Effect of Baseline HIV Disease Parameters on CD4+ T Cell Recovery After Antiretroviral Therapy Initiation in Kenyan Women

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.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.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

High prevalence of non-communicable diseases among key populations enrolled at a large HIV prevention & treatment program in Kenya.

INTRODUCTION:People Living with HIV (PLHIV) bear a disproportionate burden of non-communicable diseases (NCDs). Despite their significant toll across populations globally, the NCD burden among key populations (KP) in Kenya remains unknown. The burden of four NCD-categories (cardiovascular diseases, cancer, chronic respiratory diseases and diabetes) was evaluated among female sex workers (FSWs) and men who have sex with men (MSM) at the Sex Workers Outreach Program (SWOP) clinics in Nairobi Kenya. METHODS:A retrospective medical chart review was conducted at the SWOP clinics among KP clients ≥15 years living with HIV enrolled between October 1, 2012 and September 30, 2015. The prevalence of the four NCD-categories were assessed at enrollment and during subsequent routine quarterly follow-up care visits as per the Ministry of Health guidelines. Prevalence at enrollment was determined and distributions of co-morbidities assessed using Chi-square and t-tests as appropriate during follow-up visits. Univariate and multivariate analysis were conducted to identify factors associated with NCD diagnoses. RESULTS:Overall, 1,478 individuals' records were analyzed; 1,392 (94.2%) were from FSWs while 86 (5.8%) were from MSM over the three-year period. FSWs' median age was 35.3 years (interquartile range (IQR) 30.1-41.6) while MSM were younger at 26.8 years (IQR 23.2-32.1). At enrollment into the HIV care program, most KPs (86.6%) were at an early WHO clinical stage (stage I-II) and 1462 (98.9%) were on first-line anti-retroviral therapy (ART). A total of 271, 18.3% (95% CI: 16.4-20.4%), KPs living with HIV had an NCD diagnosis in their clinical chart records during the study period. Majority of these cases, 258 (95.2%) were noted among FSWs. Cardiovascular disease that included hypertension was present in 249/271, 91.8%, of KPs with a documented NCD. Using a proxy of two or more elevated blood pressure readings taken < 12 months apart, prevalence of hypertension rose from 1.0% (95% CI: 0.6-1.7) that was documented in the charts during the first year to 16.3% (95% CI: 14.4-18.3) in the third year. Chronic respiratory disease mainly asthma was present in 16/271, a prevalence of 1.1% (95% CI: 0.6-1.8) in the study population. Cancer in general was detected in 10/271, prevalence of 0.7% (95% CI: 0.3-1.2) over the same period. Interestingly, diabetes was not noted in the study group. Lastly, significant associations between NCD diagnosis with increasing age, body-mass index and CD4 + cell-counts were noted in univariate analysis. However, except for categories of ≥ BMI 30 kg/m2 and age ≥ 45, the associations were not sustained in adjusted risk estimates. CONCLUSION:In Kenya, KP living with HIV and on ART have a high prevalence of NCD diagnoses. Multiple NCD risk factors were also noted against a backdrop of a changing HIV epidemic in the study population. This calls for scaling up focus on both HIV and NCD prevention and care in targeted populations at increased risk of HIV acquisition and transmission. Hence, KP programs could include integrated HIV-NCD screening and care in their guidelines

Geographical associations of HIV prevalence in female sex workers from Nairobi, Kenya (2014-2017)

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). Geo-spatially-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 (SWOP) in Nairobibetween 2014 to 2017. Prevalence ratios (PRs) were used to quantify the risk of HIV by high prevalence counties (HPC) 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 Nairobiconstituency 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 HPC were at 2-fold increased risk of living with HIV in adjusted analysis (PR 1.95, 95% CI: 1.76-2.17). HIVprevalence was also highly heterogeneous by hotspot, ranging from 7% to 52% by hotspot (Gini coefficient: 0.37; 95% CI: 0.23-0.50). In contrast, constituency of residence had a Gini coefficient of 0.08 (95% CI: 0.06-0.10), suggesting minimal heterogeneity by residence. Conclusion: HIV prevalence in FSW 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

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

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

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).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 β-chemokines.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

Distance of selected hot spots from the SWOP City clinic.

<p>Distance of selected hot spots from the SWOP City clinic.</p