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.

Association Between Time to Antiretroviral Therapy and Loss to Care Among Newly Diagnosed Rwandan People Living with Human Immunodeficiency Virus.

Despite improved clinical outcomes of initiating antiretroviral therapy (ART) soon after diagnosis, conflicting evidence exists regarding the impact of same-day ART initiation on subsequent clinical outcomes. We aimed to characterize the associations of time to ART initiation with loss to care and viral suppression in a cohort of newly diagnosed people living with HIV (PLHIV) entering care after Rwanda implemented a national "Treat All" policy. We conducted a secondary analysis of routinely collected data of adult PLHIV enrolling in HIV care at 10 health facilities in Kigali, Rwanda. Time from enrollment to ART initiation was categorized as same day, 1-7 days, or >7 days. We examined associations between time to ART and loss to care (>120 days since last health facility visit) using Cox proportional hazards models, and between time to ART and viral suppression using logistic regression. Of 2,524 patients included in this analysis, 1,452 (57.5%) were women and the median age was 32 (interquartile range: 26-39). Loss to care was more frequent among patients who initiated ART on the same day (15.9%), compared with those initiating ART 1-7 days (12.3%) or >7 days (10.1%), p < .001. In multivariable analyses, same-day ART initiation was associated with a greater hazard of loss to care compared with initiating >7 days after enrollment (adjusted hazard ratio 1.39, 95% confidence interval: 1.04-1.85). A total of 1,698 (67.3%) had available data on viral load measured within 455 days after enrollment. Of these, 1,476 (87%) were virally suppressed. A higher proportion of patients initiating ART on the same day were virally suppressed (89%) compared with those initiating 1-7 days (84%) or >7 days (88%) after enrollment. This association was not statistically significant. Our findings suggest that ensuring adequate, early support for PLHIV initiating ART rapidly may be important to improve retention in care for newly diagnosed PLHIV in the era of Treat All.

Monitoring of Adverse Events in Recipients of the 2-Dose Ebola Vaccine Regimen of Ad26.ZEBOV Followed by MVA-BN-Filo in the UMURINZI Ebola Vaccination Campaign.

BACKGROUND: From 2019 to 2021, Rwandan residents of the border with the Democratic Republic of the Congo were offered the Ad26.ZEBOV (adenovirus type 26 vector vaccine encoding Ebola virus glycoprotein) and MVA-BN-Filo (modified vaccinia virus Ankara vector vaccine, encoding glycoproteins from Ebola, Sudan, Marburg, and nucleoprotein from Tai Forest viruses) Ebola vaccine regimen. METHODS: Nonpregnant persons aged ≥2 years were eligible. Unsolicited adverse events (UAEs) were reported through phone calls or visits, and serious adverse events (SAEs) were recorded per International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines. RESULTS: Following Ad26.ZEBOV, UAEs were reported by 0.68% of 216 113 vaccinees and were more common in younger children (aged 2-8 years, 1.2%) compared with older children (aged 9-17 years, 0.4%) and adults (aged ≥18 years, 0.7%). Fever and headache were the most reported symptoms. All 17 SAEs related to vaccine were in children aged 2-8 years (10 postvaccination febrile convulsions ± gastroenteritis and 7 fever and/or gastroenteritis). The incidence of febrile seizures was 8 of 26 062 (0.031%) prior to initiation of routine acetaminophen in December 2020 and 2 of 15 897 (0.013%) thereafter. Nonobstetric SAEs were similar in males and females. All 20 deaths were unrelated to vaccination. Young girls and adult women with UAEs were less likely to receive the second dose than those without UAEs. Seven unrelated SAEs occurred in 203 267 MVA-BN-Filo recipients. CONCLUSIONS: Postvaccination febrile convulsions in young children were rare but not previously described after Ad26.ZEBOV and were reduced with routine acetaminophen. The regimen was otherwise safe and well-tolerated.

Cancer in patients with and without HIV infection in the national cancer registry of Rwanda.

OBJECTIVE: As antiretroviral therapy (ART) has been widely scaled up in Rwanda, life expectancies among people with HIV (PWH) have increased. With increasing viral suppression, AIDS-defining cancers (ADCs) typically decrease; however, as the PWH population ages, non-AIDS-defining cancers (NADCs) will be expected to increase. The aim of this study was to compare cancer diagnoses between PWH and patients without HIV in Rwanda and to describe the changes in the number and types of cancer over time. DESIGN: Retrospective cohort study. METHODS: Rwanda National Cancer Registry (RNCR) recorded the HIV status, primary site, and morphological description for cancer diagnoses from 2007 to 2018. Descriptive analyses were carried out by cancer group (HIV+ and HIV-). A portion of patients whose HIV status was unknown (63%) were excluded from the present analysis. RESULTS: Among the 20 258 cases registered in the Registry, there were 1048 PWH and 6359 HIV- individuals. The proportion of ADCs were significantly higher in the PWH group compared to those without HIV ( P  < 0.001). Among PWH, there was a longitudinal increase in NADCs and a decrease in ADCs ( P  < 0.001) over time. Among the ADCs in the PWH group, there was a significant decline in Kaposi sarcoma cases over time. CONCLUSIONS: The study demonstrates a decreasing frequency of ADCs driven by declines in Kaposi sarcoma diagnoses and an increased frequency of NADCs among PWH in Rwanda over time. These findings support a need for focusing early detection and management efforts on NADCs, as they begin to play a larger role in the disease processes that affect the aging PWH population.

Safety and efficacy of sofosbuvir-velpatasvir-voxilaprevir for re-treatment of chronic hepatitis C virus infection in patients with previous direct-acting antiviral treatment failure in Rwanda (SHARED-3): a single-arm trial.

BACKGROUND: Hepatitis C virus (HCV) genotype 4 non-a/d subtypes, which frequently have NS5A resistance-associated substitutions, are highly prevalent in sub-Saharan Africa. These subtypes, particularly genotype 4r, have been associated with higher rates of failure of treatment regimens containing the NS5A inhibitors ledipasvir or daclatasvir, which are the most accessible direct-acting antivirals in low-income countries. Clinical evidence regarding the efficacy of re-treatment options for these subtypes is limited. We aimed to evaluate the safety and efficacy of sofosbuvir-velpatasvir-voxilaprevir for the treatment of adults in Rwanda with chronic HCV infection, predominantly of genotype 4, and a history of direct-acting antiviral treatment failure. METHODS: In this single-arm prospective trial, we enrolled adults (aged ≥18 years) with a HCV RNA titre of at least 1000 IU/mL, and a documented history of direct-acting antiviral failure. Patients were assessed for eligibility at a single study site after referral from hospitals with HCV treatment programmes throughout Rwanda, and participants for whom sofosbuvir-ledipasvir treatment had failed in the previous SHARED trial were also included. Participants with decompensated liver disease or hepatitis B virus co-infection were excluded. Participants were treated once daily with an oral fixed-dose combination tablet containing sofosbuvir (400 mg), velpatasvir (100 mg), and voxilaprevir (100 mg) for 12 weeks. The primary endpoint was the proportion of participants with a sustained virological response 12 weeks after completion of treatment (SVR12) in the intention-to-treat population. Viral sequencing of NS3, NS5A, and NS5B genes was done at baseline in all participants and at end of follow-up (week 24) in participants with treatment failure. The study is registered with ClinicalTrials.gov (NCT03888729) and is completed. FINDINGS: Between Sept 23, 2019, and Jan 10, 2020, 49 individuals were screened and 40 participants were enrolled. 20 (50%) were female, 20 (50%) were male, median age was 63 years (IQR 56-68), and median HCV viral load was 6·2 log10 IU/mL (5·8-6·5) at baseline. The genotype subtypes identified were 4r (18 [45%] participants), 4k (six [15%]), 4b (five [13%]), 4q (four [10%]), 4l (two [5%]), 4a (one [3%]), 4m (one [3%]), and 3h (one [3%]). One (3%) genotype 4 isolate could not be subtyped, and one (3%) isolate was of unknown genotype. All successfully sequenced isolates (33 [83%]) had at least two NS5A resistance-associated substitutions and 25 (63%) had three or more. 39 (98% [95% CI 87-100]) participants had SVR12. Seven (18%) participants had a total of ten grade 3, 4, or 5 adverse events, including three (8%) cases of hypertension, and one (3%) case each of cataract, diabetes, gastrointestinal bleeding, joint pain, low back pain, vaginal cancer, and sudden death. Four of these events were categorised as serious adverse events resulting in hospitalisation. The one sudden death occurred at home from an unknown cause 4 weeks after the completion of treatment. No serious adverse event was determined to be related to the study drug or resulted in treatment discontinuation. INTERPRETATION: A 12 week course of sofosbuvir-velpatasvir-voxilaprevir is safe and efficacious for the re-treatment of individuals infected with HCV genotype 4 non-a/d subtypes with frequent baseline NS5A resistance-associated substitutions, following failure of previous direct-acting antiviral treatment. Improved affordability and access to sofosbuvir-velpatasvir-voxilaprevir in regions with these subtypes is crucial. FUNDING: Gilead Sciences.

Safety and efficacy of sofosbuvir-velpatasvir to treat chronic hepatitis C virus infection in treatment-naive patients in Rwanda (SHARED-3): a single-arm trial.

BACKGROUND: Hepatitis C virus (HCV) genotype 4 is the predominant type of HCV found in sub-Saharan Africa. Various genotype 4 subtypes, such as 4r, frequently have resistance-associated substitutions that can increase rates of treatment failure with common direct-acting antiviral regimens. In-vitro studies suggest that the NS5A inhibitor velpatasvir is effective against viral isolates containing such resistance-associated substitutions, but its clinical efficacy against genotype 4 non-a/d subtypes in sub-Saharan Africa remains to be confirmed. We aimed to evaluate the safety and efficacy of sofosbuvir-velpatasvir among adults chronically infected with HCV and naive to direct-acting antiviral treatment in Rwanda, where genotype 4 non-a/d subtypes predominate. METHODS: In this single-arm prospective trial, we enrolled adults (age ≥18 years) in Rwanda who had chronic HCV infection and a plasma HCV RNA titre of at least 1000 IU/mL. Patients were referred from hospitals with HCV treatment programmes throughout Rwanda and were sequentially enrolled and assessed for eligibility at a single study site. Individuals with decompensated liver disease or hepatitis B virus co-infection were excluded. Participants were given an oral fixed-dose combination tablet of sofosbuvir (400 mg) and velpatasvir (100 mg) once-daily for 12 weeks. The primary endpoint was the proportion of participants with a sustained virological response 12 weeks after completion of treatment (SVR12) in the intention-to-treat population. Viral sequencing of the NS5A and NS5B genes was done at baseline for all participants and end of follow-up (week 24) for participants who did not have SVR12. This study is registered with ClinicalTrials.gov (NCT03888729) and is completed. FINDINGS: Between Sept 23, 2019, and Jan 10, 2020, 73 individuals were screened for eligibility, of whom 12 (16%) were excluded and 61 (84%) were enrolled. 40 (66%) participants were female, 21 (34%) were male, median age was 64 years (IQR 51-74), and median baseline HCV viral load was 5·7 log10 IU/mL (5·2-6·2). The genotypes identified among the participants were 4k (28 [46%] participants), 4r (11 [18%]), 4v (eight [13%]), 4q (five [8%]), 4l (three [5%]), 4b (one [2%]), 4c (one [2%]), and one undetermined genotype 4 subtype. Three isolates could not be sequenced and were of indeterminate genotype. Of the 55 HCV isolates that were successfully sequenced, all had at least two NS5A resistance-associated substitutions. 59 (97% [95% CI 89-99]) participants had SVR12. 18 (30%) participants had grade 3 adverse events (including 12 [20%] with hypertension), and none had grade 4 adverse events. Four (7%) participants had serious adverse events, including one asthma exacerbation, one abscess, one uterine myoma, and one pelvic fracture related to a motor vehicle accident. No serious adverse events were attributed to the study drug and no adverse event resulted in discontinuation of the study drug. INTERPRETATION: A 12-week regimen of sofosbuvir-velpatasvir is safe and efficacious in treating chronic HCV genotype 4 infection in patients in Rwanda. This regimen could be an effective treatment option in regions known to have a high prevalence of HCV genotype 4 of diverse non-a/d subtypes. FUNDING: Gilead Sciences.

HIV infection and engagement in HIV care cascade among men who have sex with men and transgender women in Kigali, Rwanda: a cross-sectional study.

INTRODUCTION: Given intersecting biological, network and structural risks, men who have sex with men (MSM) and transgender women (TGW) consistently have a high burden of HIV. Although MSM are a key population in Rwanda, there are limited epidemiologic data to guide programming. This study aimed to characterize HIV prevalence and care cascade among MSM and TGW in Kigali. METHODS: MSM and TGW ≥ 18 years were recruited using respondent-driven sampling (RDS) from March-August 2018 in Kigali. Participants underwent a structured interview including measures of individual, network and structural determinants. HIV and sexually transmitted infections (STI) including syphilis, Neisseria gonorrhoea (NG) and Chlamydia trachomatis (CT) were tested. Viral load was measured for MSM living with HIV. Robust Poisson regression was used to characterize the determinants of HIV infection and engagement in the HIV treatment cascade. RESULTS: A total of 736 participants were enrolled. The mean age was 27 years (range:18 to 68) and 14% (106) were TGW. HIV prevalence was 10% (RDS-adjusted: 9.2% (95% CI: 6.4 to 12.1)). Unadjusted prevalence of any STI was 20% (147); syphilis: 5.7% (42); CT: 9.1% (67) and NG: 8.8% (65). Anticipated (41%), perceived (36%) and enacted stigmas (45%) were common and higher among TGW (p < 0.001). In multivariable RDS adjusted analysis, higher age (aPR: 1.08 (95% CI: 1.05 to 1.12)) and ever having sex with women (aPR: 3.39 (95% CI: 1.31 to 8.72)) were positively associated with prevalent HIV. Being circumcised (aPR: 0.52 (95% CI: 0.28 to 0.9)) was negatively associated with prevalent HIV infection. Overall, 61% (45/74) of respondents reported knowing their HIV-positive status. Among these, 98% (44/45) reported antiretroviral therapy use (ART); 75% (33/44) were virally suppressed using a cut-off of <200 copies/mL. Of the 29 participants who did not report any previous HIV diagnosis or ART use, 38% (11/29) were virally suppressed. Cumulatively, 59% (44/74) of all participants living with HIV were virally suppressed. CONCLUSIONS: These data show a high burden of HIV among MSM/TGW in Kigali, Rwanda. Bisexual concurrency was common and associated with prevalent HIV infection, demonstrating the need of comprehensive screening for all sexual practices and preferences in the provision of comprehensive HIV prevention services in Rwanda. Viral suppression was below the UNAIDS target suggesting poor adherence and potential ART resistance. There is a need for adherence support, screening for primary and secondary ART resistance and stigma mitigation interventions to optimize HIV-related outcomes for MSM in Rwanda.

Role of unsafe medical practices and sexual behaviours in the hepatitis B and C syndemic and HIV co-infection in Rwanda: a cross-sectional study.

OBJECTIVES: This study describes the burden of the hepatitis B, C and HIV co-infections and assesses associated risk factors. SETTING: This analysis used data from a viral hepatitis screening campaign conducted in six districts in Rwanda from April to May 2019. Ten health centres per district were selected according to population size and distance. PARTICIPANTS: The campaign collected information from 156 499 participants (51 496 males and 104 953 females) on sociodemographic, clinical and behavioural characteristics. People who were not Rwandan by nationality or under 15 years old were excluded. PRIMARY AND SECONDARY OUTCOMES: The outcomes of interest included chronic hepatitis C virus (HCV) infection, chronic hepatitis B virus (HBV) infection, HIV infection, co-infection HIV/HBV, co-infection HIV/HCV, co-infection HBV/HCV and co-infection HCV/HBV/HIV. Multivariable logistic regressions were used to assess factors associated with HBV, HCV and HIV, mono and co-infections. RESULTS: Of 156 499 individuals screened, 3465 (2.2%) were hepatitis B surface antigen positive and 83% (2872/3465) of them had detectable HBV desoxy-nucleic acid (HBV DNA). A total of 4382 (2.8%) individuals were positive for antibody-HCV (anti-HCV) and 3163 (72.2%) had detectable HCV ribo-nucleic acid (RNA). Overall, 36 (0.02%) had HBV/HCV co-infection, 153 (0.1%) HBV/HIV co-infection, 238 (0.15%) HCV/HIV co-infection and 3 (0.002%) had triple infection. Scarification or receiving an operation from traditional healer was associated with all infections. Healthcare risk factors-history of surgery or transfusion-were associated with higher likelihood of HIV infection with OR 1.42 (95% CI 1.21 to 1.66) and OR 1.48 (1.29 to 1.70), respectively, while history of physical traumatic assault was associated with a higher likelihood of HIV and HBV/HIV co-infections with OR 1.69 (95% CI 1.51 to 1.88) and OR 1.82 (1.08 to 3.05), respectively. CONCLUSIONS: Overall, mono-infections were common and there were differences in significant risk factors associated with various infections. These findings highlight the magnitude of co-infections and differences in underlying risk factors that are important for designing prevention and care programmes.

Risk factors for viral hepatitis C infection in Rwanda: results from a nationwide screening program.

BACKGROUND: The epidemiology and risk factors for hepatitis C virus (HCV) infection in Rwanda are not well known; however, this information is crucial to shaping the country's public health approach to hepatitis C control. METHODS: A HCV screening campaign was conducted in the general population in 24 districts previously identified to have a high HCV disease burden. At the time of sample collection, sociodemographic information and self-reported risk factors were collected. Bivariate and multivariate logistic regressions were conducted to assess risk factors independently associated with hepatitis C antibodies (HCVAb) seroprevalence. RESULTS: Out of a total of 326,263 individuals screened for HCVAb, 22,183 (6.8%) were positive. In multivariate analysis, risk factors identified as statistically associated with HCVAb Seroprevalence include history of traditional operation or scarification (OR = 1.09, 95% CI: 1.05-1.14), presence of viral hepatitis in the family (OR = 1.27, 95% CI: 1.15-1.40), widowed or separated/divorced (OR = 1.36, 95% CI: 1.26-1.47), Southern province (OR = 1.98, 95% CI: 1.88-2.08) and aged 65 years and older (OR = 4.86, 95% CI: 4.62-5.11). Ubudehe category 3 (OR = 0.97, 95% CI: 0.93-1.01) and participants using RAMA (Health insurances for employees of public and private sectors) insurance (OR = 0.76, 95% CI: 0.70-0.85) had lower odds of HCV seroprevalence. CONCLUSIONS: Our findings provide important information for Rwanda's strategy on prevention and case-finding. Future prevention interventions should aim to reduce transmission through targeted messaging around traditional healing practices and case-finding targeting individuals with a history of exposure or advanced age.

Screening a nation for hepatitis C virus elimination: a cross-sectional study on prevalence of hepatitis C and associated risk factors in the Rwandan general population.

OBJECTIVES: We analysed data collected during programmatic screening activities conducted in 2017 to describe hepatitis C virus (HCV) seroprevalence in the general population and identify associated factors. DESIGN: We analysed data collected between June and September 2017. For both seroprevalence and viraemia, variations across demographic and geographic factors were assessed and multivariate regression models were fit to identify factors independently associated with each marker. Geospatial data were examined for visualisation. SETTING: HCV screening was organised within each of the 30 districts in Rwanda. One designated location in each district was selected as the screening site and screening took place for 1 week at each site. PARTICIPANTS: This study included 124 223 male and female volunteers. Anti-HCV-positive individuals were followed up with HCV RNA viral load (VL) testing for infection confirmation. MAIN OUTCOME MEASURES: Two markers were examined: the presence of HCV antibodies and HCV RNA VL. RESULTS: Among 124 223 individuals screened, 11 003 (8.86%, 95% CIs: 8.70% to 9.02%) were positive for anti-HCV. Anti-HCV prevalence varied by age with the oldest age group (>55 year olds) having a prevalence of 16.46% (95% CIs: 16.14% to 16.80%) and the youngest age group (<25 year olds) having a prevalence of 2.20% (95% CIs: 1.93% to 2.50%) (crude OR=8.78). After adjustment for covariates, an association remained between anti-HCV prevalence and age (p<0.001), province (p<0.001) and socioeconomic status (p<0.001). Of the 3771 anti-HCV-positive individuals who had an available HCV RNA VL result, 2099 (55.66%, 95% CI: 54.06% to 57.25%) had a detectable HCV RNA VL. Age was also associated with HCV viraemia (p<0.001). CONCLUSION: Results suggest that over 55% of individuals who screened positive for HCV-antibodies were chronically infected. Targeted screening for HCV among older individuals is recommended, given the association between age and infection. Further geographical hotspots of HCV infection can also inform targeted screening as Rwanda moves towards HCV elimination.

Better Outcomes Among HIV-Infected Rwandan Children 18-60 Months of Age After the Implementation of "Treat All".

BACKGROUND: In 2012, Rwanda introduced a Treat All approach for HIV-infected children younger than 5 years. We compared antiretroviral therapy (ART) initiation, outcomes, and retention, before and after this change. METHODS: We conducted a retrospective study of children enrolled into care between June 2009 and December 2011 [Before Treat All (BTA) cohort] and between July 2012 and April 2015 [Treat All (TA) cohort]. SETTING: Medical records of a nationally representative sample were abstracted for all eligible aged 18-60 months from 100 Rwandan public health facilities. RESULTS: We abstracted 374 medical records: 227 in the BTA and 147 in the TA cohorts. Mean (SD) age at enrollment was [3 years (1.1)]. Among BTA, 59% initiated ART within 1 year, vs. 89% in the TA cohort. Median time to ART initiation was 68 days (interquartile range 14-494) for BTA and 9 days (interquartile range 0-28) for TA (P < 0.0001), with 9 (5%) undergoing same-day initiation in BTA compared with 50 (37%) in TA (P < 0.0001). Before ART initiation, 59% in the BTA reported at least one health condition compared with 35% in the TA cohort (P < 0.0001). Although overall loss to follow-up was similar between cohorts (BTA: 13%, TA: 8%, P = 0.18), loss to follow-up before ART was significantly higher in the BTA (8%) compared with the TA cohort (2%) (P = 0.02). CONCLUSIONS: Nearly 90% of Rwandan children started on ART within 1 year of enrollment, most within 1 month, with greater than 90% retention after implementation of TA. TA was also associated with fewer morbidities.

TRACnet Internet and Short Message Service Technology Improves Time to Antiretroviral Therapy Initiation Among HIV-infected Infants in Rwanda.

BACKGROUND: Delays in testing HIV-exposed infants and obtaining results in resource-limited settings contribute to delays for initiating antiretroviral therapy (ART) in infants. To overcome this challenge, Rwanda expanded its national mobile and Internet-based HIV/AIDS informatics system, called TRACnet, to include HIV polymerase chain reaction (PCR) results in 2010. This study was performed to evaluate the impact of TRACnet technology on the time to delivery of test results and the subsequent initiation of ART in HIV-infected infants. METHODS: A retrospective cohort study was conducted on 380 infants who initiated ART in 190 health facilities in Rwanda from March 2010 to June 2013. Program data collected by the TRACnet system were extracted and analyzed. RESULTS: Since the introduction of TRACnet for processing PCR results, the time to receive results has significantly decreased from a median of 144 days [interquartile range (IQR): 121-197 days] to 23 days (IQR: 17-43 days). The number of days between PCR sampling and health facility receipt of results decreased substantially from a median of 90 days (IQR: 83-158 days) to 5 days (IQR: 2-8 days). After receiving PCR results at a health facility, it takes a median of 44 days (IQR: 32-77 days) before ART initiation. Result turnaround time was significantly associated with time to initiating ART (P < 0.001). An increased number of staff trained for HIV care and treatment was also significantly associated with decreased time to ART initiation (P = 0.004). CONCLUSIONS: The use of mobile technology for communication of HIV PCR results, coupled with well-trained and skilled personnel, can reduce delays in communicating results to providers. Such reductions may improve timely ART initiation in resource-limited settings.

Successive introduction of four new vaccines in Rwanda: High coverage and rapid scale up of Rwanda's expanded immunization program from 2009 to 2013.

As the pace of vaccine uptake accelerates globally, there is a need to document low-income country experiences with vaccine introductions. Over the course of five years, the government of Rwanda rolled out vaccines against pneumococcus, human papillomavirus, rotavirus, and measles & rubella, achieving over 90% coverage for each. To carry out these rollouts, Rwanda's Ministry of Health engaged in careful review of disease burden information and extensive, cross-sectoral planning at least one year before introducing each vaccine. Rwanda's local leaders, development partners, civil society organizations and widespread community health worker network were mobilized to support communication efforts. Community health workers were also used to confirm target population size. Support from Gavi, UNICEF and WHO was used in combination with government funds to promote country ownership and collaboration. Vaccination was also combined with additional community-based health interventions. Other countries considering rapid consecutive or simultaneous rollouts of new vaccines may consider lessons from Rwanda's experience while tailoring the strategies used to local context.

Prevalence and risk factors for cervical cancer and pre-cancerous lesions in Rwanda.

INTRODUCTION: Cervical cancer prevalence in Rwanda has not been well-described. Visual inspection with acetic acid or Lugol solution has been shown to be effective for cervical cancer screening in low resource settings. The aim of the study is to understand the prevalence and risk factors for cervical cancer and pre- cancerous lesions among Rwandan women between 30 and 50 old undergoing screening. METHODS: This cross-sectional analytical study was done in 3 districts of Rwanda from October 2010 to June 2013. Women aged 30 to 50 years screened for cervical cancer by trained doctors, nurses and midwives. Prevalence of pre-cancerous and cancerous cervical lesions was determined. Bivariate and multivariate logistic regressions were used to assess risk factors associated with cervical cancer. RESULTS: The prevalence of pre-cancer and invasive cervical cancer was 5.9% (95% CI 4.5, 7.5) and 1.7% (95% CI 0.9, 2.5), respectively. Risk factors associated with cervical cancer in multivariate analysis included initiation of sexual activity at less than 20 years (OR=1.75; 95% CI=(1.01, 3.03); being unmarried (single, divorced and widowed) (OR=3.29; 95% CI=( 1.26, 8.60)); Older age of participants (OR= 0.52; 95% CI= (0.28, 0.97)), older age at the first pregnancy (OR=2.10; 95% CI=(1.20, 3.67) and higher number of children born (OR=0.42; 95%CI =(0.23, 0.76)) were protective. CONCLUSION: Cervical cancer continues to be a public health problem in Rwanda, but screening using VIA is practical and feasible even in rural settings.

Causes of hospital admission among people living with HIV worldwide: a systematic review and meta-analysis.

BACKGROUND: Morbidity associated with HIV infection is poorly characterised, so we aimed to investigate the contribution of different comorbidities to hospital admission and in-hospital mortality in adults and children living with HIV worldwide. METHODS: Using a broad search strategy combining terms for hospital admission and HIV infection, we searched MEDLINE via PubMed, Embase, Web of Science, LILACS, AIM, IMEMR and WPIMR from inception to Jan 31, 2015, to identify studies reporting cause of hospital admission in people living with HIV. We focused on data reported after 2007, the period in which access to antiretroviral therapy started to become widespread. We estimated pooled proportions of hospital admissions and deaths per disease category by use of random-effects models. We stratified data by geographical region and age. FINDINGS: We obtained data from 106 cohorts, with reported causes of hospital admission for 313 006 adults and 6182 children living with HIV. For adults, AIDS-related illnesses (25 119 patients, 46%, 95% CI 40-53) and bacterial infections (14 034 patients, 31%, 20-42) were the leading causes of hospital admission. These two categories were the most common causes of hospital admission for adults in all geographical regions and the most common causes of mortality. Common region-specific causes of hospital admission included malnutrition and wasting, parasitic infections, and haematological disorders in the Africa region; respiratory disease, psychiatric disorders, renal disorders, cardiovascular disorders, and liver disease in Europe; haematological disorders in North America; and respiratory, neurological, digestive and liver-related conditions, viral infections, and drug toxicity in South and Central America. For children, AIDS-related illnesses (783 patients, 27%, 95% CI 19-34) and bacterial infections (1190 patients, 41%, 26-56) were the leading causes of hospital admission, followed by malnutrition and wasting, haematological disorders, and, in the African region, malaria. Mortality in individuals admitted to hospital was 20% (95% CI 18-23, 12 902 deaths) for adults and 14% (10-19, 643 deaths) for children. INTERPRETATION: This review shows the importance of prompt HIV diagnosis and treatment, and the need to reinforce existing recommendations to provide chemoprophylaxis and vaccination against major preventable infectious diseases to people living with HIV to reduce serious AIDS and non-AIDS morbidity. FUNDING: None.

HIV care continuum in Rwanda: a cross-sectional analysis of the national programme.

BACKGROUND: Rwanda has made remarkable progress towards HIV care programme with strong national monitoring and surveillance. Knowledge about the HIV care continuum model can help to improve outcomes in patients. We aimed to quantify engagement, mortality, and loss to follow-up of patients along the HIV care continuum in Rwanda in 2013. METHODS: We collated data for individuals with HIV who participated in the national HIV care programme in Rwanda and calculated the numbers of individuals or proportions of the population at each stage and the transition probabilities between stages of the continuum. We calculated factors associated with mortality and loss to follow-up by fitting Cox proportional hazards regression models, one for the stage of care before antiretroviral therapy (ART) initiation and another for stage of care during ART. FINDINGS: An estimated 204,899 individuals were HIV-positive in Rwanda in 2013. Among these individuals, 176,174 (86%) were in pre-ART or in ART stages and 129,405 (63%) had initiated ART by the end of 2013. 82·1% (95% CI 80·7-83·4) of patients with viral load measurements (n=3066) were virally suppressed (translating to 106,371 individuals or 52% of HIV-positive individuals). Mortality was 0·6% (304 patients) in the pre-ART stage and 1·0% (1255 patients) in the ART stage; 2247 (3·9%) patients were lost to follow-up in pre-ART stage and 2847 (2·2%) lost in ART stage. Risk factors for mortality among patients in both pre-ART and ART stages included older age, CD4 cell count at initiation, and male sex. Risk factors for loss to follow-up among patients at both pre-ART and ART stages included younger age (age 10-29 year) and male sex. INTERPRETATION: The HIV care continuum is a multitrajectory pathway in which patients have many opportunities to leave and re-engage in care. Knowledge about the points at which individuals are most likely to leave care could improve large-scale delivery of HIV programmes. FUNDING: The Bill & Melinda Gates Foundation.

Capacity building for oncology programmes in sub-Saharan Africa: the Rwanda experience.

Despite an estimated 456,000 deaths caused by cancer in sub-Saharan Africa in 2012 and a cancer burden that is predicted to double by 2030, the region accounts for only 0·3% of worldwide medical expenditure for cancer. Challenges to cancer care in sub-Saharan Africa include a shortage of clinicians and training programmes, weak healthcare infrastructure, and inadequate supplies. Since 2011, Rwanda has developed a national cancer programme by designing comprehensive, integrated frameworks of care, building local human resource capacity through partnerships, and delivering equitable, rights-based care. In the 2 years since the inauguration of Rwanda's first cancer centre, more than 2500 patients have been enrolled, including patients from every district in Rwanda. Based on Rwanda's national cancer programme development, we suggest principles that could guide other nations in the development of similar cancer programmes.

Life expectancy among HIV-positive patients in Rwanda: a retrospective observational cohort study.

BACKGROUND: Rwanda has achieved substantial progress in scaling up of antiretroviral therapy. We aimed to assess the effect of increased access to antiretroviral therapy on life expectancy among HIV-positive patients in two distinct periods of lower and higher antiretroviral therapy coverage (1997-2007 and 2008-11). METHODS: In a retrospective observational cohort study, we collected clinical and demographic data for all HIV-positive patients enrolled in care at 110 health facilities across all five provinces of Rwanda. We included patients aged 15 years or older with a known enrolment date between 1997 and 2014. We constructed abridged life tables from age-specific mortality rates and life expectancy stratified by sex, CD4 cell count, and WHO disease stage at enrolment in care and initiation of antiretroviral therapy. FINDINGS: We included 72,061 patients in this study, contributing 213,983 person-years of follow-up. The crude mortality rate was 33·4 deaths per 1000 person-years (95% CI 32·7-34·2). Life expectancy for the overall cohort was 25·6 additional years (95% CI 25·1-26·1) at 20 years of age and 23·3 additional years (95% CI 22·9-23·7) at 35 years of age. Life expectancy at 20 years of age in the period of 1997-2007 was 20·4 additional years (95% CI 19·5-21·3); for the period of 2008-11, life expectancy had increased to 25·6 additional years (95% CI 24·8-26·4). Individuals enrolling in care with CD4 cell counts of 500 cells per µL or more, and with WHO disease stage I, had the highest life expectancies. INTERPRETATION: This study adds to the growing body of evidence showing the benefit to HIV-positive patients of early enrolment in care and initiation of antiretroviral therapy. FUNDING: Bill & Melinda Gates Foundation.

Scaling up intensified tuberculosis case finding in HIV clinics in Rwanda.

BACKGROUND: Tuberculosis (TB) is the leading cause of morbidity and mortality among people living with HIV (PLHIV) in sub-Saharan Africa. Early TB detection and treatment is key to saving lives of PLHIV. Rwanda began implementing intensified TB case finding (ICF) in 2005 in line with World Health Organization policy on TB/HIV collaborative activities. We aimed to describe trends of ICF in PLHIV newly enrolled into HIV clinics. METHODS: We used routinely collected program data on ICF from facility-based pre-antiretroviral therapy/antiretroviral therapy registers in Rwandan HIV clinics from 2006 to 2011. Semiannual, active data collection for PLHIV newly enrolled into HIV care included proportion screened for TB, proportion screened positive, and percentage with active TB and started anti-TB drugs. RESULTS: The number of health facilities reporting TB screening indicators increased 16-fold, from 20 facilities in the first semester of 2006 to 328 facilities by the end of 2011. The proportion of patients screened increased progressively from 77% of newly enrolled patients in first semester of 2006 to 94% at the end of 2011 (P < 0.001). The proportion of patients who screened positive decreased over time, from 23% in the first semester of 2006 to 10% at the end of 2011 (P < 0.001). The proportion of active TB cases remained relatively constant over time at 2.2%. CONCLUSIONS: Rwanda has increased the proportion of newly enrolled PLHIV screened for TB using a simple screening protocol. Countries with limited resources but high HIV and TB disease prevalence should implement ICF as part of their integrated HIV-TB treatment programs.