Finding and treating early-stage HIV infections: A cost-effectiveness analysis of the Sabes study in Lima, Peru.

Background: Sabes, a treatment-as-prevention intervention among men who have sex with men and transgender women in Lima, Peru, was developed to identify HIV during early primary infection (<3 months from acquisition) through monthly serologic assays and HIV RNA tests. Newly diagnosed individuals were rapidly linked to care and offered to initiate ART. In this study we sought to study the cost-effectiveness of Sabes compared to the standard of care (SOC) for HIV testing and initiation of treatment. Methods: We adapted a compartmental model of HIV transmission to evaluate the cost-effectiveness of the Sabes approach compared to the SOC using a government health care perspective, 20-year time horizon, and 3% annual discounting. We estimated the proportion of cases of HIV detected during early primary infection, reduction in HIV incidence and prevalence, incremental cost-effectiveness ratio (ICER), and net monetary benefit. We analyzed costs using data from the Sabes study, the Peruvian Ministry of Health, published literature, and expert consultation. Findings: The Sabes intervention is projected to identify 9294 early primary HIV infections in Lima, Peru over 20 years. The intervention costs $6,896 per early primary infection diagnosed and by 2038 is expected to decrease the fraction of early infections among prevalent infections by 62%. Sabes is expected to improve health, resulting in greater total discounted QALYs per person than the SOC (16·7 vs 16·4, respectively). Sabes had an ICER of $1431 (22% per capita GDP in Peru) per QALY compared to SOC. Interpretation: Our analysis suggests that in Lima, Peru the Sabes intervention could be a cost-effective approach to reduce the burden of HIV even under stringent cost-effectiveness criteria. This finding suggests that programs that use frequent HIV testing, rapid linkage to care and initiation of ART should be considered as part of a comprehensive HIV prevention strategy. Funding: National Institutes of Health.

Perceptions Prediagnosis and Social Experiences Postdiagnosis Among a Sample of High-Risk Peruvian Men Who Have Sex With Men.

This pilot study examines associations of perceived stigma pre-diagnosis with experienced stigma and social support post-diagnosis with qualitative data; and quantifies the interplay between pre- and post-diagnosis social factors on depressive symptoms among a sample of newly diagnosed Peruvian men who have sex with men (n = 67 total). Qualitative findings highlight the differences between perceptions of stigma pre-disclosure and actual social experiences post-disclosure for most participants. Perceived stigma pre-diagnosis was significantly related to post-diagnosis social support, B = -0.35, p = 0.03, and marginally associated with experienced stigma, B = 0.29, p = 0.07. Pre-diagnosis perceived stigma was associated with greater depressive symptoms, but only among individuals who reported higher amounts of social support, B = 0.55, p = 0.01. Findings suggest the importance of addressing social perceptions in order to optimize the beneficial effects of social support resources among newly diagnosed individuals.

Homophobia and heteronormativity as dimensions of stigma that influence sexual risk behaviors among men who have sex with men (MSM) and women (MSMW) in Lima, Peru: a mixed-methods analysis.

BACKGROUND: Stigma differentially influences HIV and STI care among MSM, especially regarding partner notification practices. Recognizing the heterogeneous behaviors/identities within the category "MSM," we used mixed-methods to assess sexual risk behaviors among men who have sex with men only (MSMO) and behaviorally bisexual MSM (MSMW) with HIV and/or other STIs. METHODS: MSMO/MSMW recently diagnosed (< 30 days) with HIV, syphilis, urethritis, or proctitis completed a cross-sectional survey assessing sexual risk behaviors, anticipated disclosure, and sexual partnership characteristics (n = 332). Multivariable generalized estimating equation models assessed characteristics associated with female compared to male partners in the last three partnerships. Follow-up qualitative interviews (n = 30) probed partner-specific experiences (e.g., acts and disclosure). RESULTS: Among all participants, 13.9% (n = 46) described at least one of their last three sex partners as female (MSMW). MSMW (mean age of 31.8) reported a mean of 3.5 partners (SD = 4.5) in the past 3 months and MSMO (mean age 30.6) reported a mean of 4.6 partners (SD = 9.7) in the past 3 months. MSMW were more likely to report unprotected insertive anal sex (77.9%) than MSMO (43.1%; p < 0.01). Cisgender female partners were associated with condomless insertive sex in the last 3 months (aPR: 3.97, 95%CI: 1.98-8.00) and classification as a "primary" partnership (2.10, 1.34-3.31), and with lower prevalence of recent HIV diagnosis (0.26, 0.11-0.61). Planned notification of HIV/STI diagnoses was less common for female than for male partners (0.52, 0.31-0.85). Narratives illustrate internal (e.g., women as 'true' partners) and community-level processes (e.g., discrimination due to exposure of same-sex behavior) that position homosexual behavior and bisexual identity as divergent processes of deviance and generate vulnerability within sexual networks. CONCLUSIONS: MSMW recently diagnosed with HIV/STI in Peru report varying partnership characteristics, with different partner-specific risk contexts and prevention needs. Descriptions highlight how behaviorally bisexual partnerships cut across traditional risk group boundaries and suggest that HIV/STI prevention strategies must address diverse, partnership-specific risks.

A Qualitative Assessment of Alcohol Consumption and Sexual Risk Behaviors Among Men Who Have Sex With Men and Transgender Women in Peru.

BACKGROUND: Peruvian men who have sex with men (MSM) and transgender women (TGW) experience the double burden of a highly concentrated HIV epidemic with a high prevalence of alcohol use disorders (AUDs). Recent research has associated both with risky sexual behaviors, including unprotected sex, having multiple sexual partners, engaging in sex work, having recent sexually transmitted infections, and having HIV-infected partners. AUDs have also been associated in MSM/TGW with being unaware of HIV+ status. OBJECTIVES: This study aims to further examine issues associated with alcohol consumption, HIV infection, and risk behaviors in a qualitative analysis of focus groups conducted with MSM/TGW in Peru. METHODS: A total of 26 MSM/TGW participants with AUDs participated in three semi-structured focus groups in Lima, Peru. Content analysis was facilitated by software, and specific themes were elucidated. RESULTS: Participants described their drinking patterns, including the types of alcoholic drinks they consumed. They depicted drinking frequently and over multiple-day sessions. Problematic drinking behaviors were described, as well as the perceived characteristics of alcohol dependence. Interestingly, HIV-infected participants who were prescribed antiretroviral therapy did not believe that their drinking affected their medication adherence. These insights can aid in the design of future interventions aiming to reduce problematic drinking as well as HIV-related risk behaviors and, subsequently, HIV incidence. CONCLUSIONS: Peruvian MSM/TGW exhibit problematic drinking, which may be associated with risky sexual behaviors and HIV transmission. Interest in reducing alcohol consumption was high, suggesting the need for targeted behavioral and pharmacological interventions.

Knowledge and preferences concerning acute HIV testing programs among both Peruvian men who have sex with men and transgender women.

Immediate antiretroviral therapy (ART) for acute HIV infection (AHI) may decrease HIV transmission in high-risk populations. This study evaluated knowledge of AHI and AHI testing program preferences in Lima, Peru through four semi-structured focus groups with high-risk men who have sex with men (MSM) ( n = 20) and transgender women (TW) ( n = 16). Using content analysis, emergent themes included knowledge of AHI symptoms, AHI transmission potential, and the HIV testing window period, and preferences concerning point of care results. Participants demonstrated low familiarity with the term AHI, but many correctly identified AHI symptoms. However, these symptoms may not motivate testing because they overlap with common viral illnesses and AIDS. Some were aware that infectiousness is highest during AHI, and believe this knowledge would facilitate HIV testing. The shortened window period with AHI testing would encourage testing following high-risk sex. Delayed result notification would not decrease AHI testing demand among MSM, although it might for some TW.

Change in vitamin d levels occurs early after antiretroviral therapy initiation and depends on treatment regimen in resource-limited settings.

STUDY BACKGROUND: Vitamin D has wide-ranging effects on the immune system, and studies suggest that low serum vitamin D levels are associated with worse clinical outcomes in HIV. Recent studies have identified an interaction between antiretrovirals used to treat HIV and reduced serum vitamin D levels, but these studies have been done in North American and European populations. METHODS: Using a prospective cohort study design nested in a multinational clinical trial, we examined the effect of three combination antiretroviral (cART) regimens on serum vitamin D levels in 270 cART-naïve, HIV-infected adults in nine diverse countries, (Brazil, Haiti, Peru, Thailand, India, Malawi, South Africa, Zimbabwe and the United States). We evaluated the change between baseline serum vitamin D levels and vitamin D levels 24 and 48 weeks after cART initiation. RESULTS: Serum vitamin D levels decreased significantly from baseline to 24 weeks among those randomized to efavirenz/lamivudine/zidovudine (mean change: -7.94 [95% Confidence Interval (CI) -10.42, -5.54] ng/ml) and efavirenz/emtricitabine/tenofovir-DF (mean change: -6.66 [95% CI -9.40, -3.92] ng/ml) when compared to those randomized to atazanavir/emtricitabine/didanosine-EC (mean change: -2.29 [95% CI -4.83, 0.25] ng/ml). Vitamin D levels did not change significantly between week 24 and 48. Other factors that significantly affected serum vitamin D change included country (p<0.001), season (p<0.001) and baseline vitamin D level (p<0.001). CONCLUSION: Efavirenz-containing cART regimens adversely affected vitamin D levels in patients from economically, geographically and racially diverse resource-limited settings. This effect was most pronounced early after cART initiation. Research is needed to define the role of Vitamin D supplementation in HIV care.

Comprehensive clinical care for men who have sex with men: an integrated approach.

Men who have sex with men (MSM) have unique health-care needs, not only because of biological factors such as an increased susceptibility to infection with HIV and sexually transmitted infections associated with their sexual behaviour, but also because of internalisation of societal stigma related to homosexuality and gender non-conformity, resulting in depression, anxiety, substance use, and other adverse outcomes. Successful responses to the global HIV/AIDS epidemic will require the development of culturally sensitive clinical care programmes for MSM that address these health disparities and root causes of maladaptive behaviour (eg, societal homophobia). Health-care providers need to become familiar with local outreach agencies, hotlines, and media that can connect MSM with positive role models and social opportunities. Research is needed to understand how many MSM lead resilient and productive lives in the face of discrimination to develop assets-based interventions that build on community support. Optimum clinical care for sexual and gender minorities is a fundamental human right. MSM deserve to be treated with respect, and health-care providers need to interact with them in ways that promote disclosure of actionable health information.

Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial.

BACKGROUND: Observational data and non-human primate challenge studies suggest that cell-mediated immune responses might provide control of HIV replication. The Step Study directly assessed the efficacy of a cell-mediated immunity vaccine to protect against HIV-1 infection or change in early plasma HIV-1 levels. METHODS: We undertook a double-blind, phase II, test-of-concept study at 34 sites in North America, the Caribbean, South America, and Australia. We randomly assigned 3000 HIV-1-seronegative participants by computer-generated assignments to receive three injections of MRKAd5 HIV-1 gag/pol/nef vaccine (n=1494) or placebo (n=1506). Randomisation was prestratified by sex, adenovirus type 5 (Ad5) antibody titre at baseline, and study site. Primary objective was a reduction in HIV-1 acquisition rates (tested every 6 months) or a decrease in HIV-1 viral-load setpoint (early plasma HIV-1 RNA measured 3 months after HIV-1 diagnosis). Analyses were per protocol and modified intention to treat. The study was stopped early because it unexpectedly met the prespecified futility boundaries at the first interim analysis. This study is registered with ClinicalTrials.gov, number NCT00095576. FINDINGS: In a prespecified interim analysis in participants with baseline Ad5 antibody titre 200 or less, 24 (3%) of 741 vaccine recipients became HIV-1 infected versus 21 (3%) of 762 placebo recipients (hazard ratio [HR] 1.2 [95% CI 0.6-2.2]). All but one infection occurred in men. The corresponding geometric mean plasma HIV-1 RNA was comparable in infected male vaccine and placebo recipients (4.61 vs 4.41 log(10) copies per mL, one tailed p value for potential benefit 0.66). The vaccine elicited interferon-gamma ELISPOT responses in 75% (267) of the 25% random sample of all vaccine recipients (including both low and high Ad5 antibody titres) on whose specimens this testing was done (n=354). In exploratory analyses of all study volunteers, irrespective of baseline Ad5 antibody titre, the HR of HIV-1 infection between vaccine and placebo recipients was higher in Ad5 seropositive men (HR 2.3 [95% CI 1.2-4.3]) and uncircumcised men (3.8 [1.5-9.3]), but was not increased in Ad5 seronegative (1.0 [0.5-1.9]) or circumcised (1.0 [0.6-1.7]) men. INTERPRETATION: This cell-mediated immunity vaccine did not prevent HIV-1 infection or reduce early viral level. Mechanisms for insufficient efficacy of the vaccine and the increased HIV-1 infection rates in subgroups of vaccine recipients are being explored.