Incidence of Health Facility Switching and Associations With HIV Viral Rebound Among Persons on Antiretroviral Therapy in Uganda: A Population-based Study.

BACKGROUND: A substantial proportion of persons on antiretroviral therapy (ART) considered lost to follow-up have actually transferred their human immunodeficiency virus (HIV) care to other facilities. However, the relationship between facility switching and virologic outcomes, including viral rebound, is poorly understood. METHODS: We used data from 40 communities (2015-2020) in the Rakai Community Cohort Study to estimate incidence of facility switching and viral rebound. Persons aged 15-49 years with serologically confirmed HIV who self-reported ART use and contributed ≥1 follow-up visit were included. Facility switching and virologic outcomes were assessed between 2 consecutive study visits (ie, index and follow-up visits, interval of approximately 18 months). Those who reported different HIV treatment facilities between index and follow-up study visits were classified as having switched facilities. Virologic outcomes included viral rebound among individuals initially suppressed (<200 copies/mL). Multivariable Poisson regression was used to estimate associations between facility switching and viral rebound. RESULTS: Overall, 2257 persons who self-reported ART use (median age, 35 years; 65% female, 92% initially suppressed) contributed 3335 visit-pairs and 5959 person-years to the analysis. Facility switching was common (4.8 per 100 person-years; 95% confidence interval [CI], 4.2-5.5) and most pronounced in persons aged <30 years and fishing community residents. Among persons suppressed at their index visit (n = 2076), incidence of viral rebound was more than twice as high in persons who switched facilities (adjusted incidence rate ratio = 2.27; 95% CI, 1.16-4.45). CONCLUSIONS: Facility switching was common and associated with viral rebound among persons initially suppressed. Investments in more agile, person-centered models for mobile clients are needed to address system inefficiencies and bottlenecks that can disrupt HIV care continuity.

Inferring HIV transmission patterns from viral deep-sequence data via latent typed point processes.

Viral deep-sequencing data play a crucial role toward understanding disease transmission network flows, providing higher resolution compared to standard Sanger sequencing. To more fully utilize these rich data and account for the uncertainties in outcomes from phylogenetic analyses, we propose a spatial Poisson process model to uncover human immunodeficiency virus (HIV) transmission flow patterns at the population level. We represent pairings of individuals with viral sequence data as typed points, with coordinates representing covariates such as gender and age and point types representing the unobserved transmission statuses (linkage and direction). Points are associated with observed scores on the strength of evidence for each transmission status that are obtained through standard deep-sequence phylogenetic analysis. Our method is able to jointly infer the latent transmission statuses for all pairings and the transmission flow surface on the source-recipient covariate space. In contrast to existing methods, our framework does not require preclassification of the transmission statuses of data points, and instead learns them probabilistically through a fully Bayesian inference scheme. By directly modeling continuous spatial processes with smooth densities, our method enjoys significant computational advantages compared to previous methods that rely on discretization of the covariate space. We demonstrate that our framework can capture age structures in HIV transmission at high resolution, bringing valuable insights in a case study on viral deep-sequencing data from Southern Uganda.

Willingness to receive COVID-19 vaccines, associated factors and reasons for not taking a vaccine: a cross sectional study among persons aged 13-80 years in Wakiso, Central Uganda.

BACKGROUND: Vaccination has been recommended as one of the approaches for the control of COVID-19 pandemic. However, adequate vaccine coverage is critical to the effectiveness of the vaccine at population level. Data on acceptability of the vaccine in Ugandan urban areas are limited. This study examined the prevalence, factors associated with willingness to accept COVID-19 vaccine including reasons for not taking COVID-19 vaccine in a predominantly urban population of Wakiso, central Uganda. METHODS: Data were obtained from a cross-sectional study conducted between March 1st, 2021 and September 30th, 2021 in the urban population-based cohort of the Africa Medical and behavioral Sciences Organization (AMBSO). A Multivariable modified Poisson regression analysis was used to estimate adjusted prevalence ratios (aPR) and 95% confidence intervals of willingness to accept the COVID-19 vaccine. RESULTS: A total of 1,903 participants were enrolled in this study; 61% of whom were females. About 63% of participants indicated their willingness to accept the COVID-19 vaccine. Persons aged 13-19 years (aPR = 0.79; [95% CI: 0.74, 0.84]) or 20-29years (aPR = 0.93; [95% CI: 0.88, 0.98]) were less likely to accept the vaccine compared to persons aged 40-49 years. Persons with post-primary level of education (aPR = 1.05; [95% CI: 1.02, 1.09]) were more likely to accept the vaccine compared to persons with primary level of education. Additionally, students or individuals working in government (aPR = 1.13; [95% CI: 1.04, 1.23]) were more likely to accept the vaccine compared to individuals doing construction and Mechanic work as their main occupation. Reported reasons for not taking a COVID-19 vaccine included; concerns about side effects of the vaccine 154(57.0%), 64(23.7%) did not think the vaccines were effective, while 32(11.9%) did not like the vaccines. CONCLUSION: A substantial proportion of individuals were not willing to accept the COVID-19 vaccine. Health education campaigns on vaccination within urban communities could help reduce COVID-19 vaccine misconceptions in the urban populations more especially the young and persons with low levels of formal education.

Age Patterns of HSV-2 Incidence and Prevalence in Two Ugandan Communities: A Catalytic Incidence Model Applied to Population-Based Seroprevalence Data.

BACKGROUND: Herpes simplex virus type 2 (HSV-2) is an incurable sexually transmitted infection associated with increased risk of acquiring and transmitting human immunodeficiency virus (HIV). HSV-2 is highly prevalent in sub-Saharan Africa, but population-level estimates of incidence are sparse. METHODS: We measured HSV-2 prevalence from cross-sectional serological data among adults aged 18-49 years in 2 south-central Uganda communities (fishing, inland). We identified risk factors for seropositivity, then inferred age patterns of HSV-2 with a Bayesian catalytic model. RESULTS: HSV-2 prevalence was 53.6% (n = 975/1819; 95% confidence interval, 51.3%-55.9%). Prevalence increased with age, was higher in the fishing community, and among women, reaching 93.6% (95% credible interval, 90.2%-96.6%) by age 49 years. Factors associated with HSV-2 seropositivity included more lifetime sexual partners, HIV positive status, and lower education. HSV-2 incidence peakied at age 18 years for women and 19-20 years for men. HIV prevalence was up to 10-fold higher in HSV-2-positive individuals. CONCLUSIONS: HSV-2 prevalence and incidence were extremely high, with most infections occurring in late adolescence. Interventions against HSV-2, such as future vaccines or therapeutics, must target young populations. Remarkably higher HIV prevalence among HSV-2-positive individuals underscores this population as a priority for HIV prevention.

Costing of HIV services, Uganda and United Republic of Tanzania.

Objective: To evaluate resource allocation and costs associated with delivery of human immunodeficiency virus (HIV) services in Uganda and the United Republic of Tanzania. Methods: We used time-driven activity-based costing to determine the resources consumed and costs of providing five HIV services in Uganda and the United Republic of Tanzania: antiretroviral therapy (ART); HIV testing and counselling; prevention of mother-to-child transmission; voluntary male medical circumcision; and pre-exposure prophylaxis. Findings: Country-based teams undertook time-driven activity-based costing with 1119 adults in Uganda and 886 adults in the United Republic of Tanzania. In Uganda, service delivery costs ranged from 8.18 United States dollars (US$) per visit for HIV testing and counselling to US$ 43.43 for ART (for clients in whom HIV was suppressed). In the United Republic of Tanzania, these costs ranged from US$ 3.67 per visit for HIV testing and counselling to US$ 28.00 for voluntary male medical circumcision. In both countries, consumables were the main cost driver, accounting for more than 60% of expenditure. Process maps showed that in both countries, registration, measurement of vital signs, consultation and medication dispensing were the steps that occurred most frequently for ART clients. Conclusion: Establishing a rigorous, longitudinal system for tracking investments in HIV services that includes thousands of clients and numerous facilities is achievable in different settings with a high HIV burden. Consistent engagement of implementation partners and standardized training and data collection instruments proved essential for the success of these exercises.

In the era of universal test and treat in Uganda, recent intimate partner violence is not associated with subsequent ART use or viral suppression.

Intimate partner violence (IPV) has been associated with delays throughout the HIV care continuum. This study explored prospective associations between experiences of past-year IPV and two HIV care outcomes in the context of current universal test and treat guidelines using two consecutive rounds of an ongoing HIV surveillance study conducted in the Rakai region of Uganda. Longitudinal logistic regression models examined associations between IPV, use of antiretroviral therapy (ART) and viral load suppression (VS), adjusting for outcome variables at baseline. To address differences in ART retention by IPV, propensity scores were used to create inverse-probability-of-treatment-and-censoring-weighted (IPTCW) models. At baseline, of 1923 women with HIV (WWH), 34.6%, 26.5%, 13.5% reported past-year verbal, physical and sexual IPV; a lower proportion of persons who experienced physical IPV (79.4%) were VS than those who did not (84.3%; p = 0.01). The proportion VS at baseline also significantly differed by exposure to verbal IPV (p = 0.03). However, in adjusted longitudinal models, IPV was not associated with lower odds of ART use or VS at follow-up. Among WWH in the Rakai region, IPV does not appear to be a barrier to subsequent ART use or VS. However, given the prevalence of IPV in this population, interventions are needed.

Diagnostic and pre-treatment intervals among patients with cervical cancer attending care at the Uganda Cancer Institute: a cross-sectional study.

BACKGROUND: Majority of patients with cervical cancer in the low- and middle-income countries experience long diagnostic and pre-treatment intervals. This study sought to determine the factors associated with the diagnostic and pre-treatment intervals among patients with cervical cancer. METHODS: This was a cross-sectional study conducted at the Uganda Cancer Institute (UCI) during October 2019 to January 2020. Patients aged ≥ 18 years with histological diagnosis of cervical cancer were consecutively sampled. Data were collected using a pre-tested semi-structured questionnaire and a data abstraction form. Diagnostic intervals, defined as the time between first visit of a patient to a primary healthcare provider to time of getting confirmed diagnosis, of ≤ 3 months was defined as early & >3 months as late. Pre-treatment intervals, which is the time from histological diagnosis to starting cancer chemo-radiotherapy of ≤ 1 month was defined as early and > 1 month as late. Data were analysed using STATA version 14.0. We used modified Poisson regression models with robust variance to determine socio-demographic and clinical factors associated with the intervals. RESULTS: The mean age of the participants was 50.0 ± 11.7 years. The median diagnostic and pre-treatment intervals were 3.1 (IQR: 1.4-8.2) months and 2.4 (IQR: 1.2-4.1) months respectively. Half of the participants, 49.6% (200/403) were diagnosed early; one in 5 patients, 20.1% (81/403) promptly (within one month) initiated cancer chemo-radiotherapy. Participants more likely to be diagnosed early included those referred from district hospitals (level 5) (aPR = 2.29; 95%CI: 1.60-3.26) and with squamous cell carcinomas (aPR = 1.55; 95%CI: 1.07-2.23). Participants more likely to be diagnosed late included those who first discussed their symptoms with relatives, (aPR = 0.77; 95%CI: (0.60-0.98), had > 2 pre-referral visits (aPR = 0.75; 95%CI (0.61-0.92), and had advanced stage (stages 3 or 4) (aPR = 0.68; 95%CI: 0.55-0.85). Participants more likely to initiate cancer chemo-radiotherapy early included older patients (≥ 60 years) (aPR = 2.44; 95%CI: 1.18-5.03). Patients likely to start treatment late were those who had ≥2 pre-referral visits  (aPR = 0.63; 95%CI: 0.41-0.98) and those that took 3 - 6 months with symptoms before seeking healthcare (aPR = 0.52;95%CI: 0.29 - 0.95). CONCLUSION: Interventions to promote prompt health-seeking and early diagnosis of cervical cancer need to target primary healthcare facilities and aim to enhance capacity of primary healthcare professionals to promptly initiate diagnostic investigations. Patients aged < 60 years require targeted interventions to promote prompt initiation of chemo-radiation therapy.

Adherence to antiretroviral and cancer chemotherapy, and associated factors among patients with HIV-cancer co-morbidity at the Uganda Cancer Institute: a cross sectional study.

BACKGROUND: Human Immunodeficiency Virus is a major global public health issue affecting millions of people, and sub-Saharan Africa where Uganda lies is disproportionately affected. There has been an increase in cancer among HIV patients which has resulted into use of co-medications that sometimes affect ART and cancer chemotherapy adherence. We aimed to determine adherence to antiretroviral and cancer chemotherapy and the associated factors among patients with HIV-cancer co-morbidity at the Uganda Cancer Institute. METHODS: We conducted a cross-sectional study among 200 randomly selected adult cancer patients infected with HIV and attending the Uganda cancer institute. Antiretroviral and anti-cancer chemotherapy adherence with associated factors were assessed quantitatively. We collected the data using interviewer administered semi-structured questionnaires. Modified Poisson regression with robust standard errors was used to estimate the prevalence ratios (PR) and its 95% confidence intervals (CI) for the factors associated with adherence to Antiretroviral Therapy (ART) and cancer chemotherapy. RESULTS: Overall, 54% of the study participants adhered to both ART and chemotherapy, and 55% adhered to ART while 65% adhered to cancer chemotherapy. The mean age of the respondents was 42 (SD ± 11years), and a majority, 61% were males.More than half, 56.5% were married and at least 45% had attained a primary level of education. Patients with good adherence to antiretroviral therapy and chemotherapy were 54%. No knowledge of cancer stage (PR = 0.4, 95% CI = 0.3-0.6, P < 0.0001), having an AIDS defining cancer (PR = 0.7, 95% CI = 0.5-0.9, P = 0.005), ART clinic in district not near Uganda Cancer Institute (PR = 0.7,95% CI = 0.8-1.0, P = 0.027) and affordability of cancer chemotherapy (PR = 1.4, 95% CI = 1.0-1.9, P = 0.037) were associated with adherence to both ART and cancer chemotherapy. CONCLUSION: Adherence to both ART and cancer chemotherapy was low. Factors significantly associated with adherence were: knowledge of the cancer stage by the patient, the type of cancer diagnosis, source of ART and affordability/ availability of medications. There is a need to provide information on the stage of cancer and adherence counseling to patients. Furthermore, Integration of HIV- cancer care will be necessary for efficient and effective care for the patients.

Acceptability of integration of cervical cancer screening into routine HIV care, associated factors and perceptions among HIV-infected women: a mixed methods study at Mbarara Regional Referral Hospital, Uganda.

BACKGROUND: Integrating cervical cancer screening into routine Human Immunodeficiency Virus (HIV) care has been endorsed as an effective strategy for increasing uptake of cervical cancer screening, facilitating early detection and treatment of pre-cancerous lesions among HIV-infected women. In Uganda, this strategy has not been implemented yet in most HIV clinics. Assessing acceptability of this intervention among HIV-infected women is of great relevance to inform implementation. We assessed acceptability of integration of cervical cancer screening into routine HIV care, associated factors and perceptions among HIV-infected women enrolled in the HIV clinic at Mbarara Regional Referral Hospital. METHODOLOGY: A mixed methods study utilizing explanatory sequential approach was conducted among 327 eligible HIV-infected women. Acceptability of integration of cervical cancer screening into routine HIV care was measured based on Theoretical Framework of Acceptability. Quantitative data was collected using a pre-tested questionnaire. We conducted focus group discussions to explore perceptions regarding the intervention among purposively selected HIV-infected women. Modified Poisson regression with robust variance analysis was utilized to determine factors associated with acceptability of the intervention. Statistical significance was determined at p-value <0.05. Thematic analysis utilizing inductive coding was applied to analyse qualitative data. RESULTS: The majority of HIV-infected women (64.5%) accepted integration of cervical cancer screening into routine HIV care. Religion, perceived risk of developing cervical cancer and ever screened for cervical cancer were statistically significantly associated with acceptability of integration of cervical cancer screening into routine HIV care. Perceived benefits of the proposed intervention were: convenience to seek for cervical cancer screening, motivation to undergo cervical cancer screening, improved archiving of cervical cancer screening results, confidentiality of HIV patient information, and preference to interact with HIV clinic health workers. Shame to expose their privacy to HIV clinic health workers and increased waiting time were the only perceived challenges of the integrated strategy. CONCLUSION: Study findings highlight the need to take advantage of this acceptability to prioritize implementation of integration of cervical cancer screening into routine HIV care. HIV-infected women should be reassured of confidentiality and reduced waiting time to increase uptake of integrated cervical cancer screening and HIV services among HIV-infected women along the continuum of HIV care and treatment services.

Dissolution of transactional sex relationships during COVID-19: a qualitative study of Ugandan men's experiences during COVID-19 lockdowns.

The COVID-19 pandemic and subsequent mitigation measures led to social disruption and negative economic shocks for a large proportion of Uganda's population. The social and economic consequences of COVID-19 on Ugandan men's sexual behaviours, including transactional sex relationships, are unclear. We conducted in-depth interviews between November 2021-February 2022 with 26 men in a high HIV prevalence region of Uganda. Data were analysed thematically to understand how sexual relationships, including transactional sex, were impacted by COVID-19. We found that COVID-19 mitigation measures had far-reaching social and economic impacts on most respondents, particularly those employed in the informal economy. Men described experiencing job loss, food insecurity and restricted mobility, which limited opportunities to provide for and meet with transactional sex partners. Inability to provide financial resources meant that men could not form new transactional sex relationships and men who could no longer provide for their existing transactional sex partners consistently reported relationship dissolution. Men who reported stable employment during the pandemic described few changes in transactional sex relationships. Similarly, men in non-transactional relationships did not report relationship dissolution despite decreased financial provision. Further research should assess the potential short- and long-term impacts of COVID-19 mitigation measures on transactional sex relationships.

Severe Acute Respiratory Syndrome Coronavirus-2 seroprevalence in South-Central Uganda, during 2019-2021.

BACKGROUND: Globally, key subpopulations such as healthcare workers (HCW) may have a higher risk of contracting SARS-CoV-2. In Uganda, limited access to Personal Protective Equipment and lack of clarity on the extent/pattern of community spread may exacerbate this situation. The country established infection prevention/control measures such as lockdowns and proper hand hygiene. However, due to resource limitations and fatigue, compliance is low, posing continued onward transmission risk. This study aimed to describe extent of SARS-CoV-2 seroprevalence in selected populations within the Rakai region of Uganda. METHODS: From 30th November 2020 to 8th January 2021, we collected venous blood from 753 HCW at twenty-six health facilities in South-Central Uganda and from 227 population-cohort participants who reported specific COVID-19 like symptoms (fever, cough, loss of taste and appetite) in a prior phone-based survey conducted (between May and August 2020) during the first national lockdown. 636 plasma specimens collected from individuals considered high risk for SARS-CoV-2 infection, prior to the first confirmed COVID-19 case in Uganda were also retrieved. Specimens were tested for antibodies to SARS-CoV-2 using the CoronaChek™ rapid COVID-19 IgM/IgG lateral flow test assay. IgM only positive samples were confirmed using a chemiluminescent microparticle immunoassay (CMIA) (Architect AdviseDx SARS-CoV-2 IgM) which targets the spike protein. SARS-CoV-2 exposure was defined as either confirmed IgM, both IgM and IgG or sole IgG positivity. Overall seroprevalence in each participant group was estimated, adjusting for test performance. RESULTS: The seroprevalence of antibodies to SARS-CoV-2 in HCW was 26.7% [95%CI: 23.5, 29.8] with no difference by sex, age, or cadre. We observed no association between PPE use and seropositivity among exposed healthcare workers. Of the phone-based survey participants, 15.6% [95%CI: 10.9, 20.3] had antibodies to SARS-CoV-2, with no difference by HIV status, sex, age, or occupation. Among 636 plasma specimens collected prior to the first confirmed COVID-19 case, 2.3% [95%CI: 1.2, 3.5] were reactive. CONCLUSIONS: Findings suggest high seroprevalence of antibodies to SARS-CoV-2 among HCW and substantial exposure in persons presenting with specific COVID-19 like symptoms in the general population of South-Central Uganda. Based on current limitations in serological test confirmation, it remains unclear whether seroprevalence among plasma specimens collected prior to confirmation of the first COVID-19 case implies prior SARS-CoV-2 exposure in Uganda.

Effect of four or more antenatal care visits on facility delivery and early postnatal care services utilization in Uganda: a propensity score matched analysis.

INTRODUCTION: Maternal mortality remains a global public health issue, more predominantly in developing countries, and is associated with poor maternal health services utilization. Antenatal care (ANC) visits are positively associated with facility delivery and postnatal care (PNC) utilization. However, ANC in itself may not lead to such association but due to differences that exist among users (women). The purpose of this study, therefore, is to examine the effect of four or more ANC visits on facility delivery and early PNC and also the effect of facility-based delivery on early PNC using Propensity Score Matched Analysis (PSMA). METHODS: The present study utilized the 2016 Uganda Demographic and Health Survey (UDHS) dataset. Women aged 15 - 49 years who had given birth three years preceding the survey were considered for this study. Propensity score-matched analysis was used to analyze the effect of four or more ANC visits on facility delivery and early PNC and also the effect of facility-based delivery on early PNC. RESULTS: The results revealed a significant and positive effect of four or more ANC visits on facility delivery [ATT (Average Treatment Effect of the Treated) = 0.118, 95% CI: 0.063 - 0.173] and early PNC [ATT = 0.099, 95% CI: 0.076 - 0.121]. It also found a positive and significant effect of facility-based delivery on early PNC [ATT = 0.518, 95% CI: 0.489 - 0.547]. CONCLUSION: Policies geared towards the provision of four or more ANC visits are an effective intervention towards improved facility-based delivery and early PNC utilisation in Uganda.

Impact of an intensive facility-community case management intervention on 6-month HIV outcomes among select key and priority populations in Uganda.

INTRODUCTION: Key and priority populations (with risk behaviours and health inequities) are disproportionately affected by HIV in Uganda. We evaluated the impact of an intensive case management intervention on HIV treatment outcomes in Kalangala District, predominantly inhabited by fisher folk and female sex workers. METHODS: This quasi-experimental pre-post intervention evaluation included antiretroviral therapy naïve adults aged ≥ 18 years from six health facilities in the pre-intervention (Jan 1, 2017-December 31, 2017) and intervention phase (June 13, 2018-June 30, 2019). The primary outcomes were 6-month retention and viral suppression (VS) before and after implementation of the intervention involving facility and community case managers who supported participants through at least the first three months of ART. We used descriptive statistics to compared the characteristics, overall outcomes (i.e., retention, lost to follow up, died), and VS of participants by phase, and used mixed-effects logistic regression models to determine factors associated with 6-month retention in care. Marginal (averaging over facilities) probabilities of retention were computed from the final multivariable model. RESULTS: We enrolled 606 and 405 participants in the pre-intervention and intervention phases respectively. Approximately 75% of participants were aged 25-44 years, with similar age and gender distributions among phases. Approximately 46% of participants in the intervention were fisher folk and 9% were female sex workers. The adjusted probability of 6-month retention was higher in the intervention phase, 0.83 (95% CI: 0.77-0.90) versus pre-intervention phase, 0.73 (95% CI: 0.69-0.77, p = 0.03). The retention probability increased from 0.59 (0.49-0.68) to 0.73 (0.59-0.86), p = 0.03 among participants aged 18-24 years, and from 0.75 (0.71-0.78) to 0.85 (0.78-0.91), p = 0.03 among participants aged ≥ 25 years. VS (< 1,000 copies/mL) was approximately 87% in both phases. CONCLUSIONS: After implementation of the case management intervention, we observed significant improvement in 6-month retention in all age groups of a highly mobile population of predominantly fisher folk.

Women's support for voluntary medical male circumcision in fishing communities on the shores of Lake Victoria, Uganda.

BACKGROUND: Women's support can improve uptake of voluntary medical male circumcision (VMMC). We assessed the level of women's support for VMMC and associated factors in fishing settlements on the shores of Lake Victoria in Uganda, to inform interventions aimed at increasing the uptake of safe male circumcision services in such high-risk populations. METHODS: We conducted a cross-sectional study, employing mixed methods of data collection, at Kasenyi and Kigungu landing sites in April 2018. We included women aged 18-49 years, who had stayed at the landing sites for ≥3 months. We obtained qualitative data using focus group discussions (FGDs), and interviewer-administered semi-structured questionnaires for quantitative data. The tool captured demographic characteristics, community factors including cultural norms and beliefs, women's experiences, and health facility-related factors. The dependent variable was derived from the response to the question: "Would you encourage your partner/husband to go for VMMC?", and used as a proxy for support of VMMC. We used modified Poisson regression to identify factors associated with women's support for VMMC. Qualitative data were analysed using thematic content analysis. RESULTS: We enrolled 313 women with a mean age of 28 (SD±6.8) years. Of the 313 women, 230 (73.5%) supported VMMC. Belief that VMMC increases penile hygiene (Adjusted prevalence ratio [aPR]=1.9; CI: 1.8-3.2), performing VMMC for religious reasons (aPR=1.9; CI: 1.8-2.9), preference for a circumcised man (aPR=1.3; CI: 1.2-1.5), belief that vaginal fluids facilitate wound healing (aPR=1.9; CI: 1.3-2.7), and knowledge about when a man can resume sex (4 weeks) after circumcision (aPR=2.1; CI: 1.8-3.3) were associated with women's support for VMMC. FGDs revealed that women were not adequately involved in VMMC activities for decision making. CONCLUSION: The support for VMMC was high among women in the fishing communities. However, women perceived they were not involved in decision-making for VMMC and had several misconceptions, including a belief that vaginal fluids facilitate wound healing. The Ministry of Health and VMMC implementing partners should devise strategies to increase sensitization and involvement of women in VMMC decision-making without slowing service uptake.

Prevalence and Predictors of Persistent Human Immunodeficiency Virus Viremia and Viral Rebound After Universal Test and Treat: A Population-Based Study.

BACKGROUND: There are limited data on individual human immunodeficiency virus (HIV) viral load (VL) trajectories at the population-level after the introduction of universal test and treat (UTT) in sub-Saharan Africa. METHODS: Human immunodeficiency virus VLs were assessed among HIV-positive participants through 3 population-based surveys in 4 Ugandan fishing communities surveyed between November 2011 and August 2017. The unit of analysis was a visit-pair (2 consecutive person-visits), which were categorized as exhibiting durable VL suppression, new/renewed VL suppression, viral rebound, or persistent viremia. Adjusted relative risks (adjRRs) and 95% confidence intervals (CIs) of persistent viremia were estimated using multivariate Poisson regression. RESULTS: There were 1346 HIV-positive participants (n = 1883 visit-pairs). The population-level prevalence of durable VL suppression increased from 29.7% to 67.9% during UTT rollout, viral rebound declined from 4.4% to 2.7%, and persistent viremia declined from 20.8% to 13.3%. Younger age (15-29 vs 40-49 years; adjRR = 1.80; 95% CI = 1.19-2.71), male sex (adjRR = 2.09, 95% CI = 1.47-2.95), never being married (vs currently married; adjRR = 1.88, 95% CI = 1.34-2.62), and recent migration to the community (vs long-term resident; adjRR = 1.91, 95% CI = 1.34-2.73) were factors associated with persistent viremia. CONCLUSIONS: Despite increases in durable VL suppression during roll out of UTT in hyperendemic communities, a substantial fraction of the population, whose risk profile tended to be younger, male, and mobile, remained persistently viremic.

Effectiveness of Voluntary Medical Male Circumcision for Human Immunodeficiency Virus Prevention in Rakai, Uganda.

BACKGROUND: The efficacy of voluntary male medical circumcision (VMMC) for human immunodeficiency virus (HIV) prevention in men was demonstrated in 3 randomized trials. This led to the adoption of VMMC as an integral component of the United States President's Emergency Plan for AIDS Relief (PEPFAR) combination HIV prevention program in sub-Saharan Africa. However, evidence on the individual-level effectiveness of VMMC programs in real-world, programmatic settings is limited. METHODS: A cohort of initially uncircumcised, non-Muslim, HIV-uninfected men in the Rakai Community Cohort Study in Uganda was followed between 2009 and 2016 during VMMC scale-up. Self-reported VMMC status was collected and HIV tests performed at surveys conducted every 18 months. Multivariable Poisson regression was used to estimate the incidence rate ratio (IRR) of HIV acquisition in newly circumcised vs uncircumcised men. RESULTS: A total of 3916 non-Muslim men were followed for 17 088 person-years (PY). There were 1338 newly reported VMMCs (9.8/100 PY). Over the study period, the median age of men adopting VMMC declined from 28 years (interquartile range [IQR], 21-35 years) to 22 years (IQR, 18-29 years) (P for trend < .001). HIV incidence was 0.40/100 PY (20/4992.8 PY) among newly circumcised men and 0.98/100 PY (118/12 095.1 PY) among uncircumcised men with an adjusted IRR of 0.47 (95% confidence interval, .28-.78). The effectiveness of VMMC was sustained with increasing time from surgery and was similar across age groups and calendar time. CONCLUSIONS: VMMC programs are highly effective in preventing HIV acquisition in men. The observed effectiveness is consistent with efficacy in clinical trials and supports current recommendations that VMMC is a key component of programs to reduce HIV incidence.

Differential Performance of CoronaCHEK SARS-CoV-2 Lateral Flow Antibody Assay by Geographic Origin of Samples.

We assessed the performance of the CoronaCHEK lateral flow assay on samples from Uganda and Baltimore to determine the impact of geographic origin on assay performance. Plasma samples from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR-positive individuals (Uganda, 78 samples from 78 individuals, and Baltimore, 266 samples from 38 individuals) and from prepandemic individuals (Uganda, 1,077, and Baltimore, 532) were evaluated. Prevalence ratios (PR) were calculated to identify factors associated with a false-positive test. After the first positive PCR in Ugandan samples, the sensitivity was 45% (95% confidence interval [CI], 24,68) at 0 to 7 days, 79% (95% CI, 64 to 91) at 8 to 14 days, and 76% (95% CI, 50 to 93) at >15 days. In samples from Baltimore, sensitivity was 39% (95% CI, 30 to 49) at 0 to 7 days, 86% (95% CI, 79 to 92) at 8 to 14 days, and 100% (95% CI, 89 to 100) at 15 days after positive PCR. The specificity of 96.5% (95% CI, 97.5 to 95.2) in Ugandan samples was significantly lower than that in samples from Baltimore, 99.3% (95% CI, 98.1 to 99.8; P < 0.01). In Ugandan samples, individuals with a false-positive result were more likely to be male (PR, 2.04; 95% CI, 1.03,3.69) or individuals who had had a fever more than a month prior to sample acquisition (PR, 2.87; 95% CI, 1.12 to 7.35). Sensitivity of the CoronaCHEK was similar in samples from Uganda and Baltimore. The specificity was significantly lower in Ugandan samples than in Baltimore samples. False-positive results in Ugandan samples appear to correlate with a recent history of a febrile illness, potentially indicative of a cross-reactive immune response in individuals from East Africa.

Qualitative Assessment of Barriers and Facilitators of PrEP Use Before and After Rollout of a PrEP Program for Priority Populations in South-central Uganda.

Uganda piloted HIV pre-exposure prophylaxis (PrEP) for priority populations (sex workers, fishermen, truck drivers, discordant couples) in 2017. To assess facilitators and barriers to PrEP uptake and adherence, we explored perceptions of PrEP before and experiences after rollout among community members and providers in south-central Uganda. We conducted 75 in-depth interviews and 12 focus group discussions. We analyzed transcripts using a team-based thematic framework approach. Partners, family, peers, and experienced PrEP users provided adherence support. Occupational factors hindered adherence for sex workers and fishermen, particularly related to mobility. Pre-rollout concerns about unskilled/untrained volunteers distributing PrEP and price-gouging were mitigated. After rollout, awareness of high community HIV risk and trust in PrEP effectiveness facilitated uptake. PrEP stigma and unexpected migration persisted as barriers. Community-initiated, tailored communication with successful PrEP users may optimize future engagement by addressing fears and rumors, while flexible delivery and refill models may facilitate PrEP continuation and adherence.

RESUMEN: En 2017, Uganda introdujo profilaxis pre-exposición (PrEP), dirigida a las populaciones con alto riesgo de contraer al VIH (trabajadoras sexuales, pescadores, camioneros, parejas sero-discordantes). Para investigar facilitadores y barreras para la adopción y la adherencia a la PrEP, exploramos percepciones de PrEP antes y después de su introducción en Uganda. Realizamos 75 entrevistas y 12 grupos focales con miembros de la comunidad y trabajadores de salud. Analizamos las transcripciones temáticamente usando un marco de referencia. Parejas, familias, compañeros, y clientes usando PrEP apoyaron a los demás mantener adherencia. Movilidad fue una barrera para la adherencia a la PrEP para trabajadoras sexuales y pescadores. Preocupaciones sobre el entrenamiento de los distribuidores de PrEP y la especulación de precios no fueron realizadas. Percepciones del riesgo del VIH y confianza en la eficacia de PrEP facilitaron su adopción. Estigma y migración inesperada persistieron como barreras para la adopción de PrEP. Comunicaciones manejadas por clientes usando PrEP pueden motivar interés en PrEP y abordar rumores. Sistemas flexibles del entrego y la recarga de medicinas pueden permitir continuación de, y adherencia a, la PrEP.

HIV Prevention Efforts and Incidence of HIV in Uganda.

BACKGROUND: To assess the effect of a combination strategy for prevention of human immunodeficiency virus (HIV) on the incidence of HIV infection, we analyzed the association between the incidence of HIV and the scale-up of antiretroviral therapy (ART) and medical male circumcision in Rakai, Uganda. Changes in population-level viral-load suppression and sexual behaviors were also examined. METHODS: Between 1999 and 2016, data were collected from 30 communities with the use of 12 surveys in the Rakai Community Cohort Study, an open, population-based cohort of persons 15 to 49 years of age. We assessed trends in the incidence of HIV on the basis of observed seroconversion data, participant-reported use of ART, participant-reported male circumcision, viral-load suppression, and sexual behaviors. RESULTS: In total, 33,937 study participants contributed 103,011 person-visits. A total of 17,870 persons who were initially HIV-negative were followed for 94,427 person-years; among these persons, 931 seroconversions were observed. ART was introduced in 2004, and by 2016, ART coverage was 69% (72% among women vs. 61% among men, P<0.001). HIV viral-load suppression among all HIV-positive persons increased from 42% in 2009 to 75% by 2016 (P<0.001). Male circumcision coverage increased from 15% in 1999 to 59% by 2016 (P<0.001). The percentage of adolescents 15 to 19 years of age who reported never having initiated sex (i.e., delayed sexual debut) increased from 30% in 1999 to 55% in 2016 (P<0.001). By 2016, the mean incidence of HIV infection had declined by 42% relative to the period before 2006 (i.e., before the scale-up of the combination strategy for HIV prevention) - from 1.17 cases per 100 person-years to 0.66 cases per 100 person-years (adjusted incidence rate ratio, 0.58; 95% confidence interval [CI], 0.45 to 0.76); declines were greater among men (adjusted incidence rate ratio, 0.46; 95% CI, 0.29 to 0.73) than among women (adjusted incidence rate ratio, 0.68; 95% CI, 0.50 to 0.94). CONCLUSIONS: In this longitudinal study, the incidence of HIV infection declined significantly with the scale-up of a combination strategy for HIV prevention, which provides empirical evidence that interventions for HIV prevention can have a population-level effect. However, additional efforts are needed to overcome disparities according to sex and to achieve greater reductions in the incidence of HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and others.).

Evolution of HIV-1 within untreated individuals and at the population scale in Uganda.

HIV-1 undergoes multiple rounds of error-prone replication between transmission events, resulting in diverse viral populations within and among individuals. In addition, the virus experiences different selective pressures at multiple levels: during the course of infection, at transmission, and among individuals. Disentangling how these evolutionary forces shape the evolution of the virus at the population scale is important for understanding pathogenesis, how drug- and immune-escape variants are likely to spread in populations, and the development of preventive vaccines. To address this, we deep-sequenced two regions of the HIV-1 genome (p24 and gp41) from 34 longitudinally-sampled untreated individuals from Rakai District in Uganda, infected with subtypes A, D, and inter-subtype recombinants. This dataset substantially increases the availability of HIV-1 sequence data that spans multiple years of untreated infection, in particular for different geographical regions and viral subtypes. In line with previous studies, we estimated an approximately five-fold faster rate of evolution at the within-host compared to the population scale for both synonymous and nonsynonymous substitutions, and for all subtypes. We determined the extent to which this mismatch in evolutionary rates can be explained by the evolution of the virus towards population-level consensus, or the transmission of viruses similar to those that establish infection within individuals. Our findings indicate that both processes are likely to be important.