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.

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.

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.

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.

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.

High prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae infections among HIV-1 negative men who have sex with men in coastal Kenya.

OBJECTIVES: To assess the burden of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) in high-risk HIV-1 negative men who have sex with men (MSM) in Africa. METHODS: Before the start of a pre-exposure prophylaxis trial, HIV-1 negative volunteers were screened for sexually transmitted infection (STI) including CT and NG, using a highly sensitive and specific nucleic acid amplification test. Samples positive for CT by Aptima testing, were evaluated for the presence of lymphogranuloma venereum (LGV) serovars using an in-house PCR assay. All men were asked to submit a urine specimen, and all had a rectal swab collected by a clinician. Men were asked if they had dysuria, urethral or rectal discharge, or rectal pain. RESULTS: 43 HIV-1 negative MSM were screened, of whom 13 reported sex with men only; the majority (27/43) reported sex work. One volunteer had dysuria and another, rectal pain. Eleven MSM (26%, 95% CI 14% to 41%) had infections with either or both pathogens. Homosexual men had a higher prevalence of any infection than bisexual men (46% vs 17%, p=0.04), and all cases of rectal infections, including one with CT, two with NG and two with CT/NG co-infection. All patients with CT were negative for LGV. One patient with a rectal NG infection reported rectal pain. CONCLUSIONS: A remarkably high burden of STI infection was found among HIV-1 negative MSM. Most (12/13) infections, including three of four rectal NG infections, were subclinical. These findings suggest that high-risk MSM will benefit from effective STI screening in Kenya.