Timothy R. Muwonge

Introduction: Limited SARS-CoV-2 testing capacity during the early COVID-19 pandemic required approaches to identify individuals at highest risk of infection for prioritized testing. We assessed the association between symptoms and exposures reported at the time of SARS-CoV-2 testing and test positivity among individuals referred for testing through an interactive voice response (IVR) platform in refugee settlements in Uganda. Methods: We used Dial-COVID, a multilingual, toll-free interactive voice response (IVR) platform to survey residents of refugee settlements in Uganda regarding COVID-19 symptoms, exposures, and comorbidities. Respondents reporting symptoms or exposures were invited for SARS-CoV-2 testing using nasal or oropharyngeal swab specimens. At the time of testing, an interviewer-administered questionnaire assessed symptoms and exposures occurring within the preceding two weeks. Log-binomial regression was used to identify factors associated with SARS-CoV-2 positivity. Results: Between February 2021 and March 2022, 6,913 of 15,467 Dial-COVID callers (44.7%) completed the IVR survey. Among survey respondents, 5,184 (75.0%) reported at least one symptom or exposure. Of these, 1,361 (26.3%) were invited for testing, and samples were collected from 751 (55.2%) within seven days of survey completion. SARS-CoV-2 test results were available for 741 individuals, of whom 48 tested positive (6.5%). Among symptoms reported at the testing visit, severe muscle pain (risk ratio [RR] 2.08; 95% CI 1.20–3.57) and unusual fatigue (RR 2.34; 95% CI 1.36–4.03) were associated with SARS-CoV-2 positivity in unadjusted analyses. After adjustment for sex, refugee status, hypertension, and diabetes, only unusual fatigue remained independently associated with a positive test result (aRR 2.10, 95% CI 1.20– 3.67). Conclusion: Few self-reported symptoms were associated with SARS-CoV-2 positivity, highlighting the challenges of prioritizing testing based on symptoms alone. IVR-based platforms may provide a feasible approach for screening, surveillance, and linkage to testing in resource-constrained humanitarian settings.

Background: Until recently, community-based antiretroviral therapy (ART) delivery was only available for people living with HIV on ART for ≥6 months with a suppressed viral load. However, early attrition from HIV care is common, particularly in refugee settlements where structural and psychosocial barriers to care are pronounced, and reducing barriers to life-saving ART sooner (e.g., at ART initiation) through community-based ART delivery may improve treatment outcomes. The Head StART study will evaluate the effectiveness, implementation, and health system costs of community ART delivery for individuals newly diagnosed with HIV in refugee settlements in Uganda. Methods: In a cluster randomized trial, twelve health centers in five refugee settlements in Uganda were randomized (1:1) to intervention or standard of care (SoC), with stratification to balance site characteristics. Individuals testing positive for HIV are screened for study eligibility (inclusion criteria: diagnosed with HIV < 6 months, on ART ≤ 42 days, ≥ 18 years of age or emancipated minor or mature minor; exclusion criteria: pregnant/breastfeeding, medical reason for requiring facility-based care, concurrent trial participation) aiming to recruit up to 1,560 participants per arm (N = 3,120 total). Eligible individuals are enrolled and monitored longitudinally through abstraction of routinely collected data on HIV care outcomes. At intervention sites, participants are offered community ART delivery (Head StART intervention); at SoC sites, participants receive facility-based care. The primary outcome compares the proportion of participants virally suppressed 12 months post-ART initiation by arm in an intention-to-treat analysis. Qualitative interviews and direct observations will augment quantitative data to evaluate intervention implementation across sites. Micro-costing, time and motion observations, and costing interviews will assess intervention costs, which will inform a budget impact analysis. Discussion: This trial will generate critical effectiveness, implementation, and budget impact data on community ART delivery for individuals newly diagnosed with HIV in refugee settlements needed to optimize HIV care for humanitarian populations. Trial registration: ClinicalTrials.gov: NCT06126913. Registered 27 September 2023. https://clinicaltrials.gov/study/NCT06126913

Female university students engaging in high-risk sexual behaviours, such as transactional sex or unprotected sex, are eligible for HIV pre- and post-exposure prophylaxis (PrEP/PEP). This study aimed to determine the uptake and correlates of PEP and PrEP use among female students at a public university in Uganda. We conducted an online survey among 483 female students at Makerere University and found that 53% had ever engaged in sexual intercourse, with a median debut of 20 years (interquartile range 18 to 22 years). Overall, 20% had sex with a person with HIV or of unknown status, and 9% experienced sexual assault. Despite 32% being eligible for PEP and 20% for PrEP, uptake remained low (9% and 2%, respectively). PEP use was associated with being married/cohabiting and perceived HIV risk. Low uptake of PrEP and PEP among eligible female students highlights the need for targeted awareness and accessibility efforts in academic institutions.

Background: Despite high oral pre-exposure prophylaxis (PrEP) uptake among young heterosexual cisgender women, early discontinuation is frequent. It is unclear whether this aligns with potential HIV exposure. Methods: Young women aged 16–25 years and ≥1 of their male partners were enrolled in separate but linked longitudinal HIV PrEP studies in Kampala, Uganda, from 2018 to 2021. Data on sexual behavior, PrEP use, sexually transmitted disease positivity, and Y chromosome DNA (Yc DNA; a marker for condomless sex) were collected at enrollment and quarterly visits. Potential HIV exposure was defined as one of the following in the past 3 months: any sexually transmitted disease, detection of Yc DNA, condomless vaginal sex, or multiple sex partners. Alignment between potential HIV exposure and PrEP use by participants was examined using generalized estimating equation (GEE) regression. Results: Eighty-eight young women (median age = 20.6 years, interquartile range 19.5–22.0) and 124 male partners (median age = 23.5 years, interquartile range 21.0–26.0) were included. Women and men were dispensed PrEP in 66.9% and 60.5% of their first linked visits, respectively. PrEP dispensation was more common when women or men self-reported condomless vaginal sex and multiple sex partners or when women had Yc DNA detected in vaginal swabs. Men's self-report of multiple partners (adjusted prevalence ratio = 1.56, P = 0.012) and the detection of Yc DNA (adjusted prevalence ratio = 1.52, P = 0.040) were significantly associated with women's PrEP dispensation. Conclusions: Women and their male partners may align their PrEP use with their HIV risk behaviors, providing some reassurance that PrEP discontinuation in young people often aligns with sexual behavior. Greater attention to measurement of and mismatches in PrEP discontinuation and potential HIV exposure is needed.

Background: Peer-delivered HIV self-testing (HIVST) and sexually transmitted infection self-sampling (STISS) may promote adherence to oral pre-exposure prophylaxis (PrEP), but no studies have analyzed this approach among transgender women (TGW) in sub-Saharan Africa. Setting: The Peer study was a cluster randomized trial in Uganda (October 2020–July 2022; NCT04328025). Methods: Ten TGW peer groups, each with 1 TGW peer and 8 TGW, were randomized 1:1 to receive quarterly in-clinic HIV testing with PrEP refills as standard-of-care (SOC) or SOC plus monthly peer delivery of oral-fluid HIVST, STISS, and PrEP refills (intervention). Participants were followed for 12 months. The primary outcome was PrEP adherence. Results: We screened 85 TGW and enrolled 82 (41 per arm). The median age was 22 years (interquartile range [IQR] 20–24). Twelve-month retention was 88% (72/82). At the 3, 6, 9, and 12-month clinic visits, 10%, 5%, 5%, and 0% of TGW in the intervention arm had TFV-DP levels ≥700 fmol/punch, versus 7%, 15%, 7%, and 2% in the SOC arm, respectively (P = 0.18). At all visits, any detectable TFV-DP levels were significantly higher in SOC than the peer delivery group (P < 0.04). PrEP adherence was associated with sex work (incidence rate ratio 6.93; 95% CI: 2.33 to 20.60) and >10 years of schooling (incidence rate ratio 2.35; 95% CI: 1.14 to 4.84). There was a strong correlation between tenofovir detection in dried blood spots and urine (P < 0.001). No HIV seroconversions occurred. Conclusions: Peer-delivered HIVST and STISS did not increase low levels of oral PrEP adherence among TGW in Uganda. Long-acting PrEP formulations should be considered for this population.

Background: Intimate partner violence (IPV) is associated with increased risk of HIV acquisition and reduced engagement in HIV care. There is limited understanding of the ways in which IPV exposure and other maladaptive relationship dynamics may influence adherence to antiretroviral treatment (ART) and pre-exposure prophylaxis (PrEP) for individuals in committed, HIV serodifferent partnerships. Methods: We used binomial generalized linear mixed-effect regression models to evaluate the association between IPV exposure and ART/PrEP adherence among members of serodifferent couples in Uganda. Secondarily, we assessed the association between relationship powerlessness and ART/PrEP adherence. Results: We enrolled and followed both partners in 149 heterosexual serodifferent couples. The partner living with HIV was female in 64% of couples. IPV exposure was associated with low ART adherence (15% vs. 5% in quarters with no IPV, odds ratio: 4.78, 95% confidence interval: 1.48 to 15.42), but not low PrEP adherence (33% vs. 36%, P = 0.69). Among HIV-negative individuals, those reporting moderate relationship powerlessness were less likely to have poor PrEP adherence compared with those with low relationship powerlessness (20% vs. 30%, odds ratio: 0.57, 95% confidence interval: 0.36 to 0.90). We observed no association between relationship powerlessness and ART adherence. Conclusions: We found that IPV exposure was associated with low adherence to ART and that relationship powerlessness was associated with good adherence to PrEP. These findings contribute to the evidence base outlining the influence of IPV and relationship power on ART/PrEP adherence for individuals in HIV serodifferent unions.

Background: A better understanding of refugee mobility is needed to optimize HIV care in refugee settlements. Objectives: We aimed to characterize mobility patterns among people living with HIV in refugee settlements in Uganda and evaluate the association between mobility and retention in HIV care. Methods: Refugees and Ugandan nationals accessing HIV services at seven health centers in refugee settlements across Uganda, with access to a phone, were recruited and followed for six months. Participants received an intake survey and monthly phone surveys on mobility and HIV. Clinic visit and viral suppression data were extracted from clinic registers. Mobility and HIV data were presented descriptively, and an alluvial plot was generated characterizing mobility for participants’ most recent trip. Bivariate Poisson regression models were used to describe the associations between long-term mobility (≥1 continuous month away in the past year) and demographic characteristics, retention (≥1 clinic visit/6 months) and long-term mobility, and retention and general mobility (during any follow-up month: ≥2 trips, travel outside the district or further, or spending >1–2 weeks (8–14 nights) away). Findings: Mobility data were provided by 479 participants. At baseline, 67 participants (14%) were considered long-term mobile. Male sex was associated with an increased probability of long-term mobility (RR 2.02; 95%CI: 1.30–3.14, p < 0.01). In follow-up, 185 participants (60% of respondents) were considered generally mobile. Reasons for travel included obtaining food or supporting farming activities (45% of trips) and work or trade (33% of trips). Retention in HIV care was found for 417 (87%) participants. Long-term mobility was associated with a 14% (RR 0.86; 95%CI: 0.75–0.98) lower likelihood of retention (p = 0.03). Conclusions: Refugees and Ugandan nationals accessing HIV care in refugee settlements frequently travel to support their survival needs. Mobility is associated with inferior retention and should be considered in interventions to optimize HIV care.

Background: Persons living in refugee settlements in sub-Saharan Africa may be at increased risk for COVID-19 and experience barriers to accessing COVID-19 information. We aimed to evaluate the implementation of “Dial-COVID” a multi-lingual, toll free, telephone platform that uses interactive voice response (IVR) to track COVID-19 symptoms/exposure and disseminate COVID-19 health information in refugee settlements in Uganda. We hypothesized that IVR could provide an alternative way to screen for COVID-19 and communicate public health information to humanitarian populations when physical access and testing capacity were limited. Methods: The Dial-COVID IVR platform was created in ten languages and advertised by community health workers in refugee settlements for participants to call into toll free. In a recorded IVR symptom survey, participants were screened for COVID-19 symptoms/exposures and based on their responses, received tailored public health messages about COVID-19 risk mitigation in accordance with Uganda Ministry of Health guidelines. Here we report the challenges and lessons learned implementing this research during the pandemic. Results: Between February 2021 and March 2022, 15,465 calls were received by the Dial-COVID platform from all 31 refugee settlements in Uganda through which 6,913 symptom surveys were completed and 10,411 public health messages were disseminated in all study languages. Uptake of Dial-COVID fluctuated with the national COVID-19 caseload and was impacted by phone ownership and connectivity in refugee settlements. Intensified advertising efforts promoted Dial-COVID uptake. Flexibility to adapt IVR messages was contingent on translation capacity. Conclusion: Refugees living in refugee settlements across Uganda accessed Dial-COVID to share and obtain COVID-19 information suggesting that IVR holds potential for rapid information dissemination and screening of humanitarian populations during future infectious disease outbreaks and may be a valuable tool for routine public health programs. IVR adaptation flexibility and reach are influenced by language constraints and by contextual factors related to platform access. Registration details: World Pandemic Research Network– 490652.

Background: Scale-up of HIV pre-exposure prophylaxis (PrEP) services in Uganda is ongoing. However, health care workers (HCWs) may not be aware of PrEP nor what offering this service entails. We explored the impact of standardized HCW training on the knowledge and perspectives of PrEP service delivery in Uganda.Methods: We recruited HCWs from facilities that offered HIV-related services in Central Uganda. Using the Uganda Ministry of Health curriculum, we trained HCWs on PrEP services. We collected data about PrEP knowledge, preparedness, and willingness to deliver PrEP to multiple key populations before the training, immediately after the training, and >6 months later (exit). We additionally conducted 15 qualitative interviews after the exit survey. Quantitative data were analyzed by Fisher exact test, while qualitative interview data were analyzed inductively.Results: We recruited 80 HCWs from 35 facilities in urban (N = 24, 30%), peri-urban (N = 30, 37%), and rural (N = 26, 33%) areas. Most HCWs were nurse counselors (N = 52, 65%) or medical/clinical officers (N = 15, 18%). Surveys indicated that awareness of PrEP increased after the training and remained high. Knowledge of PrEP (i.e., as an effective, short-term antiretroviral medication to use before HIV exposure for people at high risk) generally increased with training, but significant gaps remained, and knowledge decreased with time. Most HCWs recommended PrEP for female sex workers and HIV serodifferent couples, as well as other key populations. We observed increases in the number of HCW who felt their facility was prepared to cater for HIV prevention and provide PrEP, but this view was not universal. HCWs believed in PrEP effectiveness and embraced it as an additional HIV prevention method. Concerns included patient adherence and behavioral risk compensation. HCWs noted challenges in PrEP delivery in terms of inadequate clinic preparedness, infrastructure, staff capacity, and poor attitudes toward key populations by untrained health workers. They felt further training was needed to ensure a smooth scale-up of services without stigmatization.Conclusions: Standardized training improved knowledge, willingness, and preparedness to offer PrEP services among most HCWs in Central Uganda. Ongoing training will be needed to optimize PrEP delivery services and expand delivery to levels needed for population-level impact.

Background: HIV self-testing (HIVST) and pre-exposure prophylaxis (PrEP) are complementary tools that could empower sex workers to control their HIV protection, but few studies have jointly evaluated PrEP and HIVST in any setting. Methods: The Empower Study was an open-label randomized trial in Uganda. Sex workers were offered F/tenofovir disoproxil fumarate and randomized 1:1 to monthly HIVST and quarterly in-clinic testing (intervention) or quarterly in-clinic HIV testing alone (standard of care) and followed up for 12 months. PrEP adherence was measured using electronic adherence monitoring and tenofovir diphosphate (TFV-DP) levels in dried blood spots. Adherence outcomes and sexual behaviors were compared by arm using generalized estimating equation models. Results: We enrolled 110 sex workers: 84 cisgender women, 14 transgender women, 10 men who have sex with men, and 2 transgender men. The median age was 23 years. The 12-month retention was 75%. Nearly all (99.4%) used ≥1 HIVST kit. The proportion with TFV-DP levels ≥700 fmol/punch in the HIVST and standard of care arms at the 3-, 6-, 9-, and 12-month visits was 2.4%, 2.3%, 0%, and 0% and 7.9%, 0%, 0%, and 0%, respectively, with no differences by randomization arm (P > 0.2). Self-reported condomless sex acts with paying partners was similar by arm [adjusted incidence rate ratio 0.70; 95% confidence interval (CI): 0.42 to 1.17; P = 0.18]. One seroconversion occurred (HIV incidence, 0.9/100 person-years); TFV-DP was not detected at any visit. Conclusions: A gender-diverse sample of sex workers in Uganda used HIVST but not daily oral PrEP for HIV protection. Alternate approaches to promote PrEP use, including long-acting formulations, should be considered in this population.