Faculty Bibliography

When microbicides used for HIV prevention contain antiretroviral drugs, there is concern for the potential emergence of drug-resistant HIV following use in infected individuals who are either unaware of their HIV infection status or who are aware but still choose to use the microbicide. Resistant virus could ultimately impact their responsiveness to treatment and/or result in subsequent transmission of drug-resistant virus. We tested whether drug resistance mutations (DRMs) would emerge in macaques infected with simian immunodeficiency virus expressing HIV reverse transcriptase (SHIV-RT) after sustained exposure to the potent non-nucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 delivered via an intravaginal ring (IVR). We first treated 4 SHIV-RT-infected animals with daily intramuscular injections of MIV-150 over two 21 day (d) intervals separated by a 7 d drug hiatus. In all 4 animals, NNRTI DRMs (single and combinations) were detected within 14 d and expanded in proportion and diversity with time. Knowing that we could detect in vivo emergence of NNRTI DRMs in response to MIV-150, we then tested whether a high-dose MIV-150 IVR (loaded with >10 times the amount being used in a combination microbicide IVR in development) would select for resistance in 6 infected animals, modeling use of this prevention method by an HIV-infected woman. We previously demonstrated that this MIV-150 IVR provides significant protection against vaginal SHIV-RT challenge. Wearing the MIV-150 IVR for 56 d led to only 2 single DRMs in 2 of 6 animals (430 RT sequences analyzed total, 0.46%) from plasma and lymph nodes despite MIV-150 persisting in the plasma, vaginal fluids, and genital tissues. Only wild type virus sequences were detected in the genital tissues. These findings indicate a low probability for the emergence of DRMs after topical MIV-150 exposure and support the advancement of MIV-150-containing microbicides.

OBJECTIVE:To investigate whether suicide risk among agricultural workers is higher in regions with heavier pesticide use and/or presence of tobacco farming. METHODS:Suicide mortality data were gathered from residents of the Brazilian state of Alagoas. Agricultural census data were used to arrange and classify Alagoas cities into distribution groups on the basis of variables concerning pesticide use and/or tobacco farming. Mortality odds ratio calculations were then used to compare suicide risk among agricultural and nonagricultural workers in different groups. RESULTS:Suicide risk was higher among agricultural workers than among nonagricultural workers, elevated in regions that used more pesticides, and greatest in regions that produced more tobacco. CONCLUSIONS:This is one of the first studies of its kind to suggest that combined effects of pesticide and tobacco exposure may be linked to higher suicide risk among agricultural workers.

OBJECTIVES/OBJECTIVE:We estimated race/ethnicity-specific incident AIDS diagnosis rates (IARs) among people who inject drugs (PWID) in U.S. metropolitan statistical areas (MSAs) over time to assess the change in disparities after highly active antiretroviral therapy (HAART) dissemination. METHODS:We compared IARs and 95% confidence intervals (CIs) for black/African American and Hispanic/Latino PWID with those of white PWID in 93 of the most populous MSAs. We selected two three-year periods from the years immediately preceding HAART (1993-1995) and the years with the most recent available data (2005-2007). To maximize stability, we aggregated data across three-year periods, and we aggregated data for black/African American and Hispanic/Latino PWID for most comparisons with data for white PWID. We assessed disparities by comparing IAR 95% CIs for overlap. RESULTS:IARs were significantly higher for black/African American and Hispanic/Latino PWID than for white PWID in 81% of MSAs in 1993-1995 and 77% of MSAs in 2005-2007. MSAs where disparities became non-significant over time were concentrated in the West. Significant differences were more frequent in comparisons between black/African American and white PWID (85% of MSAs in 1993-1995, 79% of MSAs in 2005-2007) than in comparisons between Hispanic/Latino and white PWID (53% of MSAs in 1993-1995, 56% of MSAs in 2005-2007). IARs declined modestly across racial/ethnic groups in most MSAs. CONCLUSIONS:AIDS diagnosis rates continue to be substantially higher for black/African American and Hispanic/Latino PWID than for white PWID in most large MSAs. This finding suggests a need for increased targeting of prevention and treatment programs, as well as research on MSA-level conditions that may serve to maintain the disparities.

In the United States, people who inject drugs continue to be at greatly increased risk of HIV infection. To estimate the effectiveness of various prevention scenarios, we modeled HIV transmission in a dynamic network of drug users and people who did not use drugs that was based on the New York Metropolitan Statistical Area population. We compared the projected HIV incidence in 2020 and 2040 if current approaches continue to be used to the incidence if one or more of the following hypothetical interventions were applied: increased HIV testing, improved access to substance abuse treatment, increased use of needle and syringe programs, scaled-up treatment as prevention, and a "high impact" combination scenario, consisting of all of the strategies listed above. No strategy completely eliminated HIV transmission. The high-impact combination strategy produced the largest decrease in HIV incidence-a 62 percent reduction compared to the status quo. Our results suggest that increased resources for and investments in multiple HIV prevention approaches will be required to eliminate HIV transmission among people who inject drugs.

Current ideas about HIV prevention include a mixture of primarily biomedical interventions, socio-mechanical interventions such as sterile syringe and condom distribution, and behavioral interventions. This article presents a framework for socially-integrated transdisciplinary HIV prevention that may improve current prevention efforts. It first describes one socially-integrated transdisciplinary intervention project, the Transmission Reduction Intervention Project. We focus on how social aspects of the intervention integrate its component parts across disciplines and processes at different levels of analysis. We then present socially-integrated perspectives about how to improve combination antiretroviral treatment (cART) processes at the population level in order to solve the problems of the treatment cascade and make "treatment as prevention" more effective. Finally, we discuss some remaining problems and issues in such a social transdisciplinary intervention in the hope that other researchers and public health agents will develop additional socially-integrated interventions for HIV and other diseases.