Temporal trends and transmission dynamics of pre-treatment HIV-1 drug resistance within and between risk groups in Kenya, 1986-2020.

BACKGROUND: Evidence on the distribution of pre-treatment HIV-1 drug resistance (HIVDR) among risk groups is limited in Africa. We assessed the prevalence, trends and transmission dynamics of pre-treatment HIVDR within and between MSM, people who inject drugs (PWID), female sex workers (FSWs), heterosexuals (HETs) and perinatally infected children in Kenya. METHODS: HIV-1 partial pol sequences from antiretroviral-naive individuals collected from multiple sources between 1986 and 2020 were used. Pre-treatment reverse transcriptase inhibitor (RTI), PI and integrase inhibitor (INSTI) mutations were assessed using the Stanford HIVDR database. Phylogenetic methods were used to determine and date transmission clusters. RESULTS: Of 3567 sequences analysed, 550 (15.4%, 95% CI: 14.2-16.6) had at least one pre-treatment HIVDR mutation, which was most prevalent amongst children (41.3%), followed by PWID (31.0%), MSM (19.9%), FSWs (15.1%) and HETs (13.9%). Overall, pre-treatment HIVDR increased consistently, from 6.9% (before 2005) to 24.2% (2016-20). Among HETs, pre-treatment HIVDR increased from 6.6% (before 2005) to 20.2% (2011-15), but dropped to 6.5% (2016-20). Additionally, 32 clusters with shared pre-treatment HIVDR mutations were identified. The majority of clusters had R0 ≥ 1.0, indicating ongoing transmissions. The largest was a K103N cluster involving 16 MSM sequences sampled between 2010 and 2017, with an estimated time to the most recent common ancestor (tMRCA) of 2005 [95% higher posterior density (HPD), 2000-08], indicating propagation over 12 years. CONCLUSIONS: Compared to HETs, children and key populations had higher levels of pre-treatment HIVDR. Introduction of INSTIs after 2017 may have abrogated the increase in pre-treatment RTI mutations, albeit in the HET population only. Taken together, our findings underscore the need for targeted efforts towards equitable access to ART for children and key populations in Kenya.

URCHOICE: Preferences for Pre-Exposure Prophylaxis (PrEP) Options for HIV Prevention Among Kenyan men who have sex with men and Transgender Women in Nairobi, Kisumu and the Coast.

HIV prevention method preferences were evaluated among Kenyan men who have sex with men (MSM) and transgender women (TW) from three sites: Kisumu, Nairobi and the Coast. Information sessions detailing the attributes, duration of protection, route of administration and probable visibility were attended by 464 HIV negative participants, of whom 423 (median age: 24 years) agreed to be interviewed. Across pairwise comparisons daily PrEP was by far the least preferred (1%); quarterly injections (26%) and monthly pills (23%) were most preferred, followed by yearly implant (19%) and condoms (12%). When participants were "forced" to choose their most preferred PrEP option, only 10 (2.4%) chose the daily pill; more (37.1%) chose the quarterly injection than the monthly pill (34.8%) and the yearly implant (25.8%). TW preferred the yearly implant over the quarterly injection. To achieve the rates of PrEP uptake and adherence necessary for protecting large proportions of vulnerable MSM and TW, a variety of long-acting products should be developed and made accessible to appeal to a diversity of preferences.

The Effect of the Shikamana Peer-and-Provider Intervention on Depressive Symptoms, Alcohol Use, and Other Drug Use Among Gay, Bisexual, and Other Men Who Have Sex with Men in Kenya.

Kenyan gay, bisexual, and other men who have sex with men (GBMSM) face stigma and discrimination, which may adversely impact mental health and limit antiretroviral therapy (ART) adherence among GBMSM living with HIV. We evaluated whether the Shikamana peer-and-provider intervention, which improved ART adherence among participants in a small randomized trial, was associated with changes in mental health or substance use. The intervention was associated with a significant decrease in PHQ-9 score between baseline and month 6 (estimated change - 2.7, 95% CI - 5.2 to - 0.2, p = 0.037) compared to standard care. In an exploratory analysis, each one-point increment in baseline HIV stigma score was associated with a - 0.7 point (95% CI - 1.3 to - 0.04, p = 0.037) greater decrease in PHQ-9 score over the study period in the intervention group. Additional research is required to understand factors that influence this intervention's effects on mental health outcomes.

Transgender women in Kenya experience greater stigma, depressive symptoms, alcohol and drug use and risky sexual practices than cis-gendered men who have sex with men.

BACKGROUND: Worldwide, sexual and gender minority individuals have disproportionate burden of HIV. There are limited quantitative data from sub-Saharan Africa on the intersection of risks experienced by transgender women (TGW) in comparison to cis-men who have sex with men (MSM). This analysis addresses this gap by comparing reported stigma, psychosocial measures of health, and sexual risk practices between TGW and cis-MSM in Kenya. METHODS: We analyzed data from the baseline visit of an ongoing prospective cohort study taking place in three diverse metropolitan areas. Eligible participants were HIV-negative, assigned male at birth, ages 18-29 years, and reported anal intercourse in the past 3 months with a man or TGW. Data collected by audio computer assisted self-interview included sociodemographic measures, and sexual practices occurring in the past 3 months. Multivariable regressions assessed differences between TGW and cis-MSM in selected sexual practices, depressive symptoms, alcohol and drug use, and stigma. RESULTS: From September, 2019, through May, 2021, 838 participants were enrolled: 108 (12.9%) TGW and 730 (87.1%) cis-MSM. Adjusting for sociodemographic variables, TGW were more likely than cis-MSM to report: receptive anal intercourse (RAI; adjusted prevalence ratio [aPR] = 1.59, 95% CI: 1.32 - 1.92), engaging in group sex (aPR = 1.15, 95% CI: 1.04 - 1.27), 4 or more male sex partners (aPR = 3.31, 95% CI: 2.52 - 4.35), and 3 or more paying male sex partners (aPR = 1.58, 95% CI: 1.04 - 2.39). TGW were also more likely to report moderate to severe depressive symptoms (aPR = 1.42, 95% CI: 1.01 - 1.55), and had similar alcohol and drug abuse scores as cis-MSM. In sensitivity analysis, similar to TGW, male-identifying individuals taking feminizing gender affirming therapy had an increased likelihood of reporting RAI and group sex, and greater numbers of male sex partners and paying male sex partners relative to cis-MSM. CONCLUSIONS: Across three metropolitan areas in Kenya, TGW were more likely to report depressive symptoms and increased sexual risk taking. We identified a need for research that better characterizes the range of gender identities. Our analysis affirms the need for programmatic gender-affirming interventions specific to transgender populations in Kenya and elsewhere in Africa.

Infection with multiple HIV-1 founder variants is associated with lower viral replicative capacity, faster CD4+ T cell decline and increased immune activation during acute infection.

HIV-1 transmission is associated with a severe bottleneck in which a limited number of variants from a pool of genetically diverse quasispecies establishes infection. The IAVI protocol C cohort of discordant couples, female sex workers, other heterosexuals and men who have sex with men (MSM) present varying risks of HIV infection, diverse HIV-1 subtypes and represent a unique opportunity to characterize transmitted/founder viruses (TF) where disease outcome is known. To identify the TF, the HIV-1 repertoire of 38 MSM participants' samples was sequenced close to transmission (median 21 days post infection, IQR 18-41) and assessment of multivariant infection done. Patient derived gag genes were cloned into an NL4.3 provirus to generate chimeric viruses which were characterized for replicative capacity (RC). Finally, an evaluation of how the TF virus predicted disease progression and modified the immune response at both acute and chronic HIV-1 infection was done. There was higher prevalence of multivariant infection compared with previously described heterosexual cohorts. A link was identified between multivariant infection and replicative capacity conferred by gag, whereby TF gag tended to be of lower replicative capacity in multivariant infection (p = 0.02) suggesting an overall lowering of fitness requirements during infection with multiple variants. Notwithstanding, multivariant infection was associated with rapid CD4+ T cell decline and perturbances in the CD4+ T cell and B cell compartments compared to single variant infection, which were reversible upon control of viremia. Strategies aimed at identifying and mitigating multivariant infection could contribute toward improving HIV-1 prognosis and this may involve strategies that tighten the stringency of the transmission bottleneck such as treatment of STI. Furthermore, the sequences and chimeric viruses help with TF based experimental vaccine immunogen design and can be used in functional assays to probe effective immune responses against TF.

Stopping and restarting PrEP and loss to follow-up among PrEP-taking men who have sex with men and transgender women at risk of HIV-1 participating in a prospective cohort study in Kenya.

OBJECTIVE: To assess frequency and predictors of switching between being on and off PrEP and being lost to follow-up (LTFU) among men who have sex with men (MSM) and transgender women (TGW) with access to PrEP services in Sub-Saharan Africa. METHODS: This was a prospective cohort study of MSM and TGW from coastal Kenya who initiated daily oral PrEP from June 2017 to June 2019. Participants were followed monthly for HIV-1 testing, PrEP refill, risk assessment and risk reduction counselling. Follow-up was censored at the last visit before 30 June 2019, or the last HIV-1-negative visit (for those with HIV-1 seroconversion), whichever occurred first. We estimated transition intensities (TI) and predictors of switching: (i) between being off and on PrEP; and (ii) from either PrEP state and being LTFU (i.e. not returning to the clinic for > 90 days) using a multi-state Markov model. RESULTS: In all, 134 participants starting PrEP were followed for a median of 20.3 months [interquartile range (IQR): 7.7-22.1]. A total of 49 (36.6%) people stopped PrEP 73 times [TI = 0.6/person-year (PY), 95% confidence interval (CI): 0.5-0.7] and, of these, 25 (51.0%) restarted PrEP 38 times (TI = 1.2/PY, 95% CI: 0.9-1.7). In multivariable analysis, stopping PrEP was related to anal sex ≤ 3 months, substance-use disorder and travelling. Restarting PrEP was related to non-Christian or non-Muslim religion and travelling. A total of 54 participants were LTFU: on PrEP (n = 47, TI = 0.3/PY, 95% CI: 0.3-0.5) and off PrEP (n = 7, TI = 0.2/PY, 95% CI: 0.1-0.4). In multivariable analysis, becoming LTFU while on PrEP was associated with secondary education or higher, living in the area for ≤ 1 year, residence outside the immediate clinic area and alcohol-use disorder. CONCLUSIONS: Switching between being on and off PrEP or becoming LTFU while on PrEP was frequent among individuals at risk of HIV-1 acquisition. Alternative PrEP options (e.g. event-driven PrEP) may need to be considered for MSM and TGW with PrEP-taking challenges, while improved engagement with care is needed for all MSM and TGW regardless of PrEP regimen.

Effect of an opt-out point-of-care HIV-1 nucleic acid testing intervention to detect acute and prevalent HIV infection in symptomatic adult outpatients and reduce HIV transmission in Kenya: a randomized controlled trial.

BACKGROUND: In sub-Saharan Africa, adult outpatients with symptoms of acute infectious illness are not routinely tested for prevalent or acute HIV infection (AHI) when seeking healthcare. METHODS: Adult symptomatic outpatients aged 18-39 years were evaluated by a consensus AHI risk score. Patients with a risk score ≥ 2 and no previous HIV diagnosis were enrolled in a stepped-wedge trial of opt-out delivery of point-of-care (POC) HIV-1 nucleic acid testing (NAAT), compared with standard provider-initiated HIV testing using rapid tests in the observation period. The primary outcome was the number of new diagnoses in each study period. Generalized estimating equations with a log-binomial link and robust variance estimates were used to account for clustering by health facility. The trial is registered with ClinicalTrials.gov NCT03508908. RESULTS: Between 2017 and 2020, 13 (0.9%) out of 1374 participants in the observation period and 37 (2.5%) out of 1500 participants in the intervention period were diagnosed with HIV infection. Of the 37 newly diagnosed cases in the intervention period, two (5.4%) had AHI. Participants in the opt-out intervention had a two-fold greater odds of being diagnosed with HIV (odds ratio = 2.2, 95% confidence interval: 1.39-3.51) after adjustment for factors imbalanced across study periods. CONCLUSIONS: Among symptomatic adults aged 18-39 years targeted by our POC NAAT intervention, we identified one chronic HIV infection for every 40 patients and one AHI patient for every 750 patients tested. Although AHI yield was low in this population, routinely offered opt-out testing could diagnose twice as many patients as an approach relying on provider discretion.

Condom failure and pre-exposure prophylaxis use experience among female sex workers in Ethiopia: a qualitative study.

BACKGROUND: Female sex workers (FSW) remain a highly exposed group for HIV/STIs due to different factors including condom failure. In Ethiopia, pre-exposure prophylaxis (PrEP) has recently been introduced as an intervention strategy to prevent new HIV infections, but knowledge about FSWs' experiences of condom failure and PrEP use remains scarce. Therefore, this study explores FSWs' experiences concerning condom failure and their attitudes towards, and experiences of, PrEP uptake. METHOD: A qualitative study using in-depth interviews was conducted among FSWs in Addis Ababa. A manifest and latent content analysis method was applied to identify categories and emerging themes. RESULT: Seventeen FSWs (10 who started on PrEP, 1 who discontinued, and 6 who didn't start) were interviewed. FSWs described the reasons behind condom failure, the mechanisms they used to minimize the harm, and their attitudes towards PrEP use. FSWs struggled with the continuous risk of condom failure due to factors related to clients' and their own behavior. PrEP was mentioned as one the strategies FSWs used to minimize the harm resulting from condom failure, but PrEP use was compounded with doubts that deterred FSWs from uptake. FSWs' misconceptions, their lack of confidence, and PrEP side effects were also mentioned as the main challenges to start taking PrEP and/or to maintain good adherence. CONCLUSION: The demands and behavior of the clients and FSWs' own actions and poor awareness were factors that increased the exposure of FSWs to condom failure. In addition, the challenges associated with PrEP uptake suggest the need for user-friendly strategies to counteract these barriers and facilitate PrEP uptake.

Validity and reliability of the Neilands sexual stigma scale among Kenyan gay, bisexual, and other men who have sex with men.

BACKGROUND: We evaluated the validity and reliability of the Neilands sexual stigma scale administered to 871 gay, bisexual, and other men who have sex with men (GBMSM) at two research locations in Kenya. METHODS: Using cross-validation, exploratory factor analysis (EFA) was performed on a randomly selected subset of participants and validated using confirmatory factor analysis (CFA) on the remaining participants. Associations of the initial and final stigma scale factors with depressive symptoms, alcohol use, and other substance use were examined for the entire dataset. RESULTS: EFA produced a two-factor scale of perceived and enacted stigma. The CFA model fit to the two-factor scale was improved after removing three cross-loaded items and adding correlated errors (chi-squared = 26.5, df 17, p = 0.07). Perceived stigma was associated with depressive symptoms (beta = 0.34, 95% CI 0.24, 0.45), alcohol use (beta = 0.14, 95% CI 0.03, 0.25) and other substance use (beta = 0.19, 95% CI 0.07, 0.31), while enacted stigma was associated with alcohol use (beta = 0.17, 95% CI 0.06, 0.27). CONCLUSIONS: Our findings suggest enacted and perceived sexual stigma are distinct yet closely related constructs among GBMSM in Kenya and are associated with poor mental health and substance use.

Predictors of testing history and new HIV diagnosis among adult outpatients seeking care for symptoms of acute HIV infection in coastal Kenya: a cross-sectional analysis of intervention participants in a stepped-wedge HIV testing trial.

BACKGROUND: HIV testing is the first step to stop transmission. We aimed to evaluate HIV testing history and new diagnoses among adult outpatients in Kenya aged 18-39 years seeking care for symptoms of acute HIV infection (AHI). METHODS: The Tambua Mapema Plus study, a stepped-wedge trial, enrolled patients presenting to care at six primary care facilities with symptoms of AHI for a targeted HIV-1 nucleic acid (NA) testing intervention compared with standard provider-initiated testing using rapid antibody tests. Intervention participants underwent a questionnaire and NA testing, followed by rapid tests if NA-positive. Multinomial logistic regression was used to analyse factors associated with never testing or testing > 1 year ago ("late retesting") relative to testing ≤ 1 year ago ("on-time testers"). Logistic regression was used to analyse factors associated with new diagnosis. All analyses were stratified by sex. RESULTS: Of 1,500 intervention participants, 613 (40.9%) were men. Overall, 250 (40.8%) men vs. 364 (41.0%) women were late retesters, and 103 (16.8%) men vs. 50 (5.6%) women had never tested prior to enrolment. Younger age, single status, lower education level, no formal employment, childlessness, sexual activity in the past 6 weeks, and > 1 sexual partner were associated with testing history among both men and women. Intimate partner violence > 1 month ago, a regular sexual partner, and concurrency were associated with testing history among women only. New diagnoses were made in 37 (2.5%) participants (17 men and 20 women), of whom 8 (21.6%) had never tested and 16 (43.2%) were late retesters. Newly-diagnosed men were more likely to have symptoms for > 14 days, lower education level and no religious affiliation and less likely to be young, single, and childless than HIV-negative men; newly-diagnosed women were more likely to report fever than HIV-negative women. Among men, never testing was associated with fivefold increased odds (95% confidence interval 1.4-20.9) of new diagnosis relative to on-time testers in adjusted analyses. CONCLUSION: Most new HIV diagnoses were among participants who had never tested or tested > 1 year ago. Strengthening provider-initiated testing targeting never testers and late retesters could decrease time to diagnosis among symptomatic adults in coastal Kenya. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03508908 registered on 26/04/2018.

A Stronger Innate Immune Response During Hyperacute Human Immunodeficiency Virus Type 1 (HIV-1) Infection Is Associated With Acute Retroviral Syndrome.

BACKGROUND: Acute retroviral syndrome (ARS) is associated with human immunodeficiency virus type 1 (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 analyzed. 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 11 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% confidence interval {CI}: 1.7-28.8], P = .003). Interferon gamma-induced protein (IP)-10 was 14-fold higher during hAHI, elevated in 7 of the 11 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.

A Randomized Controlled Trial of the Shikamana Intervention to Promote Antiretroviral Therapy Adherence Among Gay, Bisexual, and Other Men Who Have Sex with Men in Kenya: Feasibility, Acceptability, Safety and Initial Effect Size.

Gay, bisexual, and other men who have sex with men (GBMSM) living with HIV in rights-constrained settings need support for antiretroviral therapy (ART) adherence due to barriers including stigma. The Shikamana intervention combined modified Next Step Counseling by providers with support from trained peers to improve adherence among GBMSM living with HIV in Kenya. A randomized controlled trial with 6-month follow-up was used to determine feasibility, acceptability, safety, and initial intervention effects. Generalized estimating equations examined differences in self-reported adherence and virologic suppression. Sixty men enrolled, with 27 randomly assigned to the intervention and 33 to standard care. Retention did not differ by arm, and no adverse events occurred. Feedback on feasibility and acceptability was positive based on exit interviews. After adjustment for baseline viral suppression and confounding, the intervention group had a sixfold increased odds of viral suppression during follow-up. A larger trial of a scaled-up intervention is needed.

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

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.

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

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.

Trichomonas vaginalis and HIV infection acquisition: a systematic review and meta-analysis.

OBJECTIVES: Trichomoniasis is the most prevalent curable STI globally, with the highest incidence and prevalence in sub-Saharan Africa (sSA). STIs have largely been associated with an increase in HIV acquisition. Our objective was to assess the existing literature available in English regarding the association of Trichomoniasis and HIV-1 acquisition. METHODS: The review protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) under number CRD42018082702. We searched MEDLINE, Embase and Scopus databases to collect articles measuring the association of Trichomonas vaginalis infection and HIV acquisition and performed a meta-analysis and qualitative synthesis of the literature. RESULTS: We identified 1806 unduplicated citations, of which 18 papers and 1 conference abstract were eligible for inclusion in the review after applying our inclusion and exclusion criteria. All the studies included in the systematic review had been carried out in sSA. The articles reported various measures of effects, namely: HRs, rate ratios, risk ratios and ORs. In a meta-analysis restricted to 11 studies reporting HR, individuals infected with T. vaginalis were 1.5 times more likely to acquire HIV compared with individuals not infected with T. vaginalis (95% CI 1.3 to 1.7; p<0.001). CONCLUSIONS: T. vaginalis is an important factor in HIV acquisition especially in sSA where the prevalence of both T. vaginalis and HIV-1 are high. This systematic review and meta-analysis confirms the evidence that infection with T. vaginalis augments HIV acquisition with 50%. Diagnosis and treatment of T. vaginalis infection in both high-risk and low-risk individuals may be a potential tool to reduce new HIV infections. TRIAL REGISTRATION NUMBER: CRD42018082702.

Identification of Novel Neisseria gonorrhoeae Lineages Harboring Resistance Plasmids in Coastal Kenya.

Background: Africa has the highest incidence of gonorrhea in the world. However, little is known about gonococcal populations in this continent or mechanisms of antimicrobial resistance (AMR). Methods: Whole-genome sequence data were analyzed from 103 Neisseria gonorrhoeae isolates from 73 patients, mainly men who have sex with men, from coastal Kenya. We annotated loci, defined the core genome, defined mechanisms of AMR, and performed phylogenetic analysis. For patients with multiple episodes of gonorrhea, we determined whether infections occurred with related strains. Results: We identified 3 clusters of isolates that are phylogenetically distinct from isolates found elsewhere. Plasmids were virtually ubiquitous: pTetM and pblaTEM were found in 97%, and 55% of isolates, respectively. This was associated with high doxycycline use for undiagnosed sexually transmitted infections. Twenty-three percent of multiple episodes of gonorrhea in the same individual were caused by a related strain, suggesting inadequate treatment or reinfection. Conclusions: The prevalence of plasmid-mediated AMR in Kenyan gonococci contrasts with that in wealthy countries, where AMR is largely chromosomally mediated. Antimicrobials have a profound effect on the maintenance of lineages harboring plasmids. Doxycycline can select for tetracycline and penicillin resistance, through plasmid cooperation. Understanding the mechanisms of AMR in high-risk groups is required to inform treatment strategies.

Broadly Neutralizing Antibody Responses in a Large Longitudinal Sub-Saharan HIV Primary Infection Cohort.

Broadly neutralizing antibodies (bnAbs) are thought to be a critical component of a protective HIV vaccine. However, designing vaccines immunogens able to elicit bnAbs has proven unsuccessful to date. Understanding the correlates and immunological mechanisms leading to the development of bnAb responses during natural HIV infection is thus critical to the design of a protective vaccine. The IAVI Protocol C program investigates a large longitudinal cohort of primary HIV-1 infection in Eastern and South Africa. Development of neutralization was evaluated in 439 donors using a 6 cross-clade pseudo-virus panel predictive of neutralization breadth on larger panels. About 15% of individuals developed bnAb responses, essentially between year 2 and year 4 of infection. Statistical analyses revealed no influence of gender, age or geographical origin on the development of neutralization breadth. However, cross-clade neutralization strongly correlated with high viral load as well as with low CD4 T cell counts, subtype-C infection and HLA-A*03(-) genotype. A correlation with high overall plasma IgG levels and anti-Env IgG binding titers was also found. The latter appeared not associated with higher affinity, suggesting a greater diversity of the anti-Env responses in broad neutralizers. Broadly neutralizing activity targeting glycan-dependent epitopes, largely the N332-glycan epitope region, was detected in nearly half of the broad neutralizers while CD4bs and gp41-MPER bnAb responses were only detected in very few individuals. Together the findings suggest that both viral and host factors are critical for the development of bnAbs and that the HIV Env N332-glycan supersite may be a favorable target for vaccine design.

An Empiric Risk Score to Guide PrEP Targeting Among MSM in Coastal Kenya.

Men who have sex with men (MSM), who have heterogeneous HIV-acquisition risks are not specifically targeted in Kenyan pre-exposure prophylaxis (PrEP) guidelines. We used data from an open cohort, which followed 753 initially HIV-negative MSM participants for more than 1378.5 person-years, to develop an empiric risk score for targeting PrEP delivery. Independent predictors of incident HIV-1 infection in this cohort were an age of 18-24 years, having only male sex partners, having receptive anal intercourse, having any unprotected sex, and having group sex. Poisson model coefficients were used to assign a numeric score to each statistically significant predictor. A risk score of ≥ 1 corresponded to an HIV-1 incidence of ≥ 2.2 [95% confidence interval (CI) 1.2-4.1] and identified 81.3% of the cohort participants as being at high risk for HIV-1 acquisition. The area under the receiver operating characteristic curve was 0.76 (95% CI 0.71-0.80). This empiric risk score may help Kenyan health care providers to assess HIV-1 acquisition risk and encourage PrEP uptake by high-risk MSM.

Utility of Different Adherence Measures for PrEP: Patterns and Incremental Value.

Measuring PrEP adherence remains challenging. In 2009-2010, the International AIDS Vaccine Initiative randomized phase II trial participants to daily tenofovir disoproxil fumarate/emtricitabine or placebo in Uganda and Kenya. Adherence was measured by electronic monitoring (EM), self-report (SR), and drug concentrations in plasma and hair. Each adherence measure was categorised as low, moderate, or high and also considered continuously; the incremental value of combining measures was determined. Forty-five participants were followed over 4 months. Discrimination for EM adherence by area under receiver operating curves (AROC) was poor for SR (0.53) and best for hair (AROC 0.85). When combining hair with plasma or hair with self-report, discrimination was improved (AROC > 0.9). Self-reported adherence was of low utility by itself. Hair level was the single best PK measure to predict EM-assessed adherence; the other measurements had lower discrimination values. Combining short-term (plasma) and long-term (hair) metrics could be useful to assess patterns of drug-taking in the context of PrEP.

HIV care engagement and ART adherence among Kenyan gay, bisexual, and other men who have sex with men: a multi-level model informed by qualitative research.

Gay, bisexual, and other men who have sex with men (GBMSM) are highly stigmatized and male-male sex is often criminalized in sub-Saharan Africa, impeding access to quality care for sexual health, HIV prevention, and treatment. To better understand HIV care engagement and antiretroviral therapy (ART) adherence among GBMSM in this context, a conceptual model incorporating sociocultural factors is needed. We conducted a qualitative study of barriers to and facilitators of HIV care engagement and ART adherence among Kenyan GBMSM, informed by a conceptual model based on an access, information, motivation, and behavioral skills (access-IMB) model, with trust in providers and stigma and discrimination as a priori factors of interest. We conducted 30 semi-structured interviews with HIV-positive Kenyan GBMSM, of whom 20 were taking ART and 10 had not yet initiated treatment. A deductive approach was used to confirm the relevance of basic concepts of the access-IMB model, while an inductive approach was used to identify content that emerged from men's lived experiences. Access-related information, motivation, and behavioral skills appeared relevant to HIV care engagement and ART adherence, with stigma and discrimination appearing consistently across discourse exploring facilitators and barriers. Trusted providers and supportive family and friends helped many men, and resilience-related concepts such as selective disclosure of GBMSM status, connection to lesbian, gay, bisexual, and transgender (LGBT) organizations, self-acceptance, goal-setting, social identity and altruism emerged as important facilitators. Findings suggest a need to increase support from providers and peers for Kenyan GBMSM living with HIV infection. In addition, they point toward the potential value of interventions that provide opportunities to build or enhance one's sense of community belonging in order to improve HIV care engagement and promote ART adherence for this vulnerable population.