CROI -- Day 2: Selected highlights of NIH-supported research
The 18th Conference on Retroviruses and Opportunistic Infections is taking place at the Hynes Convention Center in Boston from February 27 through March 2. Day two of this major HIV/AIDS research conference included the following selected presentations from scientists supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
Diane Havlir, M.D., of the University of California, San Francisco School of Medicine, presented findings from an international clinical trial known as ACTG 5221, or STRIDE, in persons co-infected with HIV and tuberculosis (TB). The study compared the risks and benefits of immediate versus early antiretroviral therapy (ART) in HIV-infected patients being treated for TB. The findings further illuminate the delicate balance of starting HIV treatment in individuals who also have TB, as HIV treatment in this context can sometimes cause a severe immune inflammatory syndrome. For HIV/TB co-infected patients who have fewer than 250 CD4+ T cells per cubic millimeter (mm3), the researchers found that beginning ART within 2 weeks (immediate) after beginning TB treatment does not reduce the risk of AIDS or death compared with starting ART 8 to 12 weeks later (early). However, in the subset of individuals with fewer than 50 CD4+ T cells/mm3?a state of severe immune system damage?starting ART within 2 weeks after beginning TB treatment reduces the risk of AIDS or death significantly.
Peter Anton, M.D., of the David Geffen School of Medicine at the University of California, Los Angeles, presented findings from the Phase I clinical trial known as RMP-02/MTN-006, a placebo-controlled study comparing rectally applied 1% tenofovir gel to oral tenofovir disoproxil fumarate. In an earlier landmark study, tenofovir gel protected 39 percent of female participants from HIV infection when applied vaginally. In findings presented today, the gel was shown to have a strong antiviral effect when used in the rectum. These results, based on rectal tissue biopsies sampled from HIV-negative men and women who used the product daily for one week, provide the first evidence that tenofovir gel could help reduce the risk of HIV infection from anal sex, even though the vaginal gel formulation may not be optimal for rectal use. Analysis of rectal tissue samples showed that a single dose of oral tenofovir provided no protection against HIV.
Craig Hendrix, M.D., of the Johns Hopkins University School of Medicine in Baltimore, described results from a Phase II international clinical trial known as MTN-001. This is the first study to directly compare vaginal tenofovir gel and oral tenofovir?two promising approaches for preventing HIV in women. The researchers found that daily use of the vaginal gel for 6 weeks led to a more than 100-times higher concentration of active drug in vaginal tissue than did the oral tablet; additionally, a daily dose of the tablet for 6 weeks was associated with a 20-times higher active drug concentration in blood. Overall, most U.S. women in the study favored the tablet over the vaginal gel, while African participants favored the gel and tablet equally.
Race Differences and ART
According to results of a retrospective multi-study analysis presented by Heather Ribaudo, Ph.D., of Harvard University's School of Public Health in Boston, being black was associated with a 40 percent higher risk of failing to control HIV levels with an initial antiretroviral therapy regimen than being white. This finding is based on an examination of data on nearly 2,500 men and women who participated in five clinical trials conducted between 1998 and 2005. This difference could not be explained by any other variable examined, including the treatment regimen or self-reported adherence to it; age or sex; baseline CD4+ T cell level or viral load; disease status or co-morbidities; mode of HIV transmission; diagnosis of depression; self-reported education level; alcohol use; or perceived social support. Scientists are conducting further analyses to elucidate this finding.
Vaccines and Anti-HIV Antibodies
John Mascola, Ph.D., of NIAID's Vaccine Research Center in Bethesda, Md., provided an update on newly discovered anti-HIV antibodies that have been used to identify regions of the virus vulnerable to antibody-based neutralization across a wide array of HIV strains. Based on the structure of these regions, researchers are designing proteins to elicit such broadly neutralizing HIV antibodies through immunization. Scientists envision that immunization for HIV will involve coaxing the body to develop a series of antibodies that evolve from a primitive state into a mature form through a process known as affinity maturation. By determining the genetic origin of an antibody, scientists can analyze all related genetic sequences, identify the genetic precursors of the mature antibody, and develop an immunization strategy that mimics the natural antibody affinity maturation process.
Jerome H. Kim, M.D., of the U.S. Military HIV Research Program in Rockville, Md., discussed the search for antibodies that could help explain why some participants in the Thai-based RV144 HIV vaccine trial were protected against HIV. As previously reported, the vaccine regimen tested in that 16,000-person study was found to be 31.2 percent effective at preventing HIV infection. Scientists have analyzed blood samples of study participants for specific types of antibodies to the gp120 protein, a vaccine component. Although researchers found relatively few HIV neutralizing antibodies, they identified many types of HIV binding antibodies. In addition, they found that the specific design of the gp120 protein in the vaccine enhanced the binding of certain antibodies to HIV, and also exposed areas of the virus that ordinarily remain hidden until HIV binds to a CD4+ T cell.