• TMC-114: PI in Phase III
• TMC-278: NNRTI in Phase II
• Maraviroc: Two Studies
• Vicriviroc: Entry Inhibitor in Phase II
• GW-873140: Two Studies
• Treatment Intensification With T-20
• Boosted Atazanavir Maintenance Therapy
• SLAM-C: Pegylated Interferon Maintenance Therapy for HIV/HCV Coinfection
• Ezetimibe Plus Statins for High Cholesterol
• Bone Mineral Density: Alendronate, Calcium, and Vitamin D
• Project T: Tenofovir to Prevent HIV Infection

Below is a partial listing of currently enrolling clinical trials gathered from various sources. TrialSearch, operated by the AIDS Community Research Initiative of America (ACRIA), is an extensive online database of clinical trials related to HIV/AIDS. In addition to TrialSearch, ACRIA also provides a listing of trials in the mid-Atlantic region. The University of California at San Francisco's HIV InSite web site features TrialScope, a database of organizations that conduct HIV/AIDS-related research.

The federal government's AIDSinfo site includes a section on clinical trials that features an introduction to HIV/AIDS research and study listings from the National Institutes of Health's ClinicalTrials.gov database. AIDSinfo also offers personalized advice about clinical trial participation via e-mail (ContactUs@AIDSinfo.nih.gov), an interactive web site (Mon.-Fri. 9:00 am - 1:00 pm PT), and a toll-free telephone service (800-874-2572, international 301-874-2572; Mon.-Fri. 9:00 am - 2:00 pm PT).

The majority of U.S. government-sponsored HIV/AIDS trials are conducted by the AIDS Clinical Trials Group (ACTG), a nationwide network of investigators and medical centers comprised of two branches: the Adult AIDS Clinical Trials Group (AACTG) and the Pediatric AIDS Clinical Trials Group (PACTG). The National Center for Complementary and Alternative Medicine (NCCAM) conducts trials of complementary therapies for conditions related to HIV and its treatment. The HIV Vaccine Trials Network (HVTN) is an international collaboration testing preventive HIV vaccines. Community Programs for Clinical Research on AIDS (CPCRA) is a nationwide network that conducts community-based clinical trials. The Community Research Initiative of New England (CRINE) offers a listing of trials in the Northeast. CenterWatch is a commercial web site that includes trial listings for all diseases including HIV/AIDS and related conditions.

The Body web site features a database of prospective clinical trial volunteers. The service collects information about participants' city, age, viral load, CD4 cell count, current and past anti-HIV therapy, and health status. Researchers can request information about prospective subjects, who will be notified if they meet a trial's enrollment criteria.

Call the telephone numbers listed for each study or see the indicated web sites for more information about specific trials. Protocol numbers, if available, are provided in parentheses at the end of each trial description.

ACRIA

Adult ACTG

AIDSinfo

CenterWatch

ClinicalTrials.gov

CPCRA

CRINE

HIV Vaccine Trials Network

NCCAM

The Body database

TrialScope

TrialSearch

TMC-114: PI in Phase III

Researchers at this past February's Retrovirus conference presented promising data on TMC-114, Tibotec's experimental protease inhibitor (PI) (see "Drug Watch" in this issue). This new open-label trial will compare the efficacy, durability, safety, and tolerability of TMC-114 boosted with low-dose ritonavir (Norvir) vs. lopinavir/ritonavir (Kaletra) in treatment-experienced individuals. Subjects will be randomly assigned to receive either TMC-114 or lopinavir, but will know which drug they are taking. The study will last about 106 weeks including screening, treatment, and follow-up.

Eligible subjects must be at least 18 years of age. They must have viral loads of at least 1,000 copies/mL and must have been treated for 12 weeks or longer with antiretroviral regimens consisting of at least two nucleoside reverse transcriptase inhibitors (NRTIs) plus at least one non-nucleoside reverse transcriptase inhibitor (NNRTI) or PI. They may not currently be taking other experimental anti-HIV drugs, and must not have used lopinavir, tipranavir (Aptivus), or T-20 (enfuvirtide, Fuzeon) in the past. Women may not be pregnant or breast-feeding and participants must agree to use effective contraception.

This trial aims to enroll 500 participants at more than 60 sites including Atlanta (404-355-3161), Austin (512-374-0677), Berkeley (510-204-1291), Boston (617-778-5454 ext. 225), Bronx (718-918-7232), Chicago (773-396-2400), Cincinnati (573-584-8373), Denver (303-315-3203), Ft. Lauderdale (954-467-3006 ext. 224), Lexington (859-257-5467), Little Rock (501-603-0003), Los Angeles (310-423-3755), Milwaukee (414-805-6444), Minneapolis (954-524-2250), Nashville (615-936-1174), Newark (973-877-2663), Philadelphia (215-790-1788), Phoenix (602-307-5330 ext. 2225), San Francisco (415-833-3480), San Juan (787-723-5945), Seattle (206-386-2523), West Hollywood (310-358-2429), and Winston-Salem (336-716-4262); www.clinicaltrials.gov/ct/gui/show/NCT00110877. (TMC114-C214)

TMC-278: NNRTI in Phase II

Enrollment is beginning for a new study of an experimental NNRTI, TMC-278, in treatment-naive individuals. This Phase II dose-ranging study will be conducted by Tibotec, the drug's manufacturer. Subjects will be randomly assigned to receive one of three doses of TMC-278 or else efavirenz (Sustiva); all participants will also take two other backbone drugs selected by their physicians. Treatment will continue for 96 weeks.

Eligible subjects must be at least 18 years of age and have viral loads of at least 5,000 copies/mL. They must not previously have been treated with antiretroviral drugs for more than two weeks. Exclusion criteria include various medical conditions (including hepatitis B or C) or abnormal laboratory results, and current or prior use of certain medications. Women may not be pregnant or breast-feeding and participants must agree to use effective contraception.

This study aims to enroll 320 participants. Trial sites include Dallas (214-828-4702), Los Angeles (323-913-1033), Orlando (407-647-3960 ext. 2132), San Juan (787-723-5945), and Washington, DC (202-745-6150); www.clinicaltrials.gov/ct/show/NCT00110305. (TMC278-C204)

Maraviroc: Two Studies

Two trials looking at the safety and efficacy of the investigational HIV entry inhibitor maraviroc (formerly UK-427,857) began enrolling in December 2004. Both are sponsored by Pfizer, the drug's manufacturer. Studies to date suggest that maraviroc, a reversible CCR5 coreceptor antagonist, is active against HIV, including virus that is resistant to existing antiretroviral drug classes.

I) The first Phase II/III study will compare maraviroc vs efavirenz in individuals starting anti-HIV therapy for the first time. Subjects will be randomly assigned to receive 300 mg maraviroc once daily, 300 mg maraviroc twice daily, or efavirenz; all participants will also take AZT (zidovudine, Retrovir) and 3TC (lamivudine, Epivir). Participants will have regular clinic visits, some of which will include physical examinations, blood draws, electrocardiogram (EKG) heart rhythm monitoring, computerized tomography (CT) scans, and symptom questionnaires. Treatment will initially last 96 weeks and may be extended based on outcomes at that time.

Eligible subjects must be at least 16 years of age and have viral loads of at least 2,000 copies/mL. Exclusion criteria include various medical conditions or abnormal laboratory results, and current or prior use of certain medications (including all study drugs). Women may not be pregnant or breast-feeding and participants must use effective contraception.

This study will enroll more than 1,000 subjects at some 200 centers worldwide including Dallas, Los Angeles, Miami, Oakland, San Francisco, and Tampa. For more locations and contact information, call Pfizer at 734-622-7600 or send e-mail to ClinicalTrials.gov@Pfizer.com; www.clinicaltrials.gov/ct/show/NCT00098293. (A4001026)

II) The second Phase II/III study will compare maraviroc plus optimized background therapy (OBT) vs OBT plus placebo in treatment-experienced individuals. Subjects will be randomly assigned to receive 150 mg maraviroc once daily, 150 mg maraviroc twice daily, or placebo. OBT will be determined based on treatment history and resistance testing. Participants will receive regular clinic visits, some of which will include physical examinations, blood draws, and EKGs. Therapy will initially last 48 weeks and may be extended based on outcomes at that time.

Eligible subjects must be at least 16 years of age and have viral loads of at least 5,000 copies/mL. They must have been on stable HAART, or else no antiretroviral therapy, for at least four weeks. Subjects must have at least six months' experience with, or documented resistance to, the major classes of approved anti-HIV medications. Exclusion criteria include various medical conditions or abnormal laboratory results, and current or prior use of certain medications. Women may not be pregnant or breast-feeding and participants must agree to use effective contraception.

This study aims to enroll 500 participants at 100 U.S. and Canadian centers including Atlanta, Dallas, Los Angeles, Miami, New York City, Oakland, Philadelphia, Phoenix, San Francisco, and Washington, DC. For more locations and contact information, call 734-622-7600 or send e-mail to ClinicalTrials.gov@Pfizer.com; www.clinicaltrials.gov/ct/show/NCT00098306. (A4001027)

Vicriviroc: Entry Inhibitor in Phase II

This Phase II study will examine the safety and efficacy of vicriviroc (formerly known as SCH-D and SCH-417690), a novel oral HIV CCR5 antagonist, a type of entry inhibitor. The agent has demonstrated activity against HIV in laboratory studies to date. Treatment-experienced participants will be randomly assigned to receive one of three doses of vicriviroc (5, 10, or 15 mg daily), or else placebo, along with their current antiretroviral regimen. Subjects will have regular clinic visits, some of which include blood draws, EKGs, and tests for peripheral neuropathy. The study will last 48 weeks.

Eligible subjects must be at least 18 years of age and must have R5-tropic HIV (virus that uses the CCR5 coreceptor to enter cells). They must be experiencing virologcal failure (viral load of 5,000 copies/mL or greater) on a HAART regimen that contains 100-800 mg ritonavir, and must also have experienced virological failure using a previous regimen of three or more drugs. Exclusion criteria include various medical conditions (including hepatitis B or C) or abnormal laboratory results, and current or prior use of certain medications (including efavirenz or nevirapine within 30 days of study entry). Women may not be pregnant or breast-feeding.

The study aims to enroll 120 subjects at several sites including Atlanta (404-616-6313), Baltimore (410-614-2766), Boston (617-414-7082), Chicago (312-572-4545), Cleveland (216-844-2546), Denver (303-372-5535), Galveston (409-747-0241), Honolulu (808-737-2751), Indianapolis (317-274-8456), Iowa City (319-353-8441), Miami (305-243-3838), Nashville (615-467-0154 ext. 108), New York City (212-746-4393), Pittsburgh (412-647-0771), Providence (401-793-4396), San Francisco (415-514-0550 ext. 354), San Juan (787-759-9595), Stanford (650-723-2804), St. Louis (314-454-0058), and Washington, DC (202-687-7387); www.clinicaltrials.gov/ct/show/NCT00082498. (ACTG A5211)

GW-873140: Two Studies

Two studies are currently enrolling to examine the safety and efficacy of GW-873140, a new orally available CCR5 coreceptor blocker being developed by GlaxoSmithKline. So far the agent has demonstrated activity against HIV in laboratory studies and no major safety concerns have arisen in early clinical trials.

I) In the first open-label Phase II dose-ranging study, treatment-naive participants will receive GW-873140 in combination with lopinavir. Treatment will last 96 weeks. Eligible subjects must be at least 18 years of age, must have HIV viral loads of at least 50,000 copies/mL, and must be starting HAART for the first time (no more than two weeks' prior use of antiretroviral drugs). They must have either R5- or R5/X4-tropic HIV, and may not have X4-tropic virus (which can enter cells using the CXCR4 coreceptor without using the CCR5 coreceptor). Exclusion criteria include various medical conditions or abnormal laboratory results, and current or prior use of certain medications. Women may not be pregnant or breast-feeding and participants must agree to use effective contraception.

This study will be conducted at some 40 sites including Atlanta (404-876-2317), Charlotte (704-331-9054), Chicago (773-388-8883), Denver (303-393-8050), Ft. Lauderdale (954-565-4899), Houston (713-961-7100), Los Angeles (323-783-7404), New Orleans (504-895-0361), Philadelphia (215-762-3251), Phoenix (602-307-5330), San Francisco (415-292-5477 ext. 480), Santa Fe (505-989-8200 ext. 1010), Seattle (206-386-2523), Tampa (813-875-4374), Washington, DC (202-822-6311 ext. 103), and Wichita (316-293-2655); www.clinicaltrials.gov/ct/show/NCT00102778. (100136)

II) The second open-label Phase II study is similar to the first, but subjects will receive GW-873140 plus Combivir (AZT/3TC combination pill). Eligibility criteria are the same, except that subjects must have viral loads of at least 10,000 copies/mL and R5-tropic -- not R5/X4- or X4-tropic -- HIV.

Study sites include Chicago (312-942-4810), Dallas (214-941-4000), Denver (303-764-4776), Las Vegas (702-383-2691), Little Rock (501-603-0003), Los Angeles (323-869-5429), Miami (305-243-5621), Minneapolis (612-863-5241), Newark (973-877-2663), New York City (212-924-3934 ext. 126), Providence (401-456-2437), Rochester (585-244-9000 ext. 409), San Francisco (415-565-6288), and Washington, DC (202-745-0201); www.clinicaltrials.gov/ct/show/NCT00104429. (102881)

Treatment Intensification With T-20

This nonrandomized open-label study will examine the benefits of intensifying therapy using T-20 for individuals with multidrug-resistant HIV. The trial will attempt to determine whether brief, aggressive treatment promotes HIV-specific immune response and lowers viral set-point. All subjects will have T-20 added to their HAART regimens (other drugs are not provided by the study). The study will last 48 weeks and there will be 17 clinic visits with blood draws.

Eligible participants must be at least 18 years of age, be on stable antiretroviral therapy, and have multidrug-resistant HIV and viral loads above 1,000 copies/mL. They may not be taking immune-modulating drugs.

The study aims to enroll 20 subjects at San Francisco General Hospital (415-476-4082 ext. 139); www.clinicaltrials.gov/ct/show/NCT00102934. (5R21-AI055273-02; protocol 834)

Boosted Atazanavir Maintenance Therapy

Given the long-term side effects, expense, and inconvenience associated with antiretroviral treatment, researchers are looking for ways to simplify therapy. This nonrandomized open-label pilot study will attempt to determine whether atazanavir (Reyataz) boosted with ritonavir can suppress HIV in the absence of other antiretroviral drugs. At the beginning of the study, subjects will switch from their PIs to boosted atazanavir. At week 6 they will discontinue their NRTIs and remain on atazanavir/ritonavir alone. Participants will receive EKGs at the screening visit. There will be several subsequent clinic visits that will include medication assessment, physical exams, and blood work. The study will last 54 weeks.

Eligible subjects must be at least 18 years of age and must have been on initial antiretroviral regimens including at least two NRTIs and one PI for at least 48 weeks. They must have well-controlled HIV with viral loads below 50 copies/mL and CD4 cell counts of at least 250 cells/mm³. Exclusion criteria include current or prior use of NNRTIs or certain other medications, certain PI resistance mutations, and various medical conditions (including heart rhythm abnormalities). Women may not be pregnant or breastfeeding and participants must agree to use effective contraception.

This study aims to enroll 33 participants at some 20 sites including Baltimore (410-706-1476), Boston (617-732-4785), Chapel Hill (919-843-8761), Cincinnati (513-584-8373), Denver (303-372-5535), Honolulu (808-737-2751), Iowa City (319 353-8441), Miami (305-243-3838), Minneapolis (612-625-1462), New York City (212-746-4393), Omaha (402-559-8163), Pittsburgh (412-647-0771), Providence (401-793-4396), San Diego (619-543-8080), San Juan (787-759-9595), and Seattle (206-731-8877); www.clinicaltrials.gov/ct/show/NCT00084019. (ACTG A5201)

SLAM-C: Pegylated Interferon Maintenance Therapy for HIV/HCV Coinfection

Past research has shown that liver damage due to hepatitis C progresses more rapidly in HIV positive people. Coinfected people do not respond as well to hepatitis C treatment as individuals with hepatitis C virus (HCV) alone, but some studies suggest that long-term interferon maintenance therapy may help slow liver disease progression even in the absence of a sustained virological response.

In this Phase II open-label study, subjects who either have never received therapy for hepatitis C or who did not clear HCV with prior treatment will receive a standard course of HCV therapy (180 mcg Pegasys brand pegylated interferon-alfa-2a once weekly plus weight-based ribavirin daily). Subjects who respond well after 12 weeks will continue on this regimen for an additional 60 weeks. Those who respond poorly will be randomly assigned either to stop ribavirin and continue pegylated interferon for 72 weeks, or to discontinue both ribavirin and pegylated interferon. Participants will receive liver biopsies at study entry, after changing therapy, and at the end of follow-up to monitor progression of fibrosis (liver scarring). Followup will continue for 90-96 weeks.

Eligible participants must be at least 18 years of age and have chronic hepatitis C with elevated liver enzyme (ALT, AST, and alkaline phosphatase) levels and at least stage I fibrosis. They must have been on stable anti-HIV therapy for at least eight weeks or else off antiretroviral therapy for four weeks. They must have viral loads below 50,000 copies/mL and CD4 cell counts of at least 200 cells/mm³. They must either be naive to hepatitis C therapy or else still have detectable HCV RNA after previous treatment with standard or pegylated interferon with or without ribavirin. Exclusion criteria include various medical conditions (including decompensated liver cirrhosis, hepatitis B, autoimmune diseases, and uncontrolled depression or other psychiatric conditions) and current or prior use of certain medications. Women may not be pregnant or breast-feeding and participants must agree to use effective contraception.

This study aims to enroll 180 subjects at more than 40 sites including Atlanta (404-616-6313), Baltimore (410-614-2766), Birmingham (205-975-7925), Boston (617-724-0072), Buffalo (716-898-3933), Chapel Hill (919-843-8761), Chicago (312-695-5012), Cincinnati (513-584-8373), Cleveland (216-778-5489), Dallas (214-590-0414), Denver (303-372-5535), Galveston (409-747-0241), Honolulu (808-737-2751), Indianapolis (317-630-6023), Los Angeles (310-825-1301), Miami (305-243-3838), Nashville (615-467-0154 ext. 108), New York City (212-746-7198), Omaha (402-559-8163), Philadelphia (215-349-8092), Pittsburgh (412-647-0771), Providence (401-793-4396), Rochester (585-275-2740), San Francisco (415-514-0550 ext. 354), San Juan (787-759-9595), Stanford (650-723-2804), St. Louis (314-454-0058), and Washington, DC (202-687-7387); www.clinicaltrials.gov/ct/show/NCT00078403. (ACTG A5178; SLAM-C)

Ezetimibe Plus Statins for High Cholesterol

This study will attempt to determine whether a combination of two lipid-lowering medications, ezetimibe (Zetia) plus a drug in the statin class, can safely help reduce low-density lipoprotein (LDL, or "bad" cholesterol) levels in HIV positive people taking antiretroviral therapy. All subjects will take HAART and statins. In addition, in this crossover study, participants will be randomly assigned to receive either daily ezetimibe followed by placebo, or else placebo followed by ezetimibe. The study will last 28 weeks and there will be nine clinic visits.

Eligible participants must be at least 18 years of age and must have an LDL cholesterol level of 130 mg/dL or higher. They must have been on stable antiretroviral regimens for at least 30 days and have been taking one of the study-recommended statins for at least three months. They must start a lipid-lowering diet and exercise program at least one month before screening and continue both for the duration of the study. Exclusion criteria include various medical conditions (including diabetes and cardiovascular disease) and current or prior use of certain medications (including ezetimibe). Women may not be pregnant or breast-feeding and participants must agree to use effective contraception.

This study will enroll about 40 subjects at some 15 sites including Chicago (312-942-4810), Cincinnati (513-584-8373), Cleveland (216-778-5489), Dallas (214-590-0414), Galveston (409-747-0219), Honolulu (808-737-2751), Los Angeles (310-825-1301), Miami (305-243-3838), New York City (212-746-4393), Philadelphia (215-349-8092), Stanford (650-723-2804), and Washington, DC (202-687-7387); www.clinicaltrials.gov/ct/show/NCT00099684. (ACTG A5209).

Bone Mineral Density: Alendronate, Calcium, and Vitamin D

This study will examine the effects of alendronate (Fosamax), calcium, and vitamin D on bone mineral density in people with HIV. Research has shown that HIV positive individuals appear to be at greater risk for bone loss (osteopenia and osteoporosis) due to HIV itself or antiretroviral therapy. In this Phase II safety and efficacy study, participants will be randomly assigned to receive either alendronate or placebo for 48 weeks; all subjects will receive calcium and vitamin D supplements. Participants will have regular clinic visits that will include fasting blood draws and dual energy x-ray absorptiometry (DEXA) scans to evaluate bone density.

Eligible subjects must be at least 25 years of age and must have decreased bone mineral density as shown by a lumbar spine DEXA scan. Subjects must have been on stable antiretroviral therapy for at least 12 weeks prior to enrollment, and must have CD4 cell counts of at least 100 cells/mm³ and viral loads of 5,000 copies/mL or less. They must also have a serum calcium level between 8 and 11 mg/dL. Men may not have untreated hypogonadism (low testosterone level), and women on estrogen replacement therapy and individuals taking steroids must have been on stable regimens for at least 24 weeks. Exclusion criteria include various medical conditions (including esophageal problems and past spinal fractures) and use of certain medications and supplements (including glucocorticoids, calcium, vitamin D, and high doses of vitamin A). Women may not be pregnant or breast-feeding.

This study is expected to enroll 80 participants at about 25 sites including Chapel Hill (919-843-8761), Chicago (312-695-5012), Cleveland (216-778-5489), Galveston (409-747-0241), Indianapolis (317-274-8456), Los Angeles (310-206-8029), Minneapolis (612-625-1462), Nashville (615-467-0154 ext. 108), New York City (212-263-6565), Philadelphia (215-349-8092), San Diego (619-543-8080), San Francisco (415-514-0550 ext. 354), Seattle (206-731-8877), and Washington, DC (202-687-7387); www.clinicaltrials.gov/ct/show/NCT00061256. (ACTG A5163).

Project T: Tenofovir to Prevent HIV Infection

This study, coordinated by the Centers for Disease Control and Prevention (CDC), is part of a larger international research program to determine whether the nucleotide reverse transcriptase inhibitor tenofovir DF (Viread) can help prevent HIV infection. The drug has performed well in animal prophylaxis studies and appears to have fewer side effects than other antiretroviral medications. The U.S. phase of the study will focus on the clinical and behavioral safety of the drug, not its effectiveness. In particular, researchers will attempt to determine whether using a potentially preventive drug will lead to an increase in risky sexual behavior. Participants in arm A will receive either 300 mg daily oral tenofovir or placebo; those in arm B will wait nine months before starting therapy. Because it is not yet known whether tenofovir can help prevent HIV infection -- and because some subjects will be taking placebo -- participants should continue to practice safer sex, and will receive risk-reduction counseling and free condoms during the study. Should any participants become infected, the local research group will facilitate referrals for HIV care and treatment. The study is expected to last two years.

Eligible participants must be sexually active, HIV negative men who have sex with men between the ages of 18 and 60. The U.S. arm of the study will enroll 200 gay and bisexual men at each of two sites, Atlanta (404-876-2317) and San Francisco (415-554-8888; www.sfaidsresearch.org).