Tuberculosis Preventive Therapy among Persons Living with HIV, Uganda, 2016-2022.

During October 2016-March 2022, Uganda increased tuberculosis (TB) preventive therapy coverage among persons living with HIV from 0.6% to 88.8%. TB notification rates increased from 881.1 to 972.5 per 100,000 persons living with HIV. Timely TB screening, diagnosis, and earlier treatment should remain high priorities for TB/HIV prevention programming.

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.).

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

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Phylogenetic Methods Inconsistently Predict the Direction of HIV Transmission Among Heterosexual Pairs in the HPTN 052 Cohort.

BACKGROUND: We evaluated use of phylogenetic methods to predict the direction of human immunodeficiency virus (HIV) transmission. METHODS: For 33 pairs of HIV-infected patients (hereafter, "index patients") and their partners who acquired genetically linked HIV infection during the study, samples were collected from partners and index patients close to the time when the partner seroconverted (hereafter, "SC samples"); for 31 pairs, samples collected from the index patient at an earlier time point (hereafter, "early index samples") were also available. Phylogenies were inferred using env next-generation sequences (1 tree per pair/subtype). The direction of transmission (DoT) predicted from each tree was classified as correct or incorrect on the basis of which sequences (those from the index patient or the partner) were closest to the root. DoT was also assessed using maximum parsimony to infer ancestral node states for 100 bootstrap trees. RESULTS: DoT was predicted correctly for both single-pair and subtype-specific trees in 22 pairs (67%) by using SC samples and in 23 pairs (74%) by using early index samples. DoT was predicted incorrectly for 4 pairs (15%) by using SC or early index samples. In the bootstrap analysis, DoT was predicted correctly for 18 pairs (55%) by using SC samples and for 24 pairs (73%) by using early index samples. DoT was predicted incorrectly for 7 pairs (21%) by using SC samples and for 4 pairs (13%) by using early index samples. CONCLUSIONS: Phylogenetic methods based solely on the tree topology of HIV env sequences, particularly without consideration of phylogenetic uncertainty, may be insufficient for determining DoT.

Antiretroviral Therapy for the Prevention of HIV-1 Transmission.

BACKGROUND: An interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission. METHODS: We randomly assigned 1763 index participants to receive either early or delayed ART. In the early-ART group, 886 participants started therapy at enrollment (CD4+ count, 350 to 550 cells per cubic millimeter). In the delayed-ART group, 877 participants started therapy after two consecutive CD4+ counts fell below 250 cells per cubic millimeter or if an illness indicative of the acquired immunodeficiency syndrome (i.e., an AIDS-defining illness) developed. The primary study end point was the diagnosis of genetically linked HIV-1 infection in the previously HIV-1-negative partner in an intention-to-treat analysis. RESULTS: Index participants were followed for 10,031 person-years; partners were followed for 8509 person-years. Among partners, 78 HIV-1 infections were observed during the trial (annual incidence, 0.9%; 95% confidence interval [CI], 0.7 to 1.1). Viral-linkage status was determined for 72 (92%) of the partner infections. Of these infections, 46 were linked (3 in the early-ART group and 43 in the delayed-ART group; incidence, 0.5%; 95% CI, 0.4 to 0.7) and 26 were unlinked (14 in the early-ART group and 12 in the delayed-ART group; incidence, 0.3%; 95% CI, 0.2 to 0.4). Early ART was associated with a 93% lower risk of linked partner infection than was delayed ART (hazard ratio, 0.07; 95% CI, 0.02 to 0.22). No linked infections were observed when HIV-1 infection was stably suppressed by ART in the index participant. CONCLUSIONS: The early initiation of ART led to a sustained decrease in genetically linked HIV-1 infections in sexual partners. (Funded by the National Institute of Allergy and Infectious Diseases; HPTN 052 ClinicalTrials.gov number, NCT00074581 .).

Anaemia in HIV-infected pregnant women receiving triple antiretroviral combination therapy for prevention of mother-to-child transmission: a secondary analysis of the Kisumu breastfeeding study (KiBS).

OBJECTIVE: The prevalence of anaemia during pregnancy is estimated to be 35-75% in sub-Saharan Africa and is associated with an increased risk of maternal mortality. We evaluated the frequency and factors associated with anaemia in HIV-infected women undergoing antiretroviral (ARV) therapy for prevention of mother-to-child transmission (PMTCT) enrolled in The Kisumu Breastfeeding Study 2003-2009. METHODS: Maternal haematological parameters were monitored from 32 to 34 weeks of gestation to 2 years post-delivery among 522 enrolled women. Clinical and laboratory assessments for causes of anaemia were performed, and appropriate management was initiated. Anaemia was graded using the National Institutes of Health Division of AIDS 1994 Adult Toxicity Tables. Data were analysed using SAS software, v 9.2. The Wilcoxon two-sample rank test was used to compare groups. A logistic regression model was fitted to describe the trend in anaemia over time. RESULTS: At enrolment, the prevalence of any grade anaemia (Hb < 9.4 g/dl) was 61.8%, but fell during ARV therapy, reaching a nadir (7.4%) by 6 months post-partum. A total of 41 women (8%) developed severe anaemia (Hb < 7 g/dl) during follow-up; 2 (4.9%) were hospitalised for blood transfusion, whereas 3 (7.3%) were transfused while hospitalised (for delivery). The greatest proportion of severe anaemia events occurred around delivery (48.8%; n = 20). Anaemia (Hb ≥ 7 and < 9.4 g/dl) at enrolment was associated with severe anaemia at delivery (OR 5.87; 95% CI: 4.48, 7.68, P < 0.01). Few cases of severe anaemia coincided with clinical malaria (24.4%; n = 10) and helminth (7.3%; n = 3) infections. CONCLUSION: Resolution of anaemia among most participants during study follow-up was likely related to receipt of ARV therapy. Efforts should be geared towards addressing common causes of anaemia in HIV-infected pregnant women, prioritising initiation of ARV therapy and management of peripartum blood loss.

Prevention of HIV-1 infection with early antiretroviral therapy.

BACKGROUND: Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. METHODS: In nine countries, we enrolled 1763 couples in which one partner was HIV-1-positive and the other was HIV-1-negative; 54% of the subjects were from Africa, and 50% of infected partners were men. HIV-1-infected subjects with CD4 counts between 350 and 550 cells per cubic millimeter were randomly assigned in a 1:1 ratio to receive antiretroviral therapy either immediately (early therapy) or after a decline in the CD4 count or the onset of HIV-1-related symptoms (delayed therapy). The primary prevention end point was linked HIV-1 transmission in HIV-1-negative partners. The primary clinical end point was the earliest occurrence of pulmonary tuberculosis, severe bacterial infection, a World Health Organization stage 4 event, or death. RESULTS: As of February 21, 2011, a total of 39 HIV-1 transmissions were observed (incidence rate, 1.2 per 100 person-years; 95% confidence interval [CI], 0.9 to 1.7); of these, 28 were virologically linked to the infected partner (incidence rate, 0.9 per 100 person-years, 95% CI, 0.6 to 1.3). Of the 28 linked transmissions, only 1 occurred in the early-therapy group (hazard ratio, 0.04; 95% CI, 0.01 to 0.27; P<0.001). Subjects receiving early therapy had fewer treatment end points (hazard ratio, 0.59; 95% CI, 0.40 to 0.88; P=0.01). CONCLUSIONS: The early initiation of antiretroviral therapy reduced rates of sexual transmission of HIV-1 and clinical events, indicating both personal and public health benefits from such therapy. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 052 ClinicalTrials.gov number, NCT00074581.).

Pre-exposure prophylaxis (PrEP) knowledge, use, and discontinuation among Lake Victoria fisherfolk in Uganda: a cross-sectional population-based study.

Background: There are limited population-level data on the pre-exposure prophylaxis (PrEP) care continuum in eastern Africa. Here, we assessed the PrEP care continuum following PrEP rollout in a Ugandan community with ~40% HIV seroprevalence. Methods: We used cross-sectional population-based data collected between September 3 and December 19, 2018 from a Lake Victoria fishing community in southern Uganda to measure levels of self-reported PrEP knowledge, ever use, and discontinuation following 2017 PrEP rollout via a U.S. President's Emergency Plan for AIDS Relief (PEPFAR)-supported phased implementation program. Our analysis included HIV-seronegative persons reporting having ever received an HIV test result. We examined associations between demographic, behavioral, and health utilization factors with each outcome using age-adjusted modified Poisson regression. Results: There were 1,401 HIV-seronegative participants, of whom 1,363 (97.3%) reported ever receiving an HIV test result. Median age was 29 years (IQR: 23-36), and 42.3% (n=577) were women. Most (85.5%; n=1,166) participants reported PrEP knowledge, but few (14.5%; n=197) reported ever using PrEP. Among 375 (47.7%) men and 169 (29.3%) women PrEP-eligible at time of survey, 18.9% (n=71) and 27.8% (n=47) reported ever using PrEP, respectively. Over half (52.3%, n=103) of those who had ever used PrEP, self-reported current use. Conclusion: In this Lake Victoria fishing community, there were low levels of PrEP use despite high levels of PrEP awareness and eligibility, particularly among men. Efforts that enhance awareness of HIV risk and increase PrEP accessibility may help increase PrEP use among HIV-seronegative persons in African settings with high HIV burden.

HIV epidemiologic trends among occupational groups in Rakai, Uganda: A population-based longitudinal study, 1999-2016.

Certain occupations have been associated with heightened risk of HIV acquisition and spread in sub-Saharan Africa, including female bar and restaurant work and male transportation work. However, data on changes in population prevalence of HIV infection and HIV incidence within occupations following mass scale-up of African HIV treatment and prevention programs is very limited. We evaluated prospective data collected between 1999 and 2016 from the Rakai Community Cohort Study, a longitudinal population-based study of 15- to 49-year-old persons in Uganda. Adjusted prevalence risk ratios for overall, treated, and untreated, prevalent HIV infection, and incidence rate ratios for HIV incidence with 95% confidence intervals were estimated using Poisson regression to assess changes in HIV outcomes by occupation. Analyses were stratified by gender. There were 33,866 participants, including 19,113 (56%) women. Overall, HIV seroprevalence declined in most occupational subgroups among men, but increased or remained mostly stable among women. In contrast, prevalence of untreated HIV substantially declined between 1999 and 2016 in most occupations, irrespective of gender, including by 70% among men (12.3 to 4.2%; adjPRR = 0.30; 95%CI:0.23-0.41) and by 78% among women (14.7 to 4.0%; adjPRR = 0.22; 95%CI:0.18-0.27) working in agriculture, the most common self-reported primary occupation. Exceptions included men working in transportation. HIV incidence similarly declined in most occupations, but there were no reductions in incidence among female bar and restaurant workers, women working in local crafts, or men working in transportation. In summary, untreated HIV infection and HIV incidence have declined within most occupational groups in Uganda. However, women working in bars/restaurants and local crafts and men working in transportation continue to have a relatively high burden of untreated HIV and HIV incidence, and as such, should be considered priority populations for HIV programming.

Temporal dynamics and drivers of durable HIV viral load suppression and persistent high- and low-level viraemia during Universal Test and Treat scale-up in Uganda: a population-based study.

INTRODUCTION: Population-level data on durable HIV viral load suppression (VLS) following the implementation of Universal Test and Treat (UTT) in Africa are limited. We assessed trends in durable VLS and viraemia among persons living with HIV in 40 Ugandan communities during the UTT scale-up. METHODS: In 2015-2020, we measured VLS (<200 RNA copies/ml) among participants in the Rakai Community Cohort Study, a longitudinal population-based HIV surveillance cohort in southern Uganda. Persons with unsuppressed viral loads were characterized as having low-level (200-999 copies/ml) or high-level (≥1000 copies/ml) viraemia. Individual virologic outcomes were assessed over two consecutive RCCS survey visits (i.e. visit-pairs; ∼18-month visit intervals) and classified as durable VLS (<200 copies/ml at both visits), new/renewed VLS (<200 copies/ml at follow-up only), viral rebound (<200 copies/ml at initial visit only) or persistent viraemia (≥200 copies/ml at both visits). Population prevalence of each outcome was assessed over calendar time. Community-level prevalence and individual-level predictors of persistent high-level viraemia were also assessed using multivariable Poisson regression with generalized estimating equations. RESULTS: Overall, 3080 participants contributed 4604 visit-pairs over three survey rounds. Most visit-pairs (72.4%) exhibited durable VLS, with few (2.5%) experiencing viral rebound. Among those with any viraemia at the initial visit (23.5%, n = 1083), 46.9% remained viraemic through follow-up, 91.3% of which was high-level viraemia. One-fifth (20.8%) of visit-pairs exhibiting persistent high-level viraemia self-reported antiretroviral therapy (ART) use for ≥12 months. Prevalence of persistent high-level viraemia varied substantially across communities and was significantly elevated among young persons aged 15-29 years (vs. 40- to 49-year-olds; adjusted risk ratio [adjRR] = 2.96; 95% confidence interval [95% CI]: 2.21-3.96), males (vs. females; adjRR = 2.40, 95% CI: 1.87-3.07), persons reporting inconsistent condom use with non-marital/casual partners (vs. persons with marital/permanent partners only; adjRR = 1.38, 95% CI: 1.10-1.74) and persons reporting hazardous alcohol use (adjRR = 1.09, 95% CI: 1.03-1.16). The prevalence of persistent high-level viraemia was highest among males <30 years (32.0%). CONCLUSIONS: Following universal ART provision, most persons living with HIV in south-central Uganda are durably suppressed. Among persons exhibiting any viraemia, nearly half exhibited high-level viraemia for ≥12 months and reported higher-risk behaviours associated with onward HIV transmission. Intensified efforts linking individuals to HIV treatment services could accelerate momentum towards HIV epidemic control.

Longitudinal population-level HIV epidemiologic and genomic surveillance highlights growing gender disparity of HIV transmission in Uganda.

HIV incidence in eastern and southern Africa has historically been concentrated among girls and women aged 15-24 years. As new cases decline with HIV interventions, population-level infection dynamics may shift by age and gender. Here, we integrated population-based surveillance of 38,749 participants in the Rakai Community Cohort Study and longitudinal deep-sequence viral phylogenetics to assess how HIV incidence and population groups driving transmission have changed from 2003 to 2018 in Uganda. We observed 1,117 individuals in the incidence cohort and 1,978 individuals in the transmission cohort. HIV viral suppression increased more rapidly in women than men, however incidence declined more slowly in women than men. We found that age-specific transmission flows shifted: whereas HIV transmission to girls and women (aged 15-24 years) from older men declined by about one-third, transmission to women (aged 25-34 years) from men that were 0-6 years older increased by half in 2003 to 2018. Based on changes in transmission flows, we estimated that closing the gender gap in viral suppression could have reduced HIV incidence in women by half in 2018. This study suggests that HIV programmes to increase HIV suppression in men are critical to reduce incidence in women, close gender gaps in infection burden and improve men's health in Africa.

Evaluation of quantification of HIV-1 RNA viral load in plasma and dried blood spots by use of the semiautomated Cobas Amplicor assay and the fully automated Cobas Ampliprep/TaqMan assay, version 2.0, in Kisumu, Kenya.

In Kenya, HIV-1 viral load monitoring is commonly performed with the Cobas Amplicor using plasma specimens. Interest is growing in transitioning to real-time PCR (RT-PCR), such as the Cobas Ampliprep/Cobas TaqMan (CAP/CTM), using dried blood spots (DBS). Before implementation, direct evaluation of the two assays using DBS field specimens is required. This study compares the sensitivity, specificity, negative and positive predictive values (NPV and PPV, respectively), concordance, and agreement between HIV-1 viral load measurements using plasma and DBS specimens obtained from 512 HIV-1-infected pregnant females enrolled in the Kisumu Breastfeeding Study and tested with the Cobas Amplicor and CAP/CTM assays. The sensitivity and NPV of viral load detection in DBS specimens were higher with CAP/CTM (sensitivity, 100%; 95% confidence interval [CI], 99.1 to 100.0%; NPV, 100%; 95% CI, 59.0 to 100.0%) than the Cobas Amplicor (sensitivity, 96.6%; 95% CI, 94.3 to 98.1%; NPV, 58.8%; 95% CI, 40.7 to 75.4%). The PPVs were comparable between both assays when using DBS. The specificity of viral load detection in DBS specimens was lower with CAP/CTM (77.8%; 95% CI, 40.0 to 97.2%) than that of the Cobas Amplicor (95.2%; 95% CI, 76.2 to 99.9%). Good concordance and agreement were observed when paired plasma and DBS specimens were tested with both assays. Lower specificity with the CAP/CTM is likely due to proviral HIV-1 DNA amplification and lower detection limits with RT-PCR. However, the CAP/CTM has better sensitivity and higher throughput than the Cobas Amplicor. These findings suggest that DBS may be a suitable alternative to plasma when using RT-PCR, which could increase access to viral load monitoring in resource-limited settings.

Field evaluation of a broadly sensitive HIV-1 in-house genotyping assay for use with both plasma and dried blood spot specimens in a resource-limited country.

HIV-1 drug resistance (HIVDR) assays are important tools in clinical management of HIV-infected patients on antiretroviral therapy (ART) and surveillance of drug-resistant variants at population levels. The high cost associated with commercial assays hinders their use in resource-limited settings. We adopted and validated a low-cost in-house assay using 68 matched plasma and dried blood spot (DBS) samples with a median viral load (VL) of 58,187 copies/ml, ranging from 253 to 3,264,850 against the commercial assay ViroSeq. Results indicated that the in-house assay not only had a higher plasma genotyping rate than did ViroSeq (94% versus 78%) but also was able to genotype 89.5% (51/57) of the matched DBS samples with VLs of ≥ 1,000 copies/ml. The sensitivity in detecting DR mutations by the in-house assay was 98.29% (95% confidence interval [CI], 97.86 to 98.72) on plasma and 96.54 (95% CI, 95.93 to 97.15) on DBS, and the specificity was 99.97% (95% CI, 99.91 to 100.00) for both sample types compared to ViroSeq. The minor DR mutation differences detected by the in-house assay against ViroSeq did not result in clinical significance. In addition, cost analysis showed that the in-house assay could reduce the genotyping cost by about 60% for both plasma and DBS compared to ViroSeq. This field condition evaluation highlights the potential utility of a cost-effective, subtype-independent, in-house genotyping assay using both plasma and DBS specimens for HIVDR clinical monitoring and population-based surveillance in resource-limited settings.

Men who have sex with men in Kisumu, Kenya: support group membership and knowledge of HIV-risk factors.

Men who have sex with men are an important yet marginalised population for HIV prevention in Africa. We conducted a two-phase study (individual qualitative interviews and a survey) of men who have sex with men, aged 18-34 years of age and living in Kisumu, Kenya. Approximately half (27/51) of survey respondents reported belonging to a support group. The odds of belonging to support groups were greater for older men (aged 24-34 versus 18-23 years [OR = 5.20; 95% CI = 1.27-26.66]). More than two-thirds (68.6%) of survey respondents were categorised as having high knowledge of HIV-risk factors. Most respondents (94.1%) correctly reported lack of condom use during vaginal sex as a risk factor for HIV, but slightly fewer (82.4%) recognised lack of condom use during anal sex as an HIV risk factor. Among the 15 interviewees, the following were included as greatest needs: health information (n = 5), safe lubricants (n = 5), condoms (n = 4), healthcare facility or men-who-have-sex-with-men-friendly health services (n = 3) and advocacy (n = 2). Kenyan men who have sex with men have developed support groups and have unmet needs for information, lubricants and condoms and services. Partnering with support groups offers an opportunity for organisations to reach men who have sex with men with accurate health information, provision of safe sexual lubricants, condoms and other health and social services.

Population-level viremia predicts HIV incidence at the community level across the Universal Testing and Treatment Trials in eastern and southern Africa.

Universal HIV testing and treatment (UTT) strategies aim to optimize population-level benefits of antiretroviral treatment. Between 2012 and 2018, four large community randomized trials were conducted in eastern and southern Africa. While their results were broadly consistent showing decreased population-level viremia reduces HIV incidence, it remains unclear how much HIV incidence can be reduced by increasing suppression among people living with HIV (PLHIV). We conducted a pooled analysis across the four UTT trials. Leveraging data from 105 communities in five countries, we evaluated the linear relationship between i) population-level viremia (prevalence of non-suppression-defined as plasma HIV RNA >500 or >400 copies/mL-among all adults, irrespective of HIV status) and HIV incidence; and ii) prevalence of non-suppression among PLHIV and HIV incidence, using parametric g-computation. HIV prevalence, measured in 257 929 persons, varied from 2 to 41% across the communities; prevalence of non-suppression among PLHIV, measured in 31 377 persons, from 3 to 70%; population-level viremia, derived from HIV prevalence and non-suppression, from < 1% to 25%; and HIV incidence, measured over 345 844 person-years (PY), from 0.03/100PY to 3.46/100PY. Decreases in population-level viremia were strongly associated with decreased HIV incidence in all trials (between 0.45/100PY and 1.88/100PY decline in HIV incidence per 10 percentage points decline in viremia). Decreases in non-suppression among PLHIV were also associated with decreased HIV incidence in all trials (between 0.06/100PY and 0.17/100PY decline in HIV incidence per 10 percentage points decline in non-suppression). Our results support both the utility of population-level viremia as a predictor of incidence, and thus a tool for targeting prevention interventions, and the ability of UTT approaches to reduce HIV incidence by increasing viral suppression. Implementation of universal HIV testing approaches, coupled with interventions to leverage linkage to treatment, adapted to local contexts, can reduce HIV acquisition at population level.

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.

Temporal dynamics and drivers of durable HIV viral load suppression and persistent high- and low-level viremia during Universal Test and Treat scale-up in Uganda: a population-based study.

Introduction: Population-level data on durable HIV viral load suppression (VLS) following implementation of Universal Test and Treat (UTT) in Africa are limited. We assessed trends in durable VLS and viremia among persons living with HIV in 40 Ugandan communities during UTT scale-up. Methods: In 2015-2020, we measured VLS (defined as <200 RNA copies/mL) among participants in the Rakai Community Cohort Study, a longitudinal population-based HIV surveillance cohort in southern Uganda. Persons with unsuppressed viral loads were characterized as having low-level (200-999 copies/mL) or high-level (≥1,000 copies/mL) viremia. Individual virologic outcomes were assessed over two consecutive RCCS survey visits (i.e., visit-pairs; ∼18 month visit intervals) and classified as durable VLS (<200 copies/mL at both visits), new/renewed VLS (<200 copies/mL at follow-up only), viral rebound (<200 copies/mL at initial visit only), or persistent viremia (<200 copies/mL at neither visit). Population prevalence of each outcome was assessed over calendar time. Community-level prevalence and individual-level predictors of persistent high-level viremia were also assessed using multivariable Poisson regression with generalized estimating equations. Results: Overall, 3,080 participants contributed 4,604 visit-pairs over three survey rounds. Most visit-pairs (72.4%) exhibited durable VLS, with few (2.5%) experiencing viral rebound. Among those with viremia at the initial visit ( n =1,083), 46.9% maintained viremia through follow-up, 91.3% of which was high-level viremia. One-fifth (20.8%) of visit-pairs exhibiting persistent high-level viremia self-reported antiretroviral therapy (ART) use for ≥12 months. Prevalence of persistent high-level viremia varied substantially across communities and was significantly elevated among young persons aged 15-29 years (versus 40-49-year-olds; adjusted risk ratio [adjRR]=2.96; 95% confidence interval [95%CI]:2.21-3.96), men (versus women; adjRR=2.40, 95%CI:1.87-3.07), persons reporting inconsistent condom use with non-marital/casual partners (versus persons with marital/permanent partners only; adjRR=1.38, 95%CI:1.10-1.74), and persons exhibiting hazardous alcohol use (adjRR=1.09, 95%CI:1.03-1.16). The prevalence of persistent high-level viremia was highest among men <30 years (32.0%). Conclusions: Following universal ART provision, most persons living with HIV in south-central Uganda are durably suppressed. Among persons exhibiting viremia, nearly half maintain high-level viremia for ≥12 months and report higher-risk behaviors associated with onward HIV transmission. Enhanced linkage to HIV care and optimized treatment retention could accelerate momentum towards HIV epidemic control.

Longitudinal population-level HIV epidemiologic and genomic surveillance highlights growing gender disparity of HIV transmission in Uganda.

HIV incidence in eastern and southern Africa has historically been concentrated among girls and women aged 15-24 years. As new cases decline with HIV interventions, population-level infection dynamics may shift by age and gender. Here, we integrated population-based surveillance of 38,749 participants in the Rakai Community Cohort Study and longitudinal deep sequence viral phylogenetics to assess how HIV incidence and population groups driving transmission have changed from 2003 to 2018 in Uganda. We observed 1,117 individuals in the incidence cohort and 1,978 individuals in the transmission cohort. HIV viral suppression increased more rapidly in women than men, however incidence declined more slowly in women than men. We found that age-specific transmission flows shifted, while HIV transmission to girls and women (aged 15-24 years) from older men declined by about one third, transmission to women (aged 25-34 years) from men that were 0-6 years older increased by half in 2003 to 2018. Based on changes in transmission flows, we estimated that closing the gender gap in viral suppression could have reduced HIV incidence in women by half in 2018. This study suggests that HIV programs to increase HIV suppression in men are critical to reduce incidence in women, close gender gaps in infection burden and improve men's health in Africa.

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.

Investigation of a COVID-19 outbreak at a regional prison, Northern Uganda, September 2020.

Despite implementing measures to prevent introduction of COVID-19 in prisons, a COVID-19 outbreak occurred at Moroto Prison, northern Uganda in September 2020. We investigated factors associated with the introduction and spread of COVID-19 in the prison. A case was PCR-confirmed SARS-CoV-2 infection in a prisoner/staff at Moroto Prison during August-September 2020. We reviewed prison medical records to identify case-patients and interviewed prison and hospital staff to understand possible infection mechanisms for the index case-patient and opportunities for spread. In a retrospective cohort study, we interviewed all prisoners and available staff to identify risk factors. Data were analyzed using log-binomial regression. On September 1, 2020, a recently-hospitalized prisoner with unrecognized SARS-CoV-2 infection was admitted to Moroto Prison quarantine. He had become infected while sharing a hospital ward with a subsequently-diagnosed COVID-19 patient. A sample taken from the hospitalized prisoner on August 20 tested positive on September 3. Mass reactive testing at the prison on September 6, 14, and 15 revealed infection among 202/692 prisoners and 8/90 staff (overall attack rate=27%). One prison staff and one prisoner who cared for the sick prisoner while at the hospital re-entered the main prison without quarantining. Both tested positive on September 6. Food and cleaning service providers also regularly transited between quarantine and unrestricted prison areas. Using facemasks >50% of the time (adjusted risk ratio [aRR]=0.26; 95%CI: 0.13-0.54), or in combination with handwashing after touching surfaces (aRR=0.25; 95%CI: 0.14-0.46) were protective. Prisoners recently transferred from other facilities to Moroto Prison had an increased risk of infection (aRR=1.50; 95%CI: 1.02-2.22). COVID-19 was likely introduced into Moroto Prison quarantine by a prisoner with hospital-acquired infection and delayed test results, and/or by caretakers who were not quarantined after hospital exposures. The outbreak may have amplified via shared food/cleaning service providers who transited between quarantined and non-quarantined prisoners. Facemasks and handwashing were protective. Reduced test turnaround time for the hospitalized prisoner could have averted this outbreak. Testing incoming prisoners for SARS-CoV-2 before quarantine, providing unrestricted soap/water for handwashing, and universal facemask use in prisons could mitigate risk of future outbreaks.