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Abstract The 1994 genocide against the Tutsi destroyed the health system in Rwanda. It is impressive that a small country like Rwanda has advanced its health system to the point of now offering near universal health insurance coverage. Through a series of strategic structural changes to its health system, catalyzed through international assistance, Rwanda has demonstrated a commitment towards improving patient and population health indicators. In particular, the rapid scale up of antiretroviral therapy (ART) has become a great success story for Rwanda. The country achieved universal coverage of ART at a CD4 cell count of 200 cells/mm 3 in 2007 and increased the threshold for initiation of ART to ≤350 cells/mm 3 in 2008. Further, 2013 guidelines raised the threshold for initiation to ≤500 cells/mm 3 and suggest immediate therapy for key affected populations. In 2015, guidelines recommend offering immediate treatment to all patients. By reviewing the history of HIV and the scale-up of treatment delivery in Rwanda since the genocide, this paper highlights some of the key innovations of the Government of Rwanda and demonstrates the ways in which the national response to the HIV epidemic has catalyzed the implementation of interventions that have helped strengthen the overall health system.

BACKGROUND: There is unmet need for family planning in Rwanda. We previously developed an evidence-based couples' family planning counseling (C)FPC program in the capital city that combines: (1) fertility goal-based family planning counseling with a focus on long-acting reversible contraceptive (LARC) for couples wishing to delay pregnancy; (2) health center capacity building for provision of LARC methods, and (3) LARC promotion by community health workers (CHW) trained in community-based provision of oral and injectable contraception. From 2015 to 2016, this service was integrated into eight government health centers in Kigali, reaching 6072 clients and resulting in 5743 LARC insertions. METHODS: From May to July 2016, we conducted cross-sectional health center needs assessments in 30 rural health centers using surveys, key informant interviews, logbook extraction, and structured observations. The assessment focused on the infrastructure, materials, and human resources needed for LARC demand creation and provision. RESULTS: Few nurses had received training in LARC insertion [41% implant, 27% intrauterine device (IUD)]. All health centers reported working with CHW, but none trained in LARC promotion. Health centers had limited numbers of IUDs (median 10), implants (median 39), functional gynecological exam tables (median 2), and lamps for viewing the cervix (median 0). Many did not have backup power supplies (40%). Most health centers reported no funding partners for family planning assistance (60%). Per national guidelines, couples' voluntary HIV counseling and testing (CVCT) was provided at the first antenatal visit at all clinics, reaching over 80% of pregnant women and their partners. However, only 10% of health centers had integrated family planning and HIV services. CONCLUSIONS: To successfully implement (C)FPC and LARC services in rural health centers across Rwanda, material and human resource capacity for LARC provision will need to be greatly strengthened through equipment (gynecological exam tables, ...

BackgroundWith the accessibility of prevention of mother to child transmission (PMTCT) services in sub‐Saharan Africa, more women are being tested for HIV in antenatal care settings. Involving partners in the counselling and testing process could help prevent horizontal and vertical transmission of HIV. This study was conducted to assess the feasibility of couples' voluntary counseling and testing (CVCT) in antenatal care and to measure compliance with PMTCT.MethodsA prospective cohort study was conducted over eight months at two public antenatal clinics in Kigali, Rwanda, and Lusaka, Zambia. A convenience sample of 3625 pregnant women was enrolled. Of these, 1054 women were lost to follow up. The intervention consisted of same‐day individual voluntary counselling and testing (VCT) and weekend CVCT; HIV‐positive participants received nevirapine tablets. In Kigali, nevirapine syrup was provided in the labour and delivery ward; in Lusaka, nevirapine syrup was supplied in pre‐measured single‐dose syringes. The main outcome measures were nurse midwife‐recorded deliveries and reported nevirapine use.ResultsIn eight months, 1940 women enrolled in Kigali (984 VCT, 956 CVCT) and 1685 women enrolled in Lusaka (1022 VCT, 663 CVCT). HIV prevalence was 14% in Kigali, and 27% in Lusaka. Loss to follow up was more common in Kigali than Lusaka (33% vs. 24%, p = 0.000). In Lusaka, HIV‐positive and HIV‐negative women had significantly different loss‐to‐follow‐up rates (30% vs. 22%, p = 0.002). CVCT was associated with reduced loss to follow up: in Kigali, 31% of couples versus 36% of women testing alone (p = 0.011); and in Lusaka, 22% of couples versus 25% of women testing alone (p = 0.137). Among HIV‐positive women with follow up, CVCT had no impact on nevirapine use (86‐89% in Kigali; 78‐79% in Lusaka).ConclusionsWeekend CVCT, though new, was feasible in both capital cities. The beneficial impact of CVCT on loss to follow up was significant, while nevirapine compliance was similar in women tested alone or with their partners. Pre‐measured nevirapine syrup syringes provided flexibility to HIV‐positive mothers in Lusaka, but may have contributed to study loss to follow up. These two prevention interventions remain a challenge, with CVCT still operating without supportive government policy in Zambia.

The 1994 genocide against the Tutsi destroyed the health system in Rwanda. It is impressive that a small country like Rwanda has advanced its health system to the point of now offering near universal health insurance coverage. Through a series of strategic structural changes to its health system, catalyzed through international assistance, Rwanda has demonstrated a commitment towards improving patient and population health indicators. In particular, the rapid scale up of antiretroviral therapy (ART) has become a great success story for Rwanda. The country achieved universal coverage of ART at a CD4 cell count of 200 cells/mm3 in 2007 and increased the threshold for initiation of ART to ≤350 cells/mm3 in 2008. Further, 2013 guidelines raised the threshold for initiation to ≤500 cells/mm3 and suggest immediate therapy for key affected populations. In 2015, guidelines recommend offering immediate treatment to all patients. By reviewing the history of HIV and the scale-up of treatment delivery in Rwanda since the genocide, this paper highlights some of the key innovations of the Government of Rwanda and demonstrates the ways in which the national response to the HIV epidemic has catalyzed the implementation of interventions that have helped strengthen the overall health system.

OBJECTIVE: This study aims to understand the basis of continued HIV-1 transmission in Zambian and Rwandan HIV-1 discordant couples in the context of ART. DESIGN: We identified 9 Zambian and 7 Rwandan acutely-infected, epidemiologically-linked couples from government CVCT clinics where transmitting partners reported being on ART near the time of transmission. METHODS: We quantified viral load (VL) and plasma antiretroviral (ARV) drug concentrations near the time of transmission and used these as surrogate measures for adherence. We also sequenced the polymerase gene from both donor and recipient partners to determine the presence of drug resistance mutations (DRM). RESULTS: In Zambia, all transmitting partners had detectable VL and 8/9 were not on therapeutic ARV regimens. In the remaining couple, despite being on a therapeutic regimen, DRM were present and transmitted. In Rwanda, although 6/7 transmitting partners had detectable VL, therapeutic levels of ARV were detected in 4/7, but were accompanied by DRM. In the remaining 3 couples, either no ARV or sub-therapeutic regimens were detected. CONCLUSIONS: A reduction of ART effectiveness in non-trial settings was associated with lack of ARVs in plasma and detectable VL, as well as DR. In Zambia, where CVCT is not widely implemented, inconsistent adherence was high in couples unaware of their HIV discordance. In Rwanda, where CVCT is deployed country-wide, virologic failure was associated with DR and subsequent transmission. Together, these findings suggest that increasing ART availability in resource-limited settings without risk reduction strategies that promote adherence, may not be sufficient to control the HIV epidemic in the post-ART era.

Background: Long-acting reversible contraception (LARC) is highly effective at preventing pregnancy. However, in sub-Saharan Africa, LARC education for clients is relatively limited and providers are often not skilled in their insertion. Before 2009, only 1% of family planning clients in Rwanda received an LARC. Materials and Methods: We trained Rwandan government clinic nurses to promote, insert, and remove copper intrauterine devices (IUDs) and hormonal implants. Training started in two large urban clinics, and those nurses trained three successive waves of clinic nurses. Initial LARC promotions were clinic based, but in 2015 included community-based promotions in eight clinics. We compare IUD and implant insertions by year and clinic and discuss implementation successes/obstacles. Results: From 2009 to 2016, 222 nurses from 21 government clinics were LARC trained. The nurses performed 36,588 LARC insertions (19% IUD, 81% implant). LARC insertions increased over time, peaking at 8,897 in 2013. However, in 2014, the number dropped to 4,018 after closure of one large clinic, funding discontinuation, and supply stock-outs. With new funding in 2015, insertions increased reaching 8,218 in 2016. Catholic and non-Catholic and rural and urban clinics performed similarly, whereas clinics affiliated with community-based promotions performed better (p > 0.05). Between 2012 and 2014, 13% of family planning initiators chose the implant and 4% the IUD. Conclusions: LARC supply–demand services increased the proportion of family planning initiators choosing LARC to 17%. Challenges included inconsistent funding, irregular supplies, and staff turnover. Rural and Catholic clinics performed as well as urban and non-Catholic clinics. Concerted efforts to improve IUD uptake are needed.

BACKGROUND: Few family planning programs in Africa base demand creation and service delivery on theoretical models. Motivational interviewing (MI) is a counseling modality that facilitates reflection on the benefits and disadvantages of a health outcome to encourage behavior change. OBJECTIVES: We evaluate a couples-focused joint family planning and HIV counseling intervention using motivational interviewing (MI) to enhance uptake of long acting reversible contraception (LARC, Paragard copper intra-uterine device (IUD) or Jadelle hormonal implant) among Rwandan couples. STUDY DESIGN: In this experimental study, couples receiving care at eight government health clinics in Kigali, the capital city, were referred from a parent study of couples that did not want more children or wanted to wait at least two years for their next pregnancy. LARC methods were offered on site following joint HIV testing and family planning counseling. At the first follow-up visit one month after enrollment in the parent study, couples who had not yet chosen a LARC method were interviewed separately using MI, then brought together and again offered LARC. RESULTS: Following MI, 78/229 (34%) couples requested a LARC method (68 implant and 10 IUD). LARC uptake after MI was associated with the woman being Catholic (vs. Protestant/Muslim/Other, aOR 2.87, 95% C.I. 1.19-6.96, p=0.019) or having an income (vs. no income aOR 2.54, 95% C.I. 1.12-5.73, p=0.025); the couple having previously discussed LARC (aOR 8.38, 95% C.I. 2.54-27.59, p=0.0005); either partner believing that unplanned pregnancy was likely with their current method (aOR 6.67, 95% C.I. 2.77-16.11, p<0.0001) or that they might forget to take or make an appointment for their current method (aOR 4.04, 95% C.I. 1.32-12.34, p=0.014). Neither partner mentioning that condoms also prevent HIV/sexually transmitted infection (STI) was associated with LARC uptake (aOR 2.86, 95% C.I. 1.17-7.03, p=0.022), as was the woman citing long-term duration of action of the implant as an advantage (aOR ...

Background: Though the Rwandan Ministry of Health (MOH) prioritizes the scale-up of postpartum family planning (PPFP) programs, uptake and sustainability of PPFP services in Rwanda are low. Furthermore, highly effective long-acting reversible contraceptive method use (LARC), key in effective PPFP programs, is specifically low in Rwanda. We previously pilot tested a supply-demand intervention which significantly increased the use of postpartum LARC (PPLARC) in Rwandan government clinics. In this protocol, we use an implementation science framework to test whether our intervention is adaptable to large-scale implementation, cost-effective, and sustainable. Methods: In a type 2 effectiveness-implementation hybrid study, we will evaluate the impact of our PPFP intervention on postpartum LARC (PPLARC) uptake in a clinic-randomized trial in 12 high-volume health facilities in Kigali, Rwanda. We will evaluate this hybrid study using the RE-AIM framework. The independent effectiveness of each PPFP demand creation strategy on PPLARC uptake among antenatal clinic attendees who later deliver in a study facility will be estimated. To assess sustainability, we will assess the intervention adoption, implementation, and maintenance. Finally, we will evaluate intervention cost-effectiveness and develop a national costed implementation plan. Discussion: Adaptability and sustainability within government facilities are critical aspects of our proposal, and the MOH and other local stakeholders will be engaged from the outset. We expect to deliver PPFP counseling to over 21,000 women/couples during the project period. We hypothesize that the intervention will significantly increase the number of stakeholders engaged, PPFP providers and promoters trained, couples/clients receiving information about PPFP, and PPLARC uptake comparing intervention versus standard of care. We expect PPFP client satisfaction will be high. Finally, we also hypothesize that the intervention will be cost-saving relative to the standard of care. This ...

INTRODUCTION: Postpartum (PP) family planning is critical to reduce maternal-child mortality, abortion, and unintended pregnancy. As in most countries, the majority of PP women in Rwanda have an unmet need for postpartum family planning (PPFP). In particular, increasing use of the highly effective PP long-acting reversible contraceptive (LARC) methods (the intrauterine device [IUD] and implant) is a national priority. We developed a muti-level intervention to increase supply and demand for PPFP services in Kigali, Rwanda. METHODS: We implemented our intervention (which included PPFP promotional counseling for clients, training for providers, and Ministry of Health stakeholder involvement) in six government health facilities from Aug 2017-Oct 2018. While increasing knowledge and uptake of the IUD was a primary objective, all contraceptive method options were discussed and made available. Here, we report a secondary analysis of PP implant uptake and present already published data on PP IUD uptake for reference. RESULTS: Over a 15-month implementation period, 12,068 women received PPFP educational counseling and delivered at a study facility. Of these women, 1252 chose a PP implant (10.4% uptake) and 3372 chose a PPIUD (27.9% uptake). On average providers at our intervention facilities inserted 83.5 PP implants/month and 224.8 PPIUDs/month. Prior to our intervention, 30 PP implants/month and 8 PPIUDs/month were inserted at our selected facilities. Providers reported high ease of LARC insertion, and clients reported minimal insertion anxiety and pain. CONCLUSIONS: PP implant and PPIUD uptake significantly increased after implementation of our multi-level intervention. PPFP methods were well-received by clients and providers.

BACKGROUND: When integrated with couples' voluntary HIV counselling and testing (CVCT), family planning including long acting reversible contraceptives (LARC) addresses prongs one and two of prevention of mother-to-child transmission (PMTCT). METHODS: In this observational study, we enrolled equal numbers of HIV concordant and discordant couples in four rural and four urban clinics, with two Catholic and two non-Catholic clinics in each area. Eligible couples were fertile, not already using a LARC method, and wished to limit or delay fertility for at least 2 years. We provided CVCT and fertility goal-based family planning counselling with the offer of LARC and conducted multivariate analysis of clinic, couple, and individual predictors of LARC uptake. RESULTS: Of 1290 couples enrolled, 960 (74%) selected LARC: Jadelle 5-year implant (37%), Implanon 3-year implant (26%), or copper intrauterine device (IUD) (11%). Uptake was higher in non-Catholic clinics (85% vs. 63% in Catholic clinics, p < 0.0001), in urban clinics (82% vs. 67% in rural clinics, p < 0.0001), and in HIV concordant couples (79% vs. 70% of discordant couples, p = .0005). Religion of the couple was unrelated to clinic religious affiliation, and uptake was highest among Catholics (80%) and lowest among Protestants (70%) who were predominantly Pentecostal. In multivariable analysis, urban location and non-Catholic clinic affiliation, Catholic religion of woman or couple, younger age of men, lower educational level of both partners, non-use of condoms or injectable contraception at enrollment, prior discussion of LARC by the couple, and women not having concerns about negative side effects of implant were associated with LARC uptake. CONCLUSIONS: Fertility goal-based LARC recommendations combined with couples' HIV counselling and testing resulted in a high uptake of LARC methods, even among discordant couples using condoms for HIV prevention, in Catholic clinics, and in rural populations. This model successfully integrates prevention of HIV and ...

AbstractIntroductionThe chemokine receptor CCR5 is the main co‐receptor for R5‐tropic HIV‐1 variants. We have previously described a novel 24‐base pair deletion in the coding region of CCR5 among individuals from Rwanda. Here, we investigated the prevalence of hCCR5Δ24 in different cohorts and its impact on CCR5 expression and HIV‐1 infection in vitro.MethodsWe screened hCCR5Δ24 in a total of 3232 individuals which were either HIV‐1 uninfected, high‐risk HIV‐1 seronegative and seropositive partners from serodiscordant couples, Long‐Term Survivors, or HIV‐1 infected volunteers from Africa (Rwanda, Kenya, Guinea‐Conakry) and Luxembourg, using a real‐time PCR assay. The role of the 24‐base pair deletion on CCR5 expression and HIV infection was assessed in cell lines and PBMC using mRNA quantification, confocal analysis, flow and imaging cytometry.Results and DiscussionAmong the 1661 patients from Rwanda, 12 individuals were heterozygous for hCCR5Δ24 but none were homozygous. Although heterozygosity for this allele may not confer complete resistance to HIV‐1 infection, the prevalence of the mutation was 2.41% (95%CI: 0.43; 8.37) in 83 Long‐Term Survivors (LTS) and 0.99% (95%CI: 0.45; 2.14) in 613 HIV‐1 exposed seronegative members as compared with 0.35% (95% Cl: 0.06; 1.25) in 579 HIV‐1 seropositive members. The prevalence of hCCR5Δ24 was 0.55% (95%CI: 0.15; 1.69) in 547 infants from Kenya but the mutation was not detected in 224 infants from Guinea‐Conakry nor in 800 Caucasian individuals from Luxembourg. Expression of hCCR5Δ24 in cell lines and PBMC showed that the hCCR5Δ24 protein is stably expressed but is not transported to the plasma membrane due to a conformational change. Instead, the mutant receptor was retained intracellularly, colocalized with an endoplasmic reticulum marker and did not mediate HIV‐1 infection. Co‐transfection of hCCR5Δ24 and wtCCR5 did not indicate a transdominant negative effect of CCR5Δ24 on wtCCR5.ConclusionsOur findings indicate that hCCR5Δ24 is not expressed at the cell surface. This could explain the higher prevalence of the heterozygous hCCR5Δ24 in LTS and HIV‐1 exposed seronegative members from serodiscordant couples. Our data suggest an East‐African localization of this deletion, which needs to be confirmed in larger cohorts from African and non‐African countries.

AbstractIntroductionCouples' voluntary HIV counselling and testing (CVCT) is a high‐impact HIV prevention intervention in Rwanda and Zambia. Our objective was to model the cost‐per‐HIV infection averted by CVCT in six African countries guided by an HIV prevention cascade framework. The HIV prevention cascade as yet to be applied to evaluating CVCT effectiveness or cost‐effectiveness.MethodsWe defined a priority population for CVCT in Africa as heterosexual adults in stable couples. Based on our previous experience nationalizing CVCT in Rwanda and scaling‐up CVCT in 73 clinics in Zambia, we estimated HIV prevention cascade domains of motivation for use, access and effectiveness of CVCT as model parameters. Costs‐per‐couple tested were also estimated based on our previous studies. We used these parameters as well as country‐specific inputs to model the impact of CVCT over a five‐year time horizon in a previously developed and tested deterministic compartmental model. We consider six countries across Africa with varied HIV epidemics (South Africa, Zimbabwe, Kenya, Tanzania, Ivory Coast and Sierra Leone). Outcomes of interest were the proportion of HIV infections averted by CVCT, nationwide CVCT implementation costs and costs‐per‐HIV infection averted by CVCT. We applied 3%/year discounting to costs and outcomes. Univariate and Monte Carlo multivariate sensitivity analyses were conducted.ResultsWe estimated that CVCT could avert between 54% (Sierra Leone) and 62% (South Africa) of adult HIV infections. Average costs‐per‐HIV infection averted were lowest in Zimbabwe ($550) and highest in South Africa ($1272). Nationwide implementations would cost between 7% (Kenya) and 21% (Ivory Coast) of a country's President's Emergency Plan for AIDS Relief (PEPFAR) budget over five years. In sensitivity analyses, model outputs were most sensitive to estimates of cost‐per‐couple tested; the proportion of adults in heterosexual couples and HIV prevention cascade domains of CVCT motivation and access.ConclusionsOur model indicates that nationalized CVCT could prevent over half of adult HIV infections for 7% to 21% of the modelled countries' five‐year PEPFAR budgets. While other studies have indicated that CVCT motivation is high given locally relevant promotional and educational efforts, without required indicators, targets and dedicated budgets, access remains low.

BackgroundMany HIV voluntary testing and counselling centres in Africa use rapid antibody tests, in parallel or in sequence, to establish same‐day HIV status. The interpretation of indeterminate or discrepant results between different rapid tests on one sample poses a challenge. We investigated the use of an algorithm using three serial rapid HIV tests in cohabiting couples to resolve unclear serostatuses.MethodsHeterosexual couples visited the Rwanda Zambia HIV Research Group testing centres in Kigali, Rwanda, and Lusaka, Zambia, to assess HIV infection status. Individuals with unclear HIV rapid antibody test results (indeterminate) or discrepant results were asked to return for repeat testing to resolve HIV status. If either partner of a couple tested positive or indeterminate with the screening test, both partners were tested with a confirmatory test. Individuals with indeterminate or discrepant results were further tested with a tie‐breaker and monthly retesting. HIV‐RNA viral load was determined when HIV status was not resolved by follow‐up rapid testing. Individuals were classified based on two of three initial tests as "Positive", "Negative" or "Other". Follow‐up testing and/or HIV‐RNA viral load testing determined them as "Infected", "Uninfected" or "Unresolved".ResultsOf 45,820 individuals tested as couples, 2.3% (4.1% of couples) had at least one discrepant or indeterminate rapid result. A total of 65% of those individuals had follow‐up testing and of those individuals initially classified as "Negative" by three initial rapid tests, less than 1% were resolved as "Infected". In contrast, of those individuals with at least one discrepant or indeterminate result who were initially classified as "Positive", only 46% were resolved as "Infected", while the remainder was resolved as "Uninfected" (46%) or "Unresolved" (8%). A positive HIV serostatus of one of the partners was a strong predictor of infection in the other partner as 48% of individuals who resolved as "Infected" had an HIV‐infected spouse.ConclusionsIn more than 45,000 individuals counselled and tested as couples, only 5% of individuals with indeterminate or discrepant rapid HIV test results were HIV infected. This represented only 0.1% of all individuals tested. Thus, algorithms using screening, confirmatory and tie‐breaker rapid tests are reliable with two of three tests negative, but not when two of three tests are positive. False positive antibody tests may persist. HIV‐positive partner serostatus should prompt repeat testing.

Continued outbreaks of Ebola virus disease, including recent outbreaks in the Democratic Republic of the Congo (DRC), highlight the need for effective vaccine programs to combat future outbreaks. Given the population flow between DRC and Rwanda, the Rwanda Ministry of Health initiated a preventive vaccination campaign supported by a vaccination monitoring platform (VMP). The campaign aimed to vaccinate approximately 200,000 people from Rwanda's Rubavu and Rusizi districts with the two-dose vaccine regimen Ad26.ZEBOV, MVA-BN-Filo. The VMP encompassed: biometric identification (iris scanning), mobile messaging, and an interactive reporting dashboard. The VMP collected data used to register and identify participants at subsequent visits. Mobile message reminders supported compliance. To 13 November 2020, the campaign was half complete with Ad26.ZEBOV administered to 116,974 participants and MVA-BN-Filo to 76,464. MVA-BN-Filo should be given to participants approximately 8 weeks after the Ad26.ZEBOV with a compliance window of −14 and +28 days. Of the 83,850 participants who were eligible per this dosing window for the subsequent MVA-BN-Filo vaccine, 91.2% (76,453/83,850) received it and 82.9% (69,505/83,850) received it within the compliance window defined for this campaign. Utilization of the VMP was instrumental to the success of the campaign, using biometric technology, dashboard reporting of near real-time data analysis and mobile phone communication technology to support vaccine administration and monitoring. A comprehensive VMP is feasible in large-scale health-care campaigns, beneficial for public health surveillance, and can allow effective response to an infectious disease outbreak.