With two million new HIV infections annually, ongoing investigations of risk factors for HIV acquisition is critical to guide ongoing HIV prevention efforts. We conducted a prospective cohort analysis of HIV uninfected female sex workers enrolled at an HIV prevention clinic in Nairobi (n = 1640). In the initially HIV uninfected cohort (70 %), we observed 34 HIV infections during 1514 person-years of follow-up, i.e. an annual incidence of 2.2 % (95 % CI 1.6-3.1 %). In multivariable Cox Proportional Hazard analysis, HIV acquisition was associated with a shorter baseline duration of sex work (aHR 0.76, 95 % CI 0.63-0.91), minimum charge/sex act (aHR 2.74, 0.82-9.15, for low vs. intermediate; aHR 5.70, 1.96-16.59, for high vs. intermediate), N. gonorrhoeae infection (aAHR 5.89, 95 % CI 2.03-17.08), sex with casual clients during menses (aHR 6.19, 95 % CI 2.58-14.84), Depo Provera use (aHR 5.12, 95 % CI 1.98-13.22), and estimated number of annual unprotected regular partner contacts (aHR 1.004, 95 % CI 1.001-1.006). Risk profiling based on baseline predictors suggested that substantial heterogeneity in HIV risk is evident, even within a key population. These data highlight several risk factors for HIV acquisition that could help to re-focus HIV prevention messages.

Objectives: Empirical time trends in HIV prevalence in female sex workers (FSWs) are helpful to understand the evolving HIV epidemic, and to monitor the scale-up, coverage, and impact of ongoing HIV prevention and treatment programmes. Design: Serial HIV prevalence study. Methods: We analyzed time trends in HIV prevalence in FSWs accessing services at seven Sex Worker Outreach Programme (SWOP) clinics in Nairobi from 2008 to 2017 (N = 33 560). The Mantel--Haenszel test for trend and independent samples Kruskal--Wallis test were used to analyze categorical and continuous variables, respectively. Multivariable binomial regression was used to estimate prevalence ratios/year, adjusting for several covariates. Results: HIV prevalence decreased over time in all age groups. This was particularly evident among FSWs less than 25 years of age; HIV was 17.5% in 2008–2009, decreasing to 12.2% in 2010–2011, 8.3% in 2012–2013, 7.3% in 2014–2015, and 4.8% in 2016–2017 (P < 0.0001). Over time, FSWs reported increased condom use, particularly with regular partners, more frequent prior HIV testing, and were less likely to report a history of vaginal discharge (P < 0.0001). In adjusted analyses compared with 2008, HIV prevalence decreased in 2011 (aPR 0.64; 95% CI: 0.46–0.90), 2012 (aPR 0.58; 95% CI: 0.41–0.81), 2013 (aPR 0.53; 95% CI: 0.38–0.73), 2014 (aPR 0.48; 95% CI: 0.34–0.67), 2015 (aPR 0.50; 95% CI: 0.35–0.70), 2016 (aPR 0.40; 95% CI: 0.28–0.57), and 2017 (aPR 0.33; 95% CI: 0.22–0.50). Conclusion: HIV prevalence has decreased among FSW accessing SWOP in Nairobi, Kenya. This decline is consistent with the scale-up of HIV prevention and treatment efforts, both in FSWs and in the general population.

Regulatory T cells (Tregs) play important roles in tissue homeostasis, but few studies have investigated tissue Tregs in the context of genital inflammation, HIV target cell density, and vaginal microbiota in humans. In women from Nairobi (n=64), the proportion of CD4+ CD25+ CD127low Tregs in the endocervix correlated with those in blood (r=0.31, p=0.01), with a higher Treg frequency observed in the endocervix (median 3.8 vs 2.0%, p&lt;0.0001). Most Tregs expressed FOXP3 in both compartments, and CTLA-4 expression was higher on endocervical Tregs compared to blood (median 50.8 vs 6.0%, p&lt;0.0001). More than half (34/62, 55%) of participants displayed a non-Lactobacillus dominant vaginal microbiota, which was not associated with endocervical Tregs or CD4+ T cell abundance. In a multivariable linear regression, endocervical Treg proportions were inversely associated with the number of elevated pro-inflammatory cytokines (p=0.03). Inverse Treg associations were also observed for specific cytokines including IL-1β, G-CSF, Eotaxin, IL-1RA, IL-8, and MIP-1 β. Higher endocervical Treg proportions were associated with lower abundance of endocervical CD4+ T cells (0.30 log10 CD4+ T cells per log10 Treg, p=0.00028), with a similar trend for Th17 cells (p=0.09). Selectively increasing endocervical Tregs may represent a pathway to reduce genital tract inflammation in women.

Regulatory T cells (Tregs) play important roles in tissue homeostasis, but few studies have investigated tissue Tregs in the context of genital inflammation, HIV target cell density, and vaginal microbiota in humans. In women from Nairobi (n=64), the proportion of CD4+ CD25+ CD127low Tregs in the endocervix correlated with those in blood (r=0.31, p=0.01), with a higher Treg frequency observed in the endocervix (median 3.8 vs 2.0%, p<0.0001). Most Tregs expressed FoxP3 in both compartments, and CTLA-4 expression was higher on endocervical Tregs compared to blood (median 50.8 vs 6.0%, p<0.0001). More than half (34/62, 55%) of participants displayed a non-Lactobacillus dominant vaginal microbiota, which was not associated with endocervical Tregs or CD4+ T cell abundance. In a multivariable linear regression, endocervical Treg proportions were inversely associated with the number of elevated pro-inflammatory cytokines (p=0.03). Inverse Treg associations were also observed for specific cytokines including IL-1β, G-CSF, Eotaxin, IL-1RA, IL-8, and MIP-1 β. Higher endocervical Treg proportions were associated with lower abundance of endocervical CD4+ T cells (0.30 log10 CD4+ T cells per log10 Treg, p=0.00028), with a similar trend for Th17 cells (p=0.09). Selectively increasing endocervical Tregs may represent a pathway to reduce genital tract inflammation in women.

Background: Kenya's HIV epidemic is heterogeneously distributed. Although HIV incidence in Kenya has shown signs of recent decline, focused interventions are still needed for female sex workers (FSWs). Geospatially informed approaches have been advocated for targeted HIV prevention. We quantified heterogeneity in HIV burden in Nairobi-based FSWs by place of origin within Kenya and hotspots and residence within Nairobi. Methods: Data were collected as part of enrolment in the Sex Workers Outreach Program in Nairobi between 2014 and 2017. Prevalence ratios were used to quantify the risk of HIV by high-prevalence counties using modified Poisson regression analyses. Crude and fully adjusted models were fitted to the data. In heterogeneity analyses, hotspots and residences were aggregated to the Nairobi constituency level (n = 17). Inequality in the geographic distribution of HIV prevalence was measured using the Gini coefficient. Results: A total of 11,899 FSWs were included. Overall HIV prevalence was 16%. FSWs originating from a high-prevalence country were at 2-fold increased risk of living with HIV in adjusted analysis (prevalence ratio 1.95; 95% CI: 1.76 to 2.17). HIV prevalence was also highly heterogeneous by hotspot, ranging from 7% to 52% by hotspot (Gini coefficient: 0.37; 95% CI: 0.23 to 0.50). By contrast, the constituency of residence had a Gini coefficient of 0.08 (95% CI: 0.06 to 0.10), suggesting minimal heterogeneity by residence. Conclusion: HIV prevalence in FSWs is heterogeneous by place of work within Nairobi and by county of birth within Kenya. As HIV incidence declines and financial commitments flatline, tailoring interventions to FSWs at highest HIV risk becomes increasingly important.