of two dose levels of once-daily tenofovir DF (TDF) when added to stable antiretroviral therapy in people with HIV. Participants will be randomized to receive one of two doses of TDF or to receive a placebo. Neither participants nor their doctors will know which they are taking until the study ends. After 24 weeks, those persons assigned to take placebo or to take the lower dose of TDF will be switched to the higher dose of TDF. Study visits are once a month and the study lasts 48 weeks.

Eligibility requirements include a viral load between 400 and 10,000 copies/mL and being on stable antiretroviral therapy of no more than four drugs for at least eight weeks. Exclusion criteria include kidney or bone disease, prior use of tenofovir or adefovir dipivoxil, any new AIDS-defining illnesses or immunizations within 30 days prior to study entry, and significant active alcohol or substance abuse. For more information call the number listed for each location: Boston (617-636-8642); Cleveland (216-368-2437); Dallas (214-857-1522); Ft. Lauderdale (954-564-4222); Los Angeles (323-783-8959); Miami (305-856-2171); San Francisco (415-221-4810, 415-292-5481, or 415-202-3487); Torrance (310-222-3848); Vero Beach (561-978-9556); and Washington, DC (202-331-3888).

Tipranavir, Ritonavir, Saquinavir (Fortovase)

This study will compare two different doses of tipranavir (an experimental PI) when combined with ritonavir or with saquinavir and ritonavir in persons who are not achieving adequate viral suppression with their first PI combination. All subjects will take two new nucleoside reverse transcriptase inhibitors (NRTIs). In addition, subjects will be randomized to receive one of two doses of tipranavir combined with ritonavir, or combined with saquinavir and ritonavir, or tipranavir alone. Participants will know which medications they are receiving. Study visits will take place once a month for six months. Subjects who show an adequate response to the study treatments will be permitted to continue for an additional 24-week extension study. Participants must have more than 50 CD4 cells/mm3 and more than 5,000 copies/mL of HIV RNA. Participants must have used their current PI therapy for at least six months and have insufficient viral suppression using their present regimen containing indinavir, nelfinavir, or amprenavir plus two NRTIs. Active OIs or more than seven days' use of saquinavir, ritonavir, or tipranavir are not allowed. The study is being offered in Los Angeles (310-358-2429), Miami (305-661-1150), Nashville (615-936-1164), Tulsa (918-743-1000), and Washington, DC (202-745-6111). (M/3342/0016)

3TC, AZT, Efavirenz (Sustiva)

This study will evaluate the safety of 3TC given once a day versus twice a day when combined with AZT and efavirenz. All participants will take AZT twice a day and efavirenz once a day. In addition, participants will be randomized to take 3TC once a day or twice a day. Since subjects will not know if they are taking 3TC once or twice a day, those persons assigned to take 3TC once a day will also take a 3TC placebo. Study visits will take place once a month; the study will last 48 weeks. Participants must have more than 100 CD4 cells/mm3 and more than 400 copies/mL of HIV RNA; participants also must be antiretroviral naive. Study locations include Galveston (409-747-0241), Houston (713-793-4020), Los Angeles (310-222-5291), Nashville (615-936-1164), New Orleans (504-584-3608), Phoenix (602-955-4673 ext. 2227), San Francisco (415-600-6660), Tampa (813-875-4048), and Washington, DC (202-994-2417). (EPV20001)

Immunotherapy

Interleukin 2 (IL-2), HAART

This study will determine which of three different doses of L2-7001 (a new formulation of IL-2) is best when combined with antiretroviral therapy compared with Proleukin (a different form of IL-2). Participants will be randomized to take one of three doses of L2-7001 or Proleukin in addition to HAART. One group will be assigned to continue taking antiretroviral therapy alone. L2-7001 and Proleukin are given by injection under the skin every 12 hours for the first five days of an eight-week cycle. There will be from six to nine study visits per cycle (there are three cycles) and a final follow-up visit for a total of 22 visits over 32 weeks. Participants must have between 300 and 500 CD4 cells/mm3 and a viral load below 10,000 copies/mL. Subjects must be on stable (unchanged) antiretroviral therapy for at least four months prior to study entry; therapy must consist of at least two drugs, one of which is a PI. Active OIs, prior use of IL-2, cancers requiring chemotherapy, uncontrolled diabetes, and high blood pressure are not allowed. This study is being conducted in Boston (617-927-6035), Miami (305-856-2171 or 305-661-1150), and San Francisco (415-202-3480, Kaiser Permanente members only). (CS-MM-9901)

Pegylated Interferon (PEG Intron)

The purpose of this study is to determine if pegylated interferon (a long-acting form of interferon-alpha) can lower the level of HIV in the plasma of persons whose HAART regimens have failed to suppress the virus, and to see if pegylated interferon is well tolerated. Participants will have genotypic testing done during study screening to see if there are any HAART drugs that are not likely to work against their particular virus. Subjects will be randomized to take one of four doses of interferon or to receive a placebo. Pegylated interferon and its placebo will be given by subcutaneous injection once a week. At week 4, participants will change their HAART drugs based on the results of the genotypic test done during screening. Study visits will take place once a week for the first month, then once a month for the remainder of the 32-week study. Participants will have another genotypic test done at week 28 to see what, if any, changes have occurred after new HAART therapy and interferon therapy have been given. Subjects must have at least 200 CD4 cells/mm3 and at least 2,000 copies/mL of HIV RNA. Subjects must have been taking HAART for at least 16 months, and have been on the current HAART regimen for at least six weeks at study entry. Subjects must have had a three-fold viral load increase from the previous nadir (lowest level) in the last six months or a three-fold increase from a previous nadir of less than 500 copies/mL on the current HAART regimen. Active OIs and use of interferon therapy within the previous six months are not allowed. The study is being done in San Francisco (415-353-5623). (P00737)

AIDS-Related Illnesses

Dyslipidemia and PIs: Abacavir

This study will determine whether replacing a PI with abacavir is effective in lowering the amount of cholesterol in the blood of HIV-infected persons with high cholesterol. Participants are assigned by chance to continue taking their PI-containing antiretroviral therapy or to replace their PI with abacavir. Subjects will know to which group they have been assigned. Study visits will take place once a month; the study will last 32 weeks. There is no CD4 cell requirement but participants must have fewer than 50 copies/mL of HIV RNA. Participants must have been on a stable HAART regimen for at least three months prior to study entry, and the regimen must have consisted of two NRTIs plus a PI or two NRTIs plus a PI in addition to ritonavir. Prior use of any non-nucleoside reverse transcriptase inhibitors (NNRTIs) or amprenavir, past or current AIDS-defining illnesses, lipid disorders unrelated to HIV infection, and current treatment for diabetes or for elevated triglycerides/cholesterol are not allowed. Study sites include Ft. Lauderdale (954-465-4222), Irvine (714-751-5800), San Francisco (415-600-6660), and Tampa (813-870-4760). (ESS 40003)

Kaposi's Sarcoma (KS) Treatment: IM862

The purpose of this study is to compare partial and complete remission of KS lesions using IM862 and placebo, and to determine if IM862 has any effect on HIV. Participants will be assigned by chance to receive IM862 or placebo. Both IM862 and its placebo are given as a nasal solution, which will be taken every other day. Study visits will take place once a month; the study will last six months. Subjects must have KS of the skin or oral cavity and be on stable antiretroviral therapy for at least eight weeks prior to study entry. OIs, KS of the internal organs, upper respiratory congestion, and prior use of IM862 are not allowed. The study is being offered in Baltimore (410-614-5541), Boston (617-414-5160), Los Angeles (323-865-0371), New York (212-639-7161), San Francisco (415-476-9296 ext. 316 or 415-759-4126), Seattle (206-223-6835), and St. Louis (314-362-8836). (AMC 013)

Peripheral Neuropathy Treatment: Lamotrigine (Lamictal)

This study will determine if lamotrigine helps relieve the pain of peripheral neuropathy and improves the quality of life in HIV-infected persons. Subjects are assigned by chance to receive lamotrigine or placebo; both are pills taken orally. Participants will not know which they are taking until the study ends. There will be six study visits; the study will last 11 weeks. Participants taking lamotrigine will have the option to continue taking it for an additional three months. Participants must have moderate to severe peripheral neuropathy diagnosed by a neurologist. Active infections and prior use of lamotrigine are not allowed. The study is being offered in Baltimore (410-955-1895), Chicago (312-908-4511 or 312-572-4545), Galveston (409-747-0241), New York (212-241-0784), Philadelphia (215-829-6464), Rochester (716-273-2114), San Diego (619-543-8080), San Francisco (415-502-5064), and Seattle (206-731-3184). (LAM 40006)

Herpes Zoster Treatment: Valacyclovir

The purpose of this study is to determine whether valacyclovir is safe and effective in treating acute herpes zoster (shingles) in HIV positive persons. Participants will be assigned by chance to receive one of two doses of valacyclovir. Subjects will not know which dose they are receiving until the six-month study ends. Study visits will take place once a month. Subjects must have more than 50 CD4 cells/mm3. They also must have a diagnosis of uncomplicated herpes zoster and have come into the clinic within 72 hours of the appearance of the rash. Disseminated zoster (i.e., spread throughout the body) and current use of probenecid or use of any antiherpes medications within four weeks of study entry are not allowed. The study is being conducted in Houston (281-333-2288) and Los Angeles (323-930-2323).

HIV and Hepatitis C (HCV) Treatment: Pegylated Interferon, Interferon-Alpha, Ribavirin (Rebetol)

This study will compare the efficacy of pegylated interferon alone with pegylated interferon plus ribavirin and with (nonpegylated) interferon-alpha plus ribavirin against plasma HCV levels. There are three study groups. The first group will take pegylated interferon plus ribavirin placebo. The second group will take pegylated interferon and ribavirin. The third group will take interferon-alpha and ribavirin. Pegylated interferon will be given by injection under the skin once a week. Interferon-alpha will be given by injection under the skin three times a week. Ribavirin and its placebo are pills taken orally. Subjects assigned to take pegylated interferon will not know if they are taking ribavirin or placebo until the 48-week study is over. Study visits will take place every two weeks for the first two months, then at week 12, and every six weeks thereafter. Participants must have a CD4 cell count of at least 200 cells/mm3 with any viral load or between 100 and 199 CD4 cells/mm3 with a viral load below 5,000 copies/mL. Subjects must also have detectable HCV (i.e., more than 1,000 copies/mL). Participants may not be pregnant or be male partners of women who are pregnant. Prior use of ribavirin or interferon, active OIs, seizure disorder, or chronic liver diseases other than hepatitis C are not allowed. The study is being conducted in San Francisco (415-353-0800). (NR15961)

Children

T-20

The purpose of this study is to determine if T-20 (a fusion inhibitor) is safe when given to children, and to see how much T-20 enters the bloodstream when given by injection under the skin as compared with an injection through a vein. The study will also evaluate how well T-20 reduces the amount of HIV in the blood and determine how long it stays in the bloodstream. There are two parts to this study. In Part A, children will receive two injections of T-20: one under the skin and the other into a vein. The first group of children to enter the study will receive the lowest dose of T-20. If no adverse side effects are seen, the next group of children will receive a higher dose. The first injection will be given under the skin. All children who started T-20 therapy must stay in the clinic for 12 hours for eight blood tests. After a physical exam, children in Part A will then receive the second injection of T-20 through a needle inserted into a vein. Again, children who started T-20 therapy will remain in the clinic for 12 hours for eight blood tests. Part A will determine the dose used in Part B.

Children in Part B will have T-20 injections under the skin two times a day for 24 weeks in addition to prescribed antiretroviral medications. Parents and/or children will be taught how to give injections at home and how to dispose of needles safely. On day 7, new antiretroviral medicines will be prescribed; these new medications are not provided by the study. There will be six study visits in the first three weeks, then a visit every four weeks thereafter for a total of 12 visits. Children may have any CD4 cell count but they must have more than 10,000 copies/mL of HIV RNA while on current HAART. Children must be on their initial combination therapy (defined as two NRTIs alone or in combination with an NNRTI or a PI) for at least 16 weeks prior to study entry. Children must be between 3 and 12 years of age. Any opportunistic or bacterial infections requiring treatment or cancers requiring chemotherapy are not allowed. Study sites include Boston (617-355-7879), Charleston (843-792-5311), Durham (919-684-6335), Los Angeles (323-226-2342 or 323-669-4537), Philadelphia (215-590-2262), and San Francisco (415-476-6480). (ACTG P1005)

Eight-Drug Regimen

This study will determine whether taking eight drugs--some of them given at higher than normally used doses--is safe and well-tolerated by children with advanced HIV disease who do not respond adequately to other treatments. All children will take d4T, ddI (Videx), 3TC, saquinavir, nelfinavir (Viracept), ritonavir, nevirapine (Viramune), and hydroxyurea. There are no placebos in this study. Children must be admitted to the research clinic center or hospital for the first two weeks of the study. During this time, multiple blood tests will be taken to see how these drugs are being processed by the body and to see if they have any effect on lowering the amount of HIV in the blood. After the children are discharged from the clinic or hospital, a nurse will visit their homes twice a day for six weeks to observe them while they take study medications. There will be no more than 20 such visits during the 48 weeks of this study. Participants must have less than 15% CD4 cells (or fewer than 200 CD4 cells/mm3) and have more than 100,000 copies/mL of HIV RNA. Subjects must be between 7 and 22 years of age. Participants must be taking nelfinavir and ritonavir, either alone or in combination, for at least six weeks prior to study entry. Treatment for acute bacterial, viral, or opportunistic infections within 14 days of study entry, cancers requiring chemotherapy, past diabetes, hepatitis B or C, and pancreatitis are not allowed. The study is being offered in Birmingham (205-558-2328), Boston (617-355-7879), New York (212-305-5000), Seattle (206-528-5020), and Washington, DC (202-865-1248). (ACTG P1007)