Lawrence Gelmon

Effects of a mobile phone short message service on antiretroviral treatment adherence in Kenya (WelTel Kenya1): a randomised trial

BACKGROUND Mobile (cell) phone communication has been suggested as a method to improve delivery of health services. However, data on the effects of mobile health technology on patient outcomes in resource-limited settings are limited. We aimed to assess whether mobile phone communication between health-care workers and patients starting antiretroviral therapy in Kenya improved drug adherence and suppression of plasma HIV-1 RNA load. METHODS WelTel Kenya1 was a multisite randomised clinical trial of HIV-infected adults initiating antiretroviral therapy (ART) in three clinics in Kenya. Patients were randomised (1:1) by simple randomisation with a random number generating program to a mobile phone short message service (SMS) intervention or standard care. Patients in the intervention group received weekly SMS messages from a clinic nurse and were required to respond within 48 h. Randomisation, laboratory assays, and analyses were done by investigators masked to treatment allocation; however, study participants and clinic staff were not masked to treatment. Primary outcomes were self-reported ART adherence (>95% of prescribed doses in the past 30 days at both 6 and 12 month follow-up visits) and plasma HIV-1 viral RNA load suppression (<400 copies per mL) at 12 months. The primary analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT00830622. FINDINGS Between May, 2007, and October, 2008, we randomly assigned 538 participants to the SMS intervention (n=273) or to standard care (n=265). Adherence to ART was reported in 168 of 273 patients receiving the SMS intervention compared with 132 of 265 in the control group (relative risk [RR] for non-adherence 0·81, 95% CI 0·69-0·94; p=0·006). Suppressed viral loads were reported in 156 of 273 patients in the SMS group and 128 of 265 in the control group, (RR for virologic failure 0·84, 95% CI 0·71-0·99; p=0·04). The number needed to treat (NNT) to achieve greater than 95% adherence was nine (95% CI 5·0-29·5) and the NNT to achieve viral load suppression was 11 (5·8-227·3). INTERPRETATION Patients who received SMS support had significantly improved ART adherence and rates of viral suppression compared with the control individuals. Mobile phones might be effective tools to improve patient outcome in resource-limited settings. FUNDING US Presidents Emergency Plan for AIDS Relief.

Characterization of a Human Cervical CD4+ T Cell Subset Coexpressing Multiple Markers of HIV Susceptibility

The HIV pandemic disproportionately affects women, with most infections acquired through receptive vaginal sex. Although the target cells by which HIV establishes infection in the female genital tract remain poorly defined, it is known that immune activation results in CD4+ T cells with enhanced susceptibility, as does expression of the mucosal integrin α4β7 and the HIV coreceptor CCR5. Blood and cervical cytobrush specimens were collected from female sex workers (FSWs) in Nairobi, Kenya. Genital infection diagnostics were performed, T cell populations were defined by multiparameter flow cytometry based on their expression of surface receptors relevant to mucosal homing and/or HIV acquisition, and cytokine production was assayed by intracellular cytokine staining. The integrin α4β7 was expressed on 26.0% of cervical CD4+ T cells, and these cells were more likely to express both the HIV coreceptor CCR5 (p < 0.0001) and the early activation marker CD69 (p < 0.0001) but not CXCR4 (p = 0.34). Cervical Th17 frequencies were enhanced compared with blood (7.02 versus 1.24%; p < 0.0001), and cervical IL-17A+ CD4+ T cells preferentially coexpressed α4β7 and CCR5. Expression of IFN-γ and IL-22 was greater in cervical Th17 cells than in blood Th17 cells. In keeping with the hypothesis that these cells are preferential HIV targets, gp120 preferentially bound CCR5+ cervical T cells, and cervical Th17 cells were almost completely depleted in HIV+ FSWs compared with HIV− FSWs. In summary, a subset of Th17 CD4+ T cells in the cervical mucosa coexpresses multiple HIV susceptibility markers; their dramatic depletion after HIV infection suggests that these may serve as key target cells during HIV transmission.

In-depth analysis of patient-clinician cell phone communication during the WelTel Kenya1 antiretroviral adherence trial.

Background The WelTel Kenya1 trial demonstrated that text message support improved adherence to antiretroviral therapy (ART) and suppression of HIV-1 RNA load. The intervention involved sending weekly messages to patients inquiring how they were doing; participants were required to respond either that they were well or that there was a problem. Objectives 1) Describe problems participants identified through mobile phone support and reasons why participants did not respond to the messages; 2) investigate factors associated with indicating a problem and not responding; and 3) examine participant perceptions of the intervention. Design Secondary analysis of WelTel Kenya1 trial data. Methods Reasons participants indicated a problem or did not respond were extracted from the study log. Negative binomial regression was used to determine participant characteristics associated with indicating a problem and non-response. Data from follow-up questionnaires were used to describe participant perceptions of the intervention. Results Between 2007 and 2009, 271 participants generated 11,873 responses; 377 of which indicated a problem. Health issues were the primary reason for problem responses (72%). Rural residence (adjusted incidence rate ratio [IRR] 1.96; 95%CI 1.19–3.25; p = 0.009 and age were associated with indicating a problem (adjusted IRR 0.63 per increase in age group category; 95%CI 0.50–0.80; p<0.001). Higher educational level was associated with a decreased rate of non-response (adjusted IRR 0.81; 95%CI 0.69–0.94; p = 0.005). Of participants interviewed, 62% (n = 129) stated there were no barriers to the intervention; cell phone issues were the most common barrier. Benefits included reminding patients to take medication and promoting a feeling that “someone cares”. Conclusions The WelTel intervention enabled frequent communication between clinicians and patients during the WelTel Kenya1 trial. Many patients valued the service for the support it provided, with health-related concerns comprising the majority of problems identified by participants. Few sociodemographic characteristics were associated with participant engagement in the intervention.

Estimating the Size of the Female Sex Worker Population in Kenya to Inform HIV Prevention Programming

Background The high burden of HIV infections among female sex workers (FSW) in sub-Saharan Africa has been long recognised, but effective preventive interventions have largely not been taken to scale. We undertook a national geographical mapping exercise in 2011/2012 to assess the locations and population size of FSW in Kenya, to facilitate targeted HIV prevention services for this population. Methods and Findings We used a geographical mapping approach, consisting of interviews with secondary key informants to identify “hot” spots frequented by FSW, their operational dynamics and the estimated numbers of FSW in those spots. This was followed by validation of the estimates through interviews with FSW at each spot identified. The mapping covered Nairobi, the capital city of Kenya, and 50 other major urban centres. In total, 11,609 secondary key informant interviews were conducted to identify FSW spots. Further, a total of 6,360 FSW were interviewed for spot validation purposes. A total of 10,670 spots where FSW congregate were identified. The estimated FSW population in all the towns mapped was 103,298 (range 77,878 to 128, 717). Size estimates in the towns mapped were extended to smaller towns that were not mapped, using a statistical model. The national urban FSW population estimate was 138,420 (range 107, 552 to 169, 288), covering all towns of over 5,000 population. We estimated that approximately 5% of the urban female population of reproductive age in Kenya could be sex workers, which is consistent with previous estimates from other sub-Saharan African countries. Conclusions This study provides the first national level data on the size of the FSW population in Kenya. These data can be used to enhance HIV prevention programme planning and implementation for FSW, to form the basis for impact evaluations, and to improve programme coverage by directing efforts to locations with the greatest need.

High HIV risk in a cohort of male sex workers from Nairobi, Kenya

Objectives Men who have sex with men (MSM) are at high risk of HIV-1 acquisition and transmission, yet there remains limited data in the African context, and for men who sell sex to men (MSM SW) in particular. Methods We enrolled 507 male sex workers in a Nairobi-based prospective cohort study during 2009–2012. All participants were offered HIV/STI screening, counselling and completed a baseline questionnaire. Results Baseline HIV prevalence was 40.0% (95% CI 35.8% to 44.3%). Prevalent HIV infection was associated with age, less postsecondary education, marijuana use, fewer female partners and lower rates of prior HIV testing. Most participants (73%) reported at least two of insertive anal, receptive anal and insertive vaginal sex in the past 3 months. Vaginal sex was reported by 37% of participants, and exclusive MSM status was associated with higher HIV rates. Condom use was infrequent, with approximately one-third reporting 100% condom use during anal sex. HIV incidence was 10.9 per 100 person-years (95% CI 7.4 to 15.6). Predictors of HIV risk included history of urethral discharge (aHR 0.29, 95% CI 0.08 to 0.98, p=0.046), condom use during receptive anal sex (aHR 0.05, 95% CI 0.01 to 0.41, p=0.006) and frequency of sex with male partners (aHR 1.33/sex act, 95% CI 1.01 to 1.75, p=0.04). Conclusions HIV prevalence and incidence were extremely high in Nairobi MSM SW; a combination of interventions including increasing condom use, pre-exposure prophylaxis and access to effective treatment is urgently needed to decrease HIV transmission in this key population.

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 immunosupression (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 Postexposure Prophylaxis In An Urban Population Of Female Sex Workers In Nairobi, Kenya.

Objectives:To assess biological and behavioral factors in HIV-uninfected female sex workers (FSWs) accessing postexposure prophylaxis (PEP) and to characterize the circumstances preceding PEP, time to access, and adherence. Methods:Participants were HIV-uninfected FSWs enrolled in an HIV care and prevention program in Nairobi, Kenya. Those accessing PEP between 2009 and 2010 were enrolled and compared with controls. Multiple logistic regression models were used to compare PEP-related biological and behavioral parameters. Results:PEP users (n = 326) had been involved in sex work for a shorter duration than nonusers [n = 2570; 3.3 vs. 5.1 yrs, AOR: 0.92, 95% confidence interval (CI): 0.89 to 0.95] and were less likely to report a regular partner (54.9% vs. 72.5%, AOR: 0.52, 0.39 to 0.68). PEP use was associated with gonorrhea infection (6.9% vs. 2.6%, AOR: 2.37, 95% CI: 1.34 to 4.21) and alcohol use (84.3% vs. 76.1%, AOR: 1.58, 95% CI: 1.09 to 2.31), but with increased condom use (85.1% vs. 68.2%, AOR 1.80, 95% CI: 1.38-2.35) and a history of prior HIV testing (89.2 vs. 76.2%, AOR: 2.22, 95% CI: 1.45 to 3.40). Reasons for PEP access centered on issues of client mistrust. The median time from exposure to PEP was 18 hours, with an estimated adherence of 49%. Precise PEP efficacy could not be calculated, but HIV incidence was 0.6% in users (2/326) compared with 2.1% (30/1417) in nonusers (Cox regression P = 0.35). Conclusions:“PEP services were accessed by 10% of FSWs during the study period and were not implicated in any incident HIV cases.” Users had indicators of increased sexual risk and higher health care literacy. Increasing PEP access and compliance in FSWs may be an important HIV prevention strategy.

How I Wish This Thing Was Initiated 100 Years Ago! Willingness to Take Daily Oral Pre-Exposure Prophylaxis among Men Who Have Sex with Men in Kenya.

Background The MSM population in Kenya contributes to 15% of HIV incidence. This calls for innovative HIV prevention interventions. Pre-exposure prophylaxis (PrEP) has been efficacious in preventing HIV among MSM in trials. There is limited data on the willingness to take daily oral PrEP in sub-Sahara Africa. PrEP has not been approved for routine use in most countries globally. This study aimed to document the willingness to take PrEP and barriers to uptake and adherence to PrEP in Kenya. The findings will inform the design of a PrEP delivery program as part of the routine HIV combination prevention. Methods Eighty MSM were recruited in 2 Counties in December 2013. Quantitative data on sexual behaviour and willingness to take PrEP were collected using semi-structured interviews and analysed using SPSS. Qualitative data on knowledge of PrEP, motivators and barriers to uptake and adherence to PrEP were collected using in-depth interviews and FGDs and analysed using Nvivo. Analysis of data in willingness to take PrEP was conducted on the HIV negative participants (n = 55). Results 83% of MSM were willing to take daily oral HIV PrEP. Willingness to take PrEP was higher among the bi-sexual and younger men. Motivators for taking PrEP were the need to stay HIV negative and to protect their partners. History of poor medication adherence, fear of side effects and HIV stigma were identified as potential barriers to adherence. Participants were willing to buy PrEP at a subsidized price. Conclusions There is willingness to take PrEP among MSM in Kenya and there is need to invest in targeted education and messaging on PrEP to enhance adherence, proper use and reduce stigma in the general population and among policy makers.

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 areas 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.

PrEP for key populations in combination HIV prevention in Nairobi: a mathematical modelling study

BACKGROUND The HIV epidemic in the population of Nairobi as a whole is in decline, but a concentrated sub-epidemic persists in key populations. We aimed to identify an optimal portfolio of interventions to reduce HIV incidence for a given budget and to identify the circumstances in which pre-exposure prophylaxis (PrEP) could be used in Nairobi, Kenya. METHODS A mathematical model was developed to represent HIV transmission in specific key populations (female sex workers, male sex workers, and men who have sex with men [MSM]) and among the wider population of Nairobi. The scale-up of existing interventions (condom promotion, antiretroviral therapy, and male circumcision) for key populations and the wider population as have occurred in Nairobi is represented. The model includes a detailed representation of a PrEP intervention and is calibrated to prevalence and incidence estimates specific to key populations and the wider population. FINDINGS In the context of a declining epidemic overall but with a large sub-epidemic in MSM and male sex workers, an optimal prevention portfolio for Nairobi should focus on condom promotion for male sex workers and MSM in particular, followed by improved antiretroviral therapy retention, earlier antiretroviral therapy, and male circumcision as the budget allows. PrEP for male sex workers could enter an optimal portfolio at similar levels of spending to when earlier antiretroviral therapy is included; however, PrEP for MSM and female sex workers would be included only at much higher budgets. If PrEP for male sex workers cost as much as US