Characteristics and clinical outcomes of patients presenting with advanced HIV disease in the "treat all" era: a retrospective cohort study from rural Rwanda.

BACKGROUND: In 2016 Rwanda adopted "treat all" where all patients with HIV are immediately eligible for ART regardless of disease progression. Despite widespread availability of treatment, it is unknown whether presentation with advanced HIV persists. METHODS: We conducted a retrospective cohort among patients aged ≥ 15 who enrolled in care between July 2016 and July 2018 in three rural Rwandan districts. We estimated the prevalence of advanced HIV, defined as presenting with CD4 count < 200 cells/mm3 or WHO stage 3 or 4, and compared baseline characteristics of patients with and without advanced HIV. We compared cumulative incidences and time to events using Chi squared tests and Cox proportional hazards models, respectively, for (a) viral load tests; (b) viral suppression; (c) death; and (d) treatment failure (a composite of death, lost to follow up, or virologic failure). RESULTS: Among 957 patients, 105 (11.0%) presented with advanced HIV. These patients were significantly more likely to have low body mass index, come from Burera district, be older, and be identified through inpatient settings rather than through voluntary or prenatal testing. Patients with advanced HIV had significantly higher risks of death at 12-months (9.5% vs 1.5%, p < 0.001) and 18-months (10.5% vs 1.9%, p < 0.001) and significantly higher risk of treatment failure at 12-months (21.9% vs. 14.2%, p = 0.037). After adjusting for confounders, patients with advanced HIV had still higher rates of death (adjusted Hazard ratio [aHR] = 4.4, 95% CI: 1.9, 10.2, p < 0.001) and treatment failure (aHR = 1.7, 95% CI: 1.1, 2.5, p = 0.017), but no difference in viral load testing (aHR = 1.1, 95% CI: 0.8, 1.5, p = 0.442) or viral suppression (aHR = 1.0, 95% CI: 0.8, 1.4, p = 0.949). When allowing for the hazard ratio to vary over time, patients with advanced HIV experienced elevated rates of treatment failure in the first six of enrollment, but not after nine months. CONCLUSION: Presenting with advanced HIV remains common and is still associated with poor patient outcomes. Sensitization of the community to the benefits of early ART initiation, identification of patients with advanced HIV, and holistic support programs for the first 6 months of treatment may be needed to improve outcomes.

Towards elimination of mother-to-child transmission of HIV in Rwanda: a nested case-control study of risk factors for transmission.

BACKGROUND: Mother-to-child HIV transmission (MTCT) has substantially declined since the scale-up of prevention programs around the world, including Rwanda. To achieve full elimination of MTCT, it is important to understand the risk factors associated with residual HIV transmission, defined as MTCT at the population-level that still occurs despite universal access to PMTCT. METHODS: We performed a case control study of children born from mothers with HIV with known vital status at 18 months from birth, who were followed in three national cohorts between October and December 2013, 2014, and 2015 in Rwanda. Children with HIV were matched in a ratio of 1:2 with HIV-uninfected children and a conditional logistic regression model was used to investigate risk factors for MTCT. RESULTS: In total, 84 children with HIV were identified and matched with 164 non-infected children. The median age of mothers from both groups was 29 years (interquartile range (IQR): 24-33). Of these mothers, 126 (51.4 %) initiated antiretroviral therapy (ART) before their pregnancy on record. In a multivariable regression analysis, initiation of ART in the third trimester (Adjusted Odds Ratio [aOR]: 9.25; 95 % Confidence Interval [95 % CI]: 2.12-40.38) and during labour or post-partum (aOR: 8.87; 95 % CI: 1.92-40.88), compared to initiation of ART before pregnancy, increased the risk of MTCT. Similarly, offspring of single mothers (aOR: 7.15; 95 % CI: 1.15-44.21), and absence of postpartum neonatal ART prophylaxis (aOR: 7.26; 95 % CI: 1.66-31.59) were factors significantly associated with MTCT. CONCLUSIONS: Late ART initiation for PMTCT and lack of postpartum infant prophylaxis are still the most important risk factors to explain MTCT in the era of universal access. Improved early attendance at antenatal care, early ART initiation, and enhancing the continuum of care especially for single mothers is crucial for MTCT elimination in Rwanda.

Patient and healthcare provider experiences of hepatitis C treatment with direct-acting antivirals in Rwanda: a qualitative exploration of barriers and facilitators.

BACKGROUND: Direct-acting antivirals (DAAs) are increasingly accessible to patients with hepatitis C (HCV) worldwide and are being introduced through national health systems in sub-Saharan Africa. DAAs are highly efficacious when tested in controlled trials, yet patients treated outside of study settings often encounter challenges in completing the full treatment and follow-up sequence. Little information is available on the influences of successful DAA implementation in sub-Saharan Africa. This qualitative study explored the individual- and system-level barriers and enablers of DAA treatment in Rwanda between March 2015 and November 2017. METHODS: Face-to-face interviews were conducted with 39 patients who initiated care at one of four referral hospitals initially offering DAAs. Ten healthcare providers who managed HCV treatment participated in face-to-face interviews to examine system-level barriers and facilitators. Interview data were analyzed using a general inductive approach in alignment with the a priori objective of identifying barriers and facilitators of HCV care. RESULTS: Barriers to successful treatment included patients' lack of knowledge surrounding HCV and its treatment; financial burdens associated with paying for medication, laboratory testing, and transportation; the cumbersome nature of the care pathway; the relative inaccessibility of diagnostics technology; and heavy workloads of healthcare providers accompanied by a need for additional HCV-specific training. Patients and healthcare providers were highly aligned on individual- and system-level barriers to care. The positive patient-provider relationship, strong support from community and family members, lack of stigma, and mild side effect profile of DAAs all positively influenced patients' engagement in treatment. CONCLUSIONS: Several interrelated factors acted as barriers and facilitators to DAA treatment in Rwanda. Patients' and healthcare providers' perceptions were in agreement, suggesting that the impeding and enabling factors were well understood by both groups. These results can be used to enact evidence-informed interventions to help maximize the impact of DAAs as Rwanda moves towards HCV elimination.

Population Size Estimation of Men Who Have Sex With Men in Rwanda: Three-Source Capture-Recapture Method.

BACKGROUND: Globally, men who have sex with men (MSM) continue to bear a disproportionately high burden of HIV infection. Rwanda experiences a mixed HIV epidemic, which is generalized in the adult population, with aspects of a concentrated epidemic among certain key populations at higher risk of HIV infection, including MSM. Limited data exist to estimate the population size of MSM at a national scale; hence, an important piece is missing in determining the denominators to use in estimates for policy makers, program managers, and planners to effectively monitor HIV epidemic control. OBJECTIVE: The aims of this study were to provide the first national population size estimate (PSE) and geographic distribution of MSM in Rwanda. METHODS: Between October and December 2021, a three-source capture-recapture method was used to estimate the MSM population size in Rwanda. Unique objects were distributed to MSM through their networks (first capture), who were then tagged according to MSM-friendly service provision (second capture), and a respondent-driven sampling survey was used as the third capture. Capture histories were aggregated in a 2k-1 contingency table, where k indicates the number of capture occasions and "1" and "0" indicate captured and not captured, respectively. Statistical analysis was performed in R (version 4.0.5) and the Bayesian nonparametric latent-class capture-recapture package was used to produce the final PSE with 95% credibility sets (CS). RESULTS: We sampled 2465, 1314, and 2211 MSM in capture one, two, and three, respectively. There were 721 recaptures between captures one and two, 415 recaptures between captures two and three, and 422 recaptures between captures one and three. There were 210 MSM captured in all three captures. The total estimated population size of MSM above 18 years old in Rwanda was 18,100 (95% CS 11,300-29,700), corresponding to 0.70% (95% CI 0.4%-1.1%) of total adult males. Most MSM reside in the city of Kigali (7842, 95% CS 4587-13,153), followed by the Western province (2469, 95% CS 1994-3518), Northern province (2375, 95% CS 842-4239), Eastern province (2287, 95% CS 1927-3014), and Southern province (2109, 95% CS 1681-3418). CONCLUSIONS: Our study provides, for the first time, a PSE of MSM aged 18 years or older in Rwanda. MSM are concentrated in the city of Kigali and are almost evenly distributed across the other 4 provinces. The national proportion estimate bounds of MSM out of the total adult males includes the World Health Organization's minimum recommended proportion (at least 1.0%) based on 2012 census population projections for 2021. These results will inform denominators to be used for estimating service coverage and fill existing information gaps to enable policy makers and planners to monitor the HIV epidemic among MSM nationally. There is an opportunity for conducting small-area MSM PSEs for subnational-level HIV treatment and prevention interventions.

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.

HIV incidence and prevalence among adults aged 15-64 years in Rwanda: Results from the Rwanda Population-based HIV Impact Assessment (RPHIA) and District-level Modeling, 2019.

OBJECTIVES: The 2018-2019 Rwanda Population-based HIV Impact Assessment (RPHIA) was conducted to measure national HIV incidence and prevalence. District-level estimates were modeled to inform resources allocation. METHODS: RPHIA was a nationally representative cross-sectional household survey. Consenting adults were interviewed and tested for HIV using the national diagnostic algorithm followed by laboratory-based confirmation of HIV status and testing for viral load (VL), limiting antigen (LAg) avidity, and presence of antiretrovirals. Incidence was calculated using normalized optical density ≤ 1·5, VL ≥ 1,000 copies/mL, and undetectable antiretrovirals. Survey and programmatic data were used to model district-level HIV incidence and prevalence. RESULTS: Of 31,028 eligible adults, 98·7% participated in RPHIA and 934 tested HIV positive. HIV prevalence among adults in Rwanda was 3·0% (95% CI:2·7-3·3). National HIV incidence was 0·08% (95% CI:0·02-0·14) and 0·11% (95% CI:0·00-0·26) in the City of Kigali (CoK). Based on district-level modeling, HIV incidence was greatest in the 3 CoK districts (0·11% to 0·15%) and varied across other districts (0·03% to 0·10%). CONCLUSIONS: HIV prevalence among adults in Rwanda is 3.0%; HIV incidence is low at 0.08%. District-level modeling has identified disproportionately affected urban hotspots: areas to focus resources.

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.

Temperature Variability and Occurrence of Diarrhoea in Children under Five-Years-Old in Cape Town Metropolitan Sub-Districts.

This paper describes the relationship between temperature change and diarrhoea in under five-year-old children in the Cape Town Metropolitan Area (CTMA) of South Africa. The study used climatic and aggregated surveillance diarrhoea incidence data of two peak periods of seven months each over two consecutive years. A Poisson regression model and a lagged Poisson model with autocorrelation was performed to test the relationship between climatic parameters (minimum and maximum temperature) and incidence of diarrhoea. In total, 58,617 cases of diarrhoea occurred in the CTMA, which is equivalent to 8.60 cases per 100 population under five years old for the study period. The mixed effect overdispersed Poisson model showed that a cluster adjusted effect of an increase of 5 °C in minimum and maximum temperature results in a 40% (Incidence risk ratio IRR: 1.39, 95% CI 1.31-1.48) and 32% (IRR: 1.32, 95% CI: 1.22-1.41) increase in incident cases of diarrhoea, respectively, for the two periods studied. Autocorrelation of one-week lag (Autocorrelation AC 1) indicated that a 5 °C increase in minimum and maximum temperature led to 15% (IRR: 1.46, 95% CI: 1.09-1.20) and 6% (IRR: 1.06, 95% CI: 1.01-1.12) increase in diarrhoea cases, respectively. In conclusion, there was an association between an increase in minimum and maximum temperature, and the rate at which diarrhoea affected children under the age of five years old in the Cape Town Metropolitan Area. This finding may have implications for the effects of global warming and requires further investigation.