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.

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.

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.

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.

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.

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).

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.

Rectal gonorrhoea and chlamydia among men who have sex with men in coastal Kenya.

Background: Men who have sex with men (MSM) have a higher prevalence of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections compared to the rest of the population, often remaining undiagnosed. In Kenya, prevalence of rectal CT and NG infection and NG antimicrobial sensitivity are poorly described. Methods: MSM who reported receptive anal intercourse (RAI) were recruited from an ongoing human immunodeficiency virus acquisition and treatment study in coastal Kenya in 2016-2017. Rectal swabs were collected at two time points 6 months apart to estimate prevalence and incidence of CT/NG infection using a molecular point-of-care assay. Participants positive for CT or NG were treated according to national guidelines. NG culture and antimicrobial susceptibility testing was performed. Participant and risk behaviour characteristics were collected and association with baseline CT/NG prevalence assessed by multivariable regression analysis. Results: Prevalence of CT/NG in 104 MSM was 21.2% (CT 13.5%, NG 9.6%, dual infection 1.9%) at baseline and 25.9% in 81 MSM at follow-up (CT 14.8%, NG 14.8%, dual infection 3.7%). CT/NG incidence was estimated at 53.0 (95% CI, 34.5-81.3) per 100 person-years. Most CT/NG positive participants were asymptomatic: 95.5% at baseline and 100% at follow-up. CT/NG infection was associated with being paid for sex [adjusted odds ratio (aOR)=6.2, 95% CI (1.7-22.9)] and being in formal employment [aOR=7.5, 95% CI (1.1-49.2)]. Six NG isolates were obtained at follow-up; all were susceptible to ceftriaxone and cefixime and all were resistant to penicillin, tetracycline and ciprofloxacin. Conclusions: There is a high prevalence and incidence of asymptomatic rectal CT and NG in MSM reporting RAI in coastal Kenya. MSM who were paid for sex or had formal employment were more likely to be infected with CT/NG suggesting increased risk behaviour during transactional sex. Antimicrobial susceptibility results suggest that current antibiotic choices in Kenya are appropriate for NG treatment.

Hepatitis B Virus Incidence and Risk Factors Among Human Immunodeficiency Virus-1 Negative Men Who Have Sex With Men in Kenya.

No data exist on hepatitis B virus (HBV) incidence among African men who have sex with men (MSM). We tested plasma samples archived between 2005 and 2014 for HBV core antibody or surface antigen seroconversion in a cohort of 312 initially human immunodeficiency virus (HIV)-1-negative MSM with no evidence of prior HBV infection. Hepatitis B virus incidence was 6.0/100 person-years (95% confidence interval [CI], 3.9-9.1). Hepatitis B virus acquisition was associated with being uncircumcised (adjusted incidence rate ratio [aIRR], 5.0; 95% CI, 1.5-16.8), recent HIV-1 acquisition (aIRR, 2.9; 95% CI, 1.1-7.7), rape (aIRR, 5.0; 95% CI, 1.2-20.4), and any tertiary education (aIRR, 3.2; 95% CI, 1.1-9.7). African MSM have a substantial risk of HBV acquisition and require vaccination urgently.