Publications by authors named "Etienne Karita"

118 Publications

Leapfrogging with technology: introduction of a monitoring platform to support a large-scale Ebola vaccination program in Rwanda.

Hum Vaccin Immunother 2021 Jun 2:1-11. Epub 2021 Jun 2.

Johnson and Johnson Health and Wellness Solutions, Inc., New Brunswick, NJ, USA.

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.
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http://dx.doi.org/10.1080/21645515.2021.1920872DOI Listing
June 2021

Cross-sectional assessment of determinants of STIs among men who have sex with men and transgender women in Kigali, Rwanda.

Sex Transm Infect 2021 May 6. Epub 2021 May 6.

Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.

Background: STIs among men who have sex with men (MSM) and transgender women (TGW) continue to increase. In Rwanda, STI management relies on syndromic management with limited empirical data characterising the burden of specific STIs among MSM/TGW. This study evaluated the prevalence of syphilis, (NG) and (CT) and associated factors among MSM/TGW in Kigali.

Methods: From March to August 2018, 737 MSM/TGW >18 years were enrolled using respondent-driven sampling (RDS). Structured interviews and HIV/STI screening were conducted. Syphilis was screened with rapid plasma reagin confirmed by hemagglutination assay. CT/NG were tested by Cepheid GeneXpert. RDS-adjusted multivariable Poisson regression models with robust variance estimation were used to evaluate factors associated with any STI, and determinants of urethral and rectal STIs separately.

Results: Prevalence of any STI was 20% (RDS adjusted: 16.7% (95% CI: 13.2% to 20.2%)). Syphilis was 5.7% (RDS adjusted: 6.8% (95% CI: 4.3% to 9.4%)). CT was 9.1% (RDS adjusted: 6.1% (95% CI: 3.9% to 8.4%)) and NG was 8.8% (RDS adjusted: 7.1% (95% CI: 4.9% to 9.2%)). STIs were more common among older MSM and those with HIV (p<0.05). Of CT infections, 67% were urethral, 27% rectal and 6% were dual site. For NG infections, 52% were rectal, 29% urethral and 19% were dual site. Overall, 25.8% (23 of 89) of those with confirmed STI and returned for their results were symptomatic at time of testing.STI symptoms in the previous year (adjusted prevalence ratio (aPR): 1.94 (95% CI: 1.26 to 2.98)) were positively associated with any STI. Being circumcised was negatively associated with any STI (aPR: 0.47 (95% CI: 0.31 to 0.73)). HIV was positively associated with rectal STIs (aPR: 3.50 (95% CI: 1.09 to 11.21)) but negatively associated with urethral STIs.

Conclusion: MSM/TGW, especially those living with HIV, are at high risk of STIs in Rwanda with the vast majority being asymptomatic. These data suggest the potential utility of active STI surveillance strategies using highly sensitive laboratory methods among those at high risk given the anatomical distribution and limited symptomatology of STIs observed among Rwandan MSM/TGW.
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http://dx.doi.org/10.1136/sextrans-2020-054753DOI Listing
May 2021

Developing and validating a risk algorithm to diagnose Neisseria gonorrhoeae and Chlamydia trachomatis in symptomatic Rwandan women.

BMC Infect Dis 2021 Apr 28;21(1):392. Epub 2021 Apr 28.

Projet San Francisco, Rwanda Zambia HIV Research Group, Kigali, Rwanda.

Background: Algorithms that bridge the gap between syndromic sexually transmitted infection (STI) management and treatment based in realistic diagnostic options and local epidemiology are urgently needed across Africa. Our objective was to develop and validate a risk algorithm for Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) diagnosis among symptomatic Rwandan women and to compare risk algorithm performance to the current Rwandan National Criteria for NG/CT diagnosis.

Methods: The risk algorithm was derived in a cohort (n = 468) comprised of symptomatic women in Kigali who sought free screening and treatment for sexually transmitted infections and vaginal dysbioses at our research site. We used logistic regression to derive a risk algorithm for prediction of NG/CT infection. Ten-fold cross-validation internally validated the risk algorithm. We applied the risk algorithm to an external validation cohort also comprised of symptomatic Rwandan women (n = 305). Measures of calibration, discrimination, and screening performance of our risk algorithm compared to the current Rwandan National Criteria are presented.

Results: The prevalence of NG/CT in the derivation cohort was 34.6%. The risk algorithm included: age < =25, having no/primary education, not having full-time employment, using condoms only sometimes, not reporting genital itching, testing negative for vaginal candida, and testing positive for bacterial vaginosis. The model was well calibrated (Hosmer-Lemeshow p = 0.831). Higher risk scores were significantly associated with increased prevalence of NG/CT infection (p < 0.001). Using a cut-point score of > = 5, the risk algorithm had a sensitivity of 81%, specificity of 54%, positive predictive value (PPV) of 48%, and negative predictive value (NPV) of 85%. Internal and external validation showed similar predictive ability of the risk algorithm, which outperformed the Rwandan National Criteria. Applying the Rwandan National Criteria cutoff of > = 2 (the current cutoff) to our derivation cohort had a sensitivity of 26%, specificity of 89%, PPV of 55%, and NPV of 69%.

Conclusions: These data support use of a locally relevant, evidence-based risk algorithm to significantly reduce the number of untreated NG/CT cases in symptomatic Rwandan women. The risk algorithm could be a cost-effective way to target treatment to those at highest NG/CT risk. The algorithm could also aid in sexually transmitted infection risk and prevention communication between providers and clients.
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http://dx.doi.org/10.1186/s12879-021-06073-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080377PMC
April 2021

Etiologies of genital inflammation and ulceration in symptomatic Rwandan men and women responding to radio promotions of free screening and treatment services.

PLoS One 2021 20;16(4):e0250044. Epub 2021 Apr 20.

Project San Francisco, Rwanda Zambia HIV Research Group, Kigali, Rwanda.

Introduction: The longstanding inadequacies of syndromic management for genital ulceration and inflammation are well-described. The Rwanda National Guidelines for sexually transmitted infection (STI) syndromic management are not yet informed by the local prevalence and correlates of STI etiologies, a component World Health Organization guidelines stress as critical to optimize locally relevant algorithms.

Methods: Radio announcements and pharmacists recruited symptomatic patients to seek free STI services in Kigali. Clients who sought services were asked to refer sexual partners and symptomatic friends. Demographic, behavioral risk factor, medical history, and symptom data were collected. Genital exams were performed by trained research nurses and physicians. We conducted phlebotomy for rapid HIV and rapid plasma reagin (RPR) serologies and vaginal pool swab for microscopy of wet preparation to diagnose Trichomonas vaginalis (TV), bacterial vaginosis (BV), and vaginal Candida albicans (VCA). GeneXpert testing for Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) were conducted. Here we assess factors associated with diagnosis of NG and CT in men and women. We also explore factors associated with TV, BV and VCA in women. Finally, we describe genital ulcer and RPR results by HIV status, gender, and circumcision in men.

Results: Among 974 men (with 1013 visits), 20% were positive for CT and 74% were positive for NG. Among 569 women (with 579 visits), 17% were positive for CT and 27% were positive for NG. In multivariate analyses, factors associated with CT in men included younger age, responding to radio advertisements, <17 days since suspected exposure, and not having dysuria. Factors associated with NG in men included not having higher education or full-time employment, <17 days since suspected exposure, not reporting a genital ulcer, and having urethral discharge on physical exam. Factors associated with CT in women included younger age and < = 10 days with symptoms. Factors associated with NG in women included younger age, lower education and lack of full-time employment, sometimes using condoms vs. never, using hormonal vs. non-hormonal contraception, not having genital ulcer or itching, having symptoms < = 10 days, HIV+ status, having BV, endocervical discharge noted on speculum exam, and negative vaginal wet mount for VCA. In multivariate analyses, only reporting >1 partner was associated with BV; being single and RPR+ was associated with TV; and having < = 1 partner in the last month, being pregnant, genital itching, discharge, and being HIV and RPR negative were associated with VCA. Genital ulcers and positive RPR were associated with being HIV+ and lack of circumcision among men. HIV+ women were more likely to be RPR+. In HIV+ men and women, ulcers were more likely to be herpetic rather than syphilitic compared with their HIV- counterparts.

Conclusions: Syndromic management guidelines in Rwanda can be improved with consideration of the prevalence of confirmed infections from this study of symptomatic men and women representative of those who would seek care at government health centers. Inclusion of demographic and risk factor measures shown to be predictive of STI and non-STI dysbioses may also increase diagnostic accuracy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250044PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057583PMC
April 2021

A Stronger Innate Immune Response During Hyperacute HIV-1 Infection is associated with ACUTE retroviral syndrome.

Clin Infect Dis 2021 Feb 15. Epub 2021 Feb 15.

KEMRI/Wellcome Trust Research Programme, Kilifi, Kenya.

Background: Acute retroviral syndrome (ARS) is associated with HIV-1 subtype and disease progression, but the underlying immunopathological pathways are poorly understood. We aimed to elucidate associations between innate immune responses during hyperacute HIV-1 infection (hAHI) and ARS.

Methods: Plasma samples obtained from volunteers (≥18.0 years) before and during hAHI, defined as HIV-1 antibody negative and RNA or p24 antigen positive from Kenya, Rwanda, Uganda, Zambia and Sweden were analysed. Forty soluble innate immune markers were measured using multiplexed assays. Immune responses were differentiated into volunteers with stronger and comparatively weaker responses using principal component analysis. Presence or absence of ARS was defined based on eleven symptoms using latent class analysis. Logistic regression was used to determine associations between immune responses and ARS.

Results: Of 55 volunteers, 31 (56%) had ARS. Volunteers with stronger immune responses (n=36 [65%]) had increased odds of ARS which was independent of HIV-1 subtype, age, and risk group (adjusted odds ratio, 7.1 [95% CI: 1.7-28.8], p=0.003). IP-10 was fourteen-fold higher during hAHI, elevated in seven of the eleven symptoms, and independently associated with ARS. IP-10 threshold >466.0 pg/mL differentiated stronger immune responses with a sensitivity of 84.2% (95% CI: 60.4-96.6) and specificity of 100.0% (95% CI: 90.3-100.0).

Conclusions: A stronger innate immune response during hAHI was associated with ARS. Plasma IP-10 may be a candidate biomarker of stronger innate immunity. Our findings provide further insights on innate immune responses in regulating ARS and may inform the design of vaccine candidates harnessing innate immunity.
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http://dx.doi.org/10.1093/cid/ciab139DOI Listing
February 2021

Genital abnormalities, hormonal contraception, and HIV transmission risk in Rwandan serodifferent couples.

J Infect Dis 2021 Feb 9. Epub 2021 Feb 9.

Rwanda Zambia Health Research Group, Department of Pathology & Laboratory Medicine, School of Medicine and Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.

Background: We explored the role of genital abnormalities and hormonal contraception in HIV transmission among heterosexual serodifferent couples in Rwanda.

Methods: From 2002-2011, non-antiretroviral treatment using HIV serodifferent couples were followed and sociodemographic and clinical data were collected, family planning provided, and HIV-negative partners retested. Couples were assessed for genital ulcers; non-ulcerative genital sexually transmitted infection (STI) including gonorrhea, chlamydia, and trichomoniasis; and non-STI vaginal infections including bacterial vaginosis and candida. Multivariable models evaluated associations between covariates and HIV transmission genetically linked to the index partner.

Results: Among 877 couples where the man was HIV-positive, 37 linked transmissions occurred. Factors associated with women's HIV acquisition included female partner genital ulceration (adjusted hazard ratio [aHR]=14.1) and male partner non-ulcerative STI (aHR=8.6). Among 955 couples where the woman was HIV-positive, 46 linked transmissions occurred. Factors associated with men's HIV acquisition included female partner non-ulcerative STI (aHR=4.4), non-STI vaginal dysbiosis (aHR=7.1), and male partner genital ulceration (aHR=2.6). Hormonal contraception use was not associated with HIV transmission or acquisition.

Conclusions: Our findings underscore the need for integrating HIV services with care for genital abnormalities. Barriers (e.g., cost for training, demand creation, advocacy, client education; provider time; clinic space) to joint HIV/STI testing need to be considered and addressed.
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http://dx.doi.org/10.1093/infdis/jiab071DOI Listing
February 2021

Antiretroviral Therapy Use and HIV Transmission Among Discordant Couples in Nonresearch Settings in Kigali, Rwanda.

Sex Transm Dis 2021 06;48(6):424-428

From the Projet San Francisco, Rwanda Zambia HIV Research Group, Kigali, Rwanda.

Background: Antiretroviral therapy (ART) efficacy for HIV prevention among discordant couples has been demonstrated in clinical trials. Effectiveness outside of research settings is less well understood.

Methods: HIV-discordant couples were enrolled in couples' testing and follow-up at 20 government clinics in Kigali from 2010 to 2014. We performed viral linkage analysis on seroconverting couples to determine infection sources (intracouple vs. extracouple). Antiretroviral therapy use in index partners was collected at baseline and during follow-up by self-report with verification of government medical records.

Results: A total of 3777 HIV-discordant couples were identified and followed up at government health clinics. Fifty-four incident HIV infections were identified, of which 36 were confirmed linked to the index partner, 4 were unlinked, and 14 were unknown. Among the 50 linked or unknown transmission pairs, 38% occurred among couples in which the index partner was on ART (HIV incidence rate of 0.63/100 person-years), whereas 62% occurred among couples in which the index partner was not on ART (HIV incidence rate of 5.51/100 person-years; adjusted rate ratio, 6.9). HIV acquisition was higher in women than in men with non-ART using index partners (P < 0.001).

Conclusions: Couples in a government clinic couples' HIV testing and follow-up program in Rwanda had an 89% reduction in HIV incidence when index partners were using ART, slightly lower than efficacy estimates from randomized trials. Antiretroviral therapy for prevention should be prioritized for key populations including discordant couples identified via couples' voluntary counseling and testing, with increased efforts to improve uptake, adherence, and viral load monitoring.
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http://dx.doi.org/10.1097/OLQ.0000000000001350DOI Listing
June 2021

Safety and immunogenicity of two heterologous HIV vaccine regimens in healthy, HIV-uninfected adults (TRAVERSE): a randomised, parallel-group, placebo-controlled, double-blind, phase 1/2a study.

Lancet HIV 2020 10;7(10):e688-e698

Janssen Research and Development, Titusville, NJ, USA.

Background: Bioinformatically designed mosaic antigens increase the breadth of HIV vaccine-elicited immunity. This study compared the safety, tolerability, and immunogenicity of a newly developed, tetravalent Ad26 vaccine with the previously tested trivalent formulation.

Methods: This randomised, parallel-group, placebo-controlled, double-blind, phase 1/2a study (TRAVERSE) was done at 11 centres in the USA and one centre in Rwanda. Eligible participants were adults aged 18 to 50 years, who were HIV-uninfected, healthy at screening based on their medical history and a physical examination including laboratory assessment and vital sign measurements, and at low risk of HIV infection in the opinion of study staff, who applied a uniform definition of low-risk guidelines that was aligned across sites. Enrolled participants were randomly assigned at a 2:1 ratio to tetravalent and trivalent groups. Participants in tetravalent and trivalent groups were then further randomly assigned at a 5:1 ratio to adenovirus 26 (Ad26)-vectored vaccine and placebo subgroups. Randomisation was stratified by region (USA and Rwanda) and based on a computer-generated schedule using randomly permuted blocks prepared under the sponsor's supervision. We masked participants and investigators to treatment allocation throughout the study. On day 0, participants received a first injection of tetravalent vaccine (Ad26.Mos4.HIV or placebo) or trivalent vaccine (Ad26.Mos.HIV or placebo), and those injections were repeated 12 weeks later. At week 24, vaccine groups received a third dose of tetravalent or trivalent together with clade C gp140, and this was repeated at week 48, with placebos again administered to the placebo group. All study vaccines and placebo were administered by intramuscular injection in the deltoid muscle. We assessed adverse events in all participants who received at least one study injection (full analysis set) and Env-specific binding antibodies in all participants who received at least the first three vaccinations according to the protocol-specified vaccination schedule, had at least one measured post-dose blood sample collected, and were not diagnosed with HIV during the study (per-protocol set). This study is registered with Clinicaltrials.gov, NCT02788045.

Findings: Of 201 participants who were enrolled and randomly assigned, 198 received the first vaccination: 110 were in the tetravalent group, 55 in the trivalent group, and 33 in the placebo group. Overall, 185 (93%) completed two scheduled vaccinations per protocol, 180 (91%) completed three, and 164 (83%) completed four. Solicited, self-limiting local, systemic reactogenicity and unsolicited adverse events were similar in vaccine groups and higher than in placebo groups. All participants in the per-protocol set developed clade C Env binding antibodies after the second vaccination, with higher total IgG titres after the tetravalent vaccine than after the trivalent vaccine (10 413 EU/mL, 95% CI 7284-14 886 in the tetravalent group compared with 5494 EU/mL, 3759-8029 in the trivalent group). Titres further increased after the third and fourth vaccinations, persisting at least through week 72. Other immune responses were also higher with the tetravalent vaccine, including the magnitude and breadth of binding antibodies against a cross-clade panel of Env antigens, and the magnitude of IFNγ ELISPOT responses (median 521 SFU/10 peripheral blood mononuclear cells [PBMCs] in the tetravalent group and median 282 SFU/10 PBMCs in the trivalent group after the fourth vaccination) and Env-specific CD4+ T-cell response rates after the third and fourth vaccinations. No interference by pre-existing Ad26 immunity was identified.

Interpretation: The tetravalent vaccine regimen was generally safe, well-tolerated, and found to elicit higher immune responses than the trivalent regimen. Regimens that use this tetravalent vaccine component are being advanced into field trials to assess efficacy against HIV-1 infection.

Funding: National Institutes of Health, Henry M Jackson Foundation for Advancement of Military Medicine and the US Department of Defense, Ragon Institute of MGH, MIT, & Harvard, Bill & Melinda Gates Foundation, and Janssen Vaccines & Prevention.
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http://dx.doi.org/10.1016/S2352-3018(20)30229-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529856PMC
October 2020

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.

J Int AIDS Soc 2020 10;23 Suppl 6:e25604

Department of Epidemiology, Key Populations Program, Center for Public Health and Human Rights, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

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.
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http://dx.doi.org/10.1002/jia2.25604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527755PMC
October 2020

Postpartum long-acting contraception uptake and service delivery outcomes after a multilevel intervention in Kigali, Rwanda.

BMJ Sex Reprod Health 2020 Sep 16. Epub 2020 Sep 16.

Rwanda Zambia HIV Research Group, Department of Pathology & Laboratory Medicine, School of Medicine, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA

Introduction: Postpartum family planning (PPFP) 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 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 multilevel intervention to increase supply and demand for PPFP services in Kigali, Rwanda.

Methods: We implemented our intervention (which included PPFP promotional counselling for clients, training for providers, and Ministry of Health stakeholder involvement) in six government health facilities from August 2017 to October 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 PPIUD uptake for reference.

Results: Over a 15-month implementation period, 12 068 women received PPFP educational counselling 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 multilevel intervention. PPFP methods were well received by clients and providers.
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http://dx.doi.org/10.1136/bmjsrh-2020-200741DOI Listing
September 2020

Uptake of long acting reversible contraception following integrated couples HIV and fertility goal-based family planning counselling in Catholic and non-Catholic, urban and rural government health centers in Kigali, Rwanda.

Reprod Health 2020 Aug 17;17(1):126. Epub 2020 Aug 17.

Projet San Francisco, Rwanda Zambia HIV Research Group, Kigali, Rwanda.

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 unplanned pregnancy.
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http://dx.doi.org/10.1186/s12978-020-00981-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7433361PMC
August 2020

Prevalence and incidence of HIV among female sex workers and their clients: modelling the potential effects of intervention in Rwanda.

BMJ Glob Health 2020 08;5(8)

Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada, McMaster University, Hamilton, Ontario, Canada.

Background: Rwanda has identified several targeted HIV prevention strategies, such as promotion of condom use and provision of antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) for female sex workers (FSWs). Given this country's limited resources, understanding how the HIV epidemic will be affected by these strategies is crucial.

Methods: We developed a Markov model to estimate the effects of targeted strategies to FSWs on the HIV prevalence/incidence in Rwanda from 2017 to 2027. Our model consists of the six states: HIV-; HIV+ undiagnosed/diagnosed pre-ART; HIV+ diagnosed with/without ART; and death. We considered three populations: FSWs, sex clients and the general population. For the period 2017-2027, the HIV epidemic among each of these population was estimated using Rwanda's demographic, sexual risk behaviour and HIV-associated morbidity and mortality data.

Results: Between 2017 and 2027, with no changes in the current condom and ART use, the overall number of people living with HIV is expected to increase from 344,971 to 402,451. HIV incidence will also decrease from 1.36 to 1.20 100 person-years. By 2027, a 30% improvement in consistent condom use among FSWs will result in absolute reduction of HIV prevalence among FSWs, sex clients and the general population by 7.86%, 5.97% and 0.17%, respectively. While recurring HIV testing and improving the ART coverage mildly reduced the prevalence/incidence among FSWs and sex clients, worsening the two (shown by our worst-case scenario) will result in an increase in the HIV prevalence/incidence among FSWs and sex clients. Introduction of PrEP to FSWs in 2019 will reduce the HIV incidence among FSWs by 1.28%.

Conclusions: Continued efforts toward improving condom and ART use will be critical for Rwanda to continue their HIV epidemic control. Implementing a targeted intervention strategy in PrEP for FSWs will reduce the HIV epidemic in this high-risk population.
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http://dx.doi.org/10.1136/bmjgh-2020-002300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412619PMC
August 2020

African-led health research and capacity building- is it working?

BMC Public Health 2020 Jul 14;20(1):1104. Epub 2020 Jul 14.

Africa Health Research Institute, Durban, South Africa.

Background: Africa bears a disproportionately high burden of globally significant disease but has lagged in knowledge production to address its health challenges. In this contribution, we discuss the challenges and approaches to health research capacity strengthening in sub-Saharan Africa and propose that the recent shift to an African-led approach is the most optimal.

Methods And Findings: We introduce several capacity building approaches and recent achievements, explore why African-led research on the continent is a potentially paradigm-shifting and innovative approach, and discuss the advantages and challenges thereof. We reflect on the approaches used by the African Academy of Sciences (AAS)-funded Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE) consortium as an example of an effective African-led science and capacity building programme. We recommend the following as crucial components of future efforts: 1. Directly empowering African-based researchers, 2. Offering quality training and career development opportunities to large numbers of junior African scientists and support staff, and 3. Effective information exchange and collaboration. Furthermore, we argue that long-term investment from international donors and increasing funding commitments from African governments and philanthropies will be needed to realise a critical mass of local capacity and to create and sustain world-class research hubs that will be conducive to address Africa's intractable health challenges.

Conclusions: Our experiences so far suggest that African-led research has the potential to overcome the vicious cycle of brain-drain and may ultimately lead to improvement of health and science-led economic transformation of Africa into a prosperous continent.
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http://dx.doi.org/10.1186/s12889-020-08875-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359480PMC
July 2020

Cost-effectiveness of couples' voluntary HIV counselling and testing in six African countries: a modelling study guided by an HIV prevention cascade framework.

J Int AIDS Soc 2020 06;23 Suppl 3:e25522

Rwanda Zambia HIV Research Group, Department of Pathology & Laboratory Medicine, School of Medicine and Hubert Department of Global Health, Rollins School of Public Health, Laney Graduate School, Emory University, Atlanta, GA, USA.

Introduction: Couples' 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.

Methods: We 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.

Results: We 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.

Conclusions: Our 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.
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http://dx.doi.org/10.1002/jia2.25522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325504PMC
June 2020

Cost per insertion and couple year of protection for postpartum intrauterine devices and implants provided during service scale-up in Kigali, Rwanda.

Gates Open Res 2018 28;2:39. Epub 2020 Feb 28.

Projet San Francisco, Rwanda Zambia HIV Research Group, Department of Pathology & Laboratory Medicine, School of Medicine, Rollins School of Public Health, Emory University, Kigali, Rwanda.

In two high-volume government hospitals, their two affiliated health facilities, and two additional health facilities, we developed and implemented postpartum intrauterine device (PPIUD) and postpartum (PP) implant promotional counseling and service delivery procedures between May-July 2017 in Kigali, Rwanda. Between August 2017 and July 2018, 9,073 pregnant women received PPIUD/PP implant promotions who later delivered in one of our selected facilities. Of those, 2,633 had PPIUDs inserted, and 955 had PP implants inserted. The goal of the present analysis is to detail implementation expenditures and estimate incremental costs per insertion and couple years of protection (CYP) for PPIUD and PP implant users. We detail the incremental costs during the implementation from the health system perspective (including both the implementation costs and the cost of contraceptive methods) and use of standard methods to estimate the cost per insertion and CYP for PPIUD and PP implant users. In addition to the incremental costs of labor and supplies, the costs of promotional activities are included. Research costs for formative work were excluded. A total of $74,147 USD was spent on the implementation between August 2017 and July 2018. The largest expense (34% of total expenses) went toward personnel, including doctoral-level, administrative, data management and nurse counseling staff. Training for PPIUD and implant providers and promoters comprised 8% of total expenses. Recruitment and reimbursements comprised 6% of expenses. Costs of implants to the government comprised 12% of the expenses, much higher than the cost of IUDs (1%). Costs per insertion were $25/PPIUDs and $77/PP implant. Costs per CYP were $6/PPIUDs and $21/PP implant.  Understanding the cost per PPIUD/PP implant inserted and CYP can help to inform the cost of scaling up PPIUD/PP implant service implementation activities and resource allocation decision-making by the Rwandan Ministry of Health.
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http://dx.doi.org/10.12688/gatesopenres.12858.4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163922PMC
February 2020

Acceptability and tolerability of repeated intramuscular electroporation of Multi-antigenic HIV (HIVMAG) DNA vaccine among healthy African participants in a phase 1 randomized controlled trial.

PLoS One 2020 29;15(5):e0233151. Epub 2020 May 29.

University of California at San Francisco, San Francisco, California, United States of America.

Introduction: Intramuscular electroporation (IM/EP) is a vaccine delivery technique that improves the immunogenicity of DNA vaccines. We evaluated the acceptability and tolerability of electroporation among healthy African study participants.

Methods: Forty-five participants were administered a DNA vaccine (HIV-MAG) or placebo by electroporation at three visits occurring at four week-intervals. At the end of each visit, participants were asked to rate pain at four times: (1) when the device was placed on the skin and vaccine injected, before the electrical stimulation, (2) at the time of electrical stimulation and muscle contraction, and (3) at 10 minutes and (4) 30 minutes after the procedure was completed. For analyses, pain level was dichotomized as either "acceptable" (none/slight/uncomfortable) or "too much" (Intense, severe, and very severe) and examined over time using repeated measures models. Optional brief comments made by participants were summarized anecdotally.

Results: All 45 participants completed all three vaccination visits; none withdrew from the study due to the electroporation procedure. Most (76%) reported pain levels as acceptable at every time point across all vaccination visits. The majority of "unacceptable" pain was reported at the time of electrical stimulation. The majority of the participants (97%) commented that they preferred electroporation to standard injection.

Conclusion: Repeated intramuscular electroporation for vaccine delivery was found to be acceptable and feasible among healthy African HIV vaccine trial participants. The majority of participants reported an acceptable pain level at all vaccination time points. Further investigation may be warranted into the value of EP to improve immunization outcomes. ClinicalTrials.gov NCT01496989.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0233151PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7259687PMC
August 2020

Differential Vpu-Mediated CD4 and Tetherin Downregulation Functions among Major HIV-1 Group M Subtypes.

J Virol 2020 07 1;94(14). Epub 2020 Jul 1.

Faculty of Health Sciences, Simon Fraser University, Vancouver, British Columbia, Canada

Downregulation of BST-2/tetherin and CD4 by HIV-1 viral protein U (Vpu) promotes viral egress and allows infected cells to evade host immunity. Little is known however about the natural variability in these Vpu functions among the genetically diverse viral subtypes that contribute to the HIV-1 pandemic. We collected Vpu isolates from 332 treatment-naive individuals living with chronic HIV-1 infection in Uganda, Rwanda, South Africa, and Canada. Together, these Vpu isolates represent four major HIV-1 group M subtypes (A [ = 63], B [ = 84], C [ = 94], and D [ = 59]) plus intersubtype recombinants and uncommon strains ( = 32). The ability of each Vpu clone to downregulate endogenous CD4 and tetherin was quantified using flow cytometry following transfection into an immortalized T-cell line and compared to that of a reference Vpu clone derived from HIV-1 subtype B NL4.3. Overall, the median CD4 downregulation function of natural Vpu isolates was similar to that of NL4.3 (1.01 [interquartile range {IQR}, 0.86 to 1.18]), while the median tetherin downregulation function was moderately lower than that of NL4.3 (0.90 [0.79 to 0.97]). Both Vpu functions varied significantly among HIV-1 subtypes (Kruskal-Wallis  < 0.0001). Specifically, subtype C clones exhibited the lowest CD4 and tetherin downregulation activities, while subtype D and B clones were most functional for both activities. We also identified Vpu polymorphisms associated with CD4 or tetherin downregulation function and validated six of these using site-directed mutagenesis. Our results highlight the marked extent to which Vpu function varies among global HIV-1 strains, raising the possibility that natural variation in this accessory protein may contribute to viral pathogenesis and/or spread. The HIV-1 accessory protein Vpu enhances viral spread by downregulating CD4 and BST-2/tetherin on the surface of infected cells. Natural variability in these Vpu functions may contribute to HIV-1 pathogenesis, but this has not been investigated among the diverse viral subtypes that contribute to the HIV-1 pandemic. In this study, we found that Vpu function differs significantly among HIV-1 subtypes A, B, C, and D. On average, subtype C clones displayed the lowest ability to downregulate both CD4 and tetherin, while subtype B and D clones were more functional. We also identified Vpu polymorphisms that associate with functional differences among HIV-1 isolates and subtypes. Our study suggests that genetic diversity in Vpu may play an important role in the differential pathogenesis and/or spread of HIV-1.
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http://dx.doi.org/10.1128/JVI.00293-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343213PMC
July 2020

An Exploratory Analysis of Factors Associated With Interest in Postpartum Intrauterine Device Uptake Among Pregnant Women and Couples in Kigali, Rwanda.

Clin Med Insights Reprod Health 2019 3;13:1179558119886843. Epub 2019 Dec 3.

Emory University, Atlanta, GA, USA.

Background: The desire to space or prevent future pregnancies is high among postpartum women in Rwanda. However, the use of long-acting reversible contraception (LARC), especially the highly effective and cost-effective copper intrauterine device (IUD), is very low, whereas the rates of unintended pregnancy are high. This study aims to identify factors associated with pregnant women's and couple's interest in receiving a postpartum intrauterine device (PPIUD) within 6 weeks after delivery.

Methods: A total of 150 pregnant women or couples attending antenatal care (ANC) in Kigali, Rwanda participated in this cross-sectional study. After participating in a postpartum LARC counseling session, surveys assessed participants' demographics, pregnancy experiences and desires, and PPIUD knowledge, attitudes, practices, and interest. Multivariable logistic regression was used to model factors associated PPIUD interest within 6 weeks postpartum.

Results: Although only 3% of women had ever used an IUD previously, 124 (83%) women were interested in receiving a PPIUD after counseling. Self-reporting physical side effects (adjusted odds ratio [aOR], 0.21; 95% confidence interval [CI], 0.06-0.75) and infection (aOR, 0.19; 95% CI, 0.04-0.85) as disadvantages to the IUD were significantly associated with no interest in receiving a PPIUD. Interest did not differ by male involvement.

Conclusion: Recommendations to increase PPIUD uptake include educating pregnant women and couples about the method during ANC and addressing client myths and misconceptions about the IUD. This strategy allows pregnant women and couples to make informed decisions about their future contraception use, reduce unmet need for family planning, and reduce unintended pregnancy.
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http://dx.doi.org/10.1177/1179558119886843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893932PMC
December 2019

Motivational interviewing to promote long-acting reversible contraception among Rwandan couples wishing to prevent or delay pregnancy.

Am J Obstet Gynecol 2020 04 12;222(4S):S919.e1-S919.e12. Epub 2019 Dec 12.

Projet San Francisco, Rwanda Zambia HIV Research Group, University of Rwanda, Kigali, Rwanda.

Background: Few family-planning programs in Africa base demand creation and service delivery on theoretical models. Motivational interviewing 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 to enhance uptake of long-acting reversible contraception (Paragard copper intrauterine device or Jadelle hormonal implant) among Rwandan couples.

Study Design: In this experimental study, couples receiving care at 8 government health clinics in Kigali, the capital city, were referred from a parent study of couples who did not want more children or wanted to wait at least 2 years for their next pregnancy. Long-acting reversible contraception methods were offered on site following joint HIV testing and family-planning counseling. At the first follow-up visit 1 month after enrollment in the parent study, couples who had not yet chosen a long-acting reversible contraception method were interviewed separately using motivational interviewing and then brought together and again offered long-acting reversible contraception.

Results: Following motivational interviewing, 78 of 229 couples (34%) requested a long-acting reversible contraception method (68 implant and 10 intrauterine device). Long-acting reversible contraception uptake after motivational interviewing was associated with the woman being Catholic (vs Protestant/Muslim/other, adjusted odds ratio, 2.87, 95% confidence interval, 1.19-6.96, P = .019) or having an income (vs no income, adjusted odds ratio, 2.54, 95% confidence interval, 1.12-5.73, P = .025); the couple having previously discussed long-acting reversible contraception (adjusted odds ratio, 8.38, 95% confidence interval, 2.54-27.59, P = .0005); either partner believing that unplanned pregnancy was likely with their current method (adjusted odds ratio, 6.67, 95% confidence interval, 2.77-16.11, P < .0001); or that they might forget to take or make an appointment for their current method (adjusted odds ratio, 4.04, 95% confidence interval, 1.32-12.34, P = .014). Neither partner mentioning that condoms also prevent HIV/sexually transmitted infection was associated with long-acting reversible contraception uptake (adjusted odds ratio, 2.86, 95% confidence interval, 1.17-7.03, P = .022), as was the woman citing long-term duration of action of the implant as an advantage (adjusted odds ratio, 5.41, 95% confidence interval, 1.86-15.76, P = .002). The woman not listing any side effects or disadvantages of implants was associated with long-acting reversible contraception uptake (adjusted odds ratio, 5.42, 95% confidence interval, 2.33-12.59, P < .0001). Clinic location (rural vs urban), couple HIV status, and concerns about negative economic effects of an unplanned pregnancy were significant in bivariate but not multivariate analysis.

Conclusion: Encouraging couples to reflect on the benefits and disadvantages of long-acting reversible contraception methods, the likelihood of unplanned pregnancy with their current contraception, and the impact of an unplanned pregnancy is an effective motivational interviewing technique in family-planning counseling. One third of couples who did not want a pregnancy for at least 2 years but had not chosen a long-acting reversible contraception method when provided with standard family-planning counseling did so after motivational interviewing. Involving the male partner in family-planning discussions facilitates joint decision making about fertility goals and contraceptive choice. Combining family planning and joint HIV testing for couples allows targeted focus on dual-method use with discordant couples, who are advised to use condoms for HIV/sexually transmitted infection prevention along with a more effective contraceptive for added protection against unplanned pregnancy.
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http://dx.doi.org/10.1016/j.ajog.2019.11.1280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138747PMC
April 2020

Evaluation of a multi-level intervention to improve postpartum intrauterine device services in Rwanda.

Gates Open Res 2018 4;2:38. Epub 2019 Feb 4.

Pathology & Laboratory Medicine, Emory University, Atlanta, GA, 30322, USA.

The copper intrauterine device is one of the most safe, effective, and cost-effective methods for preventing unintended pregnancy. It can be used postpartum irrespective of breastfeeding to improve birth spacing and reduce unintended pregnancy and maternal-child mortality. However, this method remains highly underutilized. We developed a multi-level intervention to increase uptake of the postpartum intrauterine device (PPIUD, defined as insertion up to six weeks post-delivery) in Kigali, Rwanda. High-volume hospitals and health centers were selected for implementation of PPIUD counseling and service delivery. Formative work informed development of a PPIUD counseling flipchart to be delivered during antenatal care, labor and delivery, infant vaccination visits, or in the community. Two-day didactic counseling, insertion/removal, and follow-up trainings were provided to labor and delivery and family planning nurses followed by a mentored practicum certification process. Counseling data were collected in government clinic logbooks. Insertions and follow-up data were collected in logbooks created for the implementation. Data were collected by trained government clinic staff and abstracted/managed by study staff. Stakeholders were involved from intervention development through dissemination of results. Two hospitals (and their two associated health centers) and two additional health centers were selected. In 6-months prior to our intervention, 7.7 PPIUDs/month were inserted on average at the selected facilities. From August 2017-July 2018, we trained 83 counselors and 39 providers to provide PPIUD services. N=9,020 women received one-on-one PPIUD counseling after expressing interest in family planning who later delivered at a selected health facility. Of those, n=2,575 had PPIUDs inserted (average of 214.6 insertions/month), a 29% uptake. Most PPIUDs (62%) were inserted within 10 minutes of delivery of the placenta. This successful, comprehensive intervention has the potential to make a significant impact on PPIUD uptake in Rwanda. The intervention is scalable and adaptable to other sub-Saharan African countries.
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http://dx.doi.org/10.12688/gatesopenres.12854.3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266741PMC
February 2019

Predominance of the heterozygous CCR5 delta-24 deletion in African individuals resistant to HIV infection might be related to a defect in CCR5 addressing at the cell surface.

J Int AIDS Soc 2019 09;22(9):e25384

Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg.

Introduction: The 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.

Methods: We 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 Discussion: Among 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.

Conclusions: Our 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.
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http://dx.doi.org/10.1002/jia2.25384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727025PMC
September 2019

Performance of Cepheid Xpert HIV-1 viral load plasma assay to accurately detect treatment failure.

AIDS 2019 10;33(12):1881-1889

World Health Organization, Geneva, Switzerland.

Background: Coverage of viral load testing remains low with only half of the patients in need having adequate access. Alternative technologies to high throughput centralized machines can be used to support viral load scale-up; however, clinical performance data are lacking. We conducted a meta-analysis comparing the Cepheid Xpert HIV-1 viral load plasma assay to traditional laboratory-based technologies.

Methods: Cepheid Xpert HIV-1 and comparator laboratory technology plasma viral load results were provided from 13 of the 19 eligible studies, which accounted for a total of 3790 paired data points. We used random effects models to determine the accuracy and misclassification at various treatment failure thresholds (detectable, 200, 400, 500, 600, 800 and 1000 copies/ml).

Results: Thirty percent of viral load test results were undetectable, while 45% were between detectable and 10 000 copies/ml and the remaining 25% were above 10 000 copies/ml. The median Xpert viral load was 119 copies/ml and the median comparator viral load was 157 copies/ml, while the log10 bias was 0.04 (0.02-0.07). The sensitivity and specificity to detect treatment failure were above 95% at all treatment failure thresholds, except for detectable, at which the sensitivity was 93.33% (95% confidence interval: 88.2-96.3) and specificity was 80.56% (95% CI: 64.6-90.4).

Conclusion: The Cepheid Xpert HIV-1 viral load plasma assay results were highly comparable to laboratory-based technologies with limited bias and high sensitivity and specificity to detect treatment failure. Alternative specimen types and technologies that enable decentralized testing services can be considered to expand access to viral load.
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http://dx.doi.org/10.1097/QAD.0000000000002303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7024604PMC
October 2019

Development and Uptake of Long-Acting Reversible Contraception Services in Rwanda, 2009-2016.

J Womens Health (Larchmt) 2019 12 5;28(12):1640-1649. Epub 2019 Jul 5.

Projet San Francisco, Rwanda Zambia HIV Research Group, Department of Pathology & Laboratory Medicine, School of Medicine, Rollins School of Public Health, Emory University, Kigali, Rwanda.

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. 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. 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 ( > 0.05). Between 2012 and 2014, 13% of family planning initiators chose the implant and 4% the IUD. 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.
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http://dx.doi.org/10.1089/jwh.2018.7423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6919255PMC
December 2019

Community health worker promotions increase uptake of long-acting reversible contraception in Rwanda.

Reprod Health 2019 Jun 4;16(1):75. Epub 2019 Jun 4.

Department of Epidemiology, Rollins School of Public Health, Laney Graduate School, Emory University, Atlanta, GA, 30322, USA.

Background: We coordinated community health worker (CHW) promotions with training and support of government clinic nurses to increase uptake of long-acting reversible contraception (LARC), specifically the copper intrauterine device (IUD) and the hormonal implant, in Kigali, Rwanda.

Methods: From August 2015 to September 2016, CHW provided fertility goal-based family planning counseling focused on LARC methods, engaged couples in family planning counseling, and provided written referrals to clients expressing interest in LARC methods. Simultaneously, we provided didactic and practical training to clinic nurses on LARC insertion and removal. We evaluated: 1) aggregate pre- versus post-implementation LARC uptake as a function of CHW promotions, and 2) demographic factors associated with LARC uptake among women responding to CHW referrals.

Results: 7712 referrals were delivered by 184 CHW affiliated with eight government clinics resulting in 6072 family planning clinic visits (79% referral uptake). 95% of clinic visits resulted in LARC uptake (16% copper IUD, 79% hormonal implant). The monthly average for IUD insertions doubled from 29 prior to service implementation to 61 after (p < 0.0001), and the monthly average for implant insertions increased from 109 to 309 (p < 0.0001). In adjusted analyses, LARC uptake was associated (p < 0.05) with the CHW referral being issued to the couple (versus the woman alone, adjusted odds ratio, aOR = 2.6), having more children (aOR = 1.3), desiring more children (aOR = 0.8), and having a religious affiliation (aOR = 2.9 Protestant, aOR = 3.1 Catholic, aOR = 2.5 Muslim each versus none/other). Implant versus non-LARC uptake was associated with having little or no education; meanwhile, having higher education was associated with IUD versus implant uptake.

Conclusions: Fertility goal-based and couple-focused family planning counseling delivered by CHW, coupled with LARC training and support of nursing staff, substantially increased uptake of LARC methods.
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http://dx.doi.org/10.1186/s12978-019-0739-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549304PMC
June 2019

Control of the HIV-1 Load Varies by Viral Subtype in a Large Cohort of African Adults With Incident HIV-1 Infection.

J Infect Dis 2019 07;220(3):432-441

International AIDS Vaccine Initiative Human Immunology Laboratory, London, United Kingdom.

Few human immunodeficiency virus (HIV)-infected persons can maintain low viral levels without therapeutic intervention. We evaluate predictors of spontaneous control of the viral load (hereafter, "viral control") in a prospective cohort of African adults shortly after HIV infection. Viral control was defined as ≥2 consecutively measured viral loads (VLs) of ≤10 000 copies/mL after the estimated date of infection, followed by at least 4 subsequent measurements for which the VL in at least 75% was ≤10 000 copies/mL in the absence of ART. Multivariable logistic regression characterized predictors of viral control. Of 590 eligible volunteers, 107 (18.1%) experienced viral control, of whom 25 (4.2%) maintained a VL of 51-2000 copies/mL, and 5 (0.8%) sustained a VL of ≤50 copies/mL. The median ART-free follow-up time was 3.3 years (range, 0.3-9.7 years). Factors independently associated with control were HIV-1 subtype A (reference, subtype C; adjusted odds ratio [aOR], 2.1 [95% confidence interval {CI}, 1.3-3.5]), female sex (reference, male sex; aOR, 1.8 [95% CI, 1.1-2.8]), and having HLA class I variant allele B*57 (reference, not having this allele; aOR, 1.9 [95% CI, 1.0-3.6]) in a multivariable model that also controlled for age at the time of infection and baseline CD4+ T-cell count. We observed strong associations between infecting HIV-1 subtype, HLA type, and sex on viral control in this cohort. HIV-1 subtype is important to consider when testing and designing new therapeutic and prevention technologies, including vaccines.
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http://dx.doi.org/10.1093/infdis/jiz127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6603968PMC
July 2019

Female sex workers in Kigali, Rwanda: a key population at risk of HIV, sexually transmitted infections, and unplanned pregnancy.

Int J STD AIDS 2019 05 6;30(6):557-568. Epub 2019 Feb 6.

1 Projet San Francisco, Rwanda Zambia HIV Research Group, Kigali, Rwanda.

Female sex workers (FSWs) were recruited from known hotspots in Kigali, Rwanda, and offered free, anonymous human immunodeficiency virus (HIV) counseling and testing, diagnosis and treatment of sexually transmitted infections (STIs) and long-acting reversible contraception (LARC). From September 2012 to March 2015, 1168 FSWs sought services, including 587 (50%) who were HIV-positive. More than 90% had previously tested for HIV, and 26% who reported previously testing negative had seroconverted. Of the 349 who already knew their HIV-positive status, 74% were on antiretroviral treatment. The prevalence of serologic syphilis was 43% in HIV-positive and 19% in HIV-negative FSWs (p < 0.0001), and Trichomonas vaginalis was found in vaginal wet mounts in 21% of HIV-positive and 13% of HIV-negative FSWs (p < 0.0001). Signs and symptoms of STIs were found in 35% of HIV-positive compared with 21% of HIV-negative FSWs (p < 0.0001). Only one-third reported consistent condom use in the last month. Modern contraceptive use was reported by 43% of HIV-positive and 56% of HIV-negative FSWs (p < 0.0001). Current pregnancy was reported by 4% of HIV-positive and 6% of HIV-negative FSWs (p = 0.0409). Despite Rwanda's successes with preventing 70% of new infections in the general population through nationwide couples' testing in antenatal clinics, prevention and timely treatment in key populations including FSWs are lacking. The prevalence of HIV - including many new cases - and STIs among FSWs in Kigali is high and condom and contraceptive use are low. Tailored and integrated HIV/STIs and family planning programs are urgently needed for FSWs.
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http://dx.doi.org/10.1177/0956462418817050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512058PMC
May 2019

VH1-69 Utilizing Antibodies Are Capable of Mediating Non-neutralizing Fc-Mediated Effector Functions Against the Transmitted/Founder gp120.

Front Immunol 2018 15;9:3163. Epub 2019 Jan 15.

Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States.

Multiple antibody effector functions arise in HIV-1 infection that could be harnessed to protect against infection or clear the persistent reservoir. Here, we have investigated the genetic and functional memory B cell and antibody landscape present during early infection in six individuals infected with either subtype A, C, or an A/C recombinant HIV-1. These individuals demonstrated varying levels of plasma autologous neutralization (nAb) against the transmitted/founder envelope (T/F Env) pseudovirus and non-neutralizing Fc-mediated effector function (nnFc) antibody-dependent cell-mediated cytotoxicity (ADCC) against the T/F Env gp120 protein at ~7 months after infection. Genetic analysis of the immunoglobulin heavy (VH) and light (VL) chain variable domain gene segments from 352 autologous T/F Env gp120-specific single B cells recovered at this same 7-month time-point revealed an over-representation of the VH1-69 germline in five of six individuals. A defining feature of the VH1-69 utilizing gp120-specific antibodies was their significantly more hydrophobic complementarity-determining region-2 (CDRH2) regions compared to other VH CDRH2 sequences from each individual. While none of the VH1-69 antibodies possessed strong neutralizing activity against virions pseudotyped with the autologous T/F Env, almost a third were capable of mediating high ADCC activity, as assayed by intracellular granzyme B activity in CEM.NKr.CCR5 target cells coated with autologous T/F Env gp120. High ADCC mediating VH1-69 antibodies exhibited shorter complementarity-determining region-3 (CDRH3) lengths and a more neutral isoelectric point than antibodies lacking this function. In the individual that developed the highest autologous ADCC responses, the high granzyme B producing antibodies bound to surface expressed envelope in the absence of CD4 and were not enhanced by the addition of soluble CD4. Overall, VH1-69 utilizing antibodies are commonly induced against gp120 in diverse HIV-1 infections and a subset of these antibodies can mediate ADCC functions, serving as a bridge between the innate and adaptive immune response to HIV-1.
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http://dx.doi.org/10.3389/fimmu.2018.03163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341001PMC
October 2019

HIV testing and counselling couples together for affordable HIV prevention in Africa.

Int J Epidemiol 2019 02;48(1):217-227

Rwanda Zambia HIV Research Group, Department of Pathology and Laboratory Medicine, School of Medicine and Hubert Department of Global Health, Rollins School of Public Health, Laney Graduate School.

Background: The impact and cost-effectiveness of couples' voluntary HIV counselling and testing (CVCT) has not been quantified in real-world settings. We quantify cost-per-HIV-infection averted by CVCT in Zambia from the donor's perspective.

Methods: From 2010 to 2016, CVCT was established in 73 Zambian government clinics. The cost-per-HIV-infection averted (CHIA) of CVCT was calculated using observed expenditures and effectiveness over longitudinal follow-up. These observed measures parameterized hypothetical 5-year nationwide implementations of: 'CVCT'; 'treatment-as-prevention (TasP) for discordant couples' identified by CVCT; and 'population TasP' for all HIV+ cohabiting persons identified by individual testing.

Results: In all, 207 428 couples were tested (US $52/couple). Among discordant couples in which HIV+ partners self-reported antiretroviral therapy (ART), HIV incidence was 8.5/100 person-years before and 1.8/100 person-years after CVCT (79% reduction). Corresponding reductions for non-ART-using discordant and concordant negative couples were 63% and 47%, respectively. CVCT averted an estimated 58% of new infections at US $659 CHIA. In nationwide implementation models, CVCT would prevent 17 times the number of infections vs 'TasP for discordant couples' at 86% of the cost, and nine times the infections vs 'population TasP' at 28% of the cost.

Conclusions: CVCT is a cost-effective, feasible prevention strategy in Zambia. We demonstrate the novel, added effectiveness of providing CVCT to ART users, for whom ART use alone only partially mitigated transmission risk. Our results indicate a major policy shift (supporting development of CVCT indicators, budgets and targets) and have clinical implications (suggesting promotion of CVCT in ART clinics as a high-impact prevention strategy).
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http://dx.doi.org/10.1093/ije/dyy203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380312PMC
February 2019

Rwandan stakeholder perspectives of integrated family planning and HIV services.

Int J Health Plann Manage 2018 Oct 26;33(4):e1037-e1049. Epub 2018 Jul 26.

Rwanda Zambia HIV Research Group, Department of Pathology and Laboratory Medicine, School of Medicine and Hubert Department of Global Health, Rollins School of Public Health, Emory University, Kigali, Rwanda.

The purpose of this qualitative study was to understand the knowledge, attitudes, and practices among key Rwandan policymakers and stakeholders related to family planning (FP) and integrated HIV/FP services. Motivational in-depth interview format and content was developed after an extensive policy review. A convenience sample of 10 high-level HIV and FP Rwandan policymakers and stakeholders completed the interview. Stakeholders demonstrated strong foundational knowledge of HIV and FP. Given the choice, stakeholders would allocate more monies to FP and less to HIV than currently distributed. Respondents felt that improved FP method knowledge, especially long-acting reversible contraception, among clients/couples and providers, was needed to address myths, misconceptions, and biases. The most often cited way to integrate HIV/FP services was development of integrated tools (eg, training materials, data collection tools, and advocacy and policy guidance). We recommend strategies for policy advancement supportive of HIV/FP service integration inclusive of couples and long-acting reversible contraception methods.
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http://dx.doi.org/10.1002/hpm.2586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289844PMC
October 2018