Declines in HIV prevalence in female sex workers accessing an HIV treatment and prevention programme in Nairobi, Kenya over a 10-year period.

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.

Clade-specific evolution mediated by HLA-B*57/5801 in human immunodeficiency virus type 1 clade A1 p24.

HLA-B*57-mediated selection pressure leads to a typical escape pathway in human immunodeficiency virus type 1 (HIV-1) CD8 epitopes such as TW10. Whether this T242N pathway is shared by all clades remains unknown. We therefore assessed the nature of HLA-B*57 selection in a large, observational Kenyan cohort where clades A1 and D predominate. While T242N was ubiquitous in clade D HLA-B*57(+) subjects, this mutation was rare (15%) in clade A1. Instead, P243T and I247L were selected by clade A1-infected HLA-B*57 subjects but not by HLA-B*5801(+) subjects. Our data suggest that clade A1 consensus proline at Gag residue 243 might represent an inherent block to T242N escape in clade A1. We confirmed immunologically that P243T and I247L likely represent escape mutations. HLA-B*57 evolution also differed between clades in the KF11 and IW9 epitopes. A better understanding of clade-specific evolution is important for the development of HIV vaccines in regions with multiple clades.

Enumeration of sex workers in the central business district of Nairobi, Kenya.

Accurate program planning for populations most at risk for HIV/STI acquisition requires knowledge of the size and location where these populations can best be reached. To obtain this information for sex workers operating at 137 hotspots in the central business district (CBD) in Nairobi, Kenya, we utilized a combined mapping and capture-recapture enumeration exercise. The majority of identified hotspots in this study were bars. Based on this exercise, we estimate that 6,904 male and female sex workers (95% confidence intervals, 6690 and 7118) were working nightly in the Nairobi CBD in April 2009. Wide ranges of captures per spot were obtained, suggesting that relatively few hot spots (18%) contain a relatively high proportion of the area's sex workers (65%). We provide geographic data including relatively short distances from hotspots to our dedicated sex worker outreach program in the CBD (mean<1 km), and clustering of hotspots within a relatively small area. Given the size covered and areas where sex work is likely taking place in Nairobi, the estimate is several times lower than what would be obtained if the entire metropolitan area was enumerated. These results have important practical and policy implications for enhancing HIV/STI prevention efforts.

Does antiretroviral therapy initiation increase sexual risk taking in Kenyan female sex workers? A retrospective case-control study.

OBJECTIVES: Although antiretroviral therapy (ART) prolongs life and reduces infectiousness, in some contexts, it has been associated with increased sexual risk taking. DESIGN: Retrospective case-control study. SETTING: Nairobi-based dedicated female sex worker (FSW) clinic. PARTICIPANTS: HIV-infected FSWs before and after ART initiation (n=62); HIV-infected and -uninfected control FSWs not starting ART during the same follow-up period (n=40). INTERVENTION: Initiation of ART. PRIMARY OUTCOME MEASURES: Self-reported condom use, client numbers and sexually transmitted infection incidence over the study period (before and after ART initiation in cases). RESULTS: Sexual risk-taking behaviour with casual clients did not increase after ART initiation; condom use increased and sexually transmitted infection incidence decreased in both cases and controls, likely due to successful cohort-wide HIV prevention efforts. CONCLUSIONS: ART provision was not associated with increases in unsafe sex in this FSW population.

HIV-1 clade D is associated with increased rates of CD4 decline in a Kenyan cohort.

HIV-1 is grouped phylogenetically into clades, which may impact rates of HIV-1 disease progression. Clade D infection in particular has been shown to be more pathogenic. Here we confirm in a Nairobi-based prospective female sex worker cohort (1985-2004) that Clade D (n = 54) is associated with a more rapid CD4 decline than clade A1 (n = 150, 20.6% vs 13.4% decline per year, 1.53-fold increase, p = 0.015). This was independent of "protective" HLA and country of origin (p = 0.053), which in turn were also independent predictors of the rate of CD4 decline (p = 0.026 and 0.005, respectively). These data confirm that clade D is more pathogenic than clade A1. The precise reason for this difference is currently unclear, and requires further study. This is first study to demonstrate difference in HIV-1 disease progression between clades while controlling for protective HLA alleles.

Blunted IL17/IL22 and pro-inflammatory cytokine responses in the genital tract and blood of HIV-exposed, seronegative female sex workers in Kenya.

BACKGROUND: Identifying the immune correlates of reduced susceptibility to HIV remains a key goal for the HIV vaccine field, and individuals who are HIV-exposed, seronegative (HESN) may offer important clues. Reduced systemic immune activation has been described in HESN individuals. Conversely, pro-inflammatory T cell subsets, particularly CD4+ T cells producing the cytokine IL17 (Th17 cells), may represent a highly susceptible target for HIV infection after sexual exposure. Therefore, we characterized the cellular pro-inflammatory and IL17/IL22 cytokine immune milieu in the genital mucosa and blood of HESN female sex workers (FSWs). METHODS AND RESULTS: Blinded lab personnel characterized basal and mitogen-induced gene and cytokine immune responses in the cervix and blood of HESN FSWs (n = 116) and non-FSW controls (n = 17) using qPCR and ELISA. IL17 and IL22 production was significantly reduced in both the cervix and blood of HESNs, both in resting cells and after mitogen stimulation. In addition, HESN participants demonstrated blunted production of both pro-inflammatory cytokines and ß-chemokines. DISCUSSION AND CONCLUSIONS: We conclude that HIV exposure without infection was associated with blunted IL17/IL22 and pro-inflammatory responses, both systemically and at the site of mucosal HIV exposure. It will be important for further studies to examine the causal nature of the association and to define the cell subsets responsible for these differences.

Effect of baseline HIV disease parameters on CD4+ T cell recovery after antiretroviral therapy initiation in Kenyan women.

BACKGROUND: Antiretroviral therapy (ART) for HIV infection reconstitutes the immune system and improves survival. However, the rate and extent of CD4+ T cell recovery varies widely. We assessed the impact of several factors on immune reconstitution in a large Kenyan cohort. METHODOLOGY/PRINCIPAL FINDINGS: HIV-infected female sex workers from a longitudinal cohort, with at least 1 year of pre-ART and 6 months of post-ART follow-up (n = 79), were enrolled in the current study. The median pre-ART follow-up was 4,040 days. CD4 counts were measured biannually and viral loads where available. The median CD4 count at ART initiation was 180 cells/ul, which increased to 339 cells/ul at the most recent study visit. The rate of CD4+ T cell increase on ART was 7.91 cells/month (mean = 13, range -25.92 to 169.4). LTNP status prior to ART initiation did not associate with the rate of CD4 recovery on ART. In univariate analyses, associations were observed for CD4 recovery rate and duration of pre-ART immunosuppression (r = -0.326, p = 0.004) and CD4 nadir (r = 0.284, p = 0.012). In multivariate analysis including age, CD4 nadir, duration of HIV infection, duration of pre-ART immunosuppression, and baseline viral load, only CD4 nadir (p = 0.007) and not duration of immunosuppression (p = 0.87) remained significantly associated with the rate of CD4 recovery. CONCLUSIONS/SIGNIFICANCE: These data suggest that prior duration of immune suppression does not predict subsequent recovery once ART is initiated and confirm the previous observation that the degree of CD4 depletion prior to ART initiation is the most important determinant of subsequent immune reconstitution.

HIV viral set point and host immune control in individuals with HIV-specific CD8+ T-cell responses prior to HIV acquisition.

OBJECTIVE: Vaccine-induced CD8(+) T-cell responses in primates have been associated with a reduced simian immunodeficiency virus plasma viral load and enhanced T-cell responses, but cellular vaccines have shown limited success in human trials. We previously described HIV-specific T-cell responses in two groups of highly exposed, persistently seronegative Kenyan female sex workers, and a subset of these participants have subsequently acquired HIV. We examined the impact of pre-existing CD8(+) T-cell responses on post-acquisition outcomes. DESIGN AND METHODS: HIV-specific CD8(+) T-cell responses had been examined in highly exposed, persistently seronegative participants from the Pumwani and Kibera cohorts, using a combination of virus-specific lysis, proliferation, interferon-gamma production, or all. Plasma viral load set point and HIV-specific T-cell proliferation and cytokine production were now examined post hoc by blinded investigators in the subset of participants who acquired HIV. RESULTS: Pre-acquisition cellular immune assays and post-infection viral load were available for 46 participants, and HIV-specific CD8(+) T-cell responses had been detected in 25 of 46 (54%) participants. Pre-acquisition CD8(+) T-cell responses were associated with a lower post-acquisition HIV viral load set point in both cohorts (pooled analysis, 3.1 vs. 4.1 log(10) RNA copies/ml; P=0.0002) and with enhanced post-acquisition HIV-specific CD8(+) T-cell proliferation (3.8 vs. 1.0%, P=0.03), but with a trend to reduced post-acquisition CD8(+) T-cell interferon-gamma responses. CONCLUSION: HIV-specific CD8(+) T-cell responses prior to HIV acquisition were associated with a lower HIV viral load and an altered functional profile of post-acquisition CD8(+) T-cell responses.

Reduced rates of HIV acquisition during unprotected sex by Kenyan female sex workers predating population declines in HIV prevalence.

OBJECTIVES: Female sex workers (FSWs) form a core group at high risk of both sexual HIV acquisition and secondary transmission. The magnitude of these risks may vary by sexual risk taking, partner HIV prevalence, host immune factors and genital co-infections. We examined temporal trends in HIV prevalence and per-act incidence, adjusted for behavioral and other variables, in FSWs from Nairobi, Kenya. METHODS: An open cohort of FSWs followed since 1985. Behavioral and clinical data were collected six monthly from 1985 to 2005, and sexually transmitted infection (STI) diagnostics and HIV serology performed. A Cox proportional hazards model with time-dependent covariables was used to estimate infection risk as a function of calendar time. RESULTS: HIV prevalence in new FSW enrollees peaked at 81% in 1986, and was consistently below 50% after 1997. Initially uninfected FSWs remained at high risk of acquiring HIV throughout the study period, but the rate of HIV acquisition during unprotected sex with a casual client declined by over four-fold. This reduction correlated closely with decreases in gonorrhea prevalence, and predated reductions in the Kenyan HIV population prevalence by over a decade. CONCLUSIONS: The per-act rate of HIV acquisition in high-risk Nairobi FSWs fell dramatically between 1985 and 2005. This decline may represent the impact of improved STI prevention/therapy, immunogenetic shifts in at-risk women, or changes in the proportion of HIV exposures occurring with clients who had acute HIV infection. Declining HIV incidence in high-risk cohorts may predict and/or be causally related to future reductions in population prevalence.