Parameters for sample size estimation from a group-randomized HIV prevention trial in HIV clinics in sub-Saharan Africa.

Sample size calculations for a group-randomized trial (GRT) require an estimate of the expected intraclass correlation coefficient (ICC). However, few ICC estimates from GRTs in HIV/AIDS research have been published, leaving investigators with little data on which to base expectations. We used data from a multi-country study to estimate ICCs for variables related to physical and mental health and HIV risk behaviors. ICCs for perceptions of physical and mental health tended to be higher than those for HIV risk behavior variables, which were higher than ICCs for CD4 count. Covariate adjustment for country and socio-demographic variables reduced most ICC estimates. For risk behavior variables, adjustment for country and socio-demographic variables reduced ICC estimates by as much as 84 %. Variability in ICC estimates has important implications for study design, as a larger ICC reduces power. ICC estimates presented in this analysis will allow more precise sample size estimates for future GRTs.

Male circumcision uptake during the Botswana Combination Prevention Project.

INTRODUCTION: Voluntary medical male circumcision (VMMC) uptake has been slow in some countries, including Botswana. To inform demand creation efforts, we examined sociodemographic characteristics and referral procedures associated with VMMC uptake in the Botswana Combination Prevention Project (BCPP) and examined the effectiveness of referral of men to MC services from HIV testing venues. DESIGN: BCPP was a community-randomized trial evaluating the impact of a combination HIV prevention package which included VMMC on community HIV incidence. We conducted a sub-analysis of VMMC uptake in intervention communities. METHODS: During the initial VMMC campaign in 15 intervention communities, baseline male circumcision (MC) status was assessed among men eligible for HIV testing. Uncircumcised male community residents aged 16-49 years with negative/unknown HIV status were mobilized and linked to study VMMC services. Outcomes included MC baseline status and uptake through study services. Univariate and multivariate logistic regressions were performed to identify factors associated with MC uptake. RESULTS: Of 12,864 men eligible for testing, 50% (n = 6,448) were already circumcised. Among the uncircumcised men (n = 6,416), 10% (n = 635) underwent MC. Of the 5,071 men identified as eligible for MC through HIV testing services, 78% declined referral and less than 1% of those were circumcised. Of those accepting referral (n = 1,107), 16% were circumcised. Younger (16-24 years) (aOR: 1.51; 95%CI:1.22,1.85), unemployed men (aOR:1.34; 95%CI: 1.06,1.69), and those undergoing HIV testing at mobile venues (aOR: 1.88; 95%CI: 1.53,2.31) were more likely to get circumcised. Fear of pain was the most prevalent (27%) reason given for not being circumcised. CONCLUSION: Younger, unemployed men seeking HIV testing at mobile sites in Botswana were more likely to get VMMC. Addressing unique barriers for employed and older men may be necessary. Given the simplicity of VMMC as an intervention, the HIV testing programs offer a platform for identifying uncircumcised men and offering information and encouragement to access services.

Deep-sequence phylogenetics to quantify patterns of HIV transmission in the context of a universal testing and treatment trial - BCPP/Ya Tsie trial.

Background: Mathematical models predict that community-wide access to HIV testing-and-treatment can rapidly and substantially reduce new HIV infections. Yet several large universal test-and-treat HIV prevention trials in high-prevalence epidemics demonstrated variable reduction in population-level incidence. Methods: To elucidate patterns of HIV spread in universal test-and-treat trials, we quantified the contribution of geographic-location, gender, age, and randomized-HIV-intervention to HIV transmissions in the 30-community Ya Tsie trial in Botswana. We sequenced HIV viral whole genomes from 5114 trial participants among the 30 trial communities. Results: Deep-sequence phylogenetic analysis revealed that most inferred HIV transmissions within the trial occurred within the same or between neighboring communities, and between similarly aged partners. Transmissions into intervention communities from control communities were more common than the reverse post-baseline (30% [12.2 - 56.7] vs. 3% [0.1 - 27.3]) than at baseline (7% [1.5 - 25.3] vs. 5% [0.9 - 22.9]) compatible with a benefit from treatment-as-prevention. Conclusions: Our findings suggest that population mobility patterns are fundamental to HIV transmission dynamics and to the impact of HIV control strategies. Funding: This study was supported by the National Institute of General Medical Sciences (U54GM088558), the Fogarty International Center (FIC) of the U.S. National Institutes of Health (D43 TW009610), and the President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention (CDC) (Cooperative agreements U01 GH000447 and U2G GH001911).

Population uptake of HIV testing, treatment, viral suppression, and male circumcision following a community-based intervention in Botswana (Ya Tsie/BCPP): a cluster-randomised trial.

BACKGROUND: In settings with high HIV prevalence and treatment coverage, such as Botswana, it is unknown whether uptake of HIV prevention and treatment interventions can be increased further. We sought to determine whether a community-based intervention to identify and rapidly treat people living with HIV, and support male circumcision could increase population levels of HIV diagnosis, treatment, viral suppression, and male circumcision in Botswana. METHODS: The Ya Tsie Botswana Combination Prevention Project study was a pair-matched cluster-randomised trial done in 30 communities across Botswana done from Oct 30, 2013, to June 30, 2018. 15 communities were randomly assigned to receive HIV prevention and treatment interventions, including enhanced HIV testing, earlier antiretroviral therapy (ART), and strengthened male circumcision services, and 15 received standard of care. The first primary endpoint of HIV incidence has already been reported. In this Article, we report findings for the second primary endpoint of population uptake of HIV prevention services, as measured by proportion of people known to be HIV-positive or tested HIV-negative in the preceding 12 months; proportion of people living with HIV diagnosed and on ART; proportion of people living with HIV on ART with viral suppression; and proportion of HIV-negative men circumcised. A longitudinal cohort of residents aged 16-64 years from a random, approximately 20% sample of households across the 15 communities was enrolled to assess baseline uptake of study outcomes; we also administered an end-of-study survey to all residents not previously enrolled in the longitudinal cohort to provide study end coverage estimates. Differences in intervention uptake over time by randomisation group were tested via paired Student's t test. The study has been completed and is registered with ClinicalTrials.gov (NCT01965470). FINDINGS: In the six communities participating in the end-of-study survey, 2625 residents (n=1304 from standard-of-care communities, n=1321 from intervention communities) were enrolled into the 20% longitudinal cohort at baseline from Oct 30, 2013, to Nov 24, 2015. In the same communities, 10 791 (86%) of 12 489 eligible enumerated residents not previously enrolled in the longitudinal cohort participated in the end-of-study survey from March 30, 2017, to Feb 25, 2018 (5896 in intervention and 4895 in standard-of-care communities). At study end, in intervention communities, 1228 people living with HIV (91% of 1353) were on ART; 1166 people living with HIV (88% of 1321 with available viral load) were virally suppressed, and 673 HIV-negative men (40% of 1673) were circumcised in intervention communities. After accounting for baseline differences, at study end the proportion of people living with HIV who were diagnosed was significantly higher in intervention communities (absolute increase of 9% to 93%) compared with standard-of-care communities (absolute increase of 2% to 88%; prevalence ratio [PR] 1·08 [95% CI 1·02-1·14], p=0·032). Population levels of ART, viral suppression, and male circumcision increased from baseline in both groups, with greater increases in intervention communities (ART PR 1·12 [95% CI 1·07-1·17], p=0·018; viral suppression 1·13 [1·09-1·17], p=0·017; male circumcision 1·26 [1·17-1·35], p=0·029). INTERPRETATION: It is possible to achieve very high population levels of HIV testing and treatment in a high-prevalence setting. Maintaining these coverage levels over the next decade could substantially reduce HIV transmission and potentially eliminate the epidemic in these areas. FUNDING: US President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention.

Self-reported risky sexual practices among adolescents and young adults in Botswana.

BACKGROUND: Adolescents and young adults account for more than one-third of incident Human Immunodeficiency Virus (HIV) infections globally. Understanding sexual practices of this high-risk group is critical in designing HIV targeted prevention programming. OBJECTIVES: To describe self-reported risky sexual practices of adolescents and young adults aged 16-24 years from 30 Botswana communities. METHODS: Cross-sectional, self-reported age at sexual debut; number of sexual partners; condom and alcohol use during sex; intergenerational sex; and transactional sex data were collected. Modified Poisson estimating equations were used to obtain univariate and multivariate-adjusted prevalence ratios (PR) and 95% confidence intervals (CI) comparing engagement in different sexual practices according to gender, accounting for the clustered design of the study. RESULTS: Among the 3380 participants, 2311 reported being sexually active with more females reporting being sexually active compared to males (65% vs. 35%, respectively; p < 0.0001). In univariate analyses, female participants were more likely to report inconsistent condom use (PR 1.61; 95% CI 1.44-1.80), intergenerational sex (PR 9.00; 95% CI 5.84-13.88) and transactional sex (PR 3.46; 95% CI 2.07-5.77) than males, yet less likely to report engaging in sex before age 15 years (PR 0.59; 95% CI: 0.41-0.85), using alcohol around the time of intercourse (PR: 0.59; 95% CI 0.45-0.76) or having ≥ two partners in the last 12 months (PR 0.65; 95% CI 0.57-0.74). CONCLUSIONS: Self-reported risky sexual practices of adolescents and young adults in Botswana differed significantly between males and females. Gender-specific risky sexual practices highlight the importance of developing tailored HIV prevention programming.

High HIV-1 RNA Among Newly Diagnosed People in Botswana.

HIV-1 RNA level is strongly associated with HIV transmission risk. We sought to determine whether HIV-1 RNA level was associated with prior knowledge of HIV status among treatment-naive HIV-infected individuals in Botswana, a country with high rates of antiretroviral treatment (ART) coverage. This information may be helpful in targeting HIV diagnosis and treatment efforts in similar high HIV prevalence settings in a population-based survey. HIV-infected individuals were identified during a household survey performed in 30 communities across Botswana. ART-naive persons with detectable HIV-1 RNA (>400 copies/mL) were divided into two groups, newly diagnosed and individuals tested in the past who knew about their HIV infection at the time of household visit, but had not taken ART. Levels of HIV-1 RNA were compared between groups, overall and by age and gender. Among 815 HIV-infected ART-naive persons with detectable virus, newly diagnosed individuals had higher levels of HIV-1 RNA (n = 490, median HIV-1 RNA 4.35, interquartile range (IQR) 3.79-4.91 log10 copies/mL) than those who knew about their HIV-positive status (n = 325, median HIV-1 RNA 4.10, IQR 3.55-4.68 log10 copies/mL; p values <.001, but p value = .011 after adjusting for age and gender). A nonsignificant trend for higher HIV-1 RNA was found among newly diagnosed men 30 years of age or older (median HIV-1 RNA 4.58, IQR 4.07-5.02 log10 copies/mL vs. 4.17, 3.61-4.71 log10 copies/mL). Newly diagnosed individuals have elevated levels of HIV-1 RNA. This study highlights the need for early diagnosis and treatment of HIV infection for purposes of HIV epidemic control, even in a setting with high ART coverage.

Lack of Virological Suppression Among Young HIV-Positive Adults in Botswana.

BACKGROUND: HIV-1 RNA load is the best biological predictor of HIV transmission and treatment response. The rate of virologic suppression among key subpopulations can guide HIV prevention programs. METHODS: The Botswana Combination Prevention Project performed a population-based household survey among adults in 30 communities in Botswana. Data collected included knowledge of HIV-positive status, antiretroviral therapy (ART) coverage, and virologic suppression (HIV-1 RNA ≤400 copies per milliliter). Individuals aged 16-29 years were considered young adults. RESULTS: Among 552 young people living with HIV enrolled with RNA load data and ART status available, 51% (n = 279) had undetectable HIV-1 RNA, including 54% of young women and 32% of young men [sex prevalence ratio (PR): 0.53; 95% confidence interval (CI): 0.43 to 0.80; P < 0.001]. Compared with older adults (30-64 years old), young HIV-infected adults were significantly less likely to have undetectable HIV-1 RNA (PR: 0.65; 95% CI: 0.59 to 0.70; P < 0.0001), including both men (PR: 0.43; 95% CI: 0.34 to 0.56; P < 0.0001) and women (PR: 0.67; 95% CI: 0.62 to 0.74; P < 0.0001). Among a subset of people living with HIV receiving ART, young adults also were less likely to have undetectable HIV-1 RNA load than older adults (PR: 0.93; 95% CI: 0.90 to 0.95; P = <0.0001). Analysis of the care continuum revealed that inferior HIV diagnosis and suboptimal linkage to care are the primary reasons for low virologic suppression among young adults. CONCLUSIONS: Young adults in Botswana are significantly less likely to have undetectable HIV-1 RNA load compared with older adults. In the era of broad scale-up of ART, interventions able to diagnose young adults living with HIV and link them to effective therapy are urgently needed.

Building Capacity for Data-Driven Decision Making in African HIV Testing Programs: Field Perspectives on Data Use Workshops.

Strategic, high quality HIV testing services (HTS) delivery is an essential step towards reaching the end of AIDS by 2030. We conducted HTS Data Use workshops in five African countries to increase data use for strategic program decision-making. Feedback was collected on the extent to which workshop skills and tools were applied in practice and to identify future capacity-building needs. We later conducted six semistructured phone interviews with workshop planning teams and sent a web-based survey to 92 past participants. The HTS Data Use workshops provided accessible tools that were readily learned by most respondents. While most respondents reported increased confidence in interpreting data and frequency of using such tools over time, planning team representatives indicated ongoing needs for more automated tools that can function across data systems. To achieve ambitious global HIV/AIDS targets, national decision makers may continue to seek tools and skill-building opportunities to monitor programs and identify opportunities to refine strategies.

Ensuring quality: a key consideration in scaling-up HIV-related point-of-care testing programs.

OBJECTIVE: The objective of the WHO/US President's Emergency Plan for AIDS Relief consultation was to discuss innovative strategies, offer guidance, and develop a comprehensive policy framework for implementing quality-assured HIV-related point-of-care testing (POCT). METHODS: The consultation was attended by representatives from international agencies (WHO, UNICEF, UNITAID, Clinton Health Access Initiative), United States Agency for International Development, Centers for Disease Control and Prevention/President's Emergency Plan for AIDS Relief Cooperative Agreement Partners, and experts from more than 25 countries, including policy makers, clinicians, laboratory experts, and program implementers. MAIN OUTCOMES: There was strong consensus among all participants that ensuring access to quality of POCT represents one of the key challenges for the success of HIV prevention, treatment, and care programs. The following four strategies were recommended: implement a newly proposed concept of a sustainable quality assurance cycle that includes careful planning; definition of goals and targets; timely implementation; continuous monitoring; improvements and adjustments, where necessary; and a detailed evaluation; the importance of supporting a cadre of workers [e.g. volunteer quality corps (Q-Corps)] with the role to ensure that the quality assurance cycle is followed and sustained; implementation of the new strategy should be seen as a step-wise process, supported by development of appropriate policies and tools; and joint partnership under the leadership of the ministries of health to ensure sustainability of implementing novel approaches. CONCLUSION: The outcomes of this consultation have been well received by program implementers in the field. The recommendations also laid the groundwork for developing key policy and quality documents for the implementation of HIV-related POCT.

HIV prevention in care and treatment settings: baseline risk behaviors among HIV patients in Kenya, Namibia, and Tanzania.

UNLABELLED: HIV care and treatment settings provide an opportunity to reach people living with HIV/AIDS (PLHIV) with prevention messages and services. Population-based surveys in sub-Saharan Africa have identified HIV risk behaviors among PLHIV, yet data are limited regarding HIV risk behaviors of PLHIV in clinical care. This paper describes the baseline sociodemographic, HIV transmission risk behaviors, and clinical data of a study evaluating an HIV prevention intervention package for HIV care and treatment clinics in Africa. The study was a longitudinal group-randomized trial in 9 intervention clinics and 9 comparison clinics in Kenya, Namibia, and Tanzania (N = 3538). Baseline participants were mostly female, married, had less than a primary education, and were relatively recently diagnosed with HIV. Fifty-two percent of participants had a partner of negative or unknown status, 24% were not using condoms consistently, and 11% reported STI symptoms in the last 6 months. There were differences in demographic and HIV transmission risk variables by country, indicating the need to consider local context in designing studies and using caution when generalizing findings across African countries. Baseline data from this study indicate that participants were often engaging in HIV transmission risk behaviors, which supports the need for prevention with PLHIV (PwP). TRIAL REGISTRATION: ClinicalTrials.gov NCT01256463.