Peter Mugo

High Acceptability of HIV Pre-exposure Prophylaxis but Challenges in Adherence and Use: Qualitative Insights from a Phase I Trial of Intermittent and Daily PrEP in At-Risk Populations in Kenya

This paper used qualitative methods to explore experiences of men who have sex with men and female sex workers in Nairobi and Mtwapa, Kenya, who used oral pre-exposure prophylaxis (PrEP) for HIV prevention as part of a four-month trial of safety, acceptability and adherence. Fifty-one of 72 volunteers who took part in a randomized, placebo-controlled, blinded trial that compared daily and intermittent dosage of PrEP underwent qualitative assessments after completing the trial. Analyses identified three themes: (i) acceptability of PrEP was high, i.e. side effects were experienced early in the study but diminished over time, however characteristics of pills could improve comfort and use; (ii) social impacts such as stigma, rumors, and relationship difficulties due to being perceived as HIV positive were prevalent; (iii) adherence was challenged by complexities of daily life, in particular post-coital dosing adherence suffered from alcohol use around time of sex, mobile populations, and transactional sex work. These themes resonated across dosing regimens and gender, and while most participants favored the intermittent dosing schedule, those in the intermittent group noted particular challenges in adhering to the post-coital dose. Culturally appropriate and consistent counseling addressing these issues may be critical for PrEP effectiveness.

Safety and Adherence to Intermittent Pre-Exposure Prophylaxis (PrEP) for HIV-1 in African Men Who Have Sex with Men and Female Sex Workers

Background Little is known about safety of and adherence to intermittent HIV PrEP regimens, which may be more feasible than daily dosing in some settings. We present safety and adherence data from the first trial of an intermittent PrEP regimen among Kenyan men who have sex with men (MSM) and female sex workers (FSW). Methods/Principal Findings MSM and FSW were randomized to daily oral FTC/TDF or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day) oral FTC/TDF or placebo in a 2∶1∶2∶1 ratio; volunteers were followed monthly for 4 months. Adherence was assessed with the medication event monitoring system (MEMS). Sexual activity data were collected via daily text message (SMS) queries and timeline followback interviews with a one-month recall period. Sixty-seven men and 5 women were randomized into the study. Safety was similar among all groups. Median MEMS adherence rates were 83% [IQR: 63–92] for daily dosing and 55% [IQR:28–78] for fixed intermittent dosing (p = 0.003), while adherence to any post-coital doses was 26% [IQR:14–50]. SMS response rates were low, which may have impaired measurement of post-coital dosing adherence. Acceptability of PrEP was high, regardless of dosing regimen. Conclusions/Significance Adherence to intermittent dosing regimens, fixed doses, and in particular coitally-dependent doses, may be more difficult than adherence to daily dosing. However, intermittent dosing may still be appropriate for PrEP if intracellular drug levels, which correlate with prevention of HIV acquisition, can be attained with less than daily dosing and if barriers to adherence can be addressed. Additional drug level data, qualitative data on adherence barriers, and better methods to measure sexual activity are necessary to determine whether adherence to post-coital PrEP could be comparable to more standard regimens. Trial Registration ClinicalTrials.gov NCT00971230

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 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.

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.

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.

Uptake and Acceptability of Oral HIV Self-Testing among Community Pharmacy Clients in Kenya: A Feasibility Study

Background While HIV testing and counselling is a key entry point for treatment as prevention, over half of HIV-infected adults in Kenya are unaware they are infected. Offering HIV self-testing (HST) at community pharmacies may enhance detection of undiagnosed infections. We assessed the feasibility of pharmacy-based HST in Coastal Kenya. Methods Staff at five pharmacies, supported by on-site research assistants, recruited adult clients (≥18 years) seeking services indicative of HIV risk. Participants were offered oral HST kits (OraQuick®) at US

The plasma virome of febrile adult Kenyans shows frequent parvovirus B19 infections and a novel arbovirus (Kadipiro virus).

1 per test. Within one week of buying a test, participants were contacted for post-test data collection and counselling. The primary outcome was test uptake, defined as the proportion of invited clients who bought tests. Views of participating pharmacy staff were solicited in feedback sessions during and after the study. Results Between November 2015 and April 2016, 463 clients were invited to participate; 174 (38%) were enrolled; and 161 (35% [95% Confidence Interval (CI) 31–39%]) bought a test. Uptake was higher among clients seeking HIV testing compared to those seeking other services (84% vs. 11%, adjusted risk ratio 6.9 [95% CI 4.9–9.8]). Only 4% of non-testers (11/302) stated inability to pay as the reason they did not take up the test. All but one tester reported the process was easy (29%) or very easy (70%). Demand for HST kits persisted after the study and participating service providers expressed interest in continuing to offer the service. Conclusions Pharmacy HST is feasible in Kenya and may be in high demand. The uptake pattern observed suggests that a client-initiated approach is more feasible compared to pharmacy-initiated testing. Price is unlikely to be a barrier if set at about US

Development and pilot testing of an intervention to promote care engagement and adherence among HIV-positive Kenyan MSM.

1 per test. Further implementation research is required to assess uptake, yield, and linkage to care on a larger scale.

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.

Viral nucleic acids present in the plasma of 498 Kenyan adults with unexplained fever were characterized by metagenomics analysis of 51 sample pools. The highest to lowest fraction of plasma pools was positive for parvovirus B19 (75 %), pegivirus C (GBV-C) (67 %), alpha anellovirus (59 %), gamma anellovirus (55 %), beta anellovirus (41 %), dengue virus genotype 2 (DENV-2) (16 %), human immunodeficiency virus type 1 (6 %), human herpesvirus 6 (6 %), HBV (4 %), rotavirus (4 %), hepatitis B virus (4 %), rhinovirus C (2 %), Merkel cell polyomavirus (MCPyV; 2 %) and Kadipiro virus (2 %). Ranking by overall percentage of viral reads yielded similar results. Characterization of viral nucleic acids in the plasma of a febrile East African population showed a high frequency of parvovirus B19 and DENV infections and detected a reovirus (Kadipiro virus) previously reported only in Asian Culex mosquitoes, providing a baseline to compare with future virome studies to detect emerging viruses in this region.