Etienne Karita

• Managing Director at Projet San Francisco/Rwanda Zambia HIV Research Group (RZHRG), Kigali, Rwanda

Background Rwandan individuals bordering the Democratic Republic of the Congo (DRC) are at-risk of Ebola virus disease. A 2019 to 2021 vaccination campaign called UMURINZI offered a Janssen Vaccines & Prevention B.V. 2-dose heterologous Ebola vaccine regimen (Ad26.ZEBOV, MVA-BN-Filo) to Rwandan individuals aged ≥2 years and not pregnant. In this re...

The complex dynamics of protein expression in plasma during hyperacute HIV-1 infection and its relation to acute retroviral syndrome, viral control, and disease progression are largely unknown. Here, we quantify 1293 blood plasma proteins from 157 longitudinally linked plasma samples collected before, during, and after hyperacute HIV-1 infection of...

HIV-1 subtypes have distinct geographical distributions, with subtypes A, C, and D and inter-subtype recombinants circulating in sub-Saharan Africa. Historically, individuals living with subtype A viruses exhibit slower CD4 decline and progression to AIDS diagnosis. Despite this, there are few authentic infectious molecular clones (IMCs) of subtype...

Background Rectal sexually transmitted infections (STI) are prevalent among men who have sex with men (MSM) and transgender women (TGW). Self-collection of rectal specimens is widely used globally, but limited data exist on its implementation in Africa. We report experiences of MSM/TGW self-collecting rectal STI specimens in Kigali. Methods From Ma...

HIV-1 remains incurable and there is no effective vaccine towards the infection. A main challenge for this is the lack of a holistic understanding of the myriad of complex virus-host interactions during hyperacute HIV-1 infection (hAHI), and how these contribute to tissue damage and pathogenesis. Here, 1293 blood plasma proteins were quantified fro...

The role of HLA class I and KIR molecules in mediating acute retroviral syndrome (ARS) during HIV-1 infection is unclear. Among 72 sub-Saharan African adults, HLA-A*23 was associated with lower odds of ARS (adjusted OR, 0.10 [95%CI: 0.01-0.48], p=0.009), which warrants further studies to explore its role on HIV-1 specific immunopathogenesis.

Diversity, equity and inclusion (DEI) in science is vital to improve the scientific process and ensure societal uptake and application of scientific results. DEI challenges include a full spectrum of issues from the lack of, and promotion of, women in science, to the numerous barriers in place that limit representation of African scientists in glob...

A protective HIV-1 vaccine has been hampered by a limited understanding of how B cells acquire neutralizing activity. Our previous vaccines expressing two different HIV-1 envelopes elicited robust antigen specific serum IgG titers in 20 rhesus macaques; yet serum from only two animals neutralized the autologous virus. Here, we used high throughput...

Background: Few assessments of associations between structural-level factors and HIV among gay men and other men who have sex with men (MSM) have been conducted, especially in sub-Saharan Africa. Our objective was to examine HIV testing history, HIV status, and stigmas among MSM living in ten countries with heterogeneous legal environments. Metho...

Background Developing a cross-clade, globally effective HIV vaccine remains crucial for eliminating HIV. Methods This placebo-controlled, double-blind, phase 1/2a study (NCT02935686) enrolled healthy HIV-uninfected adults at low risk for HIV infection. They were randomized (1:4:1) to receive 4 doses of an adenovirus 26-based HIV-1 vaccine encoding...

Introduction Rwanda has high unmet need for family planning (FP), especially in the postpartum period when women are advised to space pregnancies at least two years for improved maternal-child health. Despite interest in the copper intrauterine device (IUD), a highly cost-effective method, access and uptake remain low. This study aimed to determine...

Background From 2019-2021, Rwandan residents of the border with Democratic Republic of the Congo were offered the Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen. Methods Non-pregnant ≥2 years-olds were eligible. Unsolicited adverse events (UAE) were reported through phone calls or visits, and serious adverse events (SAE) recorded per ICH guidelines...

Background Risks to mother and fetus following Ebola virus infection are very high. Evaluation of safety and immunogenicity of non-replicating Ebola vaccine candidates is a priority for use in pregnant women. This is the protocol for a randomized, open-label, single-center phase 3 clinical trial of the safety, reactogenicity, and immunogenicity of...

HIV-1 accessory proteins Nef and Vpu enhance viral pathogenesis through partially overlapping immune evasion activities. Attenuated Nef or Vpu functions have been reported in individuals who display slower disease progression, but few studies have assessed the relative impact of these proteins in non-B HIV-1 subtypes or examined paired proteins fro...

Transmitted/founder (T/F) HIV-1 envelope proteins (Envs) from infected individuals that developed neutralization breadth are likely to possess inherent features desirable for vaccine immunogen design. To explore this premise, we conducted an immunization study in rhesus macaques (RM) using T/F Env sequences from two human subjects, one of whom deve...

Background Though the Rwandan Ministry of Health (MOH) prioritizes the scale-up of postpartum family planning (PPFP) programs, uptake and sustainability of PPFP services in Rwanda are low. Furthermore, highly effective long-acting reversible contraceptive method use (LARC), key in effective PPFP programs, is specifically low in Rwanda. We previousl...

The HIV-1 Envelope glycoprotein (Env) is the sole target for broadly neutralizing antibodies (bnAbs). Env is heavily glycosylated with host-derived N-glycans, and many bnAbs bind to, or are dependent upon, Env glycans for neutralization. Although glycan-binding bnAbs are frequently detected in HIV-infected individuals, attempts to elicit them have...

Background There is unmet need for family planning in Rwanda. We previously developed an evidence-based couples’ family planning counseling (C)FPC program in the capital city that combines: (1) fertility goal-based family planning counseling with a focus on long-acting reversible contraceptive (LARC) for couples wishing to delay pregnancy; (2) heal...

To evaluate the role of sexual behavior stigma as a determinant of depressive symptoms among men who have sex with men (MSM) and transgender women (TGW) in Kigali, Rwanda. MSM/TGW aged ≥ 18 years were recruited using respondent-driven sampling (RDS) between March–August, 2018. Mental health was assessed using the Patient Health Questionnaire (PHQ-9...

Most studies of HIV-1 transmission have focused on subtypes B and C. In this study, we determined the genomic sequences of the transmitted founder (TF) viruses from acutely infected individuals enrolled between 2005 and 2011 into IAVI protocol C in Rwanda and have compared these isolates to viruses from more recent (2016–2019) acute/early infection...

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 mon...

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...

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 st...

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 ye...

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-n...

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: We followed a cohort of HIV discordant couples enrolled in couples' testing and follow-up at 20 government clinics in Kigali from 2010...

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...

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,...

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 devic...

Abstract 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 cou...

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. Met...

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 approac...

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...

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 effecti...

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...

p>Variation in the risk and severity of many autoimmune diseases, malignancies and infections is strongly associated with polymorphisms at the HLA class I loci. These genetic associations provide a powerful opportunity for understanding the etiology of human disease. HLA class I associations are often interpreted in the light of 'protective' or 'de...

Introduction: 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 J...

Background. There is unmet need for family planning in Rwanda. We previously developed an evidence-based couples’ family planning counseling (C)FPC program in the capital city that combines: 1) fertility goal-based family planning counseling with a focus on long-acting reversible contraceptive (LARC) for couples wishing to delay pregnancy; 2) healt...

Background: Few family planning programs in Africa base demand creation and service delivery on theoretical models. Motivational interviewing (MI) is a counseling modality that facilitates reflection on the benefits and disadvantages of a health outcome to encourage behavior change. Objectives: We evaluate a couples-focused joint family planning...

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 fact...

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....

Background: Long-acting reversible contraception (LARC) is highly effective at preventing pregnancy. However, in sub-Saharan Africa, LARC education for clients is relatively limited and providers are often not skilled in their insertion. Before 2009, only 1% of family planning clients in Rwanda received an LARC. Materials and Methods: We trained R...

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 ferti...

Few HIV-infected persons can maintain low viral levels without therapeutic intervention. We evaluate predictors of spontaneous viral control in a prospective cohort of African adults shortly after HIV infection. Viral control was defined as ≥2 consecutive VL ≤10,000 copies/mL post-estimated date of infection (EDI) with at least 4 subsequent VL meas...

Introduction: 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 J...

Introduction: 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 J...

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, includ...

Background. 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. Methods. We d...

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 HI...

Neutralizing and non-neutralizing Fc-mediated effector function of VH1-69 utilizing antibodies. The ability of virions pseudotyped with autologous T/F Env to infect TZM bl indicator cells in the presence of 10 μg/ml of each mAb was assayed in triplicate, and repeated independently as quantity allowed. Non-neutralizing Fc-mediated effector function...

Representative Granzyme B control and experimental flow-plots. CEM.NKr.CCR5 cells were pulsed with gp120 proteins (R66M gp120 illustrated here). After gating for size (targets) and NFL4 negative (live) cells, determination of Granzyme B activity was calculated by drawing gates based on target cells incubated alone (Targets Alone). The percentage ca...

Antibody recognition of R66M T/F Env transfected cells in the absence and presence of sCD4. 293T cells were transfected with R66M T/F Envelope expression plasmid. 48-h post-transfection, cells were stained with control and R66M VH1-69 mAbs (indicated above plots), either (A) without or (B) with pre-incubation with sCD4. X-axis indicates PE intensit...

Genetic characterization of paired heavy- and light-chain sequences isolated from autologous T/F gp120 reactive single memory B cells sorted from PBMC collected at 7.5 months after infection (Time Point 2). Sequences from paired heavy- and light-chains from autologous T/F Env gp120-reactive single B cells were analyzed via IMGT vquest (http://imgt....

Quantification of VH1-69 mAb binding affinity for autologous T/F gp120. The affinity of VH1-69 utilizing mAbs for binding to the autologous T/F Env gp120 protein was determined on an Octet RED96. The molarity of gp120 utilized for measurement, calculated KD and KD error, kon and kon error, kdis and kdis error, X2, and R2 values are reported. Averag...

Genetic features of VH1-69 utilizing antibody sequences. VH1-69 sequences were analyzed in further detail, due to their overrepresentation in isolated anti-gp120 memory B cells. Variable Joining region (VJ) alleles and heavy-chain isoelectric points were determined via IMGT vquest (http://imgt.org/IMGT_vquest/vquest). Amino acid 54 within CDRH2 is...

Impact of T/F Env gp120 proteins and effector cell donor variation on ADCC and autologous plasma control assays. The percentage of GzB positive cells between individuals was compared in reactions containing (A) only T/F Env gp120 coated CEM.NKr.CCR5 target cells and donor effector cells (background GzB activity), (B) negative control 50 μg/ml comme...

Genetic and functional comparison of VH1-69 low ADCC mAbs vs. high ADCC mAbs. VH1-69 mAbs were stratified into two groups, based on low (peak GzB percentage <10%) or high (peak GzB percentage >10%) ADCC activity. No significant differences emerged between these two groups in a number of metrics: (A) heavy-chain percent nucleotide identity to germli...

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-infec...

Background. 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. Methods. We d...

Introduction: In two high-volume government hospitals, their two affiliated health facilities, and two additional health facilities, we developed and implemented post-partum intrauterine device (PPIUD) and post-partum (PP) implant promotions and service delivery procedures between May and July 2017 in Kigali, Rwanda. Between August 2017 and July 20...

Background. The copper intrauterine device is one of the most safe, effective, and cost-effective methods for preventing unintended pregnancy. It can be used post-partum irrespective of breastfeeding to improve birth spacing and reduce unintended pregnancy and maternal-child mortality. However, this method remains highly underutilized. Methods. We...

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 a...

Background: More than 1·8 million new cases of HIV-1 infection were diagnosed worldwide in 2016. No licensed prophylactic HIV-1 vaccine exists. A major limitation to date has been the lack of direct comparability between clinical trials and preclinical studies. We aimed to evaluate mosaic adenovirus serotype 26 (Ad26)-based HIV-1 vaccine candidate...

Objective: This study aims to understand the basis of continued HIV-1 transmission in Zambian and Rwandan HIV-1 discordant couples in the context of ART. Design: We identified 9 Zambian and 7 Rwandan acutely-infected, epidemiologically-linked couples from government CVCT clinics where transmitting partners reported being on ART near the time of...

Objective Prompt identification of newly HIV-infected persons, particularly those who are most at risk of extended high viremia (EHV), allows important clinical and transmission prevention benefits. We sought to determine whether EHV could be predicted during early HIV infection (EHI) from clinical, demographic, and laboratory indicators in a large...

Immune control of HIV-1 infection depends heavily on cytotoxic T-lymphocyte responses restricted by diverse HLA class I molecules. Recent work has uncovered specific amino acid residues (AARs) that seem to dictate the extent of immune control in African Americans, which prompted us to test these emerging hypotheses in seroconverters (SCs) from sout...

Understanding how broadly neutralizing antibodies (bnAbs) to HIV envelope (Env) develop during natural infection can help guide the rational design of an HIV vaccine. Here, we described a bnAb lineage targeting the Env V2 apex and the Ab-Env co-evolution that led to development of neutralization breadth. The lineage Abs bore an anionic heavy chain...

Background: Symptoms of acute retroviral syndrome (ARS) may be used to identify patients with acute HIV-1 infection who seek care. ARS symptoms in African adults differ by region. We assessed whether reporting of ARS was associated with HIV-1 subtype in a multicentre African cohort study representing countries with predominant HIV-1 subtypes A, C...

Background. We report the first-in-human safety and immunogenicity assessment of a prototype intranasally administered, replication-competent Sendai virus (SeV)–vectored, human immunodeficiency virus type 1 (HIV-1) vaccine. Methods. Sixty-five HIV-1–uninfected adults in Kenya, Rwanda, and the United Kingdom were assigned to receive 1 of 4 prime-boo...

BACKGROUND: We report the first-in-human safety and immunogenicity assessment of a prototype intranasally administered, replication-competent Sendai virus (SeV)-vectored, human immunodeficiency virus type 1 (HIV-1) vaccine.

A recent study of plasma neutralization breadth in HIV-1 infected individuals at nine International AIDS Vaccine Initiative (IAVI) sites reported that viral load, HLA-A*03 genotype, and subtype C infection were strongly associated with the development of neutralization breadth. Here, we refine the findings of that study by analyzing the impact of t...

NXS and NXT glycan motifs within T/F Env gp120 sequences. (A) An amino acid alignment of 21 T/F Env gp120 sequences was analyzed for glycosylation sequon and position using LANL N-GlycoSite (https://www.hiv.lanl.gov/content/sequence/GLYCOSITE/glycosite.html). Numbering includes amino acid position according to the T/F Env alignment, and relative to...

Neutralization Area Under the Curve (AUC) and IC50 titers heat maps for plasma from 21 HIV- 1 infected individuals against the 12 Env global reference panel. Five-fold serial dilutions of plasma samples from each individual (RZHRG coded IDs are shown; see Fig 1) were assayed for neutralization against a panel of globally representative tier 2 Env p...

Amino acid alignments of Env for Z1800M and R66M. Env amino acid alignments are shown for Z1800M (A) and R66M (B), including sequences from the first time point after infection (estimated to be 29 days for Z1800M and 22 days for R66M, Fig 1) and the longitudinal time point used to calculate the Immunotype Diversity Index score (5-months for Z1800M...

Neutralization breadth ranking was highly correlated with that determined in the larger IAVI study. For 12 individuals that were analyzed by [36] and in the present study, a Spearman Rank correlation test was performed using the maximum breadth score (sMAX, based on plasma from multiple time points) and the neutralization breadth AUC determine here...

Highligher plots of T/F Env sequences. (A-E) Single genome PCR amplification (SGA) derived full-length env sequences were isolated from 21 patients near the time of infection (median 28 estimated days after infection, range 22 to 65 days). Translated amino acid sequences were aligned, and the LANL Highlighter tool was used to illustrate sequence va...

Phylogenetic tree and recombination breakpoints. A selection of 15 Subtype Reference Sequences was downloaded from the LANL sequence database and were aligned with the consensus of each set of patient derived T/F Env sequences. The resulting neighbor-joining phylogenetic tree, shown in (A), illustrates Zambian derived Envs clustering with the Subty...

Background: Understanding associations between pregnancy and HIV disease progression is critical to providing appropriate counseling and care to HIV-positive women. Methods: From 2006-2011, women under age 40 with incident HIV infection were enrolled in an early HIV infection cohort in Kenya, Rwanda, South Africa, Uganda, and Zambia. Time-depend...