Prevalence and control of hypertension in a high HIV-prevalence setting, insights from a population based study in Botswana.

In a population-based representative sample of adults residing in 22 communities in Botswana, a southern African country with high HIV prevalence, 1 in 4 individuals had high blood pressure. High blood pressure was less prevalent in adults with HIV than without HIV. Sixty percent of persons with high blood pressure had not previously been diagnosed. Among individuals with a prior diagnosis of high blood pressure who reported being prescribed anti-hypertension medications, almost half had elevated blood pressure, irrespective of HIV-status. One-third of adults in this setting (mainly men) declined free non-invasive blood pressure assessments in their households. In conclusion, our study highlights alarmingly high hypertension rates in the community, with low levels of awareness and control, emphasizing the urgent need for community level BP screening and active management to reach recommended targets.

Epidemiological and viral characteristics of undiagnosed HIV infections in Botswana.

BACKGROUND: HIV-1 is endemic in Botswana. The country's primary challenge is identifying people living with HIV who are unaware of their status. We evaluated factors associated with undiagnosed HIV infection using HIV-1 phylogenetic, behavioural, and demographic data. METHODS: As part of the Botswana Combination Prevention Project, 20% of households in 30 villages were tested for HIV and followed from 2013 to 2018. A total of 12,610 participants were enrolled, 3596 tested HIV-positive at enrolment, and 147 participants acquired HIV during the trial. Extensive socio-demographic and behavioural data were collected from participants and next-generation sequences were generated for HIV-positive cases. We compared three groups of participants: (1) those previously known to be HIV-positive at enrolment (n = 2995); (2) those newly diagnosed at enrolment (n = 601) and (3) those who tested HIV-negative at enrolment but tested HIV-positive during follow-up (n = 147). We searched for differences in demographic and behavioural factors between known and newly diagnosed group using logistic regression. We also compared the topology of each group in HIV-1 phylogenies and used a genetic diversity-based algorithm to classify infections as recent (< 1 year) or chronic (≥ 1 year). RESULTS: Being male (aOR = 2.23) and younger than 35 years old (aOR = 8.08) was associated with undiagnosed HIV infection (p < 0.001), as was inconsistent condom use (aOR = 1.76). Women were more likely to have undiagnosed infections if they were married, educated, and tested frequently. For men, being divorced increased their risk. The genetic diversity-based algorithm classified most incident infections as recent (75.0%), but almost none of known infections (2.0%). The estimated proportion of recent infections among new diagnoses was 37.0% (p < 0.001). CONCLUSION: Our results indicate that those with undiagnosed infections are likely to be young men and women who do not use condoms consistently. Among women, several factors were predictive: being married, educated, and testing frequently increased risk. Men at risk were more difficult to delineate. A sizeable proportion of undiagnosed infections were recent based on a genetic diversity-based classifier. In the era of "test and treat all", pre-exposure prophylaxis may be prioritized towards individuals who self-identify or who can be identified using these predictors in order to halt onward transmission in time.

Health Impact and Cost-Effectiveness of HIV Testing, Linkage, and Early Antiretroviral Treatment in the Botswana Combination Prevention Project.

BACKGROUND: The Botswana Combination Prevention Project tested the impact of combination prevention (CP) on HIV incidence in a community-randomized trial. Each trial arm had ∼55,000 people, 26% HIV prevalence, and 72% baseline ART coverage. Results showed intensive testing and linkage campaigns, expanded antiretroviral treatment (ART), and voluntary male medical circumcision referrals increased coverage and decreased incidence over ∼29 months of follow-up. We projected lifetime clinical impact and cost-effectiveness of CP in this population. SETTING: Rural and periurban communities in Botswana. METHODS: We used the Cost-Effectiveness of Preventing AIDS Complications model to estimate lifetime health impact and cost of (1) earlier ART initiation and (2) averting an HIV infection, which we applied to incremental ART initiations and averted infections calculated from trial data. We determined the incremental cost-effectiveness ratio [US$/quality-adjusted life-years (QALY)] for CP vs. standard of care. RESULTS: In CP, 1418 additional people with HIV initiated ART and an additional 304 infections were averted. For each additional person started on ART, life expectancy increased 0.90 QALYs and care costs increased by $869. For each infection averted, life expectancy increased 2.43 QALYs with $9200 in care costs saved. With CP, an additional $1.7 million were spent on prevention and $1.2 million on earlier treatment. These costs were mostly offset by decreased care costs from averted infections, resulting in an incremental cost-effectiveness ratio of $79 per QALY. CONCLUSIONS: Enhanced HIV testing, linkage, and early ART initiation improve life expectancy, reduce transmission, and can be cost-effective or cost-saving in settings like Botswana.

Efficient estimation of human immunodeficiency virus incidence rate using a pooled cross-sectional cohort study design.

Development of methods to accurately estimate human immunodeficiency virus (HIV) incidence rate remains a challenge. Ideally, one would follow a random sample of HIV-negative individuals under a longitudinal study design and identify incident cases as they arise. Such designs can be prohibitively resource intensive and therefore alternative designs may be preferable. We propose such a simple, less resource-intensive study design and develop a weighted log likelihood approach which simultaneously accounts for selection bias and outcome misclassification error. The design is based on a cross-sectional survey which queries individuals' time since last HIV-negative test, validates their test results with formal documentation whenever possible, and tests all persons who do not have documentation of being HIV-positive. To gain efficiency, we update the weighted log likelihood function with potentially misclassified self-reports from individuals who could not produce documentation of a prior HIV-negative test and investigate large sample properties of validated sub-sample only versus pooled sample estimators through extensive Monte Carlo simulations. We illustrate our method by estimating incidence rate for individuals who tested HIV-negative within 1.5 and 5 years prior to Botswana Combination Prevention Project enrolment. This article establishes that accurate estimates of HIV incidence rate can be obtained from individuals' history of testing in a cross-sectional cohort study design by appropriately accounting for selection bias and misclassification error. Moreover, this approach is notably less resource-intensive compared to longitudinal and laboratory-based methods.

Implementation of Universal HIV Testing and Treatment to Reduce HIV Incidence in Botswana: the Ya Tsie Study.

PURPOSE OF REVIEW: Antiretroviral treatment (ART) can dramatically reduce the risk of HIV transmission, but the feasibility of scaling up HIV testing, linkage and treatment to very high population levels, and its impact on population HIV incidence, were unknown. We review key findings from a community-randomized trial in which we evaluated the impact of "universal test and treat" (UTT) on population HIV incidence in Botswana, a resource-constrained country with both high HIV prevalence and high ART coverage before study inception. RECENT FINDINGS: We conducted a community-randomized trial (the "Ya Tsie" trial or Botswana Combination Prevention Project (BCPP)) in 30 villages in Botswana from 2013 to 2018, with the goal of determining whether a combination of prevention interventions-with a focus on universal HIV testing and treatment-would reduce population-level HIV incidence. The intervention included universal HIV testing (home-based and mobile), active linkage to HIV care and treatment with patient tracing for persons not linking, universal ART coverage, rapid ART start (at the first clinic visit), and enhanced male circumcision services. Botswana had very high HIV diagnosis, treatment, and viral suppression levels (approaching the UNAIDS "90-90-90" targets) prior to intervention roll-out. By study end, we were able to exceed the overall 95-95-95 coverage target of 86%: an estimated 88% of all persons living with HIV were on ART and had viral suppression in the Ya Tsie intervention arm. In addition, annual HIV incidence was 30% lower in the intervention arm as compared with the control arm over a 29-month follow-up period. With universal HIV testing and relatively simple linkage activities, it was possible to achieve one of the highest reported population levels of HIV diagnosis, linkage to care, and viral suppression globally and to reduce population HIV incidence by about one-third over a short period of time (< 3 years). We were able to significantly increase population viral suppression and to decrease HIV incidence even in a resource-constrained setting with pre-existing very high testing and treatment coverage. Universal community-based HIV testing and tracing of individuals through the HIV care cascade were key intervention components.

Mapping of HIV-1C Transmission Networks Reveals Extensive Spread of Viral Lineages Across Villages in Botswana Treatment-as-Prevention Trial.

BACKGROUND: Phylogenetic mapping of HIV-1 lineages circulating across defined geographical locations is promising for better understanding HIV transmission networks to design optimal prevention interventions. METHODS: We obtained near full-length HIV-1 genome sequences from people living with HIV (PLWH), including participants on antiretroviral treatment in the Botswana Combination Prevention Project, conducted in 30 Botswana communities in 2013-2018. Phylogenetic relationships among viral sequences were estimated by maximum likelihood. RESULTS: We obtained 6078 near full-length HIV-1C genome sequences from 6075 PLWH. We identified 984 phylogenetically distinct HIV-1 lineages (molecular HIV clusters) circulating in Botswana by mid-2018, with 2-27 members per cluster. Of these, dyads accounted for 62%, approximately 32% (n = 316) were found in single communities, and 68% (n = 668) were spread across multiple communities. Men in clusters were approximately 3 years older than women (median age 42 years, vs 39 years; P < .0001). In 65% of clusters, men were older than women, while in 35% of clusters women were older than men. The majority of identified viral lineages were spread across multiple communities. CONCLUSIONS: A large number of circulating phylogenetically distinct HIV-1C lineages (molecular HIV clusters) suggests highly diversified HIV transmission networks across Botswana communities by 2018.

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.

Sexual function after voluntary medical male circumcision for human immunodeficiency virus prevention: Results from a programmatic delivery setting in Botswana.

BACKGROUND: Uptake of voluntary medical male circumcision (VMMC) remains modest in Botswana in spite of the government's commitment and service provision availability. Data on sexual function post-VMMC in programmatic settings could help guide messaging tailored to Botswana. OBJECTIVES: At 3-month post-VMMC, we evaluated changes in sexual function and satisfaction with the VMMC procedure amongst a cohort of HIV-negative, sexually active men aged 18-49 years who underwent VMMC in a public-sector clinic in Botswana. METHODS: We assessed whether each of the following domains of sexual function had improved, stayed the same or worsened since VMMC: sexual desire, ability to use condoms, ease of vaginal penetration, ease of ejaculation, ability to achieve and maintain an erection and hygiene or cleanliness. RESULTS: Data on sexual function were available for 378 men at 3-month post-VMMC. Median age was 27 years - 54% had a higher than secondary education, 72% were employed and 27% were married. Nearly all (96%) the men reported improvement in at least one domain of sexual function, while 19% reported improvement in all six domains. One-fourth (91/378, 24%) of the men reported that at least one domain of sexual function worsened post-VMMC. The most frequently reported domain that worsened was sexual desire (11%); in all other domains, < 10% of the men reported worsening. Men who reported any worsening sexual function were 2.3-fold as likely to be less than 'very satisfied' with the VMMC procedure (risk ratio 2.36, 95% confidence interval [CI] 1.66-3.34, p < 0.001). CONCLUSION: Emphasising improved sexual function experienced after VMMC in demand-creation efforts could potentially increase VMMC uptake in Botswana.

Voluntary Medical Male Circumcision and Perceived Sexual Functioning, Satisfaction, and Risk Behavior: A Qualitative Study in Botswana.

This article examines perceptions of sexual functioning, satisfaction, and risk-taking related to voluntary medical male circumcision (VMMC) in Botswana. Twenty-seven focus group discussions were conducted in four purposively selected communities with community leaders, men, and women. Discussions were analyzed using an inductive content analytic approach. Perceptions of VMMC's impact on sexual functioning and satisfaction varied. Increased satisfaction was attributed to improved penile health and increased ejaculatory latency time, whereas decreased satisfaction was attributed to erectile dysfunction and increased vaginal irritation during sex. Most participants thought sexual disinhibition occurred after circumcision; nevertheless, some women said they used male circumcision status as a marker of HIV status, thereby influencing sexual decision-making and partner selection. Messaging should emphasize that VMMC does not afford complete HIV protection. Optimizing VMMC's impact requires increasing uptake while minimizing behavioral disinhibition, with a balance between potential messaging of improved sexual functioning and satisfaction and the potential impact on sexual disinhibition.

Sexual risk compensation following voluntary medical male circumcision: Results from a prospective cohort study amongst human immunodeficiency virus-negative adult men in Botswana.

BACKGROUND: Circumcised men may increase sexual risk-taking following voluntary medical male circumcision (VMMC) because of decreased perceptions of risk, which may negate the beneficial impact of VMMC in preventing new human immunodeficiency virus (HIV) infections. OBJECTIVES: We evaluated changes in sexual behaviour following VMMC. METHOD: We conducted a prospective cohort study amongst sexually active, HIV-negative adult men undergoing VMMC in Gaborone, Botswana, during 2013-2015. Risky sexual behaviour, defined as the number of sexual partners in the previous month and ≥ 1 concurrent sexual partnerships during the previous 3 months, was assessed at baseline (prior to VMMC) and 3 months post-VMMC. Change over time was assessed by using inverse probability weighted linear and conditional logistic regression models. RESULTS: We enrolled 523 men; 509 (97%) provided sexual behaviour information at baseline. At 3 months post-VMMC, 368 (72%) completed the follow-up questionnaire. At baseline, the mean (95% confidence interval) number of sexual partners was 1.60 (1.48, 1.65), and 111 (31% of 353 with data) men reported engaging in concurrent partnerships. At 3 months post-VMMC, 70 (23% of 311 with data) reported fewer partners and 19% had more partners. Amongst 111 men with a concurrent partnership at baseline, 52% reported none post-VMMC. Amongst the 242 (69%) without a concurrent partnership at baseline, 19% reported initiating one post-VMMC. After adjustment for loss to follow-up, risky sexual behaviour post-VMMC (measured as mean changes in a number of partners and proportion engaging in concurrency) was similar to baseline levels. CONCLUSION: We found no evidence of sexual risk compensation in the 3 months following VMMC.

Universal Testing, Expanded Treatment, and Incidence of HIV Infection in Botswana.

BACKGROUND: The feasibility of reducing the population-level incidence of human immunodeficiency virus (HIV) infection by increasing community coverage of antiretroviral therapy (ART) and male circumcision is unknown. METHODS: We conducted a pair-matched, community-randomized trial in 30 rural or periurban communities in Botswana from 2013 to 2018. Participants in 15 villages in the intervention group received HIV testing and counseling, linkage to care, ART (started at a higher CD4 count than in standard care), and increased access to male circumcision services. The standard-care group also consisted of 15 villages. Universal ART became available in both groups in mid-2016. We enrolled a random sample of participants from approximately 20% of households in each community and measured the incidence of HIV infection through testing performed approximately once per year. The prespecified primary analysis was a permutation test of HIV incidence ratios. Pair-stratified Cox models were used to calculate 95% confidence intervals. RESULTS: Of 12,610 enrollees (81% of eligible household members), 29% were HIV-positive. Of the 8974 HIV-negative persons (4487 per group), 95% were retested for HIV infection over a median of 29 months. A total of 57 participants in the intervention group and 90 participants in the standard-care group acquired HIV infection (annualized HIV incidence, 0.59% and 0.92%, respectively). The unadjusted HIV incidence ratio in the intervention group as compared with the standard-care group was 0.69 (P = 0.09) by permutation test (95% confidence interval [CI], 0.46 to 0.90 by pair-stratified Cox model). An end-of-trial survey in six communities (three per group) showed a significantly greater increase in the percentage of HIV-positive participants with an HIV-1 RNA level of 400 copies per milliliter or less in the intervention group (18 percentage points, from 70% to 88%) than in the standard-care group (8 percentage points, from 75% to 83%) (relative risk, 1.12; 95% CI, 1.09 to 1.16). The percentage of men who underwent circumcision increased by 10 percentage points in the intervention group and 2 percentage points in the standard-care group (relative risk, 1.26; 95% CI, 1.17 to 1.35). CONCLUSIONS: Expanded HIV testing, linkage to care, and ART coverage were associated with increased population viral suppression. (Funded by the President's Emergency Plan for AIDS Relief and others; Ya Tsie ClinicalTrials.gov number, NCT01965470.).

Methodological Challenges When Studying Distance to Care as an Exposure in Health Research.

Distance to care is a common exposure and proposed instrumental variable in health research, but it is vulnerable to violations of fundamental identifiability conditions for causal inference. We used data collected from the Botswana Birth Outcomes Surveillance study between 2014 and 2016 to outline 4 challenges and potential biases when using distance to care as an exposure and as a proposed instrument: selection bias, unmeasured confounding, lack of sufficiently well-defined interventions, and measurement error. We describe how these issues can arise, and we propose sensitivity analyses for estimating the degree of bias.

Low rates of nucleoside reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor drug resistance in Botswana.

BACKGROUND: Scale-up of antiretroviral therapy (ART) and introduction of treat-all strategy necessitates population-level monitoring of acquired HIV drug resistance (ADR) and pretreatment drug resistance (PDR) mutations. METHODS: Blood samples were collected from 4973 HIV-positive individuals residing in 30 communities across Botswana who participated in the Botswana Combination Prevention Project (BCPP) in 2013-2018. HIV sequences were obtained by long-range HIV genotyping. Major drug-resistance mutations (DRMs) and surveillance drug resistance mutations (SDRMs) associated with nucleoside reverse transcriptase inhibitors (NRTI) and nonnucleoside reverse transcriptase inhibitors (NNRTI) were analyzed according to the Stanford University HIV Drug Resistance Database. Viral sequences were screened for G-to-A hypermutations. A threshold of 2% was used for hypermutation adjustment. Viral suppression was considered at HIV-1 RNA load ≤400 copies/ml. RESULTS: Among 4973 participants with HIV-1C sequences, ART data were available for 4927 (99%) including 3858 (78%) on ART. Among those on ART, 3435 had viral load data and 3297 (96%) were virologically suppressed. Among 1069 (22%) HIV-infected individuals not on ART, we found NRTI-associated and NNRTI-associated SDRMs were found in 1.5% (95% confidence interval [CI] 1.0-2.5%) and 2.9% (95% CI 2.0-4.2%), respectively. Of the 138 (4%) of individuals who had detectable HIV-1 RNA, we found NRTI-associated and NNRTI-associated drug resistance mutations in 16% (95% CI 10-25%) and 33% (95% CI 25-42%), respectively. CONCLUSION: We found a low prevalence of NRTI-associated and NNRTI-associated PDR-resistance mutations among residents of rural and peri-urban communities across Botswana. However, individuals on ART with detectable virus had ADR NRTI and NNRTI mutations above 15%.

Immediate Motivators to Seeking Voluntary Medical Male Circumcision Among HIV-Negative Adult Men in an Urban Setting in Botswana.

Randomized trials have shown that voluntary medical male circumcision (VMMC) significantly reduces HIV acquisition risk in men. We sought to identify subpopulations of Botswanan men with high levels of VMMC uptake by comparing an observational cohort of men presenting for circumcision services at two high-volume clinics in Botswana's capital city, Gabo-rone, with a matched, population-based random sample of uncircumcised men. Among these high uptake VMMC subpopulations, we then examined the immediate factors that play a role in men's decision to seek VMMC services. As compared to their population-based controls, men choosing to undergo circumcision were more likely to be ages 24-34, more highly educated, to have a religious affiliation, and in a serious relationship. Our results suggest that married men and highly educated men were more likely to pursue circumcision for personal hygiene reasons. These findings have direct implications for targeted demand creation and mobilization activities to increase VMMC uptake in Botswana.

Cross-sectional estimates revealed high HIV incidence in Botswana rural communities in the era of successful ART scale-up in 2013-2015.

BACKGROUND: Botswana is close to reaching the UNAIDS "90-90-90" HIV testing, antiretroviral treatment (ART), and viral suppression goals. We sought to determine HIV incidence in this setting with both high HIV prevalence and high ART coverage. METHODS: We used a cross-sectional approach to assessing HIV incidence. A random, population-based sample of adults age 16-64 years was enrolled in 30 rural and peri-urban communities as part of the Botswana Combination Prevention Project (BCPP), from October 2013 -November 2015. Data and samples from the baseline household survey were used to estimate cross-sectional HIV incidence, following an algorithm that combined Limiting-Antigen Avidity Assay (LAg-Avidity EIA), ART status (documented or by testing ARV drugs in plasma) and HIV-1 RNA load. The LAg-Avidity EIA cut-off normalized optical density (ODn) was set at 1.5. The HIV-1 RNA cut-off was set at 400 copies/mL. For estimation purposes, the Mean Duration of Recent Infection was 130 days and the False Recent Rate (FRR) was evaluated at values of either 0 or 0.39%. RESULTS: Among 12,610 individuals participating in the baseline household survey, HIV status was available for 12,570 participants and 3,596 of them were HIV positive. LAg-Avidity EIA data was generated for 3,581 (99.6%) of HIV-positive participants. Of 326 participants with ODn ≤1.5, 278 individuals were receiving ART verified through documentation and were considered to represent longstanding HIV infections. Among the remaining 48 participants who reported no use of ART, 14 had an HIV-1 RNA load ≤400 copies/mL (including 3 participants with ARVs in plasma) and were excluded, as potential elite/viremic controllers or undisclosed ART. Thus, 34 LAg-Avidity-EIA-recent, ARV-naïve individuals with detectable HIV-1 RNA (>400 copies/mL) were classified as individuals with recent HIV infections. The annualized HIV incidence among 16-64 year old adults was estimated at 1.06% (95% CI 0.68-1.45%) with zero FRR, and at 0.64% (95% CI 0.24-1.04%) using a previously defined FRR of 0.39%. Within a subset of younger individuals 16-49 years old, the annualized HIV incidence was estimated at 1.29% (95% CI 0.82-1.77%) with zero FRR, and at 0.90% (95% CI 0.42-1.38%) with FRR set to 0.39%. CONCLUSIONS: Using a cross-sectional estimate of HIV incidence from 2013-2015, we found that at the time of near achievement of the UNAIDS 90-90-90 targets, ~1% of adults (age 16-64 years) in Botswana's rural and peri-urban communities became HIV infected annually.

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.

Undisclosed antiretroviral drug use in Botswana: implication for national estimates.

: Among 3596 HIV-positive participants enrolled in the Botswana Combination Prevention Project who self-reported no prior antiretroviral (ARV) therapy use and were tested for viral load (n = 951; 27% of all participants), 136 (14%) had HIV-1 RNA less than 400 copies/ml. ARV drugs were detected in 52 (39%) of 134 participants tested. Adjusting for undisclosed ARV use increased the overall estimate of virally suppressed individuals on ARV therapy by 1.4% from 70.2 to 71.6%.

Implementation of Instrumental Variable Bounds for Data Missing Not at Random.

Instrumental variables are routinely used to recover a consistent estimator of an exposure causal effect in the presence of unmeasured confounding. Instrumental variable approaches to account for nonignorable missing data also exist but are less familiar to epidemiologists. Like instrumental variables for exposure causal effects, instrumental variables for missing data rely on exclusion restriction and instrumental variable relevance assumptions. Yet these two conditions alone are insufficient for point identification. For estimation, researchers have invoked a third assumption, typically involving fairly restrictive parametric constraints. Inferences can be sensitive to these parametric assumptions, which are typically not empirically testable. The purpose of our article is to discuss another approach for leveraging a valid instrumental variable. Although the approach is insufficient for nonparametric identification, it can nonetheless provide informative inferences about the presence, direction, and magnitude of selection bias, without invoking a third untestable parametric assumption. An important contribution of this article is an Excel spreadsheet tool that can be used to obtain empirical evidence of selection bias and calculate bounds and corresponding Bayesian 95% credible intervals for a nonidentifiable population proportion. For illustrative purposes, we used the spreadsheet tool to analyze HIV prevalence data collected by the 2007 Zambia Demographic and Health Survey (DHS).