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/mm(3) (IQR, 197-484 cells/mm(3)). 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 2018–19 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 three 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

Use of index testing to close the gap in HIV diagnosis among older people in Rwanda: analysis of data from a public health programme

BACKGROUND: As Rwanda inches closer to the UNAIDS HIV first 95 of knowing one's HIV status by 2030, finding the remaining HIV-positive individuals could be difficult by use of passive methods. Index testing is an approach whereby the exposed contacts of an HIV-positive person are notified and offered an HIV test. We aimed to assess the factors related to the HIV-positive outcome among older people (aged 50 years and above) in Rwanda. METHODS: In Rwanda, adults (aged >/=18 years) on antiretroviral therapy (ART) who reported having had sexual partners with unknown HIV status, and individuals with newly diagnosed HIV, described as index cases, were asked to provide details of their sexual partners and invite them to the health facility for HIV testing through client referral, provider referral, or dual referral. We used logistic regression to model the odds of identifying partners who were HIV-positive or aged 50 years or older through partner notification services and to assess predictive factors related to index case and partner, after adjusting for partner related variables (age group, gender, relationship between index and sexual partner, province of residence, notification used) and index case related variables (type of index case, multiple partnership, had unprotected sex in past 12 months, viral load suppression, age difference between notified sexual partner and index case). Written informed consent was obtained from each participant before inclusion in the study. The Rwanda National Ethics Committee approved the protocol for implementation. FINDINGS: Between October, 2018, and September, 2021, 18 453 index cases were recruited and 31 227 partners were notified and tested, of whom 3156 (10.0%) were aged 50 years and older. Of the partners aged 50 years and older, 877 (27.8%) were female and 2279 (88.1%) were male, and 1638 (51.9%) were notified by index cases who were younger than them. Among partners aged 50 years and older, 6.0% (3156) were HIV-positive, with a higher prevalence in partners notified by newly diagnosed index cases 14.7% (46 of 313). In the multivariable analysis, among partners aged 50 years and older, the adjusted odds ratio was 2.66 (95% CI 1.78-3.98) for female partners compared with male partners, 3.14 (2.08-4.77) for partners of newly HIV-diagnosed index cases compared with those of index cases who were already taking ART, and 1.89 (1.07-3.37) for partners who were 15 years older than the index case compared with partners who were 5 years older or younger. INTERPRETATION: Partners of people with newly diagnosed HIV, older individuals who engaged in sexual relationship with younger individuals, and female partners had an increased risk of being diagnosed with HIV. Index testing successfully identified older people with undiagnosed HIV. FUNDING: None

Household survey of HIV incidence in Rwanda: a national observational cohort study

BACKGROUND: In Rwanda, HIV prevalence among adults aged 15-49 years has been stable at 3% since 2005. The aim of this study was to characterise HIV incidence across Rwanda. METHODS: We did a nationally representative, prospective HIV incidence survey for the period of 2013-14, which used two-stage sampling. We randomly selected 492 villages in the first sampling stage and 14 households per village in the second stage. Participants completed a questionnaire and 14 140 people were tested for HIV. 13 728 participants were HIV negative, and were enrolled in the incidence cohort. Participants were retested and surveyed again after 12 months. Weights were calculated as the inverse of the probability to select the villages and the households. FINDINGS: The study period was from Nov 5, 2013, to Nov 15, 2014. Among 14 222 respondents from 6792 households, 14 140 were tested for HIV and 13 728 were HIV negative. Of 12 593 people who participated in the endpoint data collection activities, 5965 (47·4%) were men and the mean age was 30 years (SD 10·8). 11 237 (89·2%) participants lived in rural areas, 4826 (38·3%) were single, and 7140 (56·7%) were married or cohabitating. During the year, 35 participants had seroconversion, including 13 men and 22 women, resulting in an overall incidence of 0·27 per 100 person-years (95% CI 0·18-0·35). Incidence was 0·21 per 100 person-years (0·10-0·32) in men and 0·32 per 100 person-years (0·19-0·45) in women. Our findings suggested multiple breakouts, with multiple seroconversions occurring in three villages and two households. Incidence was higher in adults aged 36-45 years (0·37 per 100 person-years, 0·12-0·62; adjusted hazard ratio [aHR] 4·49, 95% CI 1·30-14·70) relative to those aged 16-25, higher in western province (0·57 per 100 person-years, 0·31-0·87; aHR 5·90, 1·33-25·28) relative to the northern province, and higher in urban areas (0·65 per 100 person-years, 0·23-1·07; aHR 3·10, 1·28-6·99) than in rural areas. INTERPRETATION: The incidence of HIV in Rwanda was higher than that previously estimated from models, with outbreaks seeming to contribute to the ongoing epidemic. Characterisation of incident infections can help the national HIV programmes to plan for preventive interventions tailored to the most at risk populations. FUNDING: Global Fund to Fight HIV, Tuberculosis and Malaria, WHO Rwanda, UNAIDS Rwanda, and the Government of Rwanda

Drug resistance mutations after the first 12 months on antiretroviral therapy and determinants of virological failure in Rwanda

To evaluate HIV drug resistance (HIVDR) and determinants of virological failure in a large cohort of patients receiving first-line tenofovir-based antiretroviral therapy (ART) regimens.; A nationwide retrospective cohort from 42 health facilities was assessed for virological failure and development of HIVDR mutations. Data were collected at ART initiation and at 12 months of ART on patients with available HIV-1 viral load (VL) and ART adherence measurements. HIV resistance genotyping was performed on patients with VL ≥1000 copies/ml. Multiple logistic regression was used to determine factors associated with treatment failure.; Of 828 patients, 66% were women, and the median age was 37 years. Of the 597 patients from whom blood samples were collected, 86.9% were virologically suppressed, while 11.9% were not. Virological failure was strongly associated with age <25 years (adjusted odds ratio [aOR]: 6.4; 95% confidence interval [CI]: 3.2-12.9), low adherence (aOR: 2.87; 95% CI: 1.5-5.0) and baseline CD4 counts <200 cells/μl (aOR 3.4; 95% CI: 1.9-6.2). Overall, 9.1% of all patients on ART had drug resistance mutations after 1 year of ART; 27% of the patients who failed treatment had no evidence of HIVDR mutations. HIVDR mutations were not observed in patients on the recommended second-line ART regimen in Rwanda.; The last step of the UNAIDS 90-90-90 target appears within grasp, with some viral failures still due to non-adherence. Nonetheless, youth and late initiators are at higher risk of virological failure. Youth-focused programmes could help prevent further drug HIVDR development