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.
We conducted a retrospective population-based study to describe longitudinal patterns of prevalence, incidence, discontinuation, resumption, and durability of substantial HIV risk behaviors (SHR) for ...pre-exposure prophylaxis (PrEP) eligibility.
The study was conducted among HIV-negative study participants aged 15-49 years who participated in survey rounds of the Rakai Community Cohort Study between August 2011 and June 2018. Substantial HIV risk was defined based on the Uganda national PrEP eligibility as reporting sexual intercourse with >1 partner of unknown HIV status, nonmarital sex without a condom, having genital ulcers, or having transactional sex. Resumption of SHR meant resuming of SHR after stopping SHR, whereas persistence of SHR meant SHR on >1 consecutive visit. We used generalized estimation equations with log-binomial regression models and robust variance to estimate survey-specific prevalence ratios; Generalized estimation equations with modified Poisson regression models and robust variance to estimate incidence ratios for incidence, discontinuation, and resumption of PrEP eligibility.
Incidence of PrEP eligibility increased from 11.4/100 person-years (pys) in the first intersurvey period to 13.9/100 pys (adjusted incidence rate ratios = 1.28; 95%CI = 1.10-1.30) and declined to 12.6/100 pys (adjusted incidence rate ratios = 1.06; 95%CI = 0.98-1.15) in the second and third intersurvey periods, respectively. Discontinuation rates of SHR for PrEP eligibility were stable (ranging 34.9/100 pys-37.3/100 pys; P = 0.207), whereas resumption reduced from 25.0/100 pys to 14.5/100 pys ( P < 0.001). PrEP eligibility episodes lasted a median time of 20 months (IQR = 10-51).
Pre-exposure prophylaxis use should be tailored to the dynamic nature of PrEP eligibility. Preventive-effective adherence should be adopted for assessment of attrition in PrEP programs.
B-cell malignancies can potentially be cured by CD19 chimeric antigen receptor (CAR) T-cell therapy. Although clinical response rates can be up to 93% in acute lymphoblastic leukemia, ...treatment-related antigen loss and lack of therapeutic persistence contribute to disease relapse. These shortcomings of current CAR T-cell therapy indicate the need for biologically relevant target selection and for improving the efficacy and persistence of the CAR T cells, which we have addressed by developing a novel B-cell activating factor receptor (BAFF-R) CAR T-cell therapy with improved therapeutic persistence. BAFF-R is a B-cell survival receptor and highly expressed in B-cell malignancies. We developed a prototype CAR T cell that efficiently and specifically eliminated BAFF-R expressing human B-cell tumors in several xenogeneic mouse models, including models of CD19 antigen loss. We proceeded with translational development and validation of BAFF-R CAR T cells produced under current good manufacturing practices (cGMP). cGMP-grade BAFF-R CAR T cells underwent in vitro and in vivo validation in established models to confirm that the potency and efficacy of our original research modeling was replicated. Food and Drug Administration required release testing was performed to ensure our BAFF-R CAR T cells meet specifications for new drug products. Completing and exceeding these requirements, the data fully support the initiation of a first-in-human Phase 1 trial for BAFF-R-positive relapsed/refractory (r/r) B-ALL.
Limited studies exploring the impact of socioeconomic status (SES) on hypertension in Africa suggest a positive association between higher SES and hypertension. The economic development in ...sub-Saharan African countries has led to changes in SES and associated changes in lifestyle, diet, and physical activity, which may affect the relationship between hypertension and SES differently compared with higher income countries. This cross-sectional study from a large population-based cohort, the Rakai Community Cohort Study (RCCS), examines SES, hypertension prevalence, and associated risk factors in the rural Rakai Region in south-central Uganda.
Adults aged 30-49 years residing in 41 RCCS fishing, trading, and agrarian communities, were surveyed with biometric data obtained between 2016 and 2018. The primary outcome was hypertension (systolic blood pressure (BP) ≥ 130 mmHg or diastolic BP ≥ 80 mmHg). Modified Poisson regression assessed the adjusted prevalence ratios (PR) of hypertension associated with SES; body mass index (BMI) was explored as a potential mediator.
Among 9,654 adults, 20.8% had hypertension (males 21.2%; females 20.4 %). Participants with hypertension were older (39.0 ± 6.0 vs. 37.8 ± 5.0; p < 0.001). Higher SES was associated with overweight or obese BMI categories (p < 0.001). In the multivariable model, hypertension was associated with the highest SES category (aPR 1.23; confidence interval 1.09-1.38; p = 0.001), older age, male sex, alcohol use, and living in fishing communities and inversely associated with smoking and positive HIV serostatus. When BMI was included in the model, there was no association between SES and hypertension (aPR 1.02; CI 0.90-1.15, p = 0.76).
Hypertension is common in rural Uganda among individuals with higher SES and appears to be mediated by BMI. Targeted interventions could focus on lifestyle modification among highest-risk groups to optimize public health impact.
Hypertension is an important modifiable risk factor for cardiovascular disease.There are few large epidemiological studies that investigate the relationship between hypertension and socioeconomic status in low-income countries.
Hypertension is common among adults in rural South-Central Uganda, particularly among those with higher socioeconomic status.BMI is a mediator of the relationship between hypertension and socioeconomic status.
These findings suggest that public health interventions and community efforts to prevent chronic cardiovascular disease and hypertension should focus on lifestyle modification by elucidating obesity risk perception and health risk awareness, particularly among those of higher socioeconomic status.
A trial found that a community health worker (CHW) strategy using "Health Scouts" improved HIV care uptake and ART coverage. To better understand outcomes and areas for improvement, we conducted an ...implementation science evaluation.
Using the RE-AIM framework, quantitative methods included analyses of a community-wide survey (n = 1903), CHW log books, and phone application data. Qualitative methods included in-depth interviews (n = 72) with CHWs, clients, staff, and community leaders.
Thirteen Health Scouts logged 11,221 counseling sessions; 2532 unique clients were counseled. 95.7% (1789 of 1891) of residents reported awareness of the Health Scouts. Overall, reach (self-reported receipt of counseling) was 30.7% (580 of 1891). Unreached residents were more likely to be male and HIV seronegative ( P < 0.05). Qualitative themes included the following: (1) reach was promoted by perceived usefulness but deterred by busy client lifestyles and stigma, (2) effectiveness was enabled through good acceptability and consistency with the conceptual framework, (3) adoption was facilitated by positive impacts on HIV service engagement, and (4) implementation fidelity was initially promoted by the CHW phone application but deterred by mobility. Maintenance showed consistent counseling sessions over time. The findings suggested the strategy was fundamentally sound but had suboptimal reach. Future iterations could consider adaptations to improve reach to priority populations, testing the need for mobile health support, and additional community sensitization to reduce stigma.
A CHW strategy to promote HIV services was implemented with moderate success in an HIV hyperendemic setting and should be considered for adoption and scale-up in other communities as part of comprehensive HIV epidemic control efforts.
ClinicalTrials.gov Trial Number NCT02556957.
A community health worker (CHW) model can promote HIV prevention and treatment behaviors, especially in highly mobile populations. In a fishing community in Rakai, Uganda, the Rakai Health Sciences ...Program implemented a CHW HIV intervention called Health Scouts. The situated Information, Motivation, and Behavioral Skills (sIMB) framework informed the design and a qualitative evaluation of the intervention. We interviewed 51 intervention clients and coded transcripts informed by sIMB framework dimensions. Clients reported that Health Scouts provided information about HIV prevention and treatment behaviors and helped them manage personal and social motivations to carry out health-promoting behavior. Prominent barriers which moved clients away from behavior change included daily pill burdens, anticipated stigma, serostatus disclosure, substance use at social gatherings, and anticipated reactions of partners. Our study adds to the evidence establishing CHWs as facilitators of behavior change, positioned to offer supportive encouragement and navigate contextualized circumstances.
IMPORTANCE: Medical male circumcision (MMC) and antiretroviral therapy (ART) are proven HIV prevention interventions, but there are limited data on the population-level effect of scale-up of these ...interventions in sub-Saharan Africa. Such evaluation is important for planning and resource allocation. OBJECTIVE: To examine whether increasing community MMC and ART coverage was associated with reduced community HIV incidence in Rakai District, Uganda. DESIGN, SETTING, AND PARTICIPANTS: Using person-level data from population-based surveys conducted from 1999 through 2013 in 45 rural Rakai communities, community-level ART and MMC coverage, sociodemographics, sexual behaviors, and HIV prevalence and incidence were estimated in 3 periods: prior to the availability of ART and MMC (1999-2004), during early availability of ART and MMC (2004-2007), and during mature program scale-up (2007-2013). EXPOSURES: Community MMC coverage in males and ART coverage in HIV-positive persons of the opposite sex based on self-reported MMC status and ART use. MAIN OUTCOMES AND MEASURES: Adjusted incidence rate ratios (IRRs) for sex-specific community HIV incidence estimated using multivariable Poisson regression with generalized estimating equations. RESULTS: From 1999 through 2013, 44 688 persons participated in 1 or more surveys (mean age at the first survey, 24.6 years range, 15-49; female, 56.5%; mean survey participation rate, 92.6% 95% CI, 92.4%-92.7%). Median community MMC coverage increased from 19% to 39%, and median community ART coverage rose from 0% to 21% in males and from 0% to 26% in females. Median community HIV incidence declined from 1.25 to 0.84 per 100 person-years in males, and from 1.25 to 0.99 per 100 person-years in females. Among males, each 10% increase in community MMC coverage was associated with an adjusted IRR of 0.87 (95% CI, 0.82-0.93). Comparing communities with MMC coverage more than 40% (mean male community incidence, 1.03 per 100 person-years) with communities with coverage of 10% or less (mean male incidence, 1.69 per 100 person-years), the adjusted IRR was 0.61 (95% CI, 0.43-0.88). For each 10% increase in female self-reported ART coverage, there was no significant reduction in male HIV incidence (adjusted IRR, 0.95 95% CI, 0.81-1.13). Comparing communities with female ART coverage more than 20% (mean male incidence, 0.87 per 100 person-years) to communities with female ART coverage of 20% or less (mean male incidence, 1.17 per 100 person-years), the adjusted IRR was 0.77 (95% CI, 0.61-0.98). Neither MMC nor male ART coverage was associated with lower female community HIV incidence. CONCLUSIONS AND RELEVANCE: In Rakai, Uganda, increasing community MMC and female ART coverage was associated with lower community HIV incidence in males. If similar associations are found elsewhere, this would support further scale-up of MMC and ART for HIV prevention in sub-Saharan Africa.
Rapid HIV tests are critical to HIV surveillance and universal testing and treatment programs. We assessed longitudinal patterns in indeterminate HIV rapid test results in an African population-based ...cohort. Prospective HIV rapid antibody test results, defined by two parallel rapid tests, among participants aged 15-49 years from three survey rounds of the Rakai Community Cohort Study, Uganda, from 2013 to 2018, were assessed. An indeterminate result was defined as any weak positive result or when one test was negative and the other was positive. A total of 31,405 participants contributed 54,459 person-visits, with 15,713 participants contributing multiple visits and 7,351 participants contributing 3 visits. The prevalence of indeterminate results was 2.7% (1,490/54,469). Of the participants with multiple visits who initially tested indeterminate (
= 591), 40.4% were negative, 18.6% were positive, and 41.0% were indeterminate at the subsequent visit. Of the participants with two consecutive indeterminate results who had a third visit (
= 67), 20.9% were negative, 9.0% were positive, and 70.2% remained indeterminate. Compared to a prior negative result, a prior indeterminate result was strongly associated with a subsequent indeterminate result adjusted prevalence ratio, 23.0 (95% CI = 20.0-26.5). Compared to men, women were more likely to test indeterminate than negative adjusted odds ratio, 2.3 (95% CI = 2.0-2.6). Indeterminate rapid HIV test results are highly correlated within an individual and 0.6% of the population persistently tested indeterminate over the study period. A substantial fraction of people with an indeterminate result subsequently tested HIV positive at the next visit, underscoring the importance of follow-up HIV testing protocols.IMPORTANCERapid HIV tests are a critical tool for expanding HIV testing and treatment to end the HIV epidemic. The interpretation and management of indeterminate rapid HIV test results pose a unique challenge for connecting all people living with HIV to the necessary care and treatment. Indeterminate rapid HIV test results are characterized by any weak positive result or discordant results (when one test is negative and the other is positive). We systematically tested all participants of a Ugandan population-based, longitudinal cohort study regardless of prior test results or HIV status to quantify longitudinal patterns in rapid HIV test results. We found that a substantial fraction (>15%) of participants with indeterminate rapid test results subsequently tested positive upon follow-up testing at the next visit. Our findings demonstrate the importance of follow-up HIV testing protocols for indeterminate rapid HIV test results.
AimsTo understand the environmental and contextual influences of illicit cocaine and heroin use and craving using mobile health (mHealth) methods.
DesignInteractive mHealth methods of ecological ...momentary assessment (EMA) were utilized in the Exposure Assessment in Current Time (EXACT) study to assess drug use and craving among urban drug users in real time. Participants were provided with mobile devices and asked to self‐report every time they either craved (without using) or used heroin or cocaine for 30 days from November 2008 through May 2013.
SettingBaltimore, MD, USA.
ParticipantsA total of 109 participants from the AIDS Linked to the IntraVenous Experience (ALIVE) study.
MeasurementsFor each drug use or craving event, participants answered questions concerning their drug use, current mood and their social, physical and activity environments. Odds ratios (OR) of drug use versus craving were obtained from logistic regression models with generalized estimating equations of all reported events.
FindingsParticipants were a median of 48.5 years old, 90% African American, 52% male and 59% HIV‐infected. Participants were significantly more likely to report use rather than craving drugs if they were with someone who was using drugs adjusted odds ratio (aOR) = 1.45, 95% confidence interval (CI) = 1.13, 1.86), in an abandoned space (aOR = 6.65, 95% CI = 1.78, 24.84) or walking/wandering (aOR = 1.68, 95% CI = 1.11, 2.54). Craving drugs was associated with being with a child (aOR = 0.26, 95% CI = 0.12, 0.59), eating (aOR = 0.54, 95% CI = 0.34, 0.85) or being at the doctor's office (aOR = 0.31, 95% CI = 0.12, 0.80).
ConclusionsThere are distinct drug using and craving environments among urban drug users, which may provide a framework for developing real‐time context‐sensitive interventions.
Introduction
Cardiovascular disease is one of the leading causes of mortality for people living with HIV, but limited population‐based data are available from sub‐Saharan Africa. This study aimed to ...determine the prevalence of key cardiovascular disease risk factors, 10‐year risk of cardiovascular disease and type 2 diabetes mellitus through risk scores by HIV status, as well as investigate factors associated with hyperglycaemia, hypertension and dyslipidaemia in South‐Central Uganda.
Methods
A cross‐sectional study was conducted in 37 communities of the population‐based Rakai Community Cohort Study from May 2016 to May 2018. In total, 990 people living with HIV and 978 HIV‐negative participants aged 35–49 years were included. Prevalence estimates and 10‐year cardiovascular and type 2 diabetes risk were calculated by sex and HIV serostatus. Multivariable logistic regression was used to determine associations between socio‐demographic, lifestyle and body composition risk factors and hyperglycaemia, hypertension and dyslipidaemia.
Results
Overweight (21%), obesity (9%), abdominal obesity (15%), hypertension (17%) and low high‐density lipoprotein (HDL) (63%) were the most common cardiovascular risk factors found in our population. These risk factors were found to be less common in people living with HIV apart from hypertension. Ten‐year risk for cardiovascular and type 2 diabetes mellitus risk was low in this population with <1% categorized as high risk. In HIV‐adjusted multivariable analysis, obesity was associated with a higher odds of hypertension (odds ratio OR = 2.31, 95% confidence interval CI 1.35–3.96) and high triglycerides (OR = 2.08, CI 1.25–3.47), and abdominal obesity was associated with a higher odds of high triglycerides (OR = 2.55, CI 1.55–4.18) and low HDL (OR = 1.36, CI 1.09–1.71). A positive HIV status was associated with a lower odds of low HDL (OR = 0.43, CI 0.35–0.52).
Conclusions
In this population‐based study in Uganda, cardiovascular risk factors of obesity, abdominal obesity, hypertension and dyslipidaemia were found to be common, while hyperglycaemia was less common. Ten‐year risk for cardiovascular and type 2 diabetes mellitus risk was low. The majority of cardiovascular risk factors were not affected by HIV status. The high prevalence of dyslipidaemia in our study requires further research.
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