Human Immunodeficiency Virus Prevention Trials Research Articles

Cost-effectiveness of Cabotegravir Long-Acting for HIV Pre-exposure Prophylaxis in the United States.

Cabotegravir long-acting (CAB-LA) administered every 2 months was approved in the USA as pre-exposure prophylaxis (PrEP) for individuals at risk of acquiring human immunodeficiency virus (HIV)-1 infection based on the HIV Prevention Trials Network (HPTN) 083 and HPTN 084 clinical trials, which demonstrated superior reduction in HIV-1 acquisition compared with daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) in men who have sex with men (MSM), transgender women (TGW), and cisgender women. A decision-analytic model was developed to assess the lifetime cost-effectiveness of initiating CAB-LA versus generic oral FTC/TDF for HIV PrEP in the USA from a healthcare sector perspective. PrEP-eligible adults entered the Markov model receiving CAB-LA or FTC/TDF and could continue initial PrEP, transition to a second PrEP option, or discontinue PrEP over time. Efficacy was taken from the HPTN 083 and HPTN 084 clinical trials. Individuals who acquired HIV-1 infection incurred lifetime HIV-related costs, could transmit HIV onwards, and could develop PrEP-related resistance mutations. Input parameter values were obtained from public and published sources. Model outcomes were discounted at 3%. The model estimated that the CAB-LA pathway prevented 4.5 more primary and secondary HIV-1 infections per 100 PrEP users than the oral PrEP pathway, which yielded 0.2 fewer quality-adjusted life-years (QALYs) lost per person. Additional per-person lifetime costs were $9476 (2022 US dollars), resulting in an incremental cost-effectiveness ratio of $46,843 per QALY gained. Results remained consistent in sensitivity and scenario analyses, including in underserved populations with low oral PrEP usage. Our analysis suggests that initiating CAB-LA for PrEP is cost-effective versus generic daily oral FTC/TDF for individuals at risk of acquiring HIV-1 infection.

Efficacy estimates of oral pre-exposure prophylaxis for HIV prevention in cisgender women with partial adherence.

Pre-exposure prophylaxis (PrEP) with tenofovir (TFV) disoproxil fumarate and emtricitabine administered orally daily is effective in preventing human immunodeficiency virus (HIV) acquisition in both men and women with sufficient adherence; however, the adherence-efficacy relationship in cisgender women has not been well established. We calculated the adherence-efficacy curve for cisgender women by using HIV incidence and plasma TFV concentration data from three trials (FEM-PrEP, VOICE and Partners PrEP). We imputed TFV diphosphate (TFV-DP) concentrations, a measure of long-term adherence, from TFV quantification by using data from the HIV Prevention Trials Network 082 study, which measured both TFV-DP and TFV concentrations. Two, four and seven pills per week reduced HIV incidence by 59.3% (95% credible interval (CrI) 29.9-95.8%), 83.8% (95% CI 51.7-99.8%) and 95.9% (95% CI 72.6-100%), respectively. Our adherence-efficacy curve can be validated and updated by HIV prevention studies that directly measure TFV-DP concentrations. The curve suggests that high adherence confers high protection in cisgender women. However, the lower efficacy with partial adherence highlights the need for new PrEP products and interventions to increase adherence.

Study design approaches for future active-controlled HIV prevention trials.

Vigorous discussions are ongoing about future efficacy trial designs of candidate human immunodeficiency virus (HIV) prevention interventions. The study design challenges of HIV prevention interventions are considerable given rapid evolution of the prevention landscape and evidence of multiple modalities of highly effective products; future trials will likely be'active-controlled', i.e., not include a placebo arm. Thus, novel design approaches are needed to accurately assess new interventions against these highly effective active controls. To discuss active control design challenges and identify solutions, an initial virtual workshop series was hosted and supported by the International AIDS Enterprise (October 2020-March 2021). Subsequent symposia discussions continue to advance these efforts. As the non-inferiority design is an important conceptual reference design for guiding active control trials, we adopt several of its principles in our proposed design approaches. We discuss six potential study design approaches for formally evaluating absolute prevention efficacy given data from an active-controlled HIV prevention trial including using data from: 1) a registrational cohort, 2) recency assays, 3) an external trial placebo arm, 4) a biomarker of HIV incidence/exposure, 5) an anti-retroviral drug concentration as a mediator of prevention efficacy, and 6) immune biomarkers as a mediator of prevention efficacy. Our understanding of these proposed novel approaches to future trial designs remains incomplete and there are many future statistical research needs. Yet, each of these approaches, within the context of an active-controlled trial, have the potential to yield reliable evidence of efficacy for future biomedical interventions.

Information and communications technology use among young female sex workers participating in a randomised human immunodeficiency virus prevention trial in Kampala, Uganda.

BackgroundThis study was conducted to determine the level and feasibility of use of information and communication technology (ICT) and social media for research and service delivery among young female sex workers (YFSWs) in Kampala, Uganda.MethodsWe analysed baseline data from 234 YFSWs in Kampala ages 15–24 y participating in a randomized controlled trial testing a cognitive behavioural human immunodeficiency virus prevention intervention.ResultsMobile phone ownership (68.3%) and short message service use (64.9%) were moderate and significantly lower in the 15- to 19-y age group. Computer use experience and internet access were low.ConclusionsWe believe that the feasibility of ICT and social media-driven interventions among YFSWs is limited.

Characterization of Human Immunodeficiency Virus (HIV) Infection in Cisgender Men and Transgender Women Who Have Sex With Men Receiving Injectable Cabotegravir for HIV Prevention: HPTN 083.

The HIV Prevention Trials Network (HPTN) 083 trial demonstrated that long-acting cabotegravir (CAB-LA) was more effective than tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) in preventing human immunodeficiency virus (HIV) in cisgender men and transgender women who have sex with men. We characterized HIV infections that occurred in the blinded phase of HPTN 083. Retrospective testing included HIV testing, viral load testing, quantification of study drugs, and HIV drug resistance testing. Fifty-eight infections were evaluated, including 51 incident infections (12 in CAB arm and 39 in TDF/FTC arm). In many cases (5 in CAB arm and 37 in TDF/FTC arm), infection was associated with low or unquantifiable study drug concentrations. In 4 cases, infection occurred with on-time CAB-LA injections and expected plasma CAB concentrations. CAB exposure was associated with prolonged viral suppression and delayed antibody expression. In some cases, delayed HIV diagnosis resulted in CAB provision to participants with undetected infection, delayed antiretroviral therapy, and emergence of drug resistance; most of these infections would have been detected earlier with viral load testing. Early detection of HIV infection and prompt antiretroviral therapy initiation could improve clinical outcomes in persons who become infected despite CAB-LA prophylaxis. Further studies are needed to elucidate the correlates of HIV protection in persons receiving CAB-LA.

Prior Sexually Transmitted Infection and Human Immunodeficiency Virus Risk Perception in a Diverse At-Risk Population of Men Who Have Sex with Men and Transgender Individuals.

Prior sexually transmitted infections (STIs) are associated with higher rates of subsequent human immunodeficiency virus (HIV) infection, but the influence of prior STIs on perceived vulnerability to HIV remains unclear. We aimed to assess this relationship, hypothesizing that a prior STI diagnosis is associated with higher self-assessed vulnerability to HIV. We performed a cross-sectional study of men and transgender individuals who have sex with men screening for HIV prevention trials in Philadelphia. An unadjusted regression analysis found no significant association between prior STI and HIV risk perception (p = 0.71) or HIV anxiety (p = 0.32). Multivariate logistic regression models that controlled for predetermined potential cofounders known to impact HIV risk-such as condom use, preexposure prophylaxis use, and demographics-also failed to show statistically significant associations between prior STI and HIV risk perception (p = 0.87) or HIV anxiety (p = 0.10). Furthermore, there was no effect modification by HIV preventive behaviors on the relationship between prior STI and HIV vulnerability. These data suggest that a gap exists between how clinicians may attribute individual HIV risk and how individuals view their own vulnerability at a given moment in time. Future research should focus on the dynamic relationship between perceived HIV vulnerability, STI diagnosis, and adoption of preventive behavior to determine better, individualized targets for HIV prevention interventions.

HIV Prevention Trials Network 078: High Prevalence of Hepatitis C Virus Antibodies Among Urban US Men Who Have Sex With Men, Independent of Human Immunodeficiency Virus Status.

Sexual transmission of hepatitis C virus (HCV) is uncommon, yet documented among men who have sex with men (MSM), primarily among those with human immunodeficiency virus (HIV). In the HIV Prevention Trials Network 078 study (HPTN 078), which assessed an integrated strategy to achieve HIV viral suppression, 1305 MSM were screened across 4 geographically diverse US cities. At screening, demographic/behavioral/psychosocial questionnaires were completed, along with HIV and HCV testing. Multivariable logistic regression was used to evaluate associations with HCV antibody positivity. Among the 1287 (99%) of the MSM with HCV antibody results, the median age was 41, 69% were black, 85% had a high school education or more, 35% were employed, 70% had HIV, and 21% had undergone substance use counseling. The median lifetime number of male sexual partners was 17 (interquartile range, 6-50), and 246 (19%) were HCV antibody positive. HCV antibody positivity was high in MSM with HIV (20%) and MSM without HIV (17%) (P = .12) and was higher in those receiving substance use counseling (36%) than in those who had not (15%) (P ≤ .01). Substance use counseling (odds ratio, 2.51; 95% confidence interval, 1.80-3.51) and unstable housing (2.16; 1.40-3.33) were associated with HCV antibody positivity. Nearly 1 in 5 MSM screened for HPTN 078 have been infected with HCV. The prevalence is high regardless of HIV status and is high even in those who did not undergo substance use counseling. In HIV burden networks, high HCV infection prevalence may occur in MSM without HIV. As implementation of preexposure prophylaxis expands and condom use declines, routine HCV counseling and screening among MSM are important.

Modeling Combination Interventions to Prevent Human Immunodeficiency Virus in Adolescent Girls and Young Women in South Africa (HIV Prevention Trials Network 068).

Combination interventions may be an effective way to prevent human immunodeficiency virus (HIV) in adolescent girls and young women. However, current studies are not designed to understand which specific interventions and combinations will be most effective. We estimate the possible impacts of interventions on a combination of factors associated with HIV. We used the g-formula to model interventions on combinations of HIV risk factors to identify those that would prevent the most incident HIV infections, including low school attendance, intimate partner violence, depression, transactional sex, and age-disparate partnerships. We used data from the HIV Prevention Trials Network (HPTN) 068 study in rural South Africa from 2011 to 2017. We estimated HIV incidence under a potential intervention that reduced each risk factor and compared this to HIV incidence under the current distribution of these risk factors. Although many factors had strong associations with HIV, potential intervention estimates did not always suggest large reductions in HIV incidence because the prevalence of risk factors was low. When modeling combination effects, an intervention to increase schooling, decrease depression, and decease transactional sex showed the largest reduction in incident infection (risk difference, -1.4%; 95% confidence interval [CI], -2.7% to -.2%), but an intervention on only transactional sex and depression still reduced HIV incidence by -1.3% (95% CI, -2.6% to -.2%). To achieve the largest reductions in HIV, both prevalence of the risk factor and strength of association with HIV must be considered. Additionally, intervening on more risk factors may not necessarily result in larger reductions in HIV incidence.

Human Immunodeficiency Virus (HIV) Drug Resistance, Phylogenetic Analysis, and Superinfection Among Men Who Have Sex with Men and Transgender Women in Sub-Saharan Africa: HIV Prevention Trials Network (HPTN) 075 Study

The HIV Prevention Trials Network (HPTN) 075 study evaluated the feasibility of enrolling and retaining men who have sex with men (MSM) and transgender women (TGW) from Kenya, Malawi, and South Africa. During the study follow-up, 21 participants acquired human immunodeficiency virus (HIV) (seroconverters). We analyzed HIV subtype diversity, drug resistance, transmission dynamics, and HIV superinfection data among MSM and TGW enrolled in HPTN 075. HIV genotyping and drug resistance testing were performed for participants living with HIV who had viral loads >400 copies/mL at screening (prevalent cases, n = 124) and seroconverters (n = 21). HIV pol clusters were identified using Cluster Picker. Superinfection was assessed by a longitudinal analysis of env and pol sequences generated by next-generation sequencing. HIV genotyping was successful for 123/124 prevalent cases and all 21 seroconverters. The major HIV subtypes were A1 (Kenya) and C (Malawi and South Africa). Major drug resistance mutations were detected in samples from 21 (14.6%) of 144 participants; the most frequent mutations were K103N and M184V/I. Phylogenetic analyses identified 11 clusters (2-6 individuals). Clusters included seroconverters only (n = 1), prevalent cases and seroconverters (n = 4), and prevalent cases only (n = 6). Superinfections were identified in 1 prevalent case and 2 seroconverters. The annual incidence of superinfection was higher among seroconverters than among prevalent cases, and was higher than the rate of primary HIV infection in the cohort. This report provides important insights into HIV genetic diversity, drug resistance, and superinfection among MSM and TGW in sub-Saharan Africa. These findings may help to inform future HIV prevention interventions in these high-risk groups.

Evaluation of Phylogenetic Methods for Inferring the Direction of Human Immunodeficiency Virus (HIV) Transmission: HIV Prevention Trials Network (HPTN) 052.

Phylogenetic analysis can be used to assess human immunodeficiency virus (HIV) transmission in populations. We inferred the direction of HIV transmission using whole-genome HIV sequences from couples with known linked infection and known transmission direction. Complete next-generation sequencing (NGS) data were obtained for 105 unique index-partner sample pairs from 32 couples enrolled in the HIV Prevention Trials Network (HPTN) 052 study (up to 2 samples/person). Index samples were obtained up to 5.5 years before partner infection; partner samples were obtained near the time of seroconversion. The bioinformatics method, phyloscanner, was used to infer transmission direction. Analyses were performed using samples from individual sample pairs, samples from all couples (1 sample/person; group analysis), and all available samples (multisample group analysis). Analysis was also performed using NGS data from defined regions of the HIV genome (gag, pol, env). Using whole-genome NGS data, transmission direction was inferred correctly (index to partner) for 98 of 105 (93.3%) of the individual sample pairs, 99 of 105 (94.3%) sample pairs using group analysis, and 31 of the 32 couples (96.9%) using multisample group analysis. There were no cases where the incorrect transmission direction (partner to index) was inferred. The accuracy of the method was higher with greater time between index and partner sample collection. Pol region sequences performed better than env or gag sequences for inferring transmission direction. We demonstrate the potential of a phylogenetic method to infer the direction of HIV transmission between 2 individuals using whole-genome and pol NGS data.

Methods for generalized change-point models: with applications to human immunodeficiency virus surveillance and diabetes data.

In many epidemiological and biomedical studies, the association between a response variable and some covariates of interest may change at one or several thresholds of the covariates. Change-point models are suitable for investigating the relationship between the response and covariates in such situations. We present change-point models, with at least one unknown change-point occurring with respect to some covariates of a generalized linear model for independent or correlated data. We develop methods for the estimation of the model parameters and investigate their finite-sample performances in simulations. We apply the proposed methods to examine the trends in the reported estimates of the annual percentage of new human immunodeficiency virus (HIV) diagnoses linked to HIV-related medical care within 3 months after diagnosis using HIV surveillance data from the HIV prevention trial network 065 study. We also apply our methods to a dataset from the Pima Indian diabetes study to examine the effects of age and body mass index on the risk of being diagnosed with type 2 diabetes.

Building Partnerships and Stakeholder Relationships for HIV Prevention: Longitudinal Cohort Study Focuses on Community Engagement.

African American women bear disproportionate human immunodeficiency virus (HIV) burden in the United States, yet are often underrepresented in clinical research. Community engagement may decrease research mistrust and increase participation. We describe strategies used to engage community partners and female participants in a multisite HIV incidence study, HIV Prevention Trials Network (HPTN) 064. HPTN 064 assessed HIV incidence among women in 10 geographic areas chosen for both high prevalence of HIV and poverty. Women were recruited using venue-based sampling and followed for six to 12 months. Recruitment and engagement approaches aligned with the National Institutes of Health (NIH) Director's Council of Public Representatives (COPR) Community Engagement Framework's. Results showed engagement activities increased rapport and established new partnerships with community stakeholders. Study sites engaged 56 community organizations with 2,099 women enrolled in 14 months. Final retention was 94%. The COPR model maximized inclusiveness and participation of African American women impacted by HIV, supported recruitment and retention, and was the cornerstone of community engagement.

Phylogenetic Analysis of Human Immunodeficiency Virus from People Who Inject Drugs in Indonesia, Ukraine, and Vietnam: HPTN 074.

HIV Prevention Trials Network (HPTN) 074 evaluated human immunodeficiency virus (HIV) prevention interventions for people who inject drugs (PWID) in Indonesia, Ukraine, and Vietnam. Study interventions included support for HIV infection and substance use treatment. The study enrolled index participants living with HIV and injection partners who were not living with HIV. Seven partners acquired HIV infection during the study (seroconverters). We analyzed the phylogenetic relatedness between HIV strains in the cohort and the multiplicity of infection in seroconverters. Pol region consensus sequences were used for phylogenetic analysis. Data from next-generation sequencing (NGS, env region) were used to evaluate genetic linkage of HIV from the 7 seroconverters and the corresponding index participants (index-partner pairs), to analyze HIV from index participants in pol sequence clusters, and to analyze multiplicity of HIV infection. Phylogenetic analysis of pol sequences from 445 index participants and 7 seroconverters identified 18 sequence clusters (2 index-partner pairs, 1 partner-partner pair, and 15 index-only groups with 2-7 indexes/cluster). Analysis of NGS data confirmed linkage for the 2 index-partner pairs, the partner-partner pair, and 11 of the 15 index-index clusters. The remaining 5 seroconverters had infections that were not linked to the corresponding enrolled index participant. Three (42.9%) of the 7 seroconverters were infected with more than 1 HIV strain (3-8 strains per person). We identified complex patterns of HIV clustering and linkage among PWID in 3 communities. This should be considered when designing strategies for HIV prevention for PWID. NCT02935296.

Depression and Incident HIV in Adolescent Girls and Young Women in HIV Prevention Trials Network 068: Targets for Prevention and Mediating Factors.

The human immunodeficiency virus (HIV) epidemic among adolescent girls and young women (AGYW) in sub-Saharan Africa is a critical public health problem. We assessed whether depressive symptoms in AGYW were longitudinally associated with incident HIV, and identified potential social and behavioral mediators. Data came from a randomized trial of a cash transfer conditional on school attendance among AGYW (ages 13-21 years) in rural Mpumalanga Province, South Africa, during 2011-2017. We estimated the relationship between depressive symptoms and cumulative HIV incidence using a linear probability model, and we assessed mediation using inverse odds ratio weighting. Inference was calculated using the nonparametric bootstrap. AGYW with depressive symptoms had higher cumulative incidence of HIV compared with those without (risk difference=3.5, 95% confidence interval (CI): 0.1, 7.0). The strongest individual mediators of this association were parental monitoring and involvement (indirect effect=1.6, 95% CI: 0.0, 3.3) and reporting a partner would hit her if she asked him to wear a condom (indirect effect=1.5, 95% CI: -0.3, 3.3). All mediators jointly explained two-thirds (indirect effect=2.4, 95% CI: 0.2, 4.5) of the association between depressive symptoms and HIV incidence. Interventions addressing mental health might reduce risk of acquiring HIV among AGYW.

Predicted Effectiveness of Daily and Nondaily Preexposure Prophylaxis for Men Who Have Sex With Men Based on Sex and Pill-taking Patterns From the Human Immuno Virus Prevention Trials Network 067/ADAPT Study.

The HIV Prevention Trials Network (HPTN) 067/Alternative Dosing to Augment PrEP Pill Taking (ADAPT) Study evaluated the feasibility of daily and nondaily human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) regimens among high-risk populations, including men who have sex with men (MSM) and transgender women, in Bangkok, Thailand and Harlem, New York. We used a mathematical model to predict the efficacy and effectiveness of different dosing regimens. An individual-based mathematical model was used to simulate annual HIV incidence among MSM cohorts. PrEP efficacy for covered sex acts, as defined in the HPTN 067/ADAPT protocol, was estimated using subgroup efficacy estimates from the preexposure prophylaxis initiative (iPrEx) trial. Effectiveness was estimated by comparison of the HIV incidence with and without PrEP use. We estimated that PrEP was highly protective (85%-96% efficacy across regimens and sites) for fully covered acts. PrEP was more protective for partially covered acts in Bangkok (71%-88% efficacy) than in Harlem (62%-81% efficacy). Our model projects 80%, 62%, and 68% effectiveness of daily, time-driven, and event-driven PrEP for MSM in Harlem compared with 90%, 85%, and 79% for MSM in Bangkok. Halving the efficacy for partially covered acts decreases effectiveness by 8-9 percentage points in Harlem and by 5-9 percentage points in Bangkok across regimens. Our analysis suggests that PrEP was more effective among MSM in Thailand than in the United States as a result of more fully covered sex acts and more pills taken around partially covered acts. Overall, nondaily PrEP was less effective than daily PrEP, especially in the United States where the sex act coverage associated with daily use was substantially higher.

Cabotegravir Is Not Associated With Weight Gain in Human Immunodeficiency Virus-uninfected Individuals in HPTN 077.

Studies in human immunodeficiency virus (HIV)-infected individuals suggest excess weight gain with integrase inhibitor-based antiretroviral therapy. The HIV Prevention Trials Network Study 077 evaluated changes in weight and fasting metabolic parameters in HIV-uninfected individuals randomized to cabotegravir or a placebo. No differences between arms were found for change in weight or fasting metabolic parameters overall or for subgroups.

Characteristics Associated With Human Immunodeficiency Virus Transmission Networks Involving Adolescent Girls and Young Women in Human Immunodeficiency Virus Prevention Trials Network 068 Study.

We combined behavioral survey data from the human immunodeficiency virus (HIV) Prevention Trials Network 068 study with phylogenetic information to determine if cluster membership was associated with characteristics of young women and their partners. Clusters were more likely to involve young women from specific villages and schools, indicating some localized transmission.Supplemental digital content is available in the text.

Correlates of Sexually Transmitted Infections Among South African Women Using Individual- and Community-Level Factors: Results from Generalized Additive Mixed Models

South Africa has the highest burden of Human Immunodeficiency Virus (HIV) infections in the world. There is also growing evidence that an individual’s risk of contracting HIV is increased by the presence of other sexually transmitted infections (STIs). Primary objective of this study was to examine the association between the prevalence of STIs in a cohort of South African women who enrolled in HIV prevention trials (2002–2012). The current study linked the individual-factors with the community-level characteristics using geo-referencing. This multi-level data was analysed in generalized additive mixed models (GAMMS) settings. In the multivariate logistic regression model, younger age [Odds Ratio (OR):4.30, 95%CI: 3.20, 5.77 and OR:2.72, 95% CI: 2.02, 3.66 for age<25 and 25–29, respectively]; being single/not cohabiting (OR:4.57, 95% CI: 3.18, 6.53), two+ sex partners (OR:1.46, 95% CI: 1.18,1.80); parity<2 (OR:2.04, 95% CI: 1.53, 2.72 ), parity=2 (OR:1.85, 95% CI: 1.37, 2.48), and using injectables (contraceptive) (OR:1.53, 95%CI: 1.13, 2.06) were all significantly associated with increased prevalence of STIs. Besides these individual-level characteristics, women who resided in the communities where high proportions of: female headed-households (OR: 1.17, 95%CI: 1.02, 1.38), and no schooling (OR: 1.26, 95%CI: 1.08, 1.45). Because, these factors may reflect characteristics of the larger groups who share similar cultural norms and social environments, they can provide considerable insight into the spread of STIs. Prevention strategies based on individual and community-level drivers of STIs are likely to be the most effective means of targeting and reaching those at greatest risk of infection. This strategy has the potential to play a significant role in the epidemic’s trajectory.

Cross-sectional human immunodeficiency virus incidence estimation accounting for heterogeneity across communities.

Accurate estimation of human immunodeficiency virus (HIV) incidence rates is crucial for the monitoring of HIV epidemics, the evaluation of prevention programs, and the design of prevention studies. Traditional cohort approaches to measure HIV incidence require repeatedly testing large cohorts of HIV-uninfected individuals with an HIV diagnostic test (eg, enzyme-linked immunosorbent assay) for long periods of time to identify new infections, which can be prohibitively costly, time-consuming, and subject to loss to follow-up. Cross-sectional approaches based on the usual HIV diagnostic test and biomarkers of recent infection offer important advantages over standard cohort approaches, in terms of time, cost, and attrition. Cross-sectional samples usually consist of individuals from different communities. However, small sample sizes limit the ability to estimate community-specific incidence and existing methods typically ignore heterogeneity in incidence across communities. We propose a permutation test for the null hypothesis of no heterogeneity in incidence rates across communities, develop a random-effects model to account for this heterogeneity and to estimate community-specific incidence, and provide one way to estimate the coefficient of variation. We evaluate the performance of the proposed methods through simulation studies and apply them to the data from the National Institute of Mental Health Project ACCEPT, a phase 3 randomized controlled HIV prevention trial in Sub-Saharan Africa, to estimate the overall and community-specific HIV incidence rates.

Correlations Between Human Immunodeficiency Virus (HIV) Infection and Rectal Gonorrhea Incidence in Men Who Have Sex With Men: Implications for Future HIV Preexposure Prophylaxis Trials.

Using published data, we found a direct correlation between the incidence of rectal gonorrhea and human immunodeficiency virus (HIV) infection in men who have sex with men who were not using oral preexposure prophylaxis. HIV incidence was predicted using rectal gonorrhea incidence as the determinant in regression analysis. The observed correlation suggest that rectal gonorrhea incidence can potentially serve as a predictor of HIV incidence. If confirmed with additional data, a quantitative correlation for incidence of the 2 infections could be useful in active-controlled HIV prevention trials where low HIV incidence is expected. Widespread improvements in treatment as prevention and gonorrhea control can negatively impact the correlation and its utility.