The effects of revised peer-counselor support on the PMTCT cascade of care: results from a cluster-randomized trial in Kenya (the EMMA study).

BACKGROUND: This study evaluated the effect of revisions to existing peer-counselor services, called Mentor Mothers (MM), at maternal and child health clinics on medication adherence for women living with HIV (WLWH) in Kenya and on early infant HIV testing. METHODS: The Enhanced Mentor Mother Program study was a 12-site, two-arm cluster-randomized trial enrolling pregnant WLWH from March 2017 to June 2018 (with data collection through September 2020). Six clinics were randomized to continued MM-supported standard care (SC). Six clinics were randomized to the intervention arm (INT = SC plus revised MM services to include more one-on-one interactions). Primary outcomes for mothers were defined as: (PO1) the proportion of days covered (PDC) with antiretroviral therapy (ART) ≥ 0.90 during the last 24-weeks of pregnancy; and (PO2) ≥ 0.90 PDC during the first 24-weeks postpartum. Secondary outcomes were infant HIV testing according to national guidelines (at 6, 24, and 48 weeks). Crude and adjusted risk differences between study arms are reported. RESULTS: We enrolled 363 pregnant WLHV. After excluding known transfers and subjects with incomplete data extraction, data were analyzed for 309 WLWH (151 SC, 158 INT). A small share achieved high PDC during the prenatal and postnatal periods (0.33 SC/0.24 INT achieved PO1; 0.30 SC/0.31 INT achieved PO2; crude or adjusted risk differences were not statistically significant). In addition, ~ 75% in both study arms completed viral load testing during year two after enrollment, with > 90% suppressed in both arms. For infants, ≥ 90% in both arms had at least one HIV test through study follow up (76 weeks) but testing on schedule according to PMTCT guidelines was uncommon. CONCLUSIONS: While national guidelines in Kenya recommended that all HIV-infected pregnant women take a daily antiretroviral regimen for life following a HIV diagnosis, results presented here indicate that a minor share achieved high medication coverage during the prenatal and postnatal periods analyzed. In addition, adjustments to Mentor-Mother services showed no improvement in study outcomes. The lack of effect for this behavioral intervention is relatively consistent with the existing literature to improve mother-infant outcomes along the PMTCT care cascade. CLINICAL TRIAL NUMBER: NCT02848235. Date of first trial registration 28/07/2016.

Prevalence and Correlates of Viral Load Suppression and Human Immunodeficiency Virus (HIV) Drug Resistance Among Children and Adolescents in South Rift Valley and Kisumu, Kenya.

BACKGROUND: Children and adolescents living with HIV (CALHIV) face unique challenges, including poorer treatment outcomes, risk for drug-resistance mutations (HIVDRMs), and limited drug formulations. We estimated viral suppression (VS) prevalence and evaluated predictors of VS and HIVDRMs in Kenya. METHODS: From 2018-2020, CALHIV 1-19 years on antiretroviral therapy (ART) >6 months were enrolled in this cross-sectional study. Participants underwent viral load (VL) testing; those with VL ≥1000 copies/mL had HIVDRM testing. Sociodemographic questionnaires and medical record abstraction were completed. VS prevalence (VL <1000 copies/mL) was estimated; robust Poisson regression models were used to estimate prevalence ratios (PRs) and 95% CIs for associations between potential predictors of VS. RESULTS: Nine hundred and sixty-nine participants were enrolled. VS prevalence was .80 (95% CI: .78-.83). Being on ART >24 months (adjusted PR [aPR]: 1.22; 95% CI: 1.06-1.41), an integrase strand transfer inhibitor-containing regimen (1.13; 1.02-1.26), and attending a level 3 health facility (1.23; 1.11-1.36) were associated with VS. Missing ≥3 doses of ART in the past month (aPR: .73; 95% CI: .58-.92), having a viremic mother with HIV (.72; .53-.98), and having 3-7 (.90; .83-.97), 8-13 (.89; .82-.97), or ≥14 (.84; .77-.92) compared with <2 adherence counseling referrals were inversely associated with VS. A high proportion (n = 119, 81.5%) of unsuppressed participants had evidence of any major HIVDRM. CONCLUSIONS: HIV treatment programs should target interventions for pediatric patients at risk for treatment failure-namely, those with a caregiver with failed VS and those struggling with adherence.

Prevalence of TB symptoms, diagnosis and treatment among people living with HIV (PLHIV) not on ART presenting at outpatient clinics in South Africa and Kenya: baseline results from a clinical trial.

OBJECTIVE: We used screening data and routine clinic records for intervention arm patients in the Simplified Algorithm for Treatment Eligibility (SLATE) trials to describe the prevalence of tuberculosis (TB) symptoms, diagnosis and treatment among people living with HIV (PLHIV), not on antiretroviral therapy (ART) and presenting at outpatient clinics in South Africa and Kenya. We compared the performance of the WHO four-symptom TB screening tool with a baseline Xpert test. SETTING: Outpatient HIV clinics in South Africa and Kenya. PARTICIPANTS: Eligible patients were non-pregnant, PLHIV, >18 years of age, not on ART, willing to provide written informed consent. A total of 594 patients in South Africa and 240 in Kenya were eligible. RESULTS: Prevalence of any TB symptom was 38% in Kenya, 35% (SLATE I) and 47% (SLATE II) in South Africa. During SLATE I, 70% of patients in Kenya and 57% in South Africa with ≥1 TB symptom were tested for TB. In SLATE II, 79% of patients with ≥1 TB symptom were tested. Of those, 19% tested positive for TB in Kenya, 15% (SLATE I) and 5% (SLATE II) tested positive in South Africa. Of the 28 patients who tested positive in both trials, 20 initiated TB treatment. The lowest median CD4 counts were among those with active TB (Kenya 124 cells/mm3; South Africa 193 cells/mm3). When comparing the WHO four-symptom screening tool to the Xpert test (SLATE II), we found that increasing the number of symptoms required for a positive screen from one to three or four decreased sensitivity but increased the positive predictive value to >30%. CONCLUSIONS: 80% of patients assessed for ART initiation presented with ≥1 TB symptoms. Reconsideration of the 'any symptom' rule may be appropriate, with ART initiation among patients with fewer/milder symptoms commencing while TB test results are pending. TRIAL REGISTRATION NUMBER: NCT02891135 and NCT03315013.

A tool for estimating antiretroviral medication coverage for HIV-infected women during pregnancy (PMTCT-ACT).

BACKGROUND: In the typical prevention of mother to child transmission (PMTCT) of HIV cascade of care discussion or analysis, the period of analysis begins at the first visit for antenatal care (ANC) for that pregnancy. This starting point is problematic for two reasons: (1) a large number of HIV-infected women are already on life-long antiretroviral therapy (ART) when presenting for ANC; and (2) women present to ANC at different gestational ages. The PMTCT ART Coverage Tool (PMTCT-ACT), which estimates the proportion of days covered (PDC) with ART, was developed to address each of these problems. METHODS: PDC is a preferred method to measure adherence to chronic medications, such as ART. For evaluating the PMTCT cascade of care, as indicated by PDC with ART over various time periods, a "starting point" based on a specific day before delivery must be defined that applies to all women (treatment experienced or naïve at the first ANC visit at any gestational age). Using the example of 168 days prior to delivery (24 weeks), PMTCT-ACT measures PDC with ART during that period. PMTCT-ACT is provided as a STATA do-file. Using an example dataset for two women (ID1 is treatment experienced; ID2 is treatment naïve), the details of each major portion of the tool (Parts 1-5) are presented. PMTCT-ACT along with the intermediate datasets created during the analysis are provided as supplemental files. CONCLUSIONS: Evaluating the PMTCT cascade of care requires a standard definition of the follow-up period during pregnancy that applies to all HIV-infected pregnant women and a standard measure of adherence. PMTCT-ACT is a new tool that fits this purpose. PMTCT-ACT can also be easily adjusted to evaluate other ante- and post-natal periods (e.g., final 4 weeks, final 8 weeks, complete pregnancy period, initial 24 weeks postpartum, time periods consistent with infant HIV testing guidelines).

Association of the US President's Emergency Plan for AIDS Relief's Funding With Prevention of Mother-to-Child Transmission of HIV in Kenya.

Importance: From 2004 to 2014, the US President's Emergency Plan for AIDS Relief (PEPFAR) invested more than $248 000 000 in the prevention of mother-to-child transmission (PMTCT) of HIV in Kenya. Concurrently, child mortality in Kenya decreased by half. Objective: To identify the extent to which the decrease in child mortality in Kenya is associated with PEPFAR funding for PMTCT of HIV. Design, Setting, and Participants: This population-based survey study conducted in Kenya estimated the association between annual per capita PEPFAR funding for PMTCT (annual PCF) and cumulative per capita PEPFAR funding for PMTCT (cumulative PCF), extracted using 2004-2014 country operational reports as well as individual-level health outcomes, extracted from the 2003, 2008-2009, and 2014 Kenya Demographic and Health Surveys and the 2007 and 2012 Kenya AIDS Indicator Surveys. The study included children of female respondents to the 2003, 2008-2009, and 2014 Kenya Demographic and Health Surveys who were born 1 to 60 months (for neonatal mortality) or 12 to 60 months (for infant mortality) before the survey, as well as female respondents who had recently given birth and reported on HIV testing during antenatal care (ANC) during the 2007-2014 surveys. Results were adjusted for year, province, and survey respondent characteristics. Statistical analysis was performed from July 8, 2016, to December 10, 2018. Main Outcomes and Measures: Neonatal mortality was defined as death within the first month of life and infant mortality was defined as death within the first year of life. HIV testing during ANC was defined as receiving counseling on PMTCT, undergoing an HIV test, and receiving test results during ANC. Results: The analysis included 33 181 neonates (16 870 boys), 26 876 infants (13 679 boys), and 20 775 mothers (mean [SD] age, 28.0 [6.7] years). PEPFAR funding was not associated with neonatal mortality. A $0.33 increase in annual PCF, corresponding to the difference between the 75th and 25th (interquartile range) percentiles of funding, was significantly associated with a 16% (95% CI, 4%-27%) reduction in infant mortality after a 1-year lag. A 14% to 16% reduction persisted after 2- and 3-year lags, and comparable reductions were observed for unlagged and 1-year lagged cumulative PCF. An increase of 1 interquartile range in cumulative PCF was associated with a 7% (95% CI, 3%-11%) increase in HIV testing during ANC, which intensified with subsequent lags. Between 2004 and 2014, sustained funding levels of $0.33 annual PCF could have averted 118 039 to 273 924 infant deaths. Conclusions and Relevance: Evidence from publicly available data suggests that PEPFAR's PMTCT funding was associated with a reduction in infant mortality and an increase in HIV testing during ANC in Kenya. The full outcome of funding may not be realized until several years after allocation.

Simplified clinical algorithm for identifying patients eligible for same-day HIV treatment initiation (SLATE): Results from an individually randomized trial in South Africa and Kenya.

BACKGROUND: The World Health Organization recommends "same-day" initiation of antiretroviral therapy (ART) for HIV patients who are eligible and ready. Identifying efficient, safe, and feasible procedures for determining same-day eligibility and readiness is now a priority. The Simplified Algorithm for Treatment Eligibility (SLATE) study evaluated a clinical algorithm that allows healthcare workers to determine eligibility for same-day treatment and to initiate ART at the patient's first clinic visit. METHODS AND FINDINGS: SLATE was an individually randomized trial at three outpatient clinics in urban settlements in Johannesburg, South Africa and three hospital clinics in western Kenya. Adult, nonpregnant, HIV-positive, ambulatory patients presenting for any HIV care, including HIV testing, but not yet on ART were enrolled and randomized to the SLATE algorithm arm or standard care. The SLATE algorithm used four screening tools-a symptom self-report, medical history questionnaire, physical examination, and readiness assessment-to ascertain eligibility for same-day initiation or refer for further care. Follow-up was by record review, and analysis was conducted by country. We report primary outcomes of 1) ART initiation ≤28 days and 2) initiation ≤28 days and retention in care ≤8 months of enrollment. From March 7, 2017 to April 17, 2018, we enrolled 600 patients (median [IQR] age 34 [29-40] and CD4 count 286 [128-490]; 63% female) in South Africa and 477 patients in Kenya (median [IQR] age 35 [29-43] and CD4 count 283 [117-541]; 58% female). In the intervention arm, 78% of patients initiated ≤28 days in South Africa, compared to 68% in the standard arm (risk difference [RD] [95% confidence interval (CI)] 10% [3%-17%]); in Kenya, 94% of intervention-arm patients initiated ≤28 days compared to 89% in the standard arm (6% [0.5%-11%]). By 8 months in South Africa, 161/298 (54%) intervention-arm patients had initiated and were retained, compared to 146/302 (48%) in the standard arm (6% [(2% to 14%]). By 8 months in Kenya, the corresponding retention outcomes were identical in both arms (137/240 [57%] of intervention-arm patients and 136/237 [57%] of standard-arm patients). Limitations of the trial included limited geographic representativeness, exclusion of patients too ill to participate, missing viral load data, greater study fidelity to the algorithm than might be achieved in standard care, and secular changes in standard care over the course of the study. CONCLUSIONS: In South Africa, the SLATE algorithm increased uptake of ART within 28 days by 10% and showed a numerical increase (6%) in retention at 8 months. In Kenya, the algorithm increased uptake of ART within 28 days by 6% but found no difference in retention at 8 months. Eight-month retention was poor in both arms and both countries. These results suggest that a simple structured algorithm for same-day treatment initiation procedures is feasible and can increase and accelerate ART uptake but that early retention on treatment remains problematic. TRIAL REGISTRATION: Clinicaltrials.gov NCT02891135, registered September 1, 2016. First participant enrolled March 6, 2017 in South Africa and July 13, 2017 in Kenya.

Who is seeking antiretroviral treatment for HIV now? Characteristics of patients presenting in Kenya and South Africa in 2017-2018.

INTRODUCTION: Many African countries have had at least two years' experience with universal treatment eligibility for HIV. The literature contains few descriptions, though, of populations starting treatment since adoption of universal eligibility. Using baseline data from a clinical trial of same-day ART initiation, we describe the populations presenting for HIV testing or care at study clinics in Kenya and South Africa in 2017-18, during the era of same-day initiation. METHODS: The Simplified Algorithm for Treatment Eligibility (SLATE) trials in Kenya (SLATE I) and South Africa (SLATE II) were multicenter, non-blinded, individually randomized, pragmatic trials evaluating simple, standardized algorithms to determine eligibility for same-day initiation of ART without relying on laboratory results, point of care tests or multiple clinic visits. In Kenya, enrolment occurred during July 2017 to April 2018. In South Africa, enrolment occurred during March to September 2018. We describe demographic, socioeconomic and clinical characteristics of patients randomized to the same-day initiation arm for both studies. RESULTS AND DISCUSSION: A total of 240 and 296 participants were enrolled in Kenya and South Africa. The majority were female (59% and 64% respectively), with a median age of 35 years. In both countries, most subjects were newly diagnosed with HIV on the day of enrolment (62%, 55%), believed they already had adequate knowledge to begin ART (78%, 68%), and preferred to start ART immediately (same-day) (98% in both countries). About 40% of all patients had at least one symptom related to tuberculosis (cough, fever, night sweats, weight loss) and/or cryptococcal meningitis (continuous headache). More than a third of patients (37%, 36%) presented with advanced disease (CD4 <200 cells/mm3 ), a fifth presented with very advanced disease (CD4 < 100), and approximately 1 in 20 presented with very advanced disease and were asymptomatic. CONCLUSIONS: Despite >2 years of universal eligibility for ART in Kenya and South Africa, in 2017-2018 more than half of HIV-positive patients presenting at public sector clinics were not yet aware of their status, and more than a third presented for care with advanced HIV disease. These proportions remain similar to those observed before the introduction of universal eligibility.

The Enhanced Mentor Mother ProgrAm (EMMA) for the prevention of mother-to-child transmission of HIV in Kenya: study protocol for a cluster randomized controlled trial.

BACKGROUND: As of September 2014, Kenya implemented the WHO recommended Option B+ guidelines in which all newly diagnosed HIV-infected pregnant women are immediately eligible for triple antiretroviral therapy (ART) for life regardless of CD4 count. In addition, Kenya previously established the Kenya Mentor Mother Program (KMMP) in 2012 to improve peer education and psychosocial support services within the national prevention of mother-to-child transmission (PMTCT) program. The primary objectives of the study described in the current protocol are: (1) to evaluate implementation of these new guidelines (Option B+ with Mentor Mothers) as part of routine service delivery; and (2) to evaluate potential benefits of a package of services within the KMMP (called EMMA) to improve PMTCT service delivery. METHODS: We will conduct a cluster randomized controlled trial in western Kenya. We will allocate 12 clinics providing PMTCT services including ART to two study arms using pair matching: the standard of care (SOC) arm, which includes the KMMP as implemented by the clinics; and the intervention arm, which is the SOC (including KMMP) with the EMMA package of services (a targeted exit interview, visit reminders, and targeted follow-up). At the intervention clinics, the EMMA package of services is implemented as part of routine service delivery. A total of 360 (180 in each arm) pregnant women will be enrolled in the study at or near their first visit for antenatal care for prospective records review through 72 weeks post-partum. The primary and secondary outcomes are uninterrupted supplies of ART medications throughout the PMTCT cascade of care as well as infants completing HIV testing on schedule. DISCUSSION: The EMMA package of services provides specific structure to the use of Mentor Mothers within PMTCT programs. This strategy was developed in collaboration with local health facility and PMTCT program staff based on their experience providing PMTCT services within the integrated ART-MCH facilities. If successful, this approach has the potential to improve dramatically PMTCT service delivery with minor additional costs beyond the basic mother-mentor program and support global goals to eliminate mother-to-child transmission. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02848235 . Registered on 19 July 2016.

Simplified clinical algorithm for identifying patients eligible for immediate initiation of antiretroviral therapy for HIV (SLATE): protocol for a randomised evaluation.

INTRODUCTION: African countries are rapidly adopting guidelines to offer antiretroviral therapy (ART) to all HIV-infected individuals, regardless of CD4 count. For this policy of 'treat all' to succeed, millions of new patients must be initiated on ART as efficiently as possible. Studies have documented high losses of treatment-eligible patients from care before they receive their first dose of antiretrovirals (ARVs), due in part to a cumbersome, resource-intensive process for treatment initiation, requiring multiple clinic visits over a several-week period. METHODS AND ANALYSIS: The Simplified Algorithm for Treatment Eligibility (SLATE) study is an individually randomised evaluation of a simplified clinical algorithm for clinicians to reliably determine a patient's eligibility for immediate ART initiation without waiting for laboratory results or additional clinic visits. SLATE will enrol and randomise (1:1) 960 adult, HIV-positive patients who present for HIV testing or care and are not yet on ART in South Africa and Kenya. Patients randomised to the standard arm will receive routine, standard of care ART initiation from clinic staff. Patients randomised to the intervention arm will be administered a symptom report, medical history, brief physical exam and readiness assessment. Patients who have positive (satisfactory) results for all four components of SLATE will be dispensed ARVs immediately, at the same clinic visit. Patients who have any negative results will be referred for further clinical investigation, counselling, tests or other services prior to being dispensed ARVs. After the initial visit, follow-up will be by passive medical record review. The primary outcomes will be ART initiation ≤28 days and retention in care 8 months after study enrolment. ETHICS AND DISSEMINATION: Ethics approval has been provided by the Boston University Institutional Review Board, the University of the Witwatersrand Human Research Ethics Committee (Medical) and the KEMRI Scientific and Ethics Review Unit. Results will be published in peer-reviewed journals and made widely available through presentations and briefing documents. TRIAL REGISTRATION: NCT02891135.

Breast-feeding and human immunodeficiency virus infection: assessment of knowledge among clinicians in Kenya.

In Kenya, human immunodeficiency virus (HIV) prevalence ranks among the highest in the world. Approximately 60 000 infections yearly are attributed to vertical transmission including the process of labour and breast-feeding. The vast of the population affected is in the developing world. Clinical officers and nurses play an important role in provision of primary health care to antenatal and postnatal mothers. There are a few studies that have explored the clinicians' knowledge on breast-feeding in the face of HIV and in relation to vertical transmission this being a vital component in prevention of maternal-to-child transmission. The aim of this study was to evaluate clinicians' knowledge on HIV in relation to breast-feeding in Kenya. A cross-sectional survey was conducted to assess knowledge of 161 clinical officers and nurses serving in the maternity and children' wards in various hospitals in Kenya. The participants were derived from all district and provincial referral facilities in Kenya. A preformatted questionnaire containing a series of questions on HIV and breast-feeding was administered to clinicians who were then scored and analyzed. All the 161 participants responded. Majority of clinicians (92%) were knowledgeable regarding prevention of mother-to-child transmission. Regarding HIV and breast-feeding, 49.7% thought expressed breast milk from HIV-positive mothers should be heated before being given. Majority (78.3%) thought breast milk should be given regardless of availability of alternatives. According to 74.5% of the participants, exclusive breast-feeding increased chances of HIV transmission. Two-thirds (66.5%) would recommend breast-feeding for mothers who do not know their HIV status (66.5%). This study observes that a majority of the clinicians have inadequate knowledge on breast-feeding in the face of HIV. There is need to promote training programmes on breast-feeding and transmission of HIV from mother to child. This can be done as in-service training, continuous medical education and as part of the formal training within medical institutions.