Current HIV Research - Volume 15, Issue 3, 2017

Background: We review research findings and the limitations of recent qualitative and quantitative studies of HIV prevalence and risk behaviors in military populations in three Caribbean countries (Dominican Republic, Belize, and Barbados). Methods: This research shows how mental health issues, disordered substance use, and structuring aspects of the occupational field produce and reproduce patterns of risk behaviors. Results: We discuss the use of formative research, the Positive Health, Dignity, and Prevention framework, and the use of implementation science (including research methods that employ alternative methodological assumptions to better elucidate both cultural nuances and unknown components of program impact in different military populations) as a means to tailor individual prevention strategies to military populations. Conclusion: We conclude that greater adaption and ingenuity in prevention could improve behavioral prevention of HIV among military personnel in the Caribbean region.

Background: The epidemic of Human Immunodeficiency Virus (HIV) infection in Thailand began in 1988 among Injection Drug Users (IDUs) in Bangkok. It soon spread to other populations, especially Female Sex Workers (FSWs) and men attending STD clinics. Routine serologic surveillance for HIV began among military conscripts in 1991. The HIV seroprevalence data from military conscripts provided national surveillance data, since the entire population of 21 year old men were conscripted for 2 years’ service in the military by a random process during which 10% of men were selected. Men with a history of injection drug use, or other risk behavior for HIV infection were included. Methods: HIV seropositive data were analyzed from cohorts of men who were conscripted between 1991 and 2011. Comprehensive behavioral risk data were obtained from the men in these cohorts in order to evaluate behavior changes in response to the evolving HIV/AIDS epidemic. After the Ministry of Public Health established the “100% condom” program in 1991, behavioral data and HIV prevalence and incidence data from military conscripts were important for evaluating the program. Results: The HIV prevalence among Royal Thai Army (RTA) conscripts in 1991 was 4.0%. However, the prevalence was 11.2% among conscripts from the upper Northern provinces. A history of sex with a female sex worker (FSW) was reported by 85.8% of men in 1991; having had sex with a FSW was strongly associated with HIV prevalence, OR=7.40 (3.80-14.0). During the next few years, the HIV prevalence decreased progressively, reports of sex with a FWS declined and the use of condoms during sex increased. Also, the incidence of HIV among conscripts while they were in the army decreased. In the cohort enrolled in 1998, the association between a history of sex with a FSW decreased (OR=2.79; 95% CI 1.0-7.8) however the association between a history of injection drug use and HIV prevalence increased substantially (OR=14.47; 95% Ci 3.5-56.6). Among men in cohorts included in 2008-2009, the HIV prevalence was 0.5%. The most important risk behavior reported by men in these cohorts was sex with another man (MSM), adjusted OR=5.3 (95% CI 3.25- 8.65) whereas history of sex with a FSW was less of a risk. In this cohort 39.5% of HIV infected men reported MSM behavior. Conclusion: The sequential data on HIV prevalence and behavioral data from successive large randomly selected national cohorts of young men in Thailand who were conscripted into the Royal Thai Army between 1991 and 2011 has provided critically important surveillance data to monitor the epidemic and evaluate the ongoing effectiveness of public health prevention programs.

Background: The Nigerian Ministry of Defence-Walter Reed Army Institute of Research partnership was established in 2004 in response to the growing HIV/AIDS epidemic in Nigeria. Methods: Here we discuss the emergence of HIV in Nigeria, highlighting the initial barriers to treatment delivery, and outline the origins of the international military-to-military partnership developed to confront the disease. Results: With financial support from the United States President’s Plan for AIDS Relief and Nigerian Government Counterpart Funding, we demonstrate how this program led to a successful and sustainable response in the fight against HIV in Nigeria. We detail the continued value of this collaboration in the form of sustainable treatment platforms, prevention strategies, and research projects, and explore the factors which strengthened, and hindered these efforts. Conclusion: The program is a model framework for international military health partnership based on the principles of shared responsibility, country ownership and goal attainment.

Background: Clinical trials frequently enroll subjects from different study sites. Few such studies provide analysis by individual site. Between 2004-2007, the South African Military Health System (SAMHS) established 6 research sites (3 urban, 3 rural) to build capacity for clinical research and HIV care. We explore differences in clinical, virologic and CD4 outcomes by site in the context of a randomized controlled trial. Methods: Phidisa-II is the first randomised controlled trial conducted in the South African military setting, which compared 4 antiretroviral regimens in treatment-naïve advanced HIV subjects. Primary study outcome was first AIDS event or death. Kaplan-Meier curves for AIDS events and mortality were compared across sites. Hazard rates were adjusted for baseline risk factors to assess the independent effect of site. Secondary outcomes of CD4 count and viral responses are also compared across study sites. Results: 1,771 subjects [average age=35.4 ± 5.5 years old, 68% male, with median CD4 count=105 (IQR 41, 157) cells/mm3 and HIV RNA=144,000 (IQR 53,900-305,000)copies/mL] enrolled in 3 urban and 3 rural sites. Sites varied considerably in resources and diagnostic capacities. After adjusting for baseline characteristics, study site was found to be a factor significantly associated with mortality (p=0.008), with Urban 2 and Rural 2 sites had the lowest mortality. Site was also associated with the adjusted hazard for AIDS events (p=0.038). At 24 months, CD4 count was similar across sites, but HIV suppression rate varied considerably (range 40-70%). Conclusion: Site heterogeneity was found in primary clinical outcomes of mortality and AIDS event rates, but there were no clear patterns for differences between the rural versus urban sites. Site differences were also found in the proportion of confirmed AIDS events. Factors within study sites that may have contributed to poorer outcomes need further investigation.

Background: The Military International HIV Training Program (MIHTP) was established in 2002 to address the overwhelming needs of international military personnel concerning HIV and AIDS prevention, care, and treatment. The purpose of this study was to determine shortterm knowledge transfer in trainees attending the MIHTP by comparing data collected from pretraining and post-training knowledge assessments. Methods: We used identical 40-question multiple choice pre-training and post-training assessments to determine the short-term transfer of knowledge of international HIV military physicians attending the MIHTP. Results: Findings revealed a statistically significant increase in short-term transfer of knowledge of HIV prevention, care, and treatment in a population of international military physicians, nurses, and auxiliary medical personnel from 47 developing countries (n=136). Trainees had significantly higher post-test scores (67.9%) compared with pre-test scores (50.5%, p<0.001). Trainees showed a similar level of HIV knowledge as assessed by pre-training evaluations (F=1.38). Conclusion: We found significant increases in acquired individual knowledge after a 4-week HIV training program. Results of this study are important as many developing countries rely heavily on international training programs to aid in the development of health care systems in an ever-changing infrastructure.

Background: There is now intense interest in the role of HIV-specific antibodies and the engagement of FcγR functions in the control and prevention of HIV infection. The analyses of the RV144 vaccine trial, natural progression cohorts, and macaque models all point to a role for Fc-dependent effector functions, such as cytotoxicity (ADCC) or phagocytosis (ADCP), in the control of HIV. However, reliable assays that can be reproducibly used across different laboratories to measure Fcdependent functions, such as antibody dependent cellular cytotoxicity (ADCC) are limited. Method: This brief review highlights the importance of Fc properties for immunity to HIV, particularly via FcγR diversity and function. We discuss assays used to study FcR mediated functions of HIV-specific Ab, including our recently developed novel cell-free ELISA using homo-dimeric FcγR ectodomains to detect functionally relevant viral antigen-specific antibodies. Results: The binding of these dimeric FcγR ectodomains, to closely spaced pairs of IgG Fc, mimics the engagement and cross-linking of Fc receptors by IgG opsonized virions or infected cells as the essential prerequisite to the induction of Ab-dependent effector functions. The dimeric FcγR ELISA reliably correlates with ADCC in patient responses to influenza. The assay is amenable to high throughput and could be standardized across laboratories. Conclusion: We propose the assay has broader implications for the evaluation of the quality of antibody responses in viral infections and for the rapid evaluation of responses in vaccine development campaigns for HIV and other viral infections.

Objectives: Cobicistat (COBI) enhances atazanavir (ATV) pharmacokinetic parameters similarly to ritonavir (RTV) in both healthy volunteers and HIV-infected adults. Primary efficacy and safety outcomes of this Phase 3, international, randomized, double-blind, double-dummy, active- controlled trial in HIV-1-infected treatment-naïve adults (GS-US-216-0114/NCT01108510) demonstrated that ATV+COBI was non-inferior to ATV+RTV, each in combination with emtricitabine/ tenofovir disoproxil fumarate (FTC/TDF), at Weeks 48 and 144, with high rates of virologic success for both regimens (85.2% and 87.4%, respectively, at Week 48; and 72.1% and 74.1% at Week 144), and with comparable safety and tolerability. Here, we describe virologic response and treatment discontinuation by a wider range of subgroups than previously presented. Methods: Subgroup analyses by baseline CD4 count (≤200, 201-350, >350 cells/mm3), baseline HIV-1 RNA level (≤100,000, >100,000 copies/mL), race, sex, and age (<40, ≥40 years) evaluated ATV+COBI versus ATV+RTV univariate odds ratios (ORs) for virologic success (viral load <50 copies/mL, intention-to-treat US Food and Drug Administration Snapshot algorithm) and discontinuation due to adverse events (AEs) at Weeks 48 and 144. Of 692 patients randomized, 344 received ATV+COBI and 348 ATV+RTV. Results: ATV+COBI versus ATV+RTV ORs for virologic success did not significantly differ by regimen overall at Weeks 48 and 144 (OR 0.90; 95% confidence interval [CI]: 0.64, 1.26) or within subgroups, except in females, for whom ATV+COBI was favored at Week 144 (OR 2.36; 95% CI: 1.02, 5.47). However, there were more discontinuations due to withdrawal of consent and pregnancies in females receiving ATV+RTV versus ATV+COBI. ORs for discontinuation due to AEs did not significantly differ by regimen overall at Weeks 48 and 144 (OR 0.98; 95% CI: 0.61, 1.58) or within subgroups. Conclusion: These findings indicate that both ATV+COBI and ATV+RTV, each with FTC/TDF, are effective and well-tolerated treatment options across a wide demographic range of HIV-infected patients.

Background: HTLV-1/HIV co-infection is known to elevate the CD4+ T-cell counts of treatment-naïve persons. We investigated whether HTLV-1/HIV co-infected patients continued to have elevated CD4+ T-cell counts after developing virologic failure on antiretroviral therapy (ART). Methods: The data is taken from a drug resistance study located in the KwaZulu-Natal province of South Africa. All participants (N=383) presented for repeated CD4+ T-cell count and HIV viral load level testing between January 2006 and March 2014. We used a random-coefficient model to estimate the change in CD4+ T-cell count and HIV viral load level by HTLV-1/HIV co-infection status over time, adjusting for age, sex, and duration of virologic failure. Results: HTLV-1/HIV co-infected participants (n=8) had higher CD4+ T-cell counts, with a positive difference of 117.2 cells/μL at the ART initiation date (p-value=0.001), 114.7 cells/μL (pvalue< 0.001) 12 months after this date, and 112.3 cells/μL (p-value=0.005) 24 months after this date, holding all else constant. In contrast, there was no difference in the HIV viral load level by HTLV-1/HIV co-infected status throughout the observation period. Conclusion: We show that HTLV-1/HIV co-infected participants continued to have elevated CD4+ T-cell counts after developing virologic failure on ART, despite no difference in their HIV viral load levels when compared with HIV mono-infected participants. Our results indicate that CD4+ T-cell count testing may not be a useful strategy to monitor ART response in the presence of HTLV-1/HIV co-infection.