Predictors of testing history and new HIV diagnosis among adult outpatients seeking care for symptoms of acute HIV infection in coastal Kenya: a cross-sectional analysis of intervention participants in a stepped-wedge HIV testing trial.

BACKGROUND: HIV testing is the first step to stop transmission. We aimed to evaluate HIV testing history and new diagnoses among adult outpatients in Kenya aged 18-39 years seeking care for symptoms of acute HIV infection (AHI). METHODS: The Tambua Mapema Plus study, a stepped-wedge trial, enrolled patients presenting to care at six primary care facilities with symptoms of AHI for a targeted HIV-1 nucleic acid (NA) testing intervention compared with standard provider-initiated testing using rapid antibody tests. Intervention participants underwent a questionnaire and NA testing, followed by rapid tests if NA-positive. Multinomial logistic regression was used to analyse factors associated with never testing or testing > 1 year ago ("late retesting") relative to testing ≤ 1 year ago ("on-time testers"). Logistic regression was used to analyse factors associated with new diagnosis. All analyses were stratified by sex. RESULTS: Of 1,500 intervention participants, 613 (40.9%) were men. Overall, 250 (40.8%) men vs. 364 (41.0%) women were late retesters, and 103 (16.8%) men vs. 50 (5.6%) women had never tested prior to enrolment. Younger age, single status, lower education level, no formal employment, childlessness, sexual activity in the past 6 weeks, and > 1 sexual partner were associated with testing history among both men and women. Intimate partner violence > 1 month ago, a regular sexual partner, and concurrency were associated with testing history among women only. New diagnoses were made in 37 (2.5%) participants (17 men and 20 women), of whom 8 (21.6%) had never tested and 16 (43.2%) were late retesters. Newly-diagnosed men were more likely to have symptoms for > 14 days, lower education level and no religious affiliation and less likely to be young, single, and childless than HIV-negative men; newly-diagnosed women were more likely to report fever than HIV-negative women. Among men, never testing was associated with fivefold increased odds (95% confidence interval 1.4-20.9) of new diagnosis relative to on-time testers in adjusted analyses. CONCLUSION: Most new HIV diagnoses were among participants who had never tested or tested > 1 year ago. Strengthening provider-initiated testing targeting never testers and late retesters could decrease time to diagnosis among symptomatic adults in coastal Kenya. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03508908 registered on 26/04/2018.

Testing strategies to detect acute and prevalent HIV infection in adult outpatients seeking healthcare for symptoms compatible with acute HIV infection in Kenya: a cost-effectiveness analysis.

BACKGROUND: Detection of acute and prevalent HIV infection using point-of-care nucleic acid amplification testing (POC-NAAT) among outpatients with symptoms compatible with acute HIV is critical to HIV prevention, but it is not clear if it is cost-effective compared with existing HIV testing strategies. METHODS: We developed and parametrised a decision tree to compare the cost-effectiveness of (1) provider-initiated testing and counselling (PITC) using rapid tests, the standard of care; (2) scaled-up provider-initiated testing and counselling (SU-PITC) in which all patients were tested with rapid tests unless they opted out; and (3) opt-out testing and counselling using POC-NAAT, which detects both acute and prevalent infection. The model-based analysis used data from the Tambua Mapema Plus randomised controlled trial of a POC-NAAT intervention in Kenya, supplemented with results from a stochastic, agent-based network model of HIV-1 transmission and data from published literature. The analysis was conducted from the perspective of the Kenyan government using a primary outcome of cost per disability-adjusted life-year (DALY) averted over a 10-year time horizon. RESULTS: After analysing the decision-analytical model, the average per patient cost of POC-NAAT was $214.9 compared with $173.6 for SU-PITC and $47.3 for PITC. The mean DALYs accumulated per patient for POC-NAAT were 0.160 compared with 0.176 for SU-PITC and 0.214 for PITC. In the incremental analysis, SU-PITC was eliminated due to extended dominance, and the incremental cost-effectiveness ratio (ICER) comparing POC-NAAT to PITC was $3098 per DALY averted. The ICER was sensitive to disability weights for HIV/AIDS and the costs of antiretroviral therapy. CONCLUSION: POC-NAAT offered to adult outpatients in Kenya who present for care with symptoms compatible with AHI is cost-effective and should be considered for inclusion as the standard of HIV testing in this population. TRIAL REGISTRATION NUMBER: Tambua Mapema ("Discover Early") Plus study (NCT03508908) conducted in Kenya (2017-2020) i.e., Post-results.

High patient acceptability but low coverage of provider-initiated HIV testing among adult outpatients with symptoms of acute infectious illness in coastal Kenya.

BACKGROUND: Only approximately one in five adults are offered HIV testing by providers when seeking care for symptoms of acute illness in Sub-Saharan Africa. Our aims were to estimate testing coverage and identify predictors of provider-initiated testing and counselling (PITC) and barriers to PITC implementation in this population. METHODS: We assessed HIV testing coverage among adult outpatients 18-39 years of age at four public and two private health facilities in coastal Kenya, during a 3- to 6-month surveillance period at each facility. A subset of patients who reported symptoms including fever, diarrhoea, fatigue, body aches, sore throat or genital ulcers were enrolled to complete a questionnaire independently of PITC offer. We assessed predictors of PITC in this population using generalised estimating equations and identified barriers to offering PITC through focus group discussion with healthcare workers (HCW) at each facility. RESULTS: Overall PITC coverage was 13.7% (1600 of 11,637 adults tested), with 1.9% (30) testing positive. Among 1,374 participants enrolled due to symptoms, 378 (27.5%) were offered PITC and 352 (25.6%) were tested, of whom 3.7% (13) tested positive. Among participants offered HIV testing, 93.1% accepted it; among participants not offered testing, 92.8% would have taken an HIV test if offered. The odds of completed PITC were increased among older participants (adjusted odds ratio [aOR] 1.7, 95% confidence interval [CI] 1.4-2.1 for 30-39 years, relative to 18-24 years), men (aOR 1.3, 95% CI 1.1-1.7); casual labourers (aOR 1.3, 95% CI 1.0-1.7); those paying by cash (aOR 1.2, 95% CI 1.0-1.4) or insurance (aOR 3.0, 95% CI 1.5-5.8); participants with fever (aOR 1.5, 95% CI 1.2-1.8) or genital ulcers (aOR 4.0, 95% CI 2.7-6.0); and who had tested for HIV >1 year ago (aOR 1.4, 95% CI 1.0-2.0) or had never tested (aOR 2.2, 95% CI 1.5-3.1). Provider barriers to PITC implementation included lack of HCW knowledge and confidence implementing guidelines, limited capacity and health systems constraints. CONCLUSION: PITC coverage was low, though most patients would accept testing if offered. Missed opportunities to promote testing during care-seeking were common and innovative solutions are needed.

Presence, persistence and effects of pre-treatment HIV-1 drug resistance variants detected using next generation sequencing: A Retrospective longitudinal study from rural coastal Kenya.

BACKGROUND: The epidemiology of HIV-1 drug resistance (HIVDR) determined by Sanger capillary sequencing, has been widely studied. However, much less is known about HIVDR detected using next generation sequencing (NGS) methods. We aimed to determine the presence, persistence and effect of pre-treatment HIVDR variants detected using NGS in HIV-1 infected antiretroviral treatment (ART) naïve participants from rural Coastal Kenya. METHODS: In a retrospective longitudinal study, samples from HIV-1 infected participants collected prior [n = 2 time-points] and after [n = 1 time-point] ART initiation were considered. An ultra-deep amplicon-based NGS assay, calling for nucleotide variants at >2.0% frequency of viral population, was used. Suspected virologic failure (sVF) was defined as a one-off HIV-1 viral load of >1000 copies/ml whilst on ART. RESULTS: Of the 50 eligible participants, 12 (24.0% [95% CI: 13.1-38.2]) had at least one detectable pre-treatment HIVDR variant against Protease Inhibitors (PIs, n = 6 [12%]), Nucleoside Reverse Transcriptase Inhibitors (NRTIs, n = 4 [8.0%]) and Non-NRTIs (n = 3 [6.0%]). Overall, 15 pre-treatment resistance variants were detected (frequency, range: 2.3-92.0%). A positive correlation was observed between mutation frequency and absolute load for NRTI and/or NNRTI variants (r = 0.761 [p = 0.028]), but not for PI variants (r = -0.117 [p = 0.803]). Participants with pre-treatment NRTI and/or NNRTI resistance had increased odds of sVF (OR = 6.0; 95% CI = 1.0-36.9; p = 0.054). CONCLUSIONS: Using NGS, pre-treatment resistance variants were common, though observed PI variants were unlikely transmitted, but rather probably generated de novo. Even when detected from a low frequency, pre-treatment NRTI and/or NNRTI resistance variants may adversely affect treatment outcomes.

Systematic review of the performance and clinical utility of point of care HIV-1 RNA testing for diagnosis and care.

BACKGROUND: Point of-care (POC) HIV-1 RNA tests which are accurate and easy to use with limited infrastructure are needed in resource-limited settings (RLS). We systematically reviewed evidence of POC test performance compared to laboratory-based HIV-1 RNA assays and the potential utility of these tests for diagnosis and care in RLS. METHODS: Studies published up to July 2018 were identified by a search of PUBMED, EMBASE, Web of Science, CINAHL and Cochrane Central Register of Controlled Trials. Studies evaluating the use of POC HIV-1 RNA testing for early infant diagnosis (EID), acute HIV infection (AHI) diagnosis, or viral load monitoring (VL), compared to centralized testing, were included. Separate search strategies were used for each testing objective. RESULTS: 197 abstracts were screened and 34 full-text articles were assessed, of which 32 met inclusion criteria. Thirty studies evaluated performance and diagnostic accuracy of POC tests compared to standard reference tests. Two of the thirty and two additional studies with no comparative testing reported on clinical utility of POC results. Five different POC tests (Cepheid GeneXpert HIV-1 Quantitative and Qualitative assays, Alere q HIV-1/2 Detect, SAMBA, Liat HIV Quant and Aptima HIV-1 Quant) were used in 21 studies of VL, 11 of EID and 2 of AHI. POC tests were easy to use, had rapid turnaround times, and comparable accuracy and precision to reference technologies. Sensitivity and specificity were high for EID and AHI but lower for VL. For VL, lower sensitivity was reported for whole blood and dried blood spots compared to plasma samples. Reported error rates for Cepheid GeneXpert Qual (2.0%-5.0%), GeneXpert Quant (2.5%-17.0%) and Alere q HIV-1/2 Detect (3.1%-11.0%) were higher than in WHO prequalification reports. Most errors resolved with retesting; however, inadequate sample volumes often precluded repeat testing. Only two studies used POC results for clinical management, one for EID and another for VL. POC EID resulted in shorter time-to-result, rapid ART initiation, and better retention in care compared to centralised testing. CONCLUSIONS: Performance of POC HIV-1 RNA tests is comparable to reference assays, and have potential to improve patient outcomes. Additional studies on implementation in limited-resources settings are needed.

Trends and predictors of HIV positivity and time since last test at voluntary counselling and testing encounters among adults in Kilifi, Kenya, 2006-2017.

Background: Little is known about HIV retesting uptake among key populations (KP) and general populations (GP) in Kenya. We assessed trends and predictors of first-time testing (FTT), late retesting (previous test more than one year ago for GP or three months for KP), and test positivity at three voluntary counselling and testing (VCT) centres in coastal Kenya. Methods: Routine VCT data covering 2006-2017 was collected from three VCT centres in Kilifi County. We analysed HIV testing history and test results from encounters among adults 18-39 years, categorized as GP men, GP women, men who have sex with men (MSM), and female sex workers (FSW).     Results: Based on 24,728 test encounters (32% FTT), we observed declines in HIV positivity (proportion of encounters where the result was positive) among GP men, GP women, first-time testers and MSM but not among FSW. The proportion of encounters for FTT and late retesting decreased for both GP and KP but remained much higher in KP than GP. HIV positivity was higher at FTT and late retesting encounters; at FSW and MSM encounters; and at encounters with clients reporting lower educational attainment and sexually transmitted infection (STI) symptoms. HIV positivity was lower in GP men, never married clients and those less than 35 years of age. FTT was associated with town, risk group, age 18-24 years, never-married status, low educational attainment, and STI symptoms. Late retesting was less common among encounters with GP individuals who were never married, had Muslim or no religious affiliation, had lower educational attainment, or reported STI symptoms. Conclusions: HIV positive test results were most common at encounters with first-time testers and late re-testers. While the proportion of encounters at which late retesting was reported decreased steadily over the period reviewed, efforts are needed to increase retesting among the most at-risk populations.