Immunogenicity and safety of fractional doses of 17D-213 yellow fever vaccine in HIV-infected people in Kenya (YEFE): a randomised, double-blind, non-inferiority substudy of a phase 4 trial.

BACKGROUND: Evidence indicates that fractional doses of yellow fever vaccine are safe and sufficiently immunogenic for use during yellow fever outbreaks. However, there are no data on the generalisability of this observation to populations living with HIV. Therefore, we aimed to evaluate the immunogenicity of fractional and standard doses of yellow fever vaccine in HIV-positive adults. METHODS: We conducted a randomised, double-blind, non-inferiority substudy in Kilifi, coastal Kenya to compare the immunogenicity and safety of a fractional dose (one-fifth of the standard dose) versus the standard dose of 17D-213 yellow fever vaccine among HIV-positive volunteers. HIV-positive participants aged 18-59 years, with baseline CD4+ T-cell count of at least 200 cells per mL, and who were not pregnant, had no previous history of yellow fever vaccination or infection, and had no contraindication for yellow fever vaccination were recruited from the community. Participants were randomly assigned 1:1 in blocks (variable block sizes) to either a fractional dose or a standard dose of the 17D-213 yellow fever vaccine. Vaccines were administered subcutaneously by an unblinded nurse and pharmacist; all other study personnel were blinded to the vaccine allocation. The primary outcome of the study was the proportion of participants who seroconverted by the plaque reduction neutralisation test (PRNT50) 28 days after vaccination for the fractional dose versus the standard dose in the per-protocol population. Secondary outcomes were assessment of adverse events and immunogenicity during the 1-year follow-up period. Participants were considered to have seroconverted if the post-vaccination antibody titre was at least 4 times greater than the pre-vaccination titre. We set a non-inferiority margin of not less than a 17% decrease in seroconversion in the fractional dose compared with the standard dose. This study is registered with ClinicalTrials.gov, NCT02991495. FINDINGS: Between Jan 29, 2019, and May 17, 2019, 303 participants were screened, and 250 participants were included and vaccinated; 126 participants were assigned to the fractional dose and 124 to the standard dose. 28 days after vaccination, 112 (96%, 95% CI 90-99) of 117 participants in the fractional dose group and 115 (98%, 94-100) of 117 in the standard dose group seroconverted by PRNT50. The difference in seroconversion between the fractional dose and the standard dose was -3% (95% CI -7 to 2). Fractional dosing therefore met the non-inferiority criterion, and non-inferiority was maintained for 1 year. The most common adverse events were headache (n=31 [12%]), fatigue (n=23 [9%]), myalgia (n=23 [9%]), and cough (n=14 [6%]). Reported adverse events were either mild (182 [97%] of 187 adverse events) or moderate (5 [3%]) and were self-limiting. INTERPRETATION: Fractional doses of the 17D-213 yellow fever vaccine were sufficiently immunogenic and safe demonstrating non-inferiority to the standard vaccine dose in HIV-infected individuals with CD4+ T cell counts of at least 200 cells per mL. These results provide confidence that fractional dose recommendations are applicable to populations with high HIV prevalence. FUNDING: Wellcome Trust, Médecins Sans Frontières Foundation, and the UK Department for International Development.

Stopping and restarting PrEP and loss to follow-up among PrEP-taking men who have sex with men and transgender women at risk of HIV-1 participating in a prospective cohort study in Kenya.

OBJECTIVE: To assess frequency and predictors of switching between being on and off PrEP and being lost to follow-up (LTFU) among men who have sex with men (MSM) and transgender women (TGW) with access to PrEP services in Sub-Saharan Africa. METHODS: This was a prospective cohort study of MSM and TGW from coastal Kenya who initiated daily oral PrEP from June 2017 to June 2019. Participants were followed monthly for HIV-1 testing, PrEP refill, risk assessment and risk reduction counselling. Follow-up was censored at the last visit before 30 June 2019, or the last HIV-1-negative visit (for those with HIV-1 seroconversion), whichever occurred first. We estimated transition intensities (TI) and predictors of switching: (i) between being off and on PrEP; and (ii) from either PrEP state and being LTFU (i.e. not returning to the clinic for > 90 days) using a multi-state Markov model. RESULTS: In all, 134 participants starting PrEP were followed for a median of 20.3 months [interquartile range (IQR): 7.7-22.1]. A total of 49 (36.6%) people stopped PrEP 73 times [TI = 0.6/person-year (PY), 95% confidence interval (CI): 0.5-0.7] and, of these, 25 (51.0%) restarted PrEP 38 times (TI = 1.2/PY, 95% CI: 0.9-1.7). In multivariable analysis, stopping PrEP was related to anal sex ≤ 3 months, substance-use disorder and travelling. Restarting PrEP was related to non-Christian or non-Muslim religion and travelling. A total of 54 participants were LTFU: on PrEP (n = 47, TI = 0.3/PY, 95% CI: 0.3-0.5) and off PrEP (n = 7, TI = 0.2/PY, 95% CI: 0.1-0.4). In multivariable analysis, becoming LTFU while on PrEP was associated with secondary education or higher, living in the area for ≤ 1 year, residence outside the immediate clinic area and alcohol-use disorder. CONCLUSIONS: Switching between being on and off PrEP or becoming LTFU while on PrEP was frequent among individuals at risk of HIV-1 acquisition. Alternative PrEP options (e.g. event-driven PrEP) may need to be considered for MSM and TGW with PrEP-taking challenges, while improved engagement with care is needed for all MSM and TGW regardless of PrEP regimen.

PrEP uptake and adherence in relation to HIV-1 incidence among Kenyan men who have sex with men.

BACKGROUND: Data on HIV-1 incidence following programmatic pre-exposure prophylaxis (PrEP) uptake by men who have sex with men (MSM) are limited in sub-Saharan Africa. METHODS: Since June 2017, MSM participating in an ongoing cohort study in Kenya were offered daily PrEP, assessed for PrEP uptake and adherence, and evaluated for HIV-1 acquisition monthly. We determined tenofovir-diphosphate (TFV-DP) concentrations in dried blood spots 6-12 months after PrEP initiation, and tenofovir (TFV) concentrations and genotypic drug resistance in plasma samples when HIV-1 infection occurred. We assessed HIV-1 incidence by reported PrEP use. FINDINGS: Of 172 MSM, 170 (98·8%) were eligible for PrEP, 140 (82·4%) started it, and 64 (57·7%) reported PrEP use at end of study. Of nine MSM who acquired HIV-1 [incidence rate: 3·9 (95% confidence interval (CI), 2·0-7·4) per 100 person-years (PY)], five reported PrEP use at the time of HIV-1 acquisition [incidence rate: 3·6 (95% CI, 1·5-8·6) per 100 PY)] and four had stopped or had never started PrEP [incidence rate: 4·3 (95% CI, 1·6-11·3) per 100 PY]. Among 76 MSM who reported PrEP use, 11 (14·5%) had protective TFV-DP concentrations of ≥700 fmol/punch (≥4 tablets a week). Among the five MSM who acquired HIV-1 while reporting PrEP use, only one had detectable but low TFV concentrations in plasma and none had genotypic HIV-1 resistance. INTERPRETATION: HIV-1 incidence among MSM with access to programmatic PrEP was high and did not differ by reported PrEP use. Only one in seven MSM taking PrEP had protective tenofovir concentrations and four out of five MSM who acquired HIV-1 while reporting PrEP use had not taken it. Strengthened PrEP adherence support is required among MSM in Kenya. FUNDING: This work was supported by the International AIDS Vaccine Initiative (IAVI).

Risk factors for loss to follow-up among at-risk HIV negative men who have sex with men participating in a research cohort with access to pre-exposure prophylaxis in coastal Kenya.

INTRODUCTION: Retention in preventive care among at-risk men who have sex with men (MSM) is critical for successful prevention of HIV acquisition in Africa. We assessed loss to follow-up (LTFU) rates and factors associated with LTFU in an HIV vaccine feasibility cohort study following MSM with access to pre-exposure prophylaxis (PrEP) in coastal Kenya. METHODS: Between June 2017 and June 2019, MSM cohort participants attending a research clinic 20 km north of Mombasa were offered daily PrEP and followed monthly for risk assessment, risk reduction counselling and HIV testing. Participants were defined as LTFU if they were late by >90 days for their scheduled appointment. Participants who acquired HIV were censored at diagnosis. Cox proportional hazards models were used to estimate adjusted Hazard Ratio (aHR) of risk factors for LTFU. RESULTS AND DISCUSSION: A total of 179 participants with a median age of 25.0 years (interquartile range [IQR]: 23.0 to 30.0) contributed a median follow-up time of 21.2 months (IQR: 6.5 to 22.1). Of these, 143 (79.9%) participants started PrEP and 76 (42.5%) MSM were LTFU, for an incidence rate of 33.7 (95% confidence interval [CI], 26.9 to 42.2) per 100 person-years. Disordered alcohol use (aHR: 2.3, 95% CI, 1.5 to 3.7), residence outside the immediate clinic catchment area (aHR: 2.5, 95% CI, 1.3 to 4.6 for Mombasa Island; aHR: 1.8, 95% CI, 1.0 to 3.3 for south coast), tertiary education level or higher (aHR: 2.3, 95% CI, 1.1 to 4.8) and less lead-in time in the cohort prior to 19 June 2017 (aHR: 3.1, 95% CI, 1.8 to 5.6 for zero to three months; aHR: 2.4, 95% CI, 1.2 to 4.7 for four to six months) were independent predictors of LTFU. PrEP use did not differ by LTFU status (HR: 1.0, 95% CI, 0.6 to 1.5). Psychosocial support for men reporting disordered alcohol use, strengthened engagement of recently enrolled participants and focusing recruitment on areas close to the research clinic may improve retention in HIV prevention studies involving MSM in coastal Kenya. CONCLUSIONS: About one in three participants became LTFU after one year of follow-up, irrespective of PrEP use. Research preparedness involving MSM should be strengthened for HIV prevention intervention evaluations in coastal Kenya.

Assessment of PrEP eligibility and uptake among at-risk MSM participating in a HIV-1 vaccine feasibility cohort in coastal Kenya.

Introduction: Pre-exposure prophylaxis (PrEP) is provided free of costs to at-risk populations in Kenya, including men who have sex with men (MSM), but anal intercourse is not an eligibility criterion. We set out to determine PrEP eligibility, uptake and predictors of PrEP uptake among MSM enrolled in an HIV-1 vaccine feasibility cohort in coastal Kenya. Methods: We compared the number of MSM identified as eligible for PrEP from June-December 2017 by Kenyan Ministry of Health (MoH) criteria, which do not include reported anal intercourse, to those identified as eligible by a published MSM cohort-derived HIV-1 risk score (CDHRS). We determined PrEP uptake and assessed factors associated with uptake at first offer among eligible MSM followed up monthly. Results: Out of 167 MSM assessed for PrEP eligibility, 118 (70.7%) were identified by both MoH and CDHRS eligibility criteria; 33 (19.8%) by CDHRS alone, 11 (6.6%) by MoH criteria alone, and 5 (3.0%) by neither criterion. Of the men identified by CDHRS alone, the majority (24 or 72.7%) reported receptive anal intercourse (RAI). Of the 162 MSM eligible for PrEP, 113 (69.7%) accepted PrEP at first offer. Acceptance of PrEP was higher for men reporting RAI (adjusted prevalence ratio [aPR], 1.4; 95% confidence interval [CI], 1.0-1.9), having paid for sex (aPR, 1.3; 95% CI, 1.1-1.6) and group sex (aPR, 1.4; 95% CI, 1.1-1.8), after adjustment for sociodemographic factors. Conclusions: Assessing PrEP eligibility using the CDHRS identified 20% more at-risk MSM for PrEP initiation than when Kenyan MoH criteria were used. Approximately 70% of eligible men accepted PrEP at first offer, suggesting that PrEP is acceptable among at-risk MSM. MSM reporting RAI, group sex, or paying for sex were more likely to accept PrEP. Incorporating RAI into MoH PrEP eligibility criteria would enhance the impact of PrEP programming in Kenya.

HIV-1 subtype diversity, transmission networks and transmitted drug resistance amongst acute and early infected MSM populations from Coastal Kenya.

BACKGROUND: HIV-1 molecular epidemiology amongst men who have sex with men (MSM) in sub-Saharan Africa remains not well characterized. We aimed to determine HIV-1 subtype distribution, transmission clusters and transmitted drug resistance (TDR) in acute and early infected MSM from Coastal Kenya. METHODS: Analysis of HIV-1 partial pol sequences from MSM recruited 2005-2017 and sampled within six months of the estimated date of infection. Volunteers were classified as men who have sex with men exclusively (MSME) or with both men and women (MSMW). HIV-1 subtype and transmission clusters were determined by maximum-likelihood phylogenetics. TDR mutations were determined using the Stanford HIV drug resistance database. RESULTS: Of the 97 volunteers, majority (69%) were MSMW; 74%, 16%, 9% and 1% had HIV-1 subtypes A1, D, C or G, respectively. Overall, 65% formed transmission clusters, with substantial mixing between MSME and MSMW. Majority of volunteer sequences were either not linked to any reference sequence (56%) or clustered exclusively with sequences of Kenyan origin (19%). Eight (8% [95% CI: 4-16]) had at least one TDR mutation against nucleoside (n = 2 [2%]) and/or non-nucleoside (n = 7 [7%]) reverse transcriptase inhibitors. The most prevalent TDR mutation was K103N (n = 5), with sequences forming transmission clusters of two and three taxa each. There were no significant differences in HIV-1 subtype distribution and TDR between MSME and MSMW. CONCLUSIONS: This HIV-1 MSM epidemic was predominantly sub-subtype A1, of Kenyan origin, with many transmission clusters and having intermediate level of TDR. Targeted HIV-1 prevention, early identification and care interventions are warranted to break the transmission cycle amongst MSM from Coastal Kenya.

An Empiric Risk Score to Guide PrEP Targeting Among MSM in Coastal Kenya.

Men who have sex with men (MSM), who have heterogeneous HIV-acquisition risks are not specifically targeted in Kenyan pre-exposure prophylaxis (PrEP) guidelines. We used data from an open cohort, which followed 753 initially HIV-negative MSM participants for more than 1378.5 person-years, to develop an empiric risk score for targeting PrEP delivery. Independent predictors of incident HIV-1 infection in this cohort were an age of 18-24 years, having only male sex partners, having receptive anal intercourse, having any unprotected sex, and having group sex. Poisson model coefficients were used to assign a numeric score to each statistically significant predictor. A risk score of ≥ 1 corresponded to an HIV-1 incidence of ≥ 2.2 [95% confidence interval (CI) 1.2-4.1] and identified 81.3% of the cohort participants as being at high risk for HIV-1 acquisition. The area under the receiver operating characteristic curve was 0.76 (95% CI 0.71-0.80). This empiric risk score may help Kenyan health care providers to assess HIV-1 acquisition risk and encourage PrEP uptake by high-risk MSM.

Dengue and Chikungunya Virus Infections among Young Febrile Adults Evaluated for Acute HIV-1 Infection in Coastal Kenya.

BACKGROUND: Fever is common among patients seeking care in sub-Saharan Africa (sSA), but causes other than malaria are rarely diagnosed. We assessed dengue and chikungunya virus infections among young febrile adults evaluated for acute HIV infection (AHI) and malaria in coastal Kenya. METHODS: We tested plasma samples obtained in a cross-sectional study from febrile adult patients aged 18-35 years evaluated for AHI and malaria at urgent care seeking at seven health facilities in coastal Kenya in 2014-2015. Dengue virus (DENV) and chikungunya virus (CHIKV) were amplified using quantitative real-time reverse-transcription polymerase chain reaction. We conducted logistic regression analyses to determine independent predictors of dengue virus infection. RESULTS: 489 samples that were negative for both AHI and malaria were tested, of which 43 (8.8%, 95% confidence interval [CI]: 6.4-11.7) were positive for DENV infection. No participant was positive for CHIKV infection. DENV infections were associated with clinic visits in the rainy season (adjusted odds ratio (AOR) = 3.0, 95% CI: 1.3-6.5) and evaluation at a private health facility (AOR 5.2, 95% CI: 2.0-13.1) or research health facility (AOR = 25.6, 95% CI: 8.9-73.2) instead of a public health facility. CONCLUSION: A high prevalence of DENV infections was found in febrile young adult patients evaluated for AHI. Our data suggests that DENV, along with AHI and malaria, should be considered in the differential diagnosis of the adult patient seeking care for fever in coastal Kenya.

Effect of Text Message, Phone Call, and In-Person Appointment Reminders on Uptake of Repeat HIV Testing among Outpatients Screened for Acute HIV Infection in Kenya: A Randomized Controlled Trial.

BACKGROUND: Following HIV-1 acquisition, many individuals develop an acute retroviral syndrome and a majority seek care. Available antibody testing cannot detect an acute HIV infection, but repeat testing after 2-4 weeks may detect seroconversion. We assessed the effect of appointment reminders on attendance for repeat HIV testing. METHODS: We enrolled, in a randomized controlled trial, 18-29 year old patients evaluated for acute HIV infection at five sites in Coastal Kenya (ClinicalTrials.gov NCT01876199). Participants were allocated 1:1 to either standard appointment (a dated appointment card) or enhanced appointment (a dated appointment card plus SMS and phone call reminders, or in-person reminders for participants without a phone). The primary outcome was visit attendance, i.e., the proportion of participants attending the repeat test visit. Factors associated with attendance were examined by bivariable and multivariable logistic regression. PRINCIPAL FINDINGS: Between April and July 2013, 410 participants were randomized. Attendance was 41% (85/207) for the standard group and 59% (117/199) for the enhanced group, for a relative risk of 1.4 [95% Confidence Interval, CI, 1.2-1.7].Higher attendance was independently associated with older age, study site, and report of transactional sex in past month. Lower attendance was associated with reporting multiple partners in the past two months. CONCLUSIONS: Appointment reminders through SMS, phone calls and in-person reminders increased the uptake of repeat HIV test by forty percent. This low-cost intervention could facilitate detection of acute HIV infections and uptake of recommended repeat testing. TRIAL REGISTRATION: Clinicaltrials.gov NCT01876199.

Prevalence, Incidence, and Clearance of Anogenital Warts in Kenyan Men Reporting High-Risk Sexual Behavior, Including Men Who Have Sex With Men.

Background. Human papillomavirus (HPV) causes a spectrum of disease, ranging from warts to cancer. Prevalence, incidence, and factors associated with anogenital warts in East African men are unknown. Methods. Kenyan men reporting high-risk sexual behavior were inspected for anogenital warts at enrollment and follow-up visits. Logistic regression was performed to identify associations with anogenital warts at baseline. Cox regression was performed to analyze predictors of incident anogenital warts, and Kaplan-Meier curves were used to estimate clearance. Results. Baseline anogenital wart prevalence in 1137 men was 2.9% (95% confidence interval [CI], 2.0%-4.0%) overall, 2.0% in human immunodeficiency virus (HIV)-uninfected men, and 9.4% in HIV-1-infected men (adjusted odds ratio, 5.43; 95% CI, 2.03-11.29). Over a median of 1.4 years, anogenital wart incidence among 1104 men was 5.3 (95% CI, 4.3-6.5) per 100 person-years. Having HIV-1 infection at baseline (adjusted hazard ratio [aHR], 1.66; 95% CI, 1.01-2.72) or a genital syndrome during follow-up (aHR, 4.78; 95% CI, 3.03-7.56) was associated with increased wart incidence. Wart clearance was lower in HIV-1-infected men (log-rank P<.001). Conclusions. Anogenital wart prevalence and incidence were increased in HIV-1-infected men, and anogenital warts co-occurred with other genital syndromes. Quadrivalent HPV vaccination should be recommended for young men in settings with high HIV-1 prevalence.

Engaging young adult clients of community pharmacies for HIV screening in Coastal Kenya: a cross-sectional study.

BACKGROUND: Adults in developing countries frequently use community pharmacies as the first and often only source of care. The objective of this study was to assess the success of pharmacy referrals and uptake of HIV testing by young adult clients of community pharmacies in the context of a screening programme for acute HIV-1 infection (AHI). METHODS: We requested five pharmacies to refer clients meeting predefined criteria (ie, 18-29 years of age and requesting treatment for fever, diarrhoea, sexually transmitted infection (STI) symptoms or body pains) for HIV-1 testing and AHI screening at selected clinics. Using multivariable logistical regression, we determined client characteristics associated with HIV-1 test uptake. RESULTS: From February through July 2013, 1490 pharmacy clients met targeting criteria (range of weekly averages across pharmacies: 4-35). Of these, 1074 (72%) accepted a referral coupon, 377 (25%) reported at a study clinic, 353 (24%) were HIV-1 tested and 127 (9%) met criteria for the AHI study. Of those tested, 14 (4.0%) were HIV-1 infected. Test uptake varied significantly by referring pharmacy and was higher for clients who presented at the pharmacy without a prescription versus those with a prescription, and for clients who sought care for STI symptoms. CONCLUSIONS: About a quarter of targeted pharmacy clients took up HIV-1 testing. Clients seeking care directly at the pharmacy (ie, without a prescription) and those with STI symptoms were more likely to take up HIV-1 testing. Engagement of adult pharmacy clients for HIV-1 screening may identify undiagnosed individuals and offers opportunities for HIV-1 prevention research.

Diagnosing acute and prevalent HIV-1 infection in young African adults seeking care for fever: a systematic review and audit of current practice.

Fever is a common complaint in HIV-1 infected adults and may be a presenting sign of acute HIV-1 infection (AHI). We investigated the extent to which HIV-1 infection was considered in the diagnostic evaluation of febrile adults in sub-Saharan Africa (SSA) through a systematic review of published literature and guidelines in the period 2003-2014. We also performed a detailed audit of current practice for the evaluation of febrile young adults in coastal Kenya. Our review identified 43 studies investigating the aetiology of fever in adult outpatients in SSA. While the guidelines identified recommend testing for HIV-1 infection, none mentioned AHI. In our audit of current practice at nine health facilities, only 189 out of 1173 (16.1%) patients, aged 18-29 years, were tested for HIV-1. In a detailed record review, only 2 out of 39 (5.1%) young adults seeking care for fever were tested for HIV-1, and the possibility of AHI was not mentioned. Available literature on adult outpatients presenting with fever is heavily focused on diagnosing malaria and guidelines are poorly defined in terms of evaluating aetiologies other than malaria. Current practice in coastal Kenya shows poor uptake of provider-initiated HIV-1 testing and AHI is not currently considered in the differential diagnosis.

Acute HIV-1 infection is as common as malaria in young febrile adults seeking care in coastal Kenya.

BACKGROUND: Febrile adults are usually not tested for acute HIV-1 infection (AHI) in Africa. We assessed a strategy to diagnose AHI among young adult patients seeking care. METHODS: Young adults (<30 years) who met predefined AHI criteria at care seeking, including fever, sexually transmitted disease symptoms, diarrhoea, body pains or multiple partners were referred from five pharmacies and screened at five health facilities. Prevalent HIV-1 was diagnosed by nationally recommended serial rapid HIV-1 testing. Willing HIV-1-negative patients were evaluated for AHI, defined as a positive p24 antigen test, and subsequent seroconversion or RNA detection. Febrile patients evaluated for AHI were also screened for malaria using a rapid test, with PCR confirmation of positives. RESULTS: In 3602 adults seeking care, overall HIV-1 prevalence was 3.9%: 7.6% (68/897) among patients meeting AHI criteria vs. 2.6% (71/2705) among those who did not (P < 0.001). AHI was diagnosed in five of 506 HIV-1-negative or discordant patients who met AHI risk criteria and were completely evaluated [prevalence 1.0%, 95% confidence interval (CI) 0.3-2.3%]. Of these five AHI cases, four were diagnosed among the 241 patients with fever (prevalence 1.7%, 95% CI 0.5-4.2%), vs. one among 265 non-febrile patients (prevalence 0.4%, 95% CI 0.0-2.0%, P = 0.1). Malaria was confirmed by PCR in four (1.7%) of the 241 febrile patients. CONCLUSION: AHI was as common as confirmed malaria in young febrile adults seeking care. An AHI detection strategy targeting young febrile adults seeking care at pharmacies and health facilities is feasible and should be considered as an HIV-prevention strategy in high-transmission settings.

Evaluation of WHO screening algorithm for the presumptive treatment of asymptomatic rectal gonorrhoea and chlamydia infections in at-risk MSM in Kenya.

OBJECTIVES: The WHO recommends that men who have sex with men (MSM) reporting unprotected receptive anal intercourse (RAI) and either multiple partners or a partner with a sexually transmitted infection (STI) in the past 6 months should be presumptively treated for asymptomatic rectal Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) infections. We evaluated this recommendation in a cohort of 'high-risk' MSM in Coastal Kenya. METHODS: We assessed presence of genitourinary and rectal symptoms, and determined prevalence and 3-month incidence of rectal NG and CT infections. We performed nucleic acid amplification testing of urine and rectal swab samples collected from MSM followed prospectively, and assessed predictive values of the WHO algorithm at baseline screening. RESULTS: Of 244 MSM screened, 240 (98.4%) were asymptomatic, and 147 (61.3%) reported any RAI in the past 6 months. Among 85 (35.4%) asymptomatic MSM meeting criteria for the WHO presumptive treatment (PT) recommendation, we identified 20 with rectal infections (six NG, 12 CT and two NG-CT co-infections). Among 62 asymptomatic MSM who did not meet criteria, we identified seven who were infected. The sensitivity and specificity of the WHO algorithm were 74.1% (95% CI 53.7% to 88.9%) and 45.8% (95% CI 36.7% to 55.2%), respectively. The 3-month incidence of any rectal NG or CT infection in asymptomatic men reporting any RAI was 39.7 (95% CI 24.3 to 64.8) per 100 person-years. CONCLUSIONS: About one-third of asymptomatic MSM were eligible to receive PT for NG and CT infections. Among MSM who would qualify for PT of rectal STIs, the number needed to treat in order to treat one infection was four. Our results support the value of the WHO screening algorithm and recommended PT strategy in this population.

Evaluation of an empiric risk screening score to identify acute and early HIV-1 infection among MSM in Coastal Kenya.

We evaluated the University of North Carolina-Malawi Risk Screening Score (UMRSS) for detection of acute and early HIV-1 infection (AEHI) in a cohort of Kenyan MSM with approximately 8% annual HIV-1 incidence. Three components of the UMRSS (fever, diarrhea, and discordant rapid HIV tests) were also independent predictors of AEHI in our cohort. The predictive ability (area under the receiver operating characteristic curve, AUC) of the UMRSS was 0.79. A cohort-derived risk score consisting of six characteristics (fever, diarrhea, discordant rapid HIV tests, fatigue, age <30 years, and symptomatic sexually transmitted disease) had a higher AUC of 0.85. Screening for AEHI will have substantial transmission prevention benefits.

Cross-sectional survey of treatment practices for urethritis at pharmacies, private clinics and government health facilities in coastal Kenya: many missed opportunities for HIV prevention.

BACKGROUND: While bacterial sexually transmitted infections (STIs) are important cofactors for HIV transmission, STI control has received little attention in recent years. The aim of this study was to assess STI treatment and HIV testing referral practices among health providers in Kenya. METHODS: In 2011 we assessed quality of case management for male urethritis at pharmacies, private clinics and government health facilities in coastal Kenya using simulated visits at pharmacies and interviews at pharmacies and health facilities. Quality was assessed using Ministry of Health guidelines. RESULTS: Twenty (77%) of 26 pharmacies, 20 (91%) of 22 private clinics and all four government facilities in the study area took part. The median (IQR) number of adult urethritis cases per week was 5 (2-10) at pharmacies, 3 (1-3) at private clinics and 5 (2-17) at government facilities. During simulated visits, 10% of pharmacies prescribed recommended antibiotics at recommended dosages and durations and, during interviews, 28% of pharmacies and 27% of health facilities prescribed recommended antibiotics at recommended dosages and durations. Most regimens were quinolone-based. HIV testing was recommended during 10% of simulated visits, 20% of pharmacy interviews and 25% of health facility interviews. CONCLUSIONS: In an area of high STI burden, most men with urethritis seek care at pharmacies and private clinics. Most providers do not comply with national guidelines and very few recommend HIV testing. In order to reduce the STI burden and mitigate HIV transmission, there is an urgent need for innovative dissemination of up-to-date guidelines and inclusion of all health providers in HIV/STI programmes.

Adherence to antiretroviral therapy and clinical outcomes among young adults reporting high-risk sexual behavior, including men who have sex with men, in coastal Kenya.

African men who have sex with men (MSM) face significant stigma and barriers to care. We investigated antiretroviral therapy (ART) adherence among high-risk adults, including MSM, participating in a clinic-based cohort. Survival analysis was used to compare attrition across patient groups. Differences in adherence, weight gain, and CD4 counts after ART initiation were assessed. Among 250 HIV-1-seropositive adults, including 108 MSM, 15 heterosexual men, and 127 women, patient group was not associated with attrition. Among 58 participants who were followed on ART, 40 % of MSM had less than 95 % adherence, versus 28.6 % of heterosexual men and 11.5 % of women. Although MSM gained less weight after ART initiation than women (adjusted difference -3.5 kg/year), CD4 counts did not differ. More data are needed on barriers to adherence and clinical outcomes among African MSM, to ensure that MSM can access care and derive treatment and prevention benefits from ART.

Emergence of fluoroquinolone resistance in Neisseria gonorrhoeae isolates from four clinics in three regions of Kenya.

We have recently reported high levels of fluoroquinolone resistance in a single region of Kenya. In this article, we report high prevalence of fluoroquinolone resistance (53.2%) in Neisseria gonorrhoeae isolates from 4 clinics in 3 additional regions of Kenya. These findings highlight the need to change first-line treatment in these settings and the need to evaluate empirical management guidelines for treatment of gonococcal infection in Kenya.

Most adults seek urgent healthcare when acquiring HIV-1 and are frequently treated for malaria in coastal Kenya.

BACKGROUND: Acute HIV-1 infection (AHI) may present with symptoms for which urgent healthcare is sought. However, little is known about healthcare seeking around the time of HIV-1 seroconversion in sub-Saharan Africa. METHODS: Review of clinical, counselling, treatment and laboratory records of previously HIV-1 seronegative at-risk adults, followed at monthly or 3-monthly visits, who seroconverted and enrolled in an AHI cohort. All HIV-seronegative plasma samples were tested for p24 antigen (p24) and stored preseroconversion samples for HIV-1 RNA (RNA). Factors associated with malaria treatment while acquiring HIV-1 were evaluated in multiple logistic regression. RESULTS: Sixty men and 12 women (95% of 75 seroconverters) were evaluated, including 43 (60%) with either p24-positive or RNA-positive or HIV-1 discordant rapid antibodies prior to seroconversion. Prior to diagnosis, 54 patients (75%) reported fever and 50 (69%) sought urgent care for symptomatic illness, including 23 (32%) who sought care in a nonresearch setting. Twenty-nine patients (40%) received presumptive malaria treatment. Only 24% of febrile patients were tested for malaria parasites. All documented smear results were negative. Malaria treatment was strongly associated with fever [adjusted odds ratio (aOR): 46, 95% confidence interval (CI): 3-725] and nonresearch setting (aOR: 5, 95% CI: 3-64). AHI was suspected in six (12%) patients who presented for urgent care during research evaluation. CONCLUSIONS: The majority of adults with AHI seek urgent healthcare. These individuals are often presumptively treated for malaria. Improved recognition of AHI in adults presenting for care may offer opportunities for optimizing HIV prevention strategies.