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.

Sexual behavior among emerging adults in Africa: a systematic review and meta-analysis.

BACKGROUND: Estimates on sexual behavior (SB) among emerging adults (EmA) is varied in literature, which presents a challenge when designing targeted interventions. We aimed to summarize literature on prevalence and risk factors of SB among EmA in Africa. METHODS: A search for studies published in PubMed, Embase and Psych Info by March 2023 was done. Studies involving EmA (18-25 years), conducted in Africa and reporting one or more of seven SB were reviewed. Pooled prevalence estimates were summarized using forest plots. Heterogeneity in SB was explored. Risk factors were synthesized using a modified socio-ecological model. RESULTS: Overall, 143 studies were analyzed. Non-condom use had the highest pooled prevalence (47% [95% CI: 42-51]), followed by study-defined SB (37% [95% CI: 25-50]) and concurrency (37% [95% CI: 21-54]), multiple sex partners (31% [95% CI: 25-37]), younger age at sexual debut (26% [95% CI: 20-32]), age disparate relationships (24% [95% CI: 17-32]) and transactional sex (19% [95% CI: 13-26]). Heterogeneity was partially explained by sex, with female participants having higher pooled prevalence estimates compared to their male counterparts. In four of the seven outcomes, alcohol/drug use was the most common risk factor. CONCLUSIONS: SB was common among EmA and differentially higher in emerging female adults. Non-condom use had the highest pooled prevalence, which may contribute to the transmission of HIV and other sexually transmitted infections (STIs). Interventions targeting emerging female adults and alcohol/drug use may reduce SB, which may in-turn mitigate transmission of HIV and other STIs among EmA in Africa.

Leveraging electronic medical records for HIV testing, care, and treatment programming in Kenya-the national data warehouse project.

BACKGROUND: Aggregate electronic data repositories and population-level cross-sectional surveys play a critical role in HIV programme monitoring and surveillance for data-driven decision-making. However, these data sources have inherent limitations including inability to respond to public health priorities in real-time and to longitudinally follow up clients for ascertainment of long-term outcomes. Electronic medical records (EMRs) have tremendous potential to bridge these gaps when harnessed into a centralised data repository. We describe the evolution of EMRs and the development of a centralised national data warehouse (NDW) repository. Further, we describe the distribution and representativeness of data from the NDW and explore its potential for population-level surveillance of HIV testing, care and treatment in Kenya. MAIN BODY: Health information systems in Kenya have evolved from simple paper records to web-based EMRs with features that support data transmission to the NDW. The NDW design includes four layers: data warehouse application programming interface (DWAPI), central staging, integration service, and data visualization application. The number of health facilities uploading individual-level data to the NDW increased from 666 in 2016 to 1,516 in 2020, covering 41 of 47 counties in Kenya. By the end of 2020, the NDW hosted longitudinal data from 1,928,458 individuals ever started on antiretroviral therapy (ART). In 2020, there were 936,869 individuals who were active on ART in the NDW, compared to 1,219,276 individuals on ART reported in the aggregate-level Kenya Health Information System (KHIS), suggesting 77% coverage. The proportional distribution of individuals on ART by counties in the NDW was consistent with that from KHIS, suggesting representativeness and generalizability at the population level. CONCLUSION: The NDW presents opportunities for individual-level HIV programme monitoring and surveillance because of its longitudinal design and its ability to respond to public health priorities in real-time. A comparison with estimates from KHIS demonstrates that the NDW has high coverage and that the data maybe representative and generalizable at the population-level. The NDW is therefore a unique and complementary resource for HIV programme monitoring and surveillance with potential to strengthen timely data driven decision-making towards HIV epidemic control in Kenya. DATABASE LINK: ( https://dwh.nascop.org/ ).

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.

Prevalence, risk and protective indicators of common mental disorders among young people living with HIV compared to their uninfected peers from the Kenyan coast: a cross-sectional study.

BACKGROUND: In sub-Saharan Africa, common mental disorders (CMDs) like depression and anxiety are under-investigated amongst young people living with HIV (YLWH). To address the gap, in Kenya we: a) determined the prevalence of CMDs among YLWH compared to their uninfected peers; b) investigated HIV status as an independent predictor of CMDs in young people; c) investigated CMDs risk and protective indicators with more focus on YLWH. METHODS: Between November 2018 and September 2019, 819 young people aged 18-24 years (407 HIV-infected) were recruited from two Counties on the Kenyan coast. Locally adapted pre-existing mental health measures, Patient Health Questionnaire (9-item) and Generalized Anxiety Disorder scale (7-item), were administered among other questionnaires via audio computer-assisted self-interview. Logistic regression was used to determine the correlates of CMDs. RESULTS: Prevalence of CMDs was significantly elevated among YLWH compared to their uninfected peers i.e. 29% vs. 12%; p < 0.001 for depressive symptoms, 19% vs. 8%; p < 0.001 for anxiety symptoms, and 16% vs. 5%; p < 0.001 for comorbid depressive and anxiety symptoms. HIV status independently predicted depressive symptoms and its co-occurrence with anxiety symptoms. Among YLWH, negative life events, higher perceived HIV-related stigma and low adherence to antiretroviral therapy were the risk indicators for elevated CMDs. Among HIV-uninfected youths, death of both parents was a risk indicator for elevated depressive symptoms. Protective indicators against CMDs among youths with and without HIV included higher social support and health-related quality of life. CONCLUSION: At the Kenyan coast, YLWH have significantly higher burden of CMDs compared to their uninfected peers. Being HIV-positive as a youth in this setting is predictive of more depressive symptoms and its comorbidity with anxiety symptoms. YLWH at high risk of CMDs in coastal Kenya can benefit from early detection, referral and treatment if routine screening for CMDs is integrated in their care package. The mental wellbeing of bereaving HIV-unaffected youths could be improved through continued support to help them come to terms with their loss. At the community level, programmes strengthening the social capital or improving the overall quality of life of youths with or without HIV may be beneficial to their mental health.

Beyond Their HIV Status: the Occurrence of Multiple Health Risk Behavior Among Adolescents from a Rural Setting of Sub-Saharan Africa.

BACKGROUND: Health risk behaviors during adolescence may cluster into patterns that might be predicted by specific factors, among which HIV may have an important role. METHOD: In a cross-sectional study conducted between 2017 and 2018, clustering of HRB and its associated factors was investigated in rural Kenya among 588 adolescents (36% perinatally HIV infected; 28% perinatally HIV exposed but uninfected; and 36% HIV unexposed/uninfected). Latent class analysis of 22 behaviors followed by multinomial logistic regression were conducted. Four risk behavior classes were identified. RESULTS: No significant differences were found in behavioral class membership across the three HIV groups (p = 0.366). The risk of membership to the higher risk behavioral classes relative to class 1 (the substance and drug abstinent low risk takers) increased with older adolescent age (p = 0.047), increased among adolescent who experienced mental distress (p < 0.001), and those who felt unsafe in their neighborhood (p < 0.002). Better working memory (p = 0.0037) was found to be protective. CONCLUSION: The results highlight a need to include screening and interventions for internalizing mental health problems and deficits in executive functioning, as well as steps to involve family members and communities to address psychosocial risk factors in adolescents in Kenya.

Determining the Origins of Human Immunodeficiency Virus Type 1 Drug-resistant Minority Variants in People Who Are Recently Infected Using Phylogenetic Reconstruction.

BACKGROUND: Drug-resistant minority variants (DRMinVs) detected in patients who recently acquired human immunodeficiency virus type 1 (HIV-1) can be transmitted, generated de novo through virus replication, or technical errors. The first form is likely to persist and result in treatment failure, while the latter two could be stochastic and transient. METHODS: Ultradeep sequencing of plasma samples from 835 individuals with recent HIV-1 infection in the United Kingdom was performed to detect DRMinVs at a mutation frequency between 2% and 20%. Sequence alignments including >110 000 HIV-1 partial pol consensus sequences from the UK HIV Drug Resistance Database (UK-HDRD), linked to epidemiological and clinical data from the HIV and AIDS Reporting System, were used for transmission cluster analysis. Transmission clusters were identified using Cluster Picker with a clade support of >90% and maximum genetic distances of 4.5% or 1.5%, the latter to limit detection to likely direct transmission events. RESULTS: Drug-resistant majority variants (DRMajVs) were detected in 66 (7.9%) and DRMinVs in 84 (10.1%) of the recently infected individuals. High levels of clustering to sequences in UK-HDRD were observed for both DRMajV (n = 48; 72.7%) and DRMinV (n = 63; 75.0%) sequences. Of these, 43 (65.2%) with DRMajVs were in a transmission cluster with sequences that harbored the same DR mutation compared to only 3 (3.6%) sequences with DRMinVs (P < .00001, Fisher exact test). Evidence of likely direct transmission of DRMajVs was observed for 25/66 (37.9%), whereas none were observed for the DRMinVs (P < .00001). CONCLUSIONS: Using a densely sampled HIV-infected population, we show no evidence of DRMinV transmission among recently infected individuals.

Control of Viremia Enables Acquisition of Resting Memory B Cells with Age and Normalization of Activated B Cell Phenotypes in HIV-Infected Children.

HIV affects the function of all lymphocyte populations, including B cells. Phenotypic and functional defects of B cells in HIV-infected adults have been well characterized, but defects in children have not been studied to the same extent. We determined the proportion of B cell subsets and frequencies of Ag-specific memory B cells in peripheral blood from HIV-infected children and healthy controls, using flow cytometry and B cell ELISPOT, respectively. In addition, we measured the quantities and avidities of plasma Abs against various Ags by ELISA. We also determined plasma levels of BAFF and expression of BAFF receptors on B cells. Children with high HIV viremia had increased proportions of activated mature B cells, tissue-like memory B cells and plasmablasts, and low proportions of naive B cells when compared with community controls and children with low HIV viremia, similar to adults infected with HIV. HIV-infected groups had lower proportions of resting memory B cells than did community controls. Notably, high HIV viremia prevented the age-dependent accumulation of class-switched resting memory B cells. HIV-infected children, regardless of the level of viremia, showed lower quantities and avidities of IgG and lower frequencies of memory B cells against Expanded Program on Immunization vaccines. The HIV-infected children had an altered BAFF profile that could have affected their B cell compartment. Therefore, B cell defects in HIV-infected children are similar to those seen in HIV-infected adults. However, control of HIV viremia is associated with normalization of activated B cell subsets and allows age-dependent accumulation of resting memory B cells.

'Everyone has a secret they keep close to their hearts': challenges faced by adolescents living with HIV infection at the Kenyan coast.

BACKGROUND: The upsurge in the uptake of antiretroviral therapy (ART) has led to a significant increase in the survival of vertically acquired HIV infected children, many of whom are currently living into adolescence and early adulthood. However little if anything is known of the lived experiences and the challenges faced by HIV positive adolescents in the African context. We set out to investigate psychosocial challenges faced by HIV infected adolescents on the Kenyan coast. METHODS: A total of 44 participants (12 HIV-infected adolescents, 7 HIV uninfected adolescents, and 25 key informants) took part in this qualitative study, using individually administered in-depth interviews. A framework approach was used to analyze the data using NVIVO software. RESULTS: We observed that the challenges faced by adolescents in rural Kenya could be placed into six major themes: poverty, poor mental and physical health, the lack of a school system that is responsive to their needs, challenges in how to disclose to peers and family members, high levels of stigma in its various forms, and challenges of medical adherence leading to the need for close monitoring. CONCLUSION: In this African community, vertically acquired HIV-infected adolescents face a complex set of social, economic and medical challenges. Our study points to the urgent need to develop multisectorial intervention support programmes to fully address these challenges.

Incidence and predictors of attrition from antiretroviral care among adults in a rural HIV clinic in Coastal Kenya: a retrospective cohort study.

BACKGROUND: Scale up of antiretroviral therapy (ART) has led to substantial declines in HIV related morbidity and mortality. However, attrition from ART care remains a major public health concern and has been identified as one of the key reportable indicators in assessing the success of ART programs. This study describes the incidence and predictors of attrition among adults initiating ART in a rural HIV clinic in Coastal Kenya. METHODS: A retrospective cohort study design was used. Adults (≥ 15 years) initiated ART between January 2008 and December 2010 were followed up for two years. Attrition was defined as individuals who were either reported dead or lost to follow up (LFU, ≥ 180 days late since the last clinic visit). Kaplan Meier survival probabilities and Weibull baseline hazard regression analyses were used to model the incidence and predictors of time to attrition. RESULTS: Of the 928 eligible participants, 308 (33.2% [95% CI, 30.2 - 36.3]) underwent attrition at an incident rate of 23.1 (95% CI, 20.6 - 25.8)/100 pyo. Attrition at 6 and 12 months was 18.4% (95% CI, 16.0 - 21.1) and 23.2% (95% CI, 19.9 - 25.3) respectively. Gender (male vs. female, adjusted hazard ratio [95% CI], p-value: 1.5 [1.1 - 2.0], p = 0.014), age (15 - 24 vs. ≥ 45 years, 2.2 [1.3 - 3.7], p = 0.034) and baseline CD4 T-cell count (100 - 350 cells/uL vs. < 100 cells/uL, 0.5 [0.3 - 0.7], p = 0.002) were independent predictors of time to attrition. CONCLUSIONS: A third of individuals initiating ART were either reported dead or LFU during two years of care, with more than a half of these occurring within six months of treatment initiation. Practical and sustainable biomedical interventions and psychosocial support systems are warranted to improve ART retention in this setting.

HIV-1 virologic failure and acquired drug resistance among first-line antiretroviral experienced adults at a rural HIV clinic in coastal Kenya: a cross-sectional study.

BACKGROUND: An increasing number of people on antiretroviral therapy (ART) in sub-Saharan Africa has led to declines in HIV related morbidity and mortality. However, virologic failure (VF) and acquired drug resistance (ADR) may negatively affect these gains. This study describes the prevalence and correlates of HIV-1 VF and ADR among first-line ART experienced adults at a rural HIV clinic in Coastal Kenya. METHODS: HIV-infected adults on first-line ART for ≥6 months were cross-sectionally recruited between November 2008 and March 2011. The primary outcome was VF, defined as a one-off plasma viral load of ≥400 copies/ml. The secondary outcome was ADR, defined as the presence of resistance associated mutations. Logistic regression and Fishers exact test were used to describe correlates of VF and ADR respectively. RESULTS: Of the 232 eligible participants on ART over a median duration of 13.9 months, 57 (24.6% [95% CI: 19.2 - 30.6]) had VF. Fifty-five viraemic samples were successfully amplified and sequenced. Of these, 29 (52.7% [95% CI: 38.8 - 66.3]) had at least one ADR, with 25 samples having dual-class resistance mutations. The most prevalent ADR mutations were the M184V (n = 24), K103N/S (n = 14) and Y181C/Y/I/V (n = 8). Twenty-six of the 55 successfully amplified viraemic samples (47.3%) did not have any detectable resistance mutation. Younger age (15-34 vs. ≥35 years: adjusted odd ratios [95% CI], p-value: 0.3 [0.1-0.6], p = 0.002) and unsatisfactory adherence (<95% vs. ≥95%: 3.0 [1.5-6.5], p = 0.003) were strong correlates of VF. Younger age, unsatisfactory adherence and high viral load were also strong correlates of ADR. CONCLUSIONS: High levels of VF and ADR were observed in younger patients and those with unsatisfactory adherence. Youth-friendly ART initiatives and strengthened adherence support should be prioritized in this Coastal Kenyan setting. To prevent unnecessary/premature switches, targeted HIV drug resistance testing for patients with confirmed VF should be considered.

Associations between disordered eating behaviour and sexual behaviour amongst emerging adults attending a tertiary education institution in Coastal Kenya.

BACKGROUND: Sexual behavior (SB) is a well-documented pathway to HIV acquisition in emerging adults and remains common amongst African emerging adults. Previous research in high-income countries indicates a correlation between disordered eating behavior (DEB) and engaging in sexual behaviors. We aimed to describe the relationship between DEB and SB amongst emerging adults attending a tertiary educational institution at the Kenyan Coast. METHODS: We applied a cross-sectional design nested in a young adults' cohort study. Eligibility included sexually active emerging adults aged 18-24 years. Three DEBs (emotional, restrained and external eating) were assessed using the Dutch Eating Behavior Questionnaire and analysed using exploratory factor analysis. Seven SB indicators were assessed: non-condom use, casual sex, multiple sex partners, transactional sex, group sex, age-disparate relationship and anal sex, and grouped into low vs. high SB using latent class analysis. Logistic regression was used to assess the association between DEB and SB. RESULTS: Of 273 eligible participants (female, n = 110 [40.3%]), the mean of emotional, restrained and external eating was 1.9 [0.6], 2.0 [0.6] and 3.0 [0.5] respectively. Overall, 57 (20.9%) were grouped into the latent high SB class. Emotional (Adjusted odds ratio, AOR [95% confidence interval, CI]: 1.0 [0.9-1.0], p = 0.398), restrained (AOR, 1.0 [CI: 0.9-1.1], p = 0.301) and External (AOR, 1.0 [CI: 0.8-1.2], p = 0.523) eating were not independently associated with latent high SB. CONCLUSION: There was no significant association between DEB and SB in this study sample. In low- and middle-income countries like Kenya, interventions targeted at DEB among emerging adults towards controlling SB are unnecessary.

HLA-A*23 Is Associated With Lower Odds of Acute Retroviral Syndrome in Human Immunodeficiency Virus Type 1 Infection: A Multicenter Sub-Saharan African Study.

The role of human leukocyte antigen (HLA) class I and killer immunoglobulin-like receptor molecules in mediating acute retroviral syndrome (ARS) during human immunodeficiency virus type 1 (HIV-1) infection is unclear. Among 72 sub-Saharan African adults, HLA-A*23 was associated with lower odds of ARS (adjusted odds ratio, 0.10 [95% confidence interval, .01-.48]; P = .009), which warrants further studies to explore its role on HIV-1-specific immunopathogenesis.

Exposure to common infections may shape basal immunity and potentially HIV-1 acquisition amongst a high-risk population in Coastal Kenya.

Introduction: The impact of exposure to endemic infections on basal immunity and susceptibility to HIV-1 acquisition remains uncertain. We hypothesized that exposure to infections such as cytomegalovirus (CMV), malaria and sexually transmitted infections (STIs) in high-risk individuals may modulate immunity and subsequently increase susceptibility to HIV-1 acquisition. Methods: A case-control study nested in an HIV-1 negative high-risk cohort from Coastal Kenya was used. Cases were defined as volunteers who tested HIV-1 positive during follow-up and had a plasma sample collected 3 ± 2 months prior to the estimated date of HIV-1 infection. Controls were individuals who remained HIV-1 negative during the follow-up and were matched 2:1 to cases by sex, age, risk group and follow-up time. STI screening was performed using microscopic and serologic tests. HIV-1 pre-infection plasma samples were used to determined exposure to CMV and malaria using enzyme-linked immunosorbent assays and to quantify forty-one cytokines and soluble factors using multiplexing assays. Multiplexing data were analyzed using principal component analysis. Associations between cytokines and soluble factors with subsequent HIV-1 acquisition were determined using conditional logistic regression models. Results and discussion: Overall, samples from 47 cases and 94 controls were analyzed. While exposure to malaria (p=0.675) and CMV (p=0.470) were not associated with HIV-1 acquisition, exposure to STIs was (48% [95% CI, 33.3 - 63] vs. 26% [95% CI, 17.3 - 35.9]. Ten analytes were significantly altered in cases compared to controls and were clustered into four principal components: PC1 (VEGF, MIP-1ß, VEGF-C and IL-4), PC2 (MCP-1, IL-2 and IL-12p70), PC3 (VEGF-D) and PC4 (Eotaxin-3). PC1, which is suggestive of a Th2-modulatory pathway, was significantly associated with HIV-1 acquisition after controlling for STIs (adjusted odds ratio, (95% CI), p-value: 1.51 [1.14 - 2.00], p=0.004). Elevation of Th2-associated pathways may dampen responses involved in viral immunity, leading to enhanced susceptibility to HIV-1 acquisition. Immunomodulatory interventions aimed at inhibiting activation of Th2-associated pathways may be an additional strategy to STI control for HIV-1 prevention and may reduce dampening of immune responses to vaccination.

Sexual risk-taking behavior amongst emerging adults in a tertiary institution of learning in Coastal Kenya: A qualitative study of stakeholders' perspectives using causal loop mapping.

BACKGROUND: It is known from previous studies that university students in sub-Saharan Africa (sSA) engage in sexual risk-taking behaviour (SRTB). However, there is paucity of data on factors contributing to SRTB among university students (emerging adults) at the Kenyan Coast thus hindering intervention planning. This study seeks to provide an in-depth qualitative understanding of the factors contributing to SRTB and their interconnectedness among university students at the Kenyan Coast combining qualitative research with a systems thinking approach. METHODS: Using the ecological model, and employing in-depth interviews, we explored the perceptions of twenty-six key informants (twenty-one emerging adults and five other stakeholders) on what constitutes and influences SRTB among emerging adults at a tertiary institution of learning in Coastal Kenya. Data were analysed using a thematic framework approach. A causal loop diagram (CLD) was developed to map the interconnectedness of the correlates of SRTB. RESULTS: Our findings show that unprotected sex, transactional sex, cross-generational sex, multiple sex partnerships, gender-based violence, sex under influence of alcohol/drugs, early sex debut, and sharing sex toys were common SRTBs. Based on the ecological model and CLD, most of the reported risk factors were interconnected and operated at the individual level. CONCLUSION: Our study shows that emerging adults are frequently engaging in unprotected sex. Enhancing sexuality education programs for students in Kenyan universities and strengthening support systems including counselling for those using alcohol/drugs may help reduce SRTB among emerging adults in Kenyan universities.

Impact of the COVID-19 pandemic on routine HIV care and antiretroviral treatment outcomes in Kenya: A nationally representative analysis.

BACKGROUND: The COVID-19 pandemic adversely disrupted global health service delivery. We aimed to assess impact of the pandemic on same-day HIV diagnosis/ART initiation, six-months non-retention and initial virologic non-suppression (VnS) among individuals starting antiretroviral therapy (ART) in Kenya. METHODS: Individual-level longitudinal service delivery data were analysed. Random sampling of individuals aged >15 years starting ART between April 2018 -March 2021 was done. Date of ART initiation was stratified into pre-COVID-19 (April 2018 -March 2019 and April 2019 -March 2020) and COVID-19 (April 2020 -March 2021) periods. Mixed effects generalised linear, survival and logistic regression models were used to determine the effect of COVID-19 pandemic on same-day HIV diagnosis/ART initiation, six-months non-retention and VnS, respectively. RESULTS: Of 7,046 individuals sampled, 35.5%, 36.0% and 28.4% started ART during April 2018 -March 2019, April 2019 -March 2020 and April 2020 -March 2021, respectively. Compared to the pre-COVID-19 period, the COVID-19 period had higher same-day HIV diagnosis/ART initiation (adjusted risk ratio [95% CI]: 1.09 [1.04-1.13], p<0.001) and lower six-months non-retention (adjusted hazard ratio [95% CI]: 0.66 [0.58-0.74], p<0.001). Of those sampled, 3,296 (46.8%) had a viral load test done at a median 6.2 (IQR, 5.3-7.3) months after ART initiation. Compared to the pre-COVID-19 period, there was no significant difference in VnS during the COVID-19 period (adjusted odds ratio [95% CI]: 0.79 [95%% CI: 0.52-1.20], p = 0.264). CONCLUSIONS: In the short term, the COVID-19 pandemic did not have an adverse impact on HIV care and treatment outcomes in Kenya. Timely, strategic and sustained COVID-19 response may have played a critical role in mitigating adverse effects of the pandemic and point towards maturity, versatility and resilience of the HIV program in Kenya. Continued monitoring to assess long-term impact of the COVID-19 pandemic on HIV care and treatment program in Kenya is warranted.

Early loss to follow-up of recently diagnosed HIV-infected adults from routine pre-ART care in a rural district hospital in Kenya: a cohort study.

OBJECTIVE: To determine the rate and predictors of early loss to follow-up (LTFU) for recently diagnosed HIV-infected, antiretroviral therapy (ART)-ineligible adults in rural Kenya. METHODS: Prospective cohort study. Clients registering for HIV care between July 2008 and August 2009 were followed up for 6 months. Baseline data were used to assess predictors of pre-ART LTFU (not returning for care within 2 months of a scheduled appointment), LTFU before the second visit and LTFU after the second visit. Logistic regression was used to determine factors associated with LTFU before the second visit, while Cox regression was used to assess predictors of time to LTFU and LTFU after the second visit. RESULTS: Of 530 eligible clients, 178 (33.6%) were LTFU from pre-ART care (11.1/100 person-months). Of these, 96 (53.9%) were LTFU before the second visit. Distance (>5 km vs. <1 km: adjusted hazard ratio 2.6 [1.9-3.7], P < 0.01) and marital status (married vs. single: 0.5 [0.3-0.6], P < 0.01) independently predicted pre-ART LTFU. Distance and marital status were independently associated with LTFU before the second visit, while distance, education status and seasonality showed weak evidence of predicting LTFU after the second visit. HIV disease severity did not predict pre-ART LTFU. CONCLUSIONS: A third of recently diagnosed HIV-infected, ART-ineligible clients were LTFU within 6 months of registration. Predictors of LTFU among ART-ineligible clients are different from those among clients on ART. These findings warrant consideration of an enhanced pre-ART care package aimed at improving retention and timely ART initiation.

Dynamics and constraints of early infant diagnosis of HIV infection in Rural Kenya.

A cohort design was used to determine uptake and drop out of 213 HIV-exposed infants eligible for Early Infant Diagnosis (EID) of HIV. To explore service providers and care givers knowledge, attitudes and perceptions of the EID process, observations and in-depth interviews were conducted. 145 (68%) infants enrolled after 2 months of age. 139 (65%) dropped out before follow up to 18 months old. 60 (43%) drop outs occurred within 2 months of enrolment. Maternal factors associated with infant drop out were maternal loss to follow up (48 [68%] vs. 8 [20%], P < 0.001) and younger maternal age (27.2 vs. 30.1 years, P = 0.033). Service providers and caregivers had inadequate training, knowledge and understanding of EID. Poverty and lack of social support were challenges in accessing EID services. EID should be more closely aligned within PMTCT services, integrated with routine mother and child health (MCH) activities and its implementation more closely monitored.

Phylogeographic Assessment Reveals Geographic Sources of HIV-1 Dissemination Among Men Who Have Sex With Men in Kenya.

HIV-1 transmission dynamics involving men who have sex with men (MSM) in Africa are not well understood. We investigated the rates of HIV-1 transmission between MSM across three regions in Kenya: Coast, Nairobi, and Nyanza. We analyzed 372 HIV-1 partial pol sequences sampled during 2006-2019 from MSM in Coast (N = 178, 47.9%), Nairobi (N = 137, 36.8%), and Nyanza (N = 57, 15.3%) provinces in Kenya. Maximum-likelihood (ML) phylogenetics and Bayesian inference were used to determine HIV-1 clusters, evolutionary dynamics, and virus migration rates between geographic regions. HIV-1 sub-subtype A1 (72.0%) was most common followed by subtype D (11.0%), unique recombinant forms (8.9%), subtype C (5.9%), CRF 21A2D (0.8%), subtype G (0.8%), CRF 16A2D (0.3%), and subtype B (0.3%). Forty-six clusters (size range 2-20 sequences) were found-half (50.0%) of which had evidence of extensive HIV-1 mixing among different provinces. Data revealed an exponential increase in infections among MSM during the early-to-mid 2000s and stable or decreasing transmission dynamics in recent years (2017-2019). Phylogeographic inference showed significant (Bayes factor, BF > 3) HIV-1 dissemination from Coast to Nairobi and Nyanza provinces, and from Nairobi to Nyanza province. Strengthening HIV-1 prevention programs to MSM in geographic locations with higher HIV-1 prevalence among MSM (such as Coast and Nairobi) may reduce HIV-1 incidence among MSM in Kenya.