Enhanced peer-group strategies to support the prevention of mother-to-child HIV transmission leads to increased retention in care in Uganda: A randomized controlled trial.

INTRODUCTION: Despite the scale-up of Option B+, long-term retention of women in HIV care during pregnancy and the postpartum period remains an important challenge. We compared adherence to clinic appointments and antiretroviral therapy (ART) at 6 weeks, 6, and and 24 months postpartum among pregnant women living with HIV and initiating Option B+. Women were randomized to a peer group support, community-based drug distribution and income-generating intervention called "Friends for Life Circles" (FLCs) versus the standard of care (SOC). Our secondary outcome was infant HIV status and HIV-free survival at 6 weeks and 18 months postpartum. METHODS: Between 16 May 2016 and 12 September 2017, 540 ART-naïve pregnant women living with HIV at urban and rural health facilities in Uganda were enrolled in the study at any gestational age. Participants were randomized 1:1 to the unblinded FLC intervention or SOC at enrolment and assessed for adherence to the prevention of mother-to-child HIV transmission (PMTCT) clinic appointments at 6 weeks, 12, and 24 months postpartum, self-reported adherence to ART at 6 weeks, 6 and 24 months postpartum and supported by plasma HIV-1 RNA viral load (VL) measured at the same time points, retention in care through the end of study, and HIV status and HIV-free survival of infants at 18 months postpartum. The FLC groups were formed during pregnancy within 4 months of enrollment and held monthly meetings in their communites, and were followed up until the last group participant reached 24 months post delivery. We used Log-rank and Chi-Square p-values to test the equality of Kaplan-Meier survival probabilities and hazard rates (HR) for failure to retain in care for any reason by study arm. RESULTS: There was no significant difference in adherence to PMTCT clinic visits or to ART or in median viral loads between FLC and SOC arms at any follow-up time points. Retention in care through the end of study was high in both arms but significantly higher among participants randomized to FLC (86.7%) compared to SOC (79.3%), p = 0.022. The adjusted HR of visit dropout was 2.4 times greater among participants randomized to SOC compared to FLC (aHR = 2.363, 95% CI: 1.199-4.656, p = 0.013). Median VL remained < 400 copies/ml in both arms at 6 weeks, 6, and 24 months postpartum. Eight of the 431 infants tested at 18 months were HIV positive (1.9%), however, this was not statistically different among mothers enrolled in the FLC arm compared to those in the SOC arm. At 18 months, HIV-free survival of children born to mothers in the FLC arm was significantly higher than that of children born to mothers in the SOC arm. CONCLUSIONS: Our findings suggest that programmatic interventions that provide group support, community-based ART distribution, and income-generation activities may contribute to retention in PMTCT care, HIV-free survival of children born to women living with HIV, and ultimately, to the elimination of mother-to-child HIV transmission (EMTCT). TRIAL REGISTRATION: NCT02515370 (04/08/2015) on ClinicalTrials.gov.

HIV and hepatitis B, C co-infection and correlates of HIV infection among men who have sex with men in Rwanda, 2021: a respondent-driven sampling, cross-sectional study.

BACKGROUND: Men who have sex with men (MSM) are a key population group disproportionately affected by HIV and other sexually transmitted infections (STIs) worldwide. In Rwanda, the HIV epidemic remains a significant public health concern, and understanding the burden of HIV and hepatitis B and C coinfections among MSM is crucial for designing effective prevention and control strategies. This study aims to determine the prevalence of HIV, hepatitis B, and hepatitis C infections among MSM in Rwanda and identify correlates associated with HIV infection within this population. METHODS: We used respondent-driven sampling (RDS) to recruit participants between November and December 2021. A face-to-face, structured questionnaire was administered. Testing for HIV infection followed the national algorithm using two rapid tests: Alere Combo and STAT PAK as the first and second screening tests, respectively. Hepatitis B surface antigen (HBsAg) and anti-HCV tests were performed. All statistics were adjusted for RDS design, and a multivariable logistic regression model was constructed to identify factors associated with HIV infection. RESULTS: The prevalence of HIV among MSM was 6·9% (95% CI: 5·5-8·6), and among HIV-positive MSM, 12·9% (95% CI: 5·5-27·3) were recently infected. The prevalence of hepatitis B and C was 4·2% (95% CI: 3·0-5·7) and 0·7% (95% CI: 0·4-1·2), respectively. HIV and hepatitis B virus coinfection was 0·5% (95% CI: 0·2-1·1), whereas HIV and hepatitis C coinfection was 0·1% (95% CI: 0·0-0·5), and no coinfection for all three viruses was observed. MSM groups with an increased risk of HIV infection included those who ever suffered violence or abuse because of having sex with other men (AOR: 3·42; 95% CI: 1·87-6·25), those who refused to answer the question asking about 'ever been paid money, goods, or services for sex' (AOR: 10·4; 95% CI: 3·30-32·84), and those not consistently using condoms (AOR: 3·15; 95% CI: 1·31-7·60). CONCLUSION: The findings suggest more targeted prevention and treatment approaches and underscore the importance of addressing structural and behavioral factors contributing to HIV vulnerability, setting interventions to reduce violence and abuse against MSM, promoting safe and consensual sexual practices, and expanding access to HIV prevention tools such as condoms and preexposure prophylaxis (PrEP).

Factors associated with retention on pre-exposure prophylaxis among female sex workers in Kigali, Rwanda.

Pre-Exposure Prophylaxis (PrEP) is recommended as an additional HIV prevention measure for persons at substantial risk of HIV acquisition. Although uptake of PrEP among female sex workers (FSW) has increased, retention remains low, resulting in suboptimal benefits. This study aimed at determining PrEP retention rates and associated factors among FSW in Kigali, Rwanda. We retrospectively studied records of 309 FSW abstracted from five (5) health centers for the period between April-June 2020 and April-June 2021. PrEP retention was defined as presenting for a scheduled follow-up visit. We used Kaplan-Meier survival analysis to estimate survival probabilities at months 1,3,6,9, and 12 post-PrEP initiation and Cox regression to determine factors associated with 12-month PrEP retention. Data was analyzed using STATA (version 14.0). Out of 309 FSW whose records were reviewed, data for 268 (87%) were complete. One half (50%, n = 133) of the respondents were aged 25-34 years; slightly more than half (52%, n = 136) were single; nearly three-quarters (73%, n = 196) had completed primary school; majority (88%, n = 236) lived alone; while 69% (n = 184) had no formal employment besides sex work. PrEP dropout rates were 228, 65, 29, 49, and 36 per 100-persons years at months 1, 3, 6, 9 and 12 respectively, with 81%, 72%, 67%, 59% and 53% of FSW that started PrEP retained at these time periods. Multivariable Cox regression revealed that compared to FSW opposed to additional children, the desire to have two or more children (adjusted Hazard Ratio [aHR] = 1.654; 95% Confidential Interval [95%CI]: 1.008, 2.713); and using hormonal (aHR = 2.091, 95%CI: 1.181, 3.702) or no method of contraception other than condoms (aHR = 2.036, 95%CI: 1.006, 4.119) were factors positively associated with PrEP retention. Conversely, compared to consistent condom-use, not using (aHR = 0.329; 95%CI: 0.149, 0.726) or inconsistently using condoms (aHR = 0.413; 95%CI: 0.228, 0.749), and accessing PrEP from ultra-urban clinics (aHR = 0.290; 95%CI: 0.183, 0.458) compared to clinics in the outskirts of the city, were factors negatively associated with PrEP retention. The study found a continuous decline in PrEP retention among FSW with slightly more than half retained at 12 months. To improve outcomes, PrEP retention monitoring should target FSW enrolled in ultra-urban clinics and those not or inconsistently using condoms.

HIV, syphilis, and hepatitis B virus infection and male circumcision in five Sub-Saharan African countries: Findings from the Population-based HIV Impact Assessment surveys, 2015-2019.

Voluntary medical male circumcision (VMMC) has primarily been promoted for HIV prevention. Evidence also supports that male circumcision offers protection against other sexually transmitted infections. This analysis assessed the effect of circumcision on syphilis, hepatitis B virus (HBV) infection and HIV. Data from the 2015 to 2019 Population-based HIV Impact Assessments (PHIAs) surveys from Rwanda, Tanzania, Uganda, Zambia, and Zimbabwe were used for the analysis. The PHIA surveys are cross-sectional, nationally representative household surveys that include biomarking testing for HIV, syphilis and HBV infection. This is a secondary data analysis using publicly available PHIA data. Univariate and multivariable logistic regression models were created using pooled PHIA data across the five countries to assess the effect of male circumcision on HIV, active and ever syphilis, and HBV infection among sexually active males aged 15-59 years. Circumcised men had lower odds of syphilis infection, ever or active infection, and HIV, compared to uncircumcised men, after adjusting for covariates (active syphilis infection = 0.67 adjusted odds ratio (aOR), 95% confidence interval (CI), 0.52-0.87, ever having had a syphilis infection = 0.85 aOR, 95% CI, 0.73-0.98, and HIV = 0.53 aOR, 95% CI, 0.47-0.61). No difference between circumcised and uncircumcised men was identified for HBV infection (P = 0.75). Circumcised men have a reduced likelihood for syphilis and HIV compared to uncircumcised men. However, we found no statistically significant difference between circumcised and uncircumcised men for HBV infection.

Cango Lyec (Healing the Elephant): HIV Prevalence and Vulnerabilities Among Adolescent Girls and Young Women in Postconflict Northern Uganda.

OBJECTIVES: Adolescent girls and young women younger than 25 years (AGYW) account for disproportionate HIV infections in sub-Saharan Africa. Impacts of war in Northern Uganda continue to affect HIV-related health and wellbeing of young people postconflict. Prevalence and incidence of HIV infection were estimated, and factors associated with HIV prevalence among sexually active AGYW in Northern Uganda were investigated. METHODS: Cango Lyec is a cohort involving conflict-affected populations in Northern Uganda. Nine randomly selected communities in Gulu, Nwoya, and Amuru districts were mapped. House-to-house census was conducted. Consenting participants aged 13-49 years were enrolled over 3 study rounds (2011-2015), of whom 533 were AGYW and had ever had sex. Data were collected on trauma, depression, and sociodemographic-behavioral characteristics. Venous blood was taken for HIV and syphilis serology. Multivariable logistic regression determined baseline factors associated with HIV prevalence. RESULTS: HIV prevalence among AGYW was 9.7% (95% CI: 7.3 to 12.6). AGYW living in Gulu (adjusted risk ratio, aRR: 2.48; 95% CI: 1.12 to 5.51) or Nwoya (aRR: 2.65; 95% CI: 1.03 to 6.83) were more likely than in Amuru to be living with HIV. Having self-reported genital ulcers (aRR: 1.93; 95% CI: 0.97 to 3.85) or active syphilis (aRR: 3.79; 95% CI: 2.35 to 6.12) was associated with increased risk of HIV infection. The likelihood of HIV was higher for those who experienced sexual violence in the context of war (aRR: 2.37; 95% CI: 1.21 to 4.62) and/or probable depression (aRR: 1.95; 95% CI: 1.08 to 3.54). HIV incidence was 8.9 per 1000 person-years. CONCLUSION: Ongoing legacies of war, especially gender violence and trauma, contribute to HIV vulnerability among sexually active AGYW. Wholistic approaches integrating HIV prevention with culturally safe initiatives promoting sexual and mental health in Northern Uganda are essential.

Enhanced Peer-Group strategies to support prevention of Mother-to-Child HIV transmission leads to increased retention in care in Uganda: A Randomized controlled trial.

Introduction: Despite scale up of Option B+, long-term retention of women in HIV care during pregnancy and the postpartum period remains an important challenge. We compared adherence to clinic appointments and antiretroviral therapy (ART) at different follow-up time points between enrolment and 24 months postpartum among pregnant women living with HIV and initiating Option B+ randomized to a peer group support, community-based drug distribution and income-generating intervention called "Friends for Life Circles" (FLCs) versus the standard of care (SOC). Methods: Between 16 May 2016 and 12 September 2017, 540 ART-naïve pregnant women living with HIV at urban and rural health facilities in Uganda were enrolled in the study. Participants were randomized 1:1 to the FLC intervention or SOC and assessed for adherence to prevention of mother to child HIV transmission (PMTCT) clinic appointments at 6 weeks, 12 and 24 months postpartum, self-reported adherence to ART at 6 weeks, 6 and 24 months postpartum validated by plasma HIV-1 RNA viral load (VL) measured at the same time points, and HIV status and HIV-free survival of infants at 18 months postpartum. We used Log-rank and Chi-Square p-values to test the equality of Kaplan-Meier survival probabilities and hazard rates (HR) for failure to retain in care for any reason by study arm. Results: There was no significant difference in adherence to PMTCT clinic visits or to ART or in median viral loads between FLC and SOC arms at any follow-up time points. Retention in care through the end of study was high in both arms but significantly higher among participants randomized to FLC (86.7%) compared to SOC (79.3%), p=0.022. The adjusted HR of visit dropout was 2.5 times greater among participants randomized to SOC compared to FLC (aHR=2.498, 95% CI: 1.417 - 4.406, p=0.002). Median VL remained < 400 copies/ml in both arms at 6 weeks, 6 and 24 months postpartum. Conclusions: Our findings suggest that programmatic interventions that provide group support, community based ART distribution and income-generation activities may contribute to retention in PMTCT care, HIV-free survival of children born to women living with HIV, and to the elimination of mother to child HIV transmission (MTCT).

Co-Surveillance of Rotaviruses in Humans and Domestic Animals in Central Uganda Reveals Circulation of Wide Genotype Diversity in the Animals.

Rotavirus genotypes are species specific. However, interspecies transmission is reported to result in the emergence of new genotypes. A cross-sectional study of 242 households with 281 cattle, 418 goats, 438 pigs, and 258 humans in Uganda was undertaken between 2013 and 2014. The study aimed to determine the prevalence and genotypes of rotaviruses across co-habiting host species, as well as potential cross-species transmission. Rotavirus infection in humans and animals was determined using NSP3 targeted RT-PCR and ProSpecT Rotavirus ELISA tests, respectively. Genotyping of rotavirus-positive samples was by G- and P-genotype specific primers in nested RT-PCR assays while genotyping of VP4 and VP7 proteins for the non-typeable human positive sample was done by Sanger sequencing. Mixed effect logistic regression was used to determine the factors associated with rotavirus infection in animals. The prevalence of rotavirus was 4.1% (95% CI: 3.0-5.5%) among the domestic animals and 0.8% (95% CI: 0.4-1.5%) in humans. The genotypes in human samples were G9P[8] and P[4]. In animals, six G-genotypes, G3(2.5%), G8(10%), G9(10%), G11(26.8%), G10(35%), and G12(42.5%), and nine P-genotypes, P[1](2.4%), P[4](4.9%), P[5](7.3%), P[6](14.6%), P[7](7.3%), P[8](9.8%), P[9](9.8%), P[10](12.2%), and P[11](17.1%), were identified. Animals aged 2 to 18 months were less likely to have rotavirus infection in comparison with animals below 2 months of age. No inter-host species transmission was identified.

Engagement in HIV continuum of care: Another step needed to close the gap toward UNAIDS 90-90-90 targets among younger men in Rwanda.

In this study, we measured Rwandan men's engagement in HIV services based on the UNAIDS 90-90-90 targets and assessed factors associated with linkage to HIV services. We analyzed the Rwanda Population-based HIV Impact Assessment (RPHIA) data for 15- to 64-year-old males. We conducted bivariate analysis to assess the distribution and association of sociodemographic characteristics with UNAIDS 90-90-90 targets. We adjusted multivariable models to understand the effect measurement of associated factors and determine the factors that best predict the achievement of UNAIDS 90-90-90. Of 13 780 males aged 15-64 years who participated in the RPHIA and consented to the blood draw and HIV testing, 302 had a positive HIV result, while 301 had valid responses to all variables analyzed in this paper and were included in the analysis. We found that age group was an explanatory and predictive factor for achievement of UNAIDS 90-90-90. Younger men living with HIV (MLHIV) are less likely to have achieved UNAIDS 90-90-90 compared to MLHIV 50-64 years old: adjusted odds ratio (aOR) for MLHIV aged 15-34 years was 0.21 (0.08-0.53) and aOR for MLHIV aged 35-49 years was 0.77 (0.36-1.66). To close the UNAIDS 90-90-90 gap in Rwanda, innovative service delivery strategies are needed to support young MLHIV to reach 90-90-90.

Cango Lyec (Healing the Elephant): Probable post-traumatic stress disorder (PTSD) and depression in Northern Uganda five years after a violent conflict.

Background: From 1986 to 2006, Northern Uganda experienced an atrocious civil war between the Lord's Resistance Army (LRA) and the Ugandan government. Acholi people living in the region continue to be impacted by trauma sequelae of the war and a wide range of daily stressors including poverty, hunger, and high rates of HIV infection. To date, there is a dearth of gender-differentiated mental health research in this post-conflict setting. The current study aimed to estimate the prevalence of probable post-traumatic stress disorder (PTSD) and depression in three districts most affected by the Northern Ugandan conflict and examine socio-structural, war-related, and sexual vulnerability factors associated with mental health. Methods: Cango Lyec (Healing the Elephant) is an open cohort study involving participants from eight randomly selected communities in Amuru, Gulu, and Nwoya districts of Northern Uganda. Between November 2011 and July 2012, the baseline cohort (N = 2,458) completed the Harvard Trauma Questionnaire (HTQ) and Hopkins Symptom Checklist-25 (HSCL-25) for screening PTSD and depression, in addition to a detailed questionnaire assessing socio-demographic-behavioral characteristics. Baseline categorical variables were compared between males and females using Fisher's exact test. Multivariate logistic regression was used to model correlates of probable PTSD and depression. All analyses were stratified by gender. Results: The overall prevalence of probable PTSD and depression was 11.7% and 15.2% respectively. Among former abductees, the prevalence was 23.2% for probable PTSD and 26.6% for probable depression. Women were significantly more likely to experience mental distress than men. Factors associated with mental distress included wartime trauma (adjusted odds ratios ranging from 2.80 to 7.19), experiences of abduction (adjusted odds ratios ranging from 1.97 to 3.03), and lack of housing stability and safety (adjusted odds ratios ranging from 1.95 to 4.59). Additional risk factors for women included HIV infection (AOR=1.90; 95% CI: 1.29-2.80), sexual abuse in the context of war (AOR=1.58; 95% CI: 1.02-2.45), and intimate partner violence (AOR=2.45; 95% CI: 1.07-5.63). Conclusion: Cango Lyec participants displayed lower than previously reported yet significant levels of probable PTSD and depression. Based on findings from this study, providing trauma-informed care, ensuring food and housing security, eliminating gender-based violence, and reintegrating former abductees remain important tasks to facilitate post-conflict rehabilitation in Northern Uganda.

Acquired HIV drug resistance among adults living with HIV receiving first-line antiretroviral therapy in Rwanda: A cross-sectional nationally representative survey.

BACKGROUND: We assessed the prevalence of acquired HIV drug resistance (HIVDR) and associated factors among patients receiving first-line antiretroviral therapy (ART) in Rwanda. METHODS: This cross-sectional study included 702 patients receiving first-line ART for at least 6 months with last viral load (VL) results ≥1000 copies/mL. Blood plasma samples were subjected to VL testing; specimens with unsuppressed VL were genotyped to identify HIVDR-associated mutations. Data were analysed using STATA/SE. RESULTS: Median time on ART was 86.4 months (interquartile range [IQR], 44.8-130.2 months), and median CD4 count at ART initiation was 311 cells/mm3 (IQR, 197-484 cells/mm3). Of 414 (68.2%) samples with unsuppressed VL, 378 (88.3%) were genotyped. HIVDR included 347 (90.4%) non-nucleoside reverse transcriptase inhibitor- (NNRTI), 291 (75.5%) nucleoside reverse transcriptase inhibitor- (NRTI) and 13 (3.5%) protease inhibitor (PI) resistance-associated mutations. The most common HIVDR mutations were K65R (22.7%), M184V (15.4%) and D67N (9.8%) for NRTIs and K103N (34.4%) and Y181C/I/V/YC (7%) for NNRTIs. Independent predictors of acquired HIVDR included current ART regimen of zidovudine + lamivudine + nevirapine (adjusted odds ratio [aOR], 3.333 [95% confidence interval (CI): 1.022-10.870]; p = 0.046) for NRTI resistance and current ART regimen of tenofovir + emtricitabine + nevirapine (aOR, 0.148 [95% CI: 0.028-0.779]; p = 0.025), zidovudine + lamivudine + efavirenz (aOR, 0.105 [95% CI: 0.016-0.693]; p = 0.020) and zidovudine + lamivudine + nevirapine (aOR, 0.259 [95% CI: 0.084-0.793]; p = 0.019) for NNRTI resistance. History of ever switching ART regimen was associated with NRTI resistance (aOR, 2.53 [95% CI: 1.198-5.356]; p = 0.016) and NNRTI resistance (aOR, 3.23 [95% CI: 1.435-7.278], p = 0.005). CONCLUSION: The prevalence of acquired HIV drug resistance (HIVDR) was high among patient failing to re-suppress VL and was associated with current ART regimen and ever switching ART regimen. The findings of this study support the current WHO guidelines recommending that patients on an NNRTI-based regimen should be switched based on a single viral load test and suggests that national HIV VL monitoring of patients receiving ART has prevented long-term treatment failure that would result in the accumulation of TAMs and potential loss of efficacy of all NRTI used in second-line ART as the backbone in combination with either dolutegravir or boosted PIs.

Lessons Learned from Programmatic Gains in HIV Service Delivery During the COVID-19 Pandemic - 41 PEPFAR-Supported Countries, 2020.

The U.S. President's Emergency Plan for AIDS Relief (PEPFAR) supports country programs in identifying persons living with HIV infection (PLHIV), providing life-saving treatment, and reducing the spread of HIV in countries around the world (1,2). CDC used Monitoring, Evaluation, and Reporting (MER) data* to assess the extent to which COVID-19 mitigation strategies affected HIV service delivery across the HIV care continuum† globally during the first year of the COVID-19 pandemic. Indicators included the number of reported HIV-positive test results, the number of PLHIV who were receiving antiretroviral therapy (ART), and the rates of HIV viral load suppression. Percent change in performance was assessed between countries during the first 3 months of 2020, before COVID-19 mitigation efforts began (January-March 2020), and the last 3 months of the calendar year (October-December 2020). Data were reviewed for all 41 countries to assess total and country-level percent change for each indicator. Then, qualitative data were reviewed among countries in the upper quartile to assess specific strategies that contributed to programmatic gains. Overall, positive percent change was observed in PEPFAR-supported countries in HIV treatment (5%) and viral load suppression (2%) during 2020. Countries reporting the highest gains across the HIV care continuum during 2020 attributed successes to reducing or streamlining facility attendance through strategies such as enhancing index testing (offering of testing to the biologic children and partners of PLHIV)§ and community- and home-based testing; treatment delivery approaches; and improvements in data use through monitoring activities, systems, and data quality checks. Countries that reported program improvements during the first year of the COVID-19 pandemic offer important information about how lifesaving HIV treatment might be provided during a global public health crisis.

Brief Report: Active HIV Case Finding in the City of Kigali, Rwanda: Assessment of Voluntary Assisted Partner Notification Modalities to Detect Undiagnosed HIV Infections.

BACKGROUND: Voluntary assisted partner notification (VAPN) services that use contract, provider, or dual referral modalities may be efficient to identify individuals with undiagnosed HIV infection. We aimed to assess the relative effectiveness of VAPN modalities in identifying undiagnosed HIV infections. SETTING: VAPN was piloted in 23 health facilities in Kigali, Rwanda. METHODS: We identified individuals with a new HIV diagnosis before antiretroviral therapy initiation or individuals on antiretroviral therapy (index cases), who reported having had sexual partners with unknown HIV status, to assess the association between referral modalities and the odds of identifying HIV-positive partners using a Bayesian hierarchical logistic regression model. We adjusted our model for important factors identified through a Bayesian variable selection. RESULTS: Between October 2018 and December 2019, 6336 index cases were recruited, leading to the testing of 7690 partners. HIV positivity rate was 7.1% (546/7690). We found no association between the different referral modalities and the odds of identifying HIV-positive partners. Notified partners of male individuals (adjusted odds ratio 1.84; 95% credible interval: 1.50 to 2.28) and index cases with a new HIV diagnosis (adjusted odds ratio 1.82; 95% credible interval: 1.45 to 2.30) were more likely to be infected with HIV. CONCLUSION: All 3 VAPN modalities were comparable in identifying partners with HIV. Male individuals and newly diagnosed index cases were more likely to have partners with HIV. HIV-positive yield from index testing was higher than the national average and should be scaled up to reach the first UNAIDS-95 target by 2030.

HIV genotypic resistance among pregnant women initiating ART in Uganda: a baseline evaluation of participants in the Option B+ clinical trial.

Background: Pre-treatment HIV drug resistance is a threat to elimination of mother to child HIV transmission and could lead to virological failure among HIV-positive pregnant women. We analysed genotypic HIV drug resistance (HIVDR) of baseline samples of participants enrolled in the Option B+ clinical trial in Uganda. Methods: HIV-infected pregnant women attending antenatal care were enrolled from Uganda's National Referral Hospital (Mulago) and Mityana District general hospital and surrounding health centers (HCs). Genotypic HIV testing was performed on blood samples from the first 135 enrolled women out of a subset of 136 participants (25%) who had a baseline VL>1000 copies/mL as one sample failed to amplify. Results: 159/540 (29.4%) had a VL < 1000 copies/ml and 381/540 (70.6%) had a VL >1,000 copies/ml. Of the women with VL>1000 copies/ml, 32 (23.7%) had resistance mutations including 29/135 (21.5%) NNRTI mutations, 6/135 (4.4%) NRTI mutations and 3/135 (2.2%) had both NNRTI and NRTI mutations. The most common NNRTI resistance mutations were: K103KN (5), K103N (5), V179T (4) and E138A (4). Conclusions: One quarter of the HIV-infected pregnant women in this trial at baseline had NNRTI genotypic resistance mutations. Our findings support new WHO guidelines for first-line ART that were changed to dolutegravir-based regimens.

Recent infections among individuals with a new HIV diagnosis in Rwanda, 2018-2020.

BACKGROUND: Despite Rwanda's progress toward HIV epidemic control, 16.2% of HIV-positive individuals are unaware of their HIV positive status. Tailoring the public health strategy could help reach these individuals with new HIV infection and achieve epidemic control. Recency testing is primarily for surveillance, monitoring, and evaluation but it's not for diagnostic purposes. However, it's important to know what proportion of the newly diagnosed are recent infections so that HIV prevention can be tailored to the profile of people who are recently infected. We therefore used available national data to characterize individuals with recent HIV infection in Rwanda to inform the epidemic response. METHODS: We included all national-level data for recency testing reported from October 2018 to June 2020. Eligible participants were adults (aged ≥15 years) who had a new HIV diagnosis, who self-reported being antiretroviral therapy (ART) naïve, and who had consented to recency testing. Numbers and proportions of recent HIV infections were estimated, and precision around these estimates was calculated with 95% confidence intervals (CI). Logistic regression was used to assess factors associated with being recently (within 12 months) infected with HIV. RESULTS: Of 7,785 eligible individuals with a new HIV-positive diagnosis, 475 (6.1%) met the criteria for RITA recent infection. The proportion of RITA recent infections among individuals with newly identified HIV was high among those aged 15-24 years (9.6%) and in men aged ≥65 years (10.3%) compared to other age groups; and were higher among women (6.7%) than men (5.1%). Of all recent cases, 68.8% were women, and 72.2% were aged 15-34 years. The Northern province had the fewest individuals with newly diagnosed HIV but had the highest proportion of recent infections (10.0%) compared to other provinces. Recent infections decreased by 19.6% per unit change in time (measured in months). Patients aged ≥25 years were less likely to have recent infection than those aged 15-24 years with those aged 35-49 years being the least likely to have recent infection compared to those aged 15-24 years (adjusted odds ratio [aOR], 0.415 [95% CI: 0.316-0.544]). CONCLUSION: Public health surveillance targeting the areas and the identified groups with high risk of recent infection could help improve outcomes.

Prevalence of undetectable and suppressed viral load in HIV-infected pregnant women initiating Option B+ in Uganda: an observational study nested within a randomized controlled trial.

BACKGROUND: Viral load (VL) testing is key in monitoring adherence to antiretroviral therapy (ART) and documenting HIV treatment response. As per HIV treatment guidelines in Uganda, the first VL test is recommended 6 months after initiation of ART. Undetectable VL (uVL) at ART initiation may be helpful in detecting elite controllers in the absence of previous ART use. We investigated viral suppression at ART initiation among a cohort of HIV-positive pregnant women enrolled in the Friends for Life Circles (FLC) for Option B+ randomized controlled trial (RCT). METHODS: Pregnant women ≥ 18 years of age testing positive for HIV at their first antenatal care visit and starting on ART Option B+ as per the National PMTCT Program guidelines were enrolled into the FLC for Option B+ RCT in urban Kampala and rural Mityana districts of Uganda. Each participant had whole blood samples collected at enrolment to assess baseline VL. Plasma HIV-1 RNA was quantified using COBAS Ampliprep /COBAS Taqman. Baseline VL below 400 RNA copies/ml was considered as viral suppression while baseline VL below 20 RNA copies/ml was considered uVL. RESULTS: The mean duration from the date of ART initiation to time of sample collection for baseline VL assessment was 4.4 days (SD 3.6). Of the 532 HIV-positive pregnant women enrolled in the FLC for Option B+ study and newly starting Option B+ without a self-reported history of prior ART use, 29 (5.5%) had uVL and 113 (21.4%) had suppressed VL at baseline. There was no association between participants' age, gravidity, marital status, mean monthly income, educational level, disclosure of HIV status to partner, and uVL or viral suppression at baseline. However, non-disclosure of HIV status to any other person was associated with decreased odds of viral suppression at baseline (OR 0.640; 0.416-0.982). CONCLUSION: Twenty-one percent of HIV-positive Ugandan pregnant women initiating ART (Option B+) showed virological suppression at baseline and were presumed to be "elite controllers" or to have misreported being ART-naive. Further studies are needed to better understand the biologic mechanisms of elite controllers among pregnant women as well as to differentiate elite controllers from concealed ART use. Trial Registration The trial was registered as NCT02515370 (04/08/2015) on Clinicaltrials.gov.

Unawareness of HIV Infection Among Men Aged 15-59 Years in 13 Sub-Saharan African Countries: Findings From the Population-Based HIV Impact Assessments, 2015-2019.

BACKGROUND: Identifying men living with HIV in sub-Saharan Africa (SSA) is critical to end the epidemic. We describe the underlying factors of unawareness among men aged 15-59 years who ever tested for HIV in 13 SSA countries. METHODS: Using pooled data from the nationally representative Population-based HIV Impact Assessments, we fit a log-binomial regression model to identify characteristics related to HIV positivity among HIV-positive unaware and HIV-negative men ever tested for HIV. RESULTS: A total of 114,776 men were interviewed and tested for HIV; 4.4% were HIV-positive. Of those, 33.7% were unaware of their HIV-positive status, (range: 20.2%-58.7%, in Rwanda and Cote d'Ivoire). Most unaware men reported they had ever received an HIV test (63.0%). Age, region, marital status, and education were significantly associated with HIV positivity. Men who had HIV-positive sexual partners (adjusted prevalence ratio [aPR]: 5.73; confidence interval [95% CI]: 4.13 to 7.95) or sexual partners with unknown HIV status (aPR: 2.32; 95% CI: 1.89 to 2.84) were more likely to be HIV-positive unaware, as were men who tested more than 12 months compared with HIV-negative men who tested within 12 months before the interview (aPR: 1.58; 95% CI: 1.31 to 1.91). Tuberculosis diagnosis and not being circumcised were also associated with HIV positivity. CONCLUSION: Targeting subgroups of men at risk for infection who once tested negative could improve yield of testing programs. Interventions include improving partner testing, frequency of testing, outreach and educational strategies, and availability of HIV testing where men are accessing routine health services.

Cango Lyec (Healing the Elephant): Chronic Hepatitis B Virus among post-conflict affected populations living in mid-Northern Uganda.

BACKGROUND: The legacy of war in Northern Uganda continues to impact people's health and wellbeing in the Acholi region. Despite increasing attention to Hepatitis B Virus (HBV) in Uganda and globally, concerns remain that unique drivers of infection, and barriers to screening, and treatment, persist among those affected by conflict. METHODS: Cango Lyec (Healing the Elephant) cohort survey involved conflict-affected adults aged 13-49 in three mid-Northern Uganda districts (Gulu, Amuru and Nwoya). Baseline (2011-2012) samples were tested for HBV surface antigen (HBsAg), HBV e-antigen (HBeAg), antibodies to HBV surface antigen (HBsAb), antibodies to HBV e-antigen (HBeAb), and antibodies to HBV core antigen (HBcAb). All HBsAg positive samples were tested for IgM antibodies to HBV B core antigen (HBc-IgM) and where available, >6-month follow-up samples were tested for HBeAg and HBV DNA. Data were analyzed using STATA 15 software. Logistic regression accounted for variance due to complex two-stage sampling that included stratification, unequal selection probabilities and community clustering. Odds ratios measured effect potential risk factors associated with chronic HBV infection. RESULTS: Among 2,421 participants, 45.7% were still susceptible to HBV infection. HBsAg seropositivity was 11.9% (10.9-13.0), chronic HBV was 11.6% (10.4-12.8), acquired immunity resulting from vaccination was 10.9%, and prior natural infection was 31.5%. Older age (OR:0.570; 95%CI:0.368-0.883) and higher education (OR:0.598; 95%CI:0.412-0.868) were associated with reduced odds of chronic HBV infection. Being male (OR:1.639; 95%CI:1.007-2.669) and having been abducted (OR:1.461; 95%CI:1.055-2.023) were associated with increased odds of infection. Among women, having 1 or 2 pregnancies (compared to none or >2) was associated with increased odds of infection (OR:1.764; 95%CI:1.009-3.084). CONCLUSION: Chronic HBV is endemic in Gulu, Amuru and Nwoya districts. Recommended strategies to reduce post-conflict prevalence include establishment of Northern Uganda Liver Wellness Centres, integration of screening and treatment into antenatal care, and roll out of birth-dose vaccination.

Child mortality associated with maternal HIV status: a retrospective analysis in Rwanda, 2005-2015.

INTRODUCTION: Child mortality remains highest in regions of the world most affected by HIV/AIDS. The aim of this study was to assess child mortality rates in relation to maternal HIV status from 2005 to 2015, the period of rapid HIV treatment scale-up in Rwanda. METHODS: We used data from the 2005, 2010 and 2015 Rwanda Demographic Health Surveys to derive under-2 mortality rates by survey year and mother's HIV status and to build a multivariable logistic regression model to establish the association of independent predictors of under-2 mortality stratified by mother's HIV status. RESULTS: In total, 12 010 live births were reported by mothers in the study period. Our findings show a higher mortality among children born to mothers with HIV compared with HIV negative mothers in 2005 (216.9 vs 100.7 per 1000 live births) and a significant reduction in mortality for both groups in 2015 (72.0 and 42.4 per 1000 live births, respectively). In the pooled reduced multivariable model, the odds of child mortality was higher among children born to mothers with HIV, (adjusted OR, AOR 2.09; 95% CI 1.57 to 2.78). The odds of child mortality were reduced in 2010 (AOR 0.69; 95% CI 0.59 to 0.81) and 2015 (AOR 0.35; 95% CI 0.28 to 0.44) compared with 2005. Other independent predictors of under-2 mortality included living in smaller families of 1-2 members (AOR 5.25; 95% CI 3.59 to 7.68), being twin (AOR 4.93; 95% CI 3.51 to 6.92) and being offspring from mothers not using contraceptives at the time of the survey (AOR 1.6; 95% CI 1.38 to 1.99). Higher education of mothers (completed primary school: (AOR 0.74; 95% CI 0.64 to 0.87) and secondary or higher education: (AOR 0.53; 95% CI 0.38 to 0.74)) was also associated with reduced child mortality. CONCLUSIONS: This study shows an important decline in under-2 child mortality among children born to both mothers with and without HIV in Rwanda over a 10-year span.

Sex Differences in HIV Testing - 20 PEPFAR-Supported Sub-Saharan African Countries, 2019.

Despite progress toward controlling the human immunodeficiency virus (HIV) epidemic, testing gaps remain, particularly among men and young persons in sub-Saharan Africa (1). This observational study used routinely collected programmatic data from 20 African countries reported to the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) from October 2018 to September 2019 to assess HIV testing coverage and case finding among adults (defined as persons aged ≥15 years). Indicators included number of HIV tests conducted, number of HIV-positive test results, and percentage positivity rate. Overall, the majority of countries reported higher HIV case finding among women than among men. However, a slightly higher percentage positivity was recorded among men (4.7%) than among women (4.1%). Provider-initiated counseling and testing (PITC) in health facilities identified approximately two thirds of all new cases, but index testing had the highest percentage positivity in all countries among both sexes. Yields from voluntary counseling and testing (VCT) and mobile testing varied by sex and by country. These findings highlight the need to identify and implement the most efficient strategies for HIV case finding in these countries to close coverage gaps. Strategies might need to be tailored for men who remain underrepresented in the majority of HIV testing programs.

Cango Lyec (Healing the Elephant): HIV incidence in post-conflict Northern Uganda.

BACKGROUND: Civil war in Northern Uganda resulted in widespread atrocities, human rights violations, and death, and caused millions to flee to internally displaced persons camps. War-related traumas combined with difficulties accessing HIV prevention and health services has led to extreme HIV-related vulnerability among conflict-affected people who survived the war. Objectives were to (1) determine HIV incidence among conflict-affected people in Northern Uganda and (2) identify vulnerabilities associated with HIV infection. METHODS: The Cango Lyec (Healing the Elephant) Project is a prospective cohort involving conflict-affected populations in three districts in Northern Uganda. In 2011, eight randomly selected communities were mapped, and a census was conducted. Consenting participants aged 13-49 years were followed over three rounds of follow-up. Longitudinal data collected included war-related experiences, sexual vulnerabilities, and sociodemographics. Blood samples were tested for HIV-1 at baseline and each 12-month follow-up. Multivariable Cox proportional hazard models determined factors associated with HIV incidence. FINDINGS: Overall, 1920 baseline HIV-negative participants with at least one follow-up contributed 3877 person-years (py) for analysis. Thirty-nine (23 female, 16 male) participants contracted HIV during follow-up. Age- and gender-standardised HIV incidence rate was 10•2 per 1000py (95%CI: 7•2-14•0). Stratified by sex, the age-adjusted HIV incidence was 11•0 per 1000py (95%CI: 6•9-16•6) among women and 9•4 per 1000py (95%CI: 5•3-15•3) among men. Adjusting for confounders, factors associated with risk of HIV included: having been abducted (HR: 3•70; 95%CI: 1•87-7•34), experiencing ≥12 war-related traumatic events (HR: 2•91 95%CI: 1•28-6•60), suicide ideation (HR: 2•83; 95%CI: 1•00-8•03), having ≥2 sexual partners (HR: 4•68; 95%CI: 1•36-16•05), inconsistent condom use (HR: 6•75; 95%CI: 2•49-18•29), and self-reported genital ulcers (HR: 4•39; 95%CI: 2•04-9•45). INTERPRETATION: Conflict-affected participants who had experienced abduction and multiple traumas during the war were at greater risk of HIV infection. Trauma-informed HIV prevention and treatment services, and culturally-safe mental health initiatives, are urgent for Northern Uganda.