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.

Challenges with PrEP Uptake and Adherence Among Gay, Bisexual, and Other Men Who Have Sex with Men in Kisumu, Kenya.

Data on challenges with pre-exposure prophylaxis (PrEP) uptake and adherence among Kenyan gay, bisexual, and other men who have sex with men (GBMSM) are limited. In this mixed-methods sequential explanatory design study, our quantitative phase followed 157 at-risk, HIV-negative GBMSM who accepted PrEP and enrolled in a cohort with 12-month follow-up. Stored dried blood spots collected at two intervals were batch tested for tenofovir diphosphate (TFV-DP) concentrations at study end. Despite high self-reported adherence, only 14.6% of individuals had protective TFV-DP levels at any visit. Protective TFV-DP levels were positively associated with injection drug use and a self-assessed moderate risk of acquiring HIV, and negatively associated with time since enrolment. In our subsequent qualitative phase, an intensive workshop was conducted with the GBMSM community to identify barriers and facilitators to PrEP uptake and adherence. These data revealed numerous challenges with traditional PrEP programs that must be addressed through community collaborations.

RESUMEN: La evidencia respecto a desafíos existentes con aceptación y adherencia de la profilaxis previa a la exposición (PrEP) de VIH, entre los hombres homosexuales, bisexuales y otros hombres que tienen sexo con hombres (GBMSM) en Kenia es limitada. Condujimos un estudio de métodos mixtos y diseño explicativo secuencial. En la fase cuantitativa seguimos a 157 GBMSM VIH-negativos en riesgo que aceptaron PrEP y se inscribieron en una cohorte con un seguimiento de 12 meses. Analizamos, por lotes y al final del estudio, gotas de sangre seca recolectada a dos intervalos de tiempo y previamente almacenada, para determinar las concentraciones de difosfato de tenofovir (TFV-DP). A pesar de la alta adherencia autoinformada, solo el 14,6% de las personas tenían niveles protectores de TFV-DP en alguna visita. Los niveles protectores de TFV-DP se asociaron positivamente con el uso de drogas inyectables y un riesgo moderado autoevaluado de contraer el VIH, y negativamente con el tiempo transcurrido desde la inscripción. En la fase cualitativa posterior, conversamos con GBMSM de la comunidad para identificar las barreras y los facilitadores para la concientización, aceptación, adherencia y retención a PrEP. Estos datos revelaron numerosos desafíos con los programas tradicionales de PrEP que deben abordarse mediante colaboraciones comunitarias.

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.

Vaginal and Penile Microbiome Associations With Herpes Simplex Virus Type 2 in Women and Their Male Sex Partners.

BACKGROUND: We determined how the vaginal and penile microbiomes contribute to herpes simplex virus type 2 (HSV-2) serostatus within sexual partnerships. METHODS: Microbiomes were characterized in cervicovaginal lavage and penile meatal swab specimens through high-throughput 16s ribosomal RNA gene amplicon sequencing. HSV-2 antibody was detected in serum specimens. We modeled vaginal and penile taxa and covariates contributing to HSV-2 status in women and men using bivariate probit analysis. RESULTS: Among 231 couples, HSV-2 was detected in both partners in 78 couples (33.8%), in the woman only in 52 (22.5%),in the man only in 27 (11.7%), and in neither in 74 (32.0%). Among the women (median age, 22 years) 10.9% had human immunodeficiency virus (HIV), and 21.4% had Bacterial vaginosis. Among men (median age, 26 years), 11.8% had HIV, and 55.0% circumcised. In an analysis with adjustment for sociodemographics and Bacterial vaginosis, enrichment of vaginal Gardnerella vaginalis and Lactobacillus iners was associated with increased likelihood of HSV-2 in both partners. Penile taxa (including Ureaplasma and Aerococcus) were associated with HSV-2 in women. CONCLUSIONS: We demonstrate that penile taxa are associated with HSV-2 in female partners, and vaginal taxa are associated with HSV-2 in male partners. Our findings suggest that couples-level joint consideration of genital microbiome and sexually transmitted infection or related outcomes could lead to new avenues for prevention.

Behavior Change and Sexually Transmitted Incidence in Relation to PREP Use Among Men Who Have Sex with Men in Kenya.

We measured change in sexual practices and the incidence of C. trachomatis (CT) and N. gonorrhoeae (NG) within a prospective cohort of Kenyan MSM taking PrEP in Kenya. Over the one year of study participation, CT and NG were diagnosed in urine at baseline, 6- and 12- months. Multivariable Cox regression identified factors associated with incident infection. Sexual practices were assessed at baseline and every 3 months. We evaluated changes over time and in relation to PrEP adherence via generalized estimating equation analysis. From October 2017-January 2018, 158 participants initiated PrEP, having 10.3% baseline CT/NG prevalence (either or both). The incidence was 17.2 cases per 100 person-years (95% CI 11.7-25.5). Incident CT/NG increased with report of: transactional male sex partner (adjusted Hazard Ratio (aHR) = 2.46, p = 0.016, z = 2.40), regular female sex partner (aHR = 2.22, p = 0.051, z = 1.96), greater social support (highest vs. lowest quartile, aHR = 6.24, p = 0.012, z = 2.51), and CT/NG infection prior to enrollment (aHR = 2.90, p = 0.002, z = 3.03). Multiple sex partners, condomless sex, and transactional sex decreased over time and were not associated with PrEP adherence. Urethral CT/NG incidence remained high and there was no evidence of PrEP-related behavioral change. There is need for ongoing etiologic testing, improved understanding of risk from female sex partners, and development of more effective risk reduction interventions.

Revisiting COVID-19 policies: 10 evidence-based recommendations for where to go from here.

BACKGROUND: Strategies to control coronavirus 2019 disease (COVID-19) have often been based on preliminary and limited data and have tended to be slow to evolve as new evidence emerges. Yet knowledge about COVID-19 has grown exponentially, and the expanding rollout of vaccines presents further opportunity to reassess the response to the pandemic more broadly. MAIN TEXT: We review the latest evidence concerning 10 key COVID-19 policy and strategic areas, specifically addressing: 1) the expansion of equitable vaccine distribution, 2) the need to ease restrictions as hospitalization and mortality rates eventually fall, 3) the advantages of emphasizing educational and harm reduction approaches over coercive and punitive measures, 4) the need to encourage outdoor activities, 5) the imperative to reopen schools, 6) the far-reaching and long-term economic and psychosocial consequences of sustained lockdowns, 7) the excessive focus on surface disinfection and other ineffective measures, 8) the importance of reassessing testing policies and practices, 9) the need for increasing access to outpatient therapies and prophylactics, and 10) the necessity to better prepare for future pandemics. CONCLUSIONS: While remarkably effective vaccines have engendered great hope, some widely held assumptions underlying current policy approaches call for an evidence-based reassessment. COVID-19 will require ongoing mitigation for the foreseeable future as it transforms from a pandemic into an endemic infection, but maintaining a constant state of emergency is not viable. A more realistic public health approach is to adjust current mitigation goals to be more data-driven and to minimize unintended harms associated with unfocused or ineffective control efforts. Based on the latest evidence, we therefore present recommendations for refining 10 key policy areas, and for applying lessons learned from COVID-19 to prevent and prepare for future pandemics.

Integration of voluntary male medical circumcision for HIV prevention into norms of masculinity: findings from Kisumu, Kenya.

While it is clear that in many communities ideas about masculinity and circumcision are connected, it is still unclear how young Kenyan men in the former Nyanza province from the traditionally non-circumcising Luo people perceive voluntary medical male circumcision as connected to masculinity and the role of voluntary medical male circumcision in the transition from boyhood to manhood. The objective of this study was to explore norms of masculinity and the decision-making process among Luo young men to provide a better understanding of how circumcision and masculinity relate to cultural norms within this community. The methodology consisted of eight FGDs with male peer groups and 24 in-depth interviews to elicit young men's perceptions of masculinity and voluntary medical male circumcision. Findings from thematic analysis reveal that young men described several key characteristics of masculinity including responsibility, bravery and sexual attractiveness. For some young men, voluntary medical male circumcision has embedded itself into cultural norms of masculinity by being a step in the transition from boyhood to manhood and by being a marker of some of these masculine characteristics. In the case of voluntary medical male circumcision, there may be opportunities to integrate other programming that helps men transition into healthy adulthood.

Incident gonorrhoea and chlamydia among a prospective cohort of men who have sex with men in Kisumu, Kenya.

OBJECTIVE: STIs disproportionately affect men who have sex with men (MSM) in sub-Saharan Africa. We identified factors associated with incident Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections among MSM in the Anza Mapema cohort study in Kisumu, Kenya. METHODS: We enrolled 711 MSM who underwent HIV testing and counselling, medical history and examination, and collection of demographic and behavioural information. They also provided urine and rectal swab specimens for CT and NG testing by qualitative PCR at baseline and at months 6 and 12. Separate multivariable Cox regression models identified factors associated with first incident urethral or rectal infection. RESULTS: Among the 619 men aged 18-54 years included in this analysis, there were 83 first incident urethral CT/NG infections (14.4 cases per 100 person-years (PY)) and 40 first incident rectal infections (6.84 cases per 100 PY), and an overall incidence of 18.0 cases per 100 PY (95% CI 14.8 to 21.8). Most urethral (84%) and rectal (81%) infections were asymptomatic. In the adjusted model, the risk of first incident urethral CT/NG decreased by 4% for each 1-year increase in age and was 41% lower for men who reported their partner used condom at last sexual encounter. Men who were HIV-positive had a 68% less risk of urogenital CT/NG compared with those who were negative. Men who reported being usually receptive or versatile as compared with usually insertive had an 81% increased risk of incident urogenital CT/NG. CONCLUSION: Our study demonstrated a high incidence of urethral CT/NG infection, with somewhat lower incidence of rectal CT/NG infection, despite repeated testing and treatment, highlighting the need for preventive interventions to decrease the burden of CT/NG among Kenyan MSM. Most infections were asymptomatic, and routine aetiological screening for STIs is recommended.

Characteristics of Women and Their Male Sex Partners Predict Bacterial Vaginosis Among a Prospective Cohort of Kenyan Women With Nonoptimal Vaginal Microbiota.

BACKGROUND: Up to 50% of women with nonoptimal vaginal microbial community state type (CST) have bacterial vaginosis (BV). Little is known about what distinguishes women with and without BV diagnosis within nonoptimal CST. We identified features of women and their male sex partners associated with BV among women with nonoptimal vaginal CST. METHODS: In this prospective study, 252 heterosexual couples were observed at 1, 6, and 12 months after baseline. Microbiomes were characterized in cervicovaginal lavage and penile meatal swabs through high-throughput 16s ribosomal RNA gene amplicon sequencing. Nonoptimal CST was defined as CST-IV. Bacterial vaginosis was defined as a Nugent score of 7 to 10. Generalized estimating equation analysis estimated adjusted odds ratios (aORs) for BV among women with nonoptimal CST. RESULTS: At baseline, women with nonoptimal CST were a median age of 22 years, 44% had BV, 16% had HIV, and 66% had herpes simplex virus (HSV) type 2. Male partners were a median age of 27 years, 12% had HIV, 48% had HSV-2, and 55% were circumcised. Within nonoptimal CST, Sneathia sanguinegens, Prevotella species, Prevotella amnii, and Clostridiales, BV-associated bacteria-2 were statistically significantly enriched in observations with BV. In multivariable generalized estimating equation controlling for CST, HIV, and HSV-2, BV was increased among women with CST-IVA (aOR, 1.91; P = 0.087), HIV (aOR, 2.30; P = 0.051), HSV-2 (aOR, 1.75; P = 0.065), and enrichment of male partner penile taxa: Dialister (aOR, 1.16; P = 0.034), Megasphaera (aOR, 1.22; P = 0.001), and Brevibacterium (aOR, 1.13; P = 0.019).These results provide insights into factors differentiating women with BV among those with nonoptimal vaginal CST. Interrupting the sexual exchange of penile and vaginal taxa may be beneficial for preventing pathologic state of vaginal microbiome.