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HIV pre-exposure prophylaxis (PrEP) is a recent, yet significant, development in HIV prevention. This mixed-methods research followed PrEP’s introduction in Australia, and examined how gay, bisexual and queer (GBQ) men in relationships have adapted to and incorporated PrEP in their sex practices, relationships, and everyday lives. As PrEP raises the prospect of having condomless sex both within and outside primary relationships without risking HIV infection, this research revisited the concept of negotiated safety (Kippax et al., 1997) to explore how HIV-negative GBQ men practice and negotiate safe sex in the era of biomedical HIV prevention. Quantitative data were collected in two national cross-sectional survey projects, The Gay Community Periodic Surveys (GCPS; 2013–2018) and the PrEPARE Project (2013–2021). The GCPS analysis showed a rapid shift away from relationship agreements in which condomless sex is only sanctioned between regular partners. The PrEPARE Project analysis found that men in relationships who used PrEP were more likely to have spoken and non-monogamous agreements, and to have partners that also used PrEP, compared to men in relationships who did not use PrEP. Qualitative data were generated using semi-structured, in-depth interviews conducted between January and August 2019 with 26 GBQ men in Sydney, Melbourne and Perth. Thematic analysis of these data identified new shared meanings and social practices that were enabled or mediated by PrEP, with an analytic focus on complexity, situatedness, contingency and relationality. Participant accounts illustrated diverse sexual practices and views about risk, but most participants adopted PrEP due to perceived HIV risk from casual sex rather than sex with their primary partners. PrEP complicated views about what counted as ‘safe sex’ and revealed changing understandings and practices of intimacy, pleasure, trust and risk. There was, however, an enduring narrative of individual responsibility to practice effective HIV prevention. Participants diverged in how they discussed and disclosed sexual practices with their primary and casual partners, revealing tensions about what disclosures were believed to be necessary or expected. Together, these quantitative and qualitative data collected as PrEP use became more common refocus attention on the practicality and complexity of relationship agreements among GBQ men.

The HIV epidemic remains one of the most significant public health issues in the United States, particularly among men who have sex with men (MSM). New avenues for partner-seeking have emerged over the past three decades, including through the Internet, social media, and geosocial networking applications. Consisting of three cross-sectional studies, this dissertation research aimed to determine associations between the use of various online tools for partner-seeking (hereafter collectively referred to as “apps”) and HIV-related sexual behaviors among 252 young adult MSM residing in small/midsized towns or rural areas in Central Kentucky, a group that has been under-represented in the literature to date on this topic. Most participants (181, 72%) reported app use for partner-seeking. Using multivariable logistic regression models, the first study revealed associations of online partner-seeking with decreased condomless insertive and receptive anal intercourse. App use, however, was also associated with increased number of insertive and receptive anal sex partners, alcohol/drug use before or during sex, and rectal douching among partners of MSM with higher education. Findings of the second study indicated that HIV-related sexual behaviors varied by the type of apps used for partner-seeking. Latent class analysis identified four subgroups of MSM by app use patterns: (1) a class who almost exclusively used Grindr and Tinder (Grindr/Tinder class); (2) a class with higher probabilities of using multiple MSM-oriented apps (Poly App Use class); (3) a class with higher probabilities of using general social media such as Facebook, Craigslist, Twitter, and Backpage (General Social Media class), and (4) a class with the highest probability of reporting using Bumble (Bumble class). Adjusting for other covariates, members of the Poly App Use class were more likely to be older, to report any illicit drug use in the past six months, and PrEP use in the lifetime, compared to MSM in other classes. Worth noting that in the unadjusted analyses, the number of receptive anal sex partners, percentages of condomless receptive anal sex, engagement in group sex, lifetime history of STI diagnosis, and reporting sex with HIV-positive individuals in the lifetime were significantly higher among members of the Poly App Use class than other classes. In the third study, dyadic analysis using multivariable generalized linear mixed effects modeling revealed no clear differences in reporting recent (past six months) condomless anal sex (CAS) – a sexual behavior that can increase risk for HIV transmission – by MSM who met sex partners on apps (i.e., “app facilitated” relationships), compared to their counterparts who met partners elsewhere. Engagement in CAS did not differ significantly between app-facilitated and non-app-facilitated relationships. Increasing age of partners (especially within non-app-facilitated relationships); White, non-Hispanic race/ethnicity of respondents; maintaining daily communication with partners; and respondents’ lifetime history of sex with HIV-positive individuals were associated with higher odds of CAS. This dissertation reveals novel insights into the app- and relationship-level nuances of online partner-seeking among MSM residing in small/midsized towns or rural areas in Kentucky. Although app use was associated with some risk behaviors (i.e., substance use before/during sex, increased number of partners), it was not associated at the individual- or relationship-level with condomless sex, the sexual behavior most relevant to HIV transmission. Study participants who used multiple MSM-oriented apps to meet partners had an elevated risk profile, but there were no significant differences in sexual risk behaviors after adjustment for other factors in the multivariable modeling. These findings highlight the need for future research to consider nuances of which apps are being used and to consider how sexual risk behaviors can vary by different app use patterns. Furthermore, our results underscore the need for HIV outreach organizations to continue using multiple strategies for HIV prevention that include dissemination of sexual health-related information not only via apps, but also via conventional venue outreach (e.g., at LGBTQ-friendly bars, social organizations) to increase testing, promote condom use and PrEP uptake to help stem HIV epidemic.

Men who have sex with men (MSM) remain at high risk of HIV infection globally. In Vietnam, HIV prevalence, understanding of risk factors, and barriers to testing and treatment among MSM are poorly understood. This thesis aimed to determine the prevalence of infectious syphilis, HIV, and HIV testing and associated factors among male sex workers (MSWs) and MSM, estimate the cascade of care, and identify barriers to treatment for HIV-positive MSM in Hanoi. Data from the first wave of baseline recruitment for the HIM-Hanoi study, and the Hanoi arm of the SHEATH study, together with in-depth interview with HIV-positive MSM were utilised. Syphilis prevalence (21.2%) among 316 MSWs was high and independently associated with recent STI testing, HIV positive status, longer duration of sex work, and recent oral sex with non-client male partners. Weighted HIV prevalence among 796 MSM was 10.9%, and independently associated with lifetime sex with male clients, recent condomless anal intercourse (CLAI) with non-commercial male partners, three or more recent non-commercial anal sex partners, recent group sex with party drugs, STI symptoms, syphilis infection, and past/current hepatitis B infection. HIV testing uptake was suboptimal, with 33.1% never tested, 11.7% tested >12 months ago, and 55.2% tested ≤ 12 months. Non-recent testers were older, less educated, and less likely to receive free condoms than recent testers. Never testers were less engaged with the MSM community, less likely to disclose their homosexuality and to have been diagnosed with an STI, but more likely to report recent CLAI with male clients. Among 79 HIV-positive MSM, 35.2% were aware of their status, 27.9% were on antiretroviral therapy (ART) and 17.1% were virally suppressed. Qualitative interviews revealed barriers to ART uptake including inadequate preparation for a positive diagnosis, dual stigmatisation of homosexuality and HIV, confusion about treatment access, failure to protect confidentiality, and providers’ reticence to discuss same-sex issues. Findings increase understanding of the epidemiology of HIV among MSM in Vietnam and potentially inform policy and practice. Programmatic responses are needed, including HIV pre-exposure prophylaxis, scaled-up HIV testing, integration of STI and HIV screening, and expanded access to timely, MSM-friendly treatment and care.

This cross-sectional study aimed to determine the cost–effectiveness of two HIV prevention interventions: 1. a community-based friend centre (P1) versus 2. a training course (P2) for men who have sex with men (MSM) in Ubon Ratchathani province, Thailand. The interventions were implemented for two rounds (R1 and R2) during 2008-2010. The study involved 224 MSM who were enrolled in the two interventions between 2008 and 2010. Participants were interviewed using questionnaires to assess their knowledge and attitude towards HIV/AIDS. Cost-effectiveness analysis was carried out to compare the two interventions. There were 37 (51.4%) participants in R1 and 47 (65.3%) in R2 with sound knowledge for P1. For P2, 8 (20%) out of 40 in R1 and 17 (42.5%) in R2 were found to have sound knowledge of HIV/AIDS. 57 (79%) participants in R1 and 64 (88.9%) in R2 had preferable attitude for P1. 77.5% of participants in R1 and 85% in R2 had preferable attitude for P2. The costs per MSM with sound knowledge were 869 baht (27 USD) per person in R1 and 682 baht (21 USD) per person in R2 of P1, which were significantly lower compared to those of P2 for the same period (3,820 baht per person for P2R1, 1,899 baht per person for P2R2). The costs per one MSM with preferable attitude of P1, 564 baht (18 USD) per person for R1, 501 baht (16 USD) per person in R2 were significantly higher compared to that of P2 for the same round (1,455 baht per person in R1, 949 baht per person in R2). The results from our study suggest that establishing a community-based friend centre (P1) was more effective and cost-effective than implementing a training course (P2) for achieving desired outcomes with less cost. Therefore, the HIV prevention program for MSM should consider establishing a communitybased friend centre in the long run rather than implementing a training course.

The cost burden associated with providing effective treatment for people living with human immunodeficiency virus (HIV) and implementing appropriate prevention strategies to stop further spread of the virus has become a significant global challenge. In this thesis, four studies were conducted using mathematical modelling and economic evaluation methodology to better understand, prioritise, and optimise a number of HIV initiatives. First, a mathematical model was developed to evaluate the likely epidemiological impact of expanding prevention efforts in Thailand to include the provision of the partially efficacious HIV vaccine used in the RV144 trials. This study found that due to the short duration of protection the vaccine provides, limited epidemiological impact is expected from a single round of mass vaccination. However, significant public health benefit could be achieved from a high level of coverage, sustained implementation, and re-vaccination. The second study evaluated the cost-effectiveness of expanding HIV prevention efforts in Australia to include pre-exposure prophylaxis (PrEP) to men who have sex with men (MSM). Pre-exposure prophylaxis was not found to be cost-effective when targeting the general MSM population, however, this study illustrated that targeting MSM at higher risk of infection improved the cost-effectiveness of PrEP. The third study investigated the cost-effectiveness of expanding treatment management to include viral load (VL) monitoring and second-line antiretroviral therapy (ART) for HIV-infected children in Thailand. This study illustrated that VL monitoring and access to second-line ART has substantial clinical benefit. However, the costs associated with second-line therapies remain a barrier to its economic feasibility. The final study considers the attrition of standard of care second-line ART in low- and middle-income settings and the economic feasibility of introducing a new alternative second-line therapy, raltegravir (RAL). The introduction of RAL was considered to be cost-effective for upper-middle income countries, but not lower-income settings. The studies described in this thesis have aimed to provide insight to policymakers across different resource settings on whether a number of HIV initiatives are a cost-effective use of resources. Together, they show that we must be strategic in our use of resources to effectively combat HIV now and in to the future.

Despite decades of prevention and treatment efforts, human immunodeficiency virus (HIV) infection is a global pandemic, with HIV/acquired immunodeficiency syndrome (AIDS) among the leading causes of death for children and adults in developing countries. HIV/AIDS disproportionately affects men who have sex with men (MSM), including in the United States, where MSM account for over half of all new HIV infections. Existing HIV prevention tools have not been sufficient to curb the pandemic, and biomedical prevention strategies, such as circumcision and microbicides, had not been shown to be effective in preventing HIV infection in MSM until 2010, when the multi-national iPrEx study found that daily oral preexposure prophylaxis (PrEP) using antiretroviral therapy (emtricitabine/tenofovir, or FTC/TDF) prevented HIV infection among MSM and transgender women. Although the success of FTC/TDF PrEP in such trials has given new hope to the HIV prevention field, excitement has been tempered by concerns about low adherence to daily pill use among trial participants. Adherence, as measured by self-reported pill use, was high among participants in the iPrEx trial, but testing for evidence of the drug in blood specimens from a subset of participants indicated that actual pill use was much lower than reported pill use. Adherence is critical for PrEP effectiveness; iPrEx participants in whom antiretroviral drug was detected in blood experienced a substantially greater reduction in HIV risk than was seen overall. The iPrEx results suggest that low adherence may be a barrier to successful implementation of PrEP as an HIV prevention strategy among MSM. Identification of effective strategies for supporting the consistent use of prophylactic medications could provide much needed guidance in the development of interventions to support adherence to PrEP.In addition to concerns about adherence, there is a widespread concern that PrEP could result in an increase in sexual risk behaviors by lowering users' perception of their risk of acquiring HIV infection; such risk compensation could reduce or even negate the benefits of PrEP. Foundational to most models of health behavior is the hypothesis that perceived risk is a primary motivation for self-protective behavior. Based on this theory, when a new prevention strategy, such as PrEP, is introduced, risk compensation could be prevented by sustaining individuals' perceptions of their own HIV risk. While the act of taking PrEP on a daily basis could result in risk compensation, it could also provide a daily opportunity to contemplate and manage HIV risk, thus motivating condom use and other self-protective behaviors. A better understanding of whether, and how, PrEP use affects sexual risk behavior could inform the development of risk-reduction interventions for individuals prescribed PrEP. In addition to preventing HIV infection, there is evidence that FTC/TDF PrEP may also be protective against infection with Herpes simplex virus type 2 (HSV-2). HSV-2 is the primary cause of genital ulcer disease worldwide, and HSV-2 infection is known to increase the risk of sexual transmission and acquisition of HIV infection. In the CAPRISA 004 study, a topical 1% tenofovir gel used as PrEP against HIV infection also reduced the risk of HSV-2 acquisition by 51% in women. In the Partners PrEP study, oral FTC/TDF reduced HSV-2 acquisition by 35% among heterosexual couples. Protection against HSV-2 acquisition or expression could enhance the public health impact of PrEP, but it is unknown whether FTC/TDF has anti-herpetic properties in men who have sex with men. The effectiveness of FTC/TDF PrEP in protecting against HIV infection depends on individual-level behaviors, including adherence and sustained risk reduction, as well as its effect on other sexually transmitted infections (STI) that increase the risk of HIV acquisition. Chapter 1 of this dissertation describes a systematic review that aimed to identify interventions that have been used to support adherence to daily oral medications prescribed to healthy or asymptomatic individuals. This review found evidence of interventions that demonstrated short-term improvements in medication adherence across a variety of prevention settings, thus identifying potential strategies for adherence support among PrEP users. Chapter 2 describes an analysis of data from the randomized phase of the iPrEx study to determine whether sexual risk compensation occurred among trial participants. Consistent with other PrEP studies, this analysis found no evidence of increased sexual risk behavior or STIs among participants who believed they had been assigned to the FTC/TDF arm and that the drug was highly effective. Finally, Chapter 3 describes an analysis that used data from the randomized phase of iPrEx to measure the effect of FTC/TDF on HSV-2 acquisition and expression among men who have sex with men. Although there was no effect of FTC/TDF on HSV-2 acquisition, participants receiving the active drug had a lower prevalence of herpetic ulcers than participants receiving the placebo. Taken together, these papers contribute to the HIV prevention field by providing guidance on behavioral support strategies for daily oral PrEP and identifying anti-herpetic properties of FTC/TDF that could increase its effectiveness as a novel prevention tool.

This study compared the perceived threat of HIV/AIDS and explored the sexual risky behaviors between men who have sex with men (MSM) and heterosexual males. Participants were asked to complete a 33 question survey which included 22 Likert-type scale questions developed to measure the perceived threat of HIV/AIDS, 8 dichotomous questions designed to measure sexual risk behavior and 3 demographic variables; age, sexual orientation and race. The case group consisted of 52 MSM and the control group consisted of 96 heterosexual males. No statistical significant diffrence was found among sexual risky behaviors. Findings from this study indicate that HIV/AIDS prevention efforts should continue to address sexual behavior practices of MSM. Increased sexual risky behavioral practices could lead to higher STD and HIV incidence and prevalence rates.