The development of task sharing policy and guidelines in Kenya.

BACKGROUND: The global critical shortage of health workers prevents expansion of healthcare services and universal health coverage. Like most countries in sub-Saharan Africa, Kenya's healthcare workforce density of 13.8 health workers per 10,000 population falls below the World Health Organization (WHO) recommendation of at least 44.5 doctors, nurses, and midwives per 10,000 population. In response to the health worker shortage, the WHO recommends task sharing, a strategy that can increase access to quality health services. To improve the utilization of human and financial health resources in Kenya for HIV and other essential health services, the Kenya Ministry of Health (MOH) in collaboration with various institutions developed national task sharing policy and guidelines (TSP). To advance task sharing, this article describes the process of developing, adopting, and implementing the Kenya TSP. CASE PRESENTATION: The development and approval of Kenya's TSP occurred from February 2015 to May 2017. The U.S. Centers for Disease Control and Prevention (CDC) allocated funding to Emory University through the United States President's Emergency Plan for AIDS Relief (PEPFAR) Advancing Children's Treatment initiative. After obtaining support from leadership in Kenya's MOH and health professional institutions, the TSP team conducted a desk review of policies, guidelines, scopes of practice, task analyses, grey literature, and peer-reviewed research. Subsequently, a Policy Advisory Committee was established to guide the process and worked collaboratively to form technical working groups that arrived at consensus and drafted the policy. The collaborative, multidisciplinary process led to the identification of gaps in service delivery resulting from health workforce shortages. This facilitated the development of the Kenya TSP, which provides a general orientation of task sharing in Kenya. The guidelines list priority tasks for sharing by various cadres as informed by evidence, such as HIV testing and counseling tasks. The TSP documents were disseminated to all county healthcare facilities in Kenya, yet implementation was stopped by order of the judiciary in 2019 after a legal challenge from an association of medical laboratorians. CONCLUSIONS: Task sharing may increase access to healthcare services in resource-limited settings. To advance task sharing, TSP and clinical practice could be harmonized, and necessary adjustments made to other policies that regulate practice (e.g., scopes of practice). Revisions to pre-service training curricula could be conducted to ensure health professionals have the requisite competencies to perform shared tasks. Monitoring and evaluation can help ensure that task sharing is implemented appropriately to ensure quality outcomes.

'They can stigmatize you': a qualitative assessment of the influence of school factors on engagement in care and medication adherence among adolescents with HIV in Western Kenya.

School-related factors may influence retention in care and adherence to antiretroviral therapy (ART) among adolescents with human immunodeficiency virus (HIV). We analyzed data from in-depth interviews with 40 adolescents with HIV (aged 14 -19 years), 40 caregivers of adolescents with HIV, and 4 focus group discussions with healthcare workers to evaluate contextual factors affecting adherence to ART and clinic attendance among adolescents, with a focus on the school environment. Informed by Anderson's Model of Health Services Utilization, transcripts were systematically coded and synthesized to identify school-related themes. All groups identified the school environment as a critical barrier to engagement in HIV care and medication adherence for adolescents with HIV. Adolescent participants reported inflexible school schedules and disclosure to school staff as the biggest challenges adhering to clinic appointments and ART. Adolescents described experiencing stigma and discrimination by peers and school staff and would adjust when, where and how often they took ART to avoid inadvertent disclosure. Boarding school students faced challenges because they had limited private space or time. Caregivers were often instrumental in navigating school permissions, including identifying a treatment supporter among school staff. Additional research engaging school staff may guide interventions for schools to reduce stigma and improve adherence and retention.

Piperaquine Pharmacokinetics during Intermittent Preventive Treatment for Malaria in Pregnancy.

Dihydroartemisinin-piperaquine (DP) is a long-acting artemisinin combination treatment that provides effective chemoprevention and has been proposed as an alternative antimalarial drug for intermittent preventive therapy in pregnancy (IPTp). Several pharmacokinetic studies have shown that dose adjustment may not be needed for the treatment of malaria in pregnancy with DP. However, there are limited data on the optimal dosing for IPTp. This study aimed to evaluate the population pharmacokinetics of piperaquine given as IPTp in pregnant women. Pregnant women were enrolled in clinical trials conducted in Kenya and Indonesia and treated with standard 3-day courses of DP, administered in 4- to 8-week intervals from the second trimester until delivery. Pharmacokinetic blood samples were collected for piperaquine drug measurements before each treatment round, at the time of breakthrough symptomatic malaria, and at delivery. Piperaquine population pharmacokinetic properties were investigated using nonlinear mixed-effects modeling with a prior approach. In total, data from 366 Kenyan and 101 Indonesian women were analyzed. The pharmacokinetic properties of piperaquine were adequately described using a flexible transit absorption (n = 5) followed by a three-compartment disposition model. Gestational age did not affect the pharmacokinetic parameters of piperaquine. After three rounds of monthly IPTp, 9.45% (95% confidence interval [CI], 1.8 to 26.5%) of pregnant women had trough piperaquine concentrations below the suggested target concentration (10.3 ng/ml). Translational simulations suggest that providing the full treatment course of DP at monthly intervals provides sufficient protection to prevent malaria infection. Monthly administration of DP has the potential to offer optimal prevention of malaria during pregnancy. (This study has been registered at ClinicalTrials.gov under identifier NCT01669941 and in the ISRCTN under number ISRCTN34010937.).

A clinical decision support system is associated with reduced loss to follow-up among patients receiving HIV treatment in Kenya: a cluster randomized trial.

BACKGROUND: Loss to follow-up (LFTU) among HIV patients remains a major obstacle to achieving treatment goals with the risk of failure to achieve viral suppression and thereby increased HIV transmission. Although use of clinical decision support systems (CDSS) has been shown to improve adherence to HIV clinical guidance, to our knowledge, this is among the first studies conducted to show its effect on LTFU in low-resource settings. METHODS: We analyzed data from a cluster randomized controlled trial in adults and children (aged ≥ 18 months) who were receiving antiretroviral therapy at 20 HIV clinics in western Kenya between Sept 1, 2012 and Jan 31, 2014. Participating clinics were randomly assigned, via block randomization. Clinics in the control arm had electronic health records (EHR) only while the intervention arm had an EHR with CDSS. The study objectives were to assess the effects of a CDSS, implemented as alerts on an EHR system, on: (1) the proportion of patients that were LTFU, (2) LTFU patients traced and successfully linked back to treatment, and (3) time from enrollment on the study to documentation of LTFU. RESULTS: Among 5901 eligible patients receiving ART, 40.6% (n = 2396) were LTFU during the study period. CDSS was associated with lower LTFU among the patients (Adjusted Odds Ratio-aOR 0.70 (95% CI 0.65-0.77)). The proportions of patients linked back to treatment were 25.8% (95% CI 21.5-25.0) and 30.6% (95% CI 27.9-33.4)) in EHR only and EHR with CDSS sites respectively. CDSS was marginally associated with reduced time from enrollment on the study to first documentation of LTFU (adjusted Hazard Ratio-aHR 0.85 (95% CI 0.78-0.92)). CONCLUSION: A CDSS can potentially improve quality of care through reduction and early detection of defaulting and LTFU among HIV patients and their re-engagement in care in a resource-limited country. Future research is needed on how CDSS can best be combined with other interventions to reduce LTFU. Trial registration NCT01634802. Registered at www.clinicaltrials.gov on 12-Jul-2012. Registered prospectively.

Male partner antenatal clinic attendance is associated with increased uptake of maternal health services and infant BCG immunization: a national survey in Kenya.

BACKGROUND: Male partner antenatal clinic (ANC) attendance may improve maternal uptake of maternal child health (MCH) services. METHODS: We conducted a cross-sectional survey of mother-infant pairs attending week-6 or month-9 infant immunizations at 120 high-volume MCH clinics throughout Kenya. Clinics were selected using probability proportionate to size sampling. Women were interviewed using structured questionnaires and clinical data was verified using MCH booklets. Among married women, survey-weighted logistic regression models accounting for clinic-level clustering were used to compare outcomes by male ANC attendance and to identify its correlates. RESULTS: Among 2521 women attending MCH clinics and had information on male partner ANC attendance, 2141 (90%) were married of whom 806 (35%) had male partners that attended ANC. Among married women, male partner ANC attendance was more frequent among women with higher education, women who requested their partners to attend ANC, had male partners with higher education, did not report partner violence, and had disclosed their HIV status (p < 0·001 for each). Additionally, male ANC attendance was associated with higher uptake of ANC visits [adjusted Odds Ratio (AOR) = 1·67, 95% confidence interval (CI) 1·36-2·05,], skilled delivery (AOR = 2·00, 95% CI 1·51-2·64), exclusive breastfeeding (AOR = 1·70, 95% CI 1·00-2·91), infant Bacille Calmette Guerin (BCG) immunization (AOR = 3·59, 95% CI 1·00-12·88), and among HIV-infected women, antiretroviral drugs (aOR = 6·16, 95% CI 1·26-30·41). CONCLUSION: Involving male partners in MCH activities amplifies benefits of MCH services by engaging partner support for maternal uptake of services.

Noncommunicable disease burden among HIV patients in care: a national retrospective longitudinal analysis of HIV-treatment outcomes in Kenya, 2003-2013.

BACKGROUND: Over the last decade, the Kenyan HIV treatment program has grown exponentially, with improved survival among people living with HIV (PLHIV). In the same period, noncommunicable diseases (NCDs) have become a leading contributor to disease burden. We sought to characterize the burden of four major NCDs (cardiovascular diseases, cancer, chronic respiratory diseases and diabetes mellitus) among adult PLHIV in Kenya. METHODS: We conducted a nationally representative retrospective medical chart review of HIV-infected adults aged ≥15 years enrolled in HIV care in Kenya from October 1, 2003 through September 30, 2013. We estimated proportions of four NCD categories among PLHIV at enrollment into HIV care, and during subsequent HIV care visits. We compared proportions and assessed distributions of co-morbidities using the Chi-Square test. We calculated NCD incidence rates and their confidence intervals in assessing cofactors for developing NCDs. RESULTS: We analyzed 3170 records of HIV-infected patients; 2115 (66.3%) were from women. Slightly over half (51.1%) of patient records were from PLHIVs aged above 35 years. Close to two-thirds (63.9%) of PLHIVs were on ART. Proportion of any documented NCD among PLHIV was 11.5% (95% confidence interval [CI] 9.3, 14.1), with elevated blood pressure as the most common NCD 343 (87.5%) among PLHIV with a diagnosed NCD. Despite this observation, only 17 (4.9%) patients had a corresponding documented diagnosis of hypertension in their medical record. Overall NCD incidence rates for men and women were (42.3 per 1000 person years [95% CI 35.8, 50.1] and 31.6 [95% CI 27.7, 36.1], respectively. Compared to women, the incidence rate ratio for men developing an NCD was 1.3 [95% CI 1.1, 1.7], p = 0.0082). No differences in NCD incidence rates were seen by marital or employment status. At one year of follow up 43.8% of PLHIV not on ART had been diagnosed with an NCD compared to 3.7% of patients on ART; at five years the proportions with a diagnosed NCD were 88.8 and 39.2% (p < 0.001), respectively. CONCLUSIONS: PLHIV in Kenya have a high prevalence of NCD diagnoses. In the absence of systematic, effective screening, NCD burden is likely underestimated in this population. Systematic screening and treatment for NCDs using standard guidelines should be integrated into HIV care and treatment programs in sub-Saharan Africa.

Preexposure Prophylaxis for Human Immunodeficiency Virus (HIV) Prevention Among HIV-uninfected Pregnant Women: Estimated Coverage Using Risk-based Versus Regional Prevalence Approaches.

Antenatal register data from 62 clinics in 5 regions of Kenya were used to estimate women with human immunodeficiency virus (HIV) risk (partner HIV status, syphilis). With individual risk-guided preexposure prophylaxis (PrEP) offer in all regions, 39% of pregnant women would be offered PrEP nationally. Offering PrEP to all women in high-prevalence regions reached 26% of the pregnant women.

Non-disclosure to male partners and incomplete PMTCT regimens associated with higher risk of mother-to-child HIV transmission: a national survey in Kenya.

Health worker experience and community support may be higher in high HIV prevalence regions than low prevalence regions, leading to improved prevention of mother-to-child HIV transmission (PMTCT) programs. We evaluated 6-week and 9-month infant HIV transmission risk (TR) in a high prevalence region and nationally. Population-proportionate-to-size sampling was used to select 141 clinics in Kenya, and mobile teams surveyed mother-infant pairs attending 6-week and 9-month immunizations. HIV DNA testing was performed on HIV-exposed infants. Among 2521 mother-infant pairs surveyed nationally, 2423 (94.7%) reported HIV testing in pregnancy or prior diagnosis, of whom 200 (7.4%) were HIV-infected and 188 infants underwent HIV testing. TR was 8.8% (4.0%-18.3%) in 6-week and 8.9% (3.2%-22.2%) in 9-month cohorts including mothers with HIV diagnosed postpartum, of which 53% of infant infections were due to previously undiagnosed mothers. Of 276 HIV-exposed infants in the Nyanza survey, TR was 1.4% (0.4%-5.3%) at 6-week and 5.1% (2.5%-9.9%) at 9-months. Overall TR was lower in Nyanza, high HIV region, than nationally (3.3% vs. 7.2%, P = 0.02). HIV non-disclosure to male partners and incomplete ARVs were associated with TR in both surveys [aOR = 12.8 (3.0-54.3); aOR = 5.6 (1.2-27.4); aOR = 4.5 (1.0-20.0), aOR = 2.5, (0.8-8.4), respectively]. TR was lower in a high HIV prevalence region which had better ARV completion and partner HIV disclosure, possibly due to programmatic efficiencies or community/peer/partner support. Most 9-month infections were among infants of mothers without prior HIV diagnosis. Strategies to detect incident or undiagnosed maternal infections will be important to achieve PMTCT.

Prevalence and correlates of non-disclosure of maternal HIV status to male partners: a national survey in Kenya.

BACKGROUND: Prevention of mother-to-child HIV transmission (PMTCT) programs usually test pregnant women for HIV without involving their partners. Non-disclosure of maternal HIV status to male partners may deter utilization of PMTCT interventions since partners play a pivotal role in decision-making within the home including access to and utilization of health services. METHODS: Mothers attending routine 6-week and 9-month infant immunizations were enrolled at 141 maternal and child health (MCH) clinics across Kenya from June-December 2013. The current analysis was restricted to mothers with known HIV status who had a current partner. Multivariate logistic regression models adjusted for marital status, relationship length and partner attendance at antenatal care (ANC) were used to determine correlates of HIV non-disclosure among HIV-uninfected and HIV-infected mothers, separately, and to evaluate the relationship of non-disclosure with uptake of PMTCT interventions. All analyses accounted for facility-level clustering, RESULTS: Overall, 2522 mothers (86% of total study population) met inclusion criteria, 420 (17%) were HIV-infected. Non-disclosure of HIV results to partners was higher among HIV-infected than HIV-uninfected women (13% versus 3% respectively, p < 0.001). HIV-uninfected mothers were more likely to not disclose their HIV status to male partners if they were unmarried (adjusted odds ratio [aOR] = 3.79, 95% CI: 1.56-9.19, p = 0.004), had low (≤KSH 5000) income (aOR = 1.85, 95% CI: 1.00-3.14, p = 0.050), experienced intimate partner violence (aOR = 3.65, 95% CI: 1.84-7.21, p < 0.001) and if their partner did not attend ANC (aOR = 4.12, 95% CI: 1.89-8.95, p < 0.001). Among HIV-infected women, non-disclosure to male partners was less likely if women had salaried employment (aOR = 0.42, 95%CI: 0.18-0.96, p = 0.039) and each increasing year of relationship length was associated with decreased likelihood of non-disclosure (aOR = 0.90, 95% CI: 0.82-0.98, p = 0.015 for each year increase). HIV-infected women who did not disclose their HIV status to partners were less likely to uptake CD4 testing (aOR = 0.32, 95% CI: 0.15-0.69, p = 0.004), to use antiretrovirals (ARVs) during labor (OR = 0.38, 95% CI 0.15-0.97, p = 0.042), or give their infants ARVs (OR = 0.08, 95% CI 0.02-0.31, p < 0.001). CONCLUSION: HIV-infected women were less likely to disclose their status to partners than HIV-uninfected women. Non-disclosure was associated with lower use of PMTCT services. Facilitating maternal disclosure to male partners may enhance PMTCT uptake.

Intermittent screening and treatment or intermittent preventive treatment with dihydroartemisinin-piperaquine versus intermittent preventive treatment with sulfadoxine-pyrimethamine for the control of malaria during pregnancy in western Kenya: an open-label, three-group, randomised controlled superiority trial.

BACKGROUND: Every year, more than 32 million pregnancies in sub-Saharan Africa are at risk of malaria infection and its adverse consequences. The effectiveness of the intermittent preventive treatment with sulfadoxine-pyrimethamine strategy recommended by WHO is threatened by high levels of parasite resistance. We aimed to assess the efficacy and safety of two alternative strategies: intermittent screening with malaria rapid diagnostic tests and treatment of women who test positive with dihydroartemisinin-piperaquine, and intermittent preventive treatment with dihydroartemisinin-piperaquine. METHODS: We did this open-label, three-group, randomised controlled superiority trial at four sites in western Kenya with high malaria transmission and sulfadoxine-pyrimethamine resistance. HIV-negative pregnant women between 16 and 32 weeks' gestation were randomly assigned (1:1:1), via computer-generated permuted-block randomisation (block sizes of three, six, and nine), to receive intermittent screening and treatment with dihydroartemisinin-piperaquine, intermittent preventive treatment with dihydroartemisinin-piperaquine, or intermittent preventive treatment with sulfadoxine-pyrimethamine. Study participants, study clinic nurses, and the study coordinator were aware of treatment allocation, but allocation was concealed from study investigators, delivery unit nurses, and laboratory staff. The primary outcome was malaria infection at delivery, defined as a composite of peripheral or placental parasitaemia detected by placental histology, microscopy, or rapid diagnostic test. The primary analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01669941. FINDINGS: Between Aug 21, 2012, and June 19, 2014, we randomly assigned 1546 women to receive intermittent screening and treatment with dihydroartemisinin-piperaquine (n=515), intermittent preventive treatment with dihydroartemisinin-piperaquine (n=516), or intermittent preventive treatment with sulfadoxine-pyrimethamine (n=515); 1368 (88%) women comprised the intention-to-treat population for the primary endpoint. Prevalence of malaria infection at delivery was lower in the intermittent preventive treatment with dihydroartemisinin-piperaquine group than in the intermittent preventive treatment with sulfadoxine-pyrimethamine group (15 [3%] of 457 women vs 47 [10%] of 459 women; relative risk 0·32, 95% CI 0·18-0·56; p<0·0001), but not in the intermittent screening and treatment with dihydroartemisinin-piperaquine group (57 [13%] of 452 women; 1·23, 0·86-1·77; p=0·26). Compared with intermittent preventive treatment with sulfadoxine-pyrimethamine, intermittent preventive treatment with dihydroartemisinin-piperaquine was associated with a lower incidence of malaria infection during pregnancy (192·0 vs 54·4 events per 100 person-years; incidence rate ratio [IRR] 0·28, 95% CI 0·22-0·36; p<0·0001) and clinical malaria during pregnancy (37·9 vs 6·1 events; 0·16, 0·08-0·33; p<0·0001), whereas intermittent screening and treatment with dihydroartemisinin-piperaquine was associated with a higher incidence of malaria infection (232·0 events; 1·21, 1·03-1·41; p=0·0177) and clinical malaria (53·4 events; 1·41, 1·00-1·98; p=0·0475). We recorded 303 maternal and infant serious adverse events, which were least frequent in the intermittent preventive treatment with dihydroartemisinin-piperaquine group. INTERPRETATION: At current levels of rapid diagnostic test sensitivity, intermittent screening and treatment is not a suitable alternative to intermittent preventive treatment with sulfadoxine-pyrimethamine in the context of high sulfadoxine-pyrimethamine resistance and malaria transmission. However, dihydroartemisinin-piperaquine is a promising alternative drug to replace sulfadoxine-pyrimethamine for intermittent preventive treatment. Future studies should investigate the efficacy, safety, operational feasibility, and cost-effectiveness of intermittent preventive treatment with dihydroartemisinin-piperaquine. FUNDING: The Malaria in Pregnancy Consortium, which is funded through a grant from the Bill & Melinda Gates Foundation to the Liverpool School of Tropical Medicine.

Pharmacokinetics of mefloquine and its effect on sulfamethoxazole and trimethoprim steady-state blood levels in intermittent preventive treatment (IPTp) of pregnant HIV-infected women in Kenya.

BACKGROUND: Intermittent preventive treatment in pregnancy with sulfadoxine/pyrimethamine is contra-indicated in HIV-positive pregnant women receiving sulfamethoxazole/trimethoprim prophylaxis. Since mefloquine is being considered as a replacement for sulfadoxine/pyrimethamine in this vulnerable population, an investigation on the pharmacokinetic interactions of mefloquine, sulfamethoxazole and trimethoprim in pregnant, HIV-infected women was performed. METHODS: A double-blinded, placebo-controlled study was conducted with 124 HIV-infected, pregnant women on a standard regimen of sulfamethoxazole/trimethoprim prophylaxis. Seventy-two subjects received three doses of mefloquine (15 mg/kg) at monthly intervals. Dried blood spots were collected from both placebo and mefloquine arms four to 672 h post-administration and on day 7 following a second monthly dose of mefloquine. A novel high-performance liquid chromatographic method was developed to simultaneously measure mefloquine, sulfamethoxazole and trimethoprim from each blood spot. Non-compartmental methods using a naïve-pooled data approach were used to determine mefloquine pharmacokinetic parameters. RESULTS: Sulfamethoxazole/trimethoprim prophylaxis did not noticeably influence mefloquine pharmacokinetics relative to reported values. The mefloquine half-life, observed clearance (CL/f), and area-under-the-curve (AUC0→∞) were 12.0 days, 0.035 l/h/kg and 431 µg-h/ml, respectively. Although trimethoprim steady-state levels were not significantly different between arms, sulfamethoxazole levels showed a significant 53% decrease after mefloquine administration relative to the placebo group and returning to pre-dose levels at 28 days. CONCLUSIONS: Although a transient decrease in sulfamethoxazole levels was observed, there was no change in hospital admissions due to secondary bacterial infections, implying that mefloquine may have provided antimicrobial protection.

Maternal Tenofovir Disoproxil Fumarate Use in Pregnancy and Growth Outcomes among HIV-Exposed Uninfected Infants in Kenya.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) is commonly used in antiretroviral treatment (ART) and preexposure prophylaxis regimens. We evaluated the relationship of prenatal TDF use and growth outcomes among Kenyan HIV-exposed uninfected (HEU) infants. MATERIALS AND METHODS: We included PCR-confirmed HEU infants enrolled in a cross-sectional survey of mother-infant pairs conducted between July and December 2013 in Kenya. Maternal ART regimen during pregnancy was determined by self-report and clinic records. Six-week and 9-month z-scores for weight-for-age (WAZ), weight-for-length (WLZ), length-for-age (LAZ), and head circumference-for-age (HCAZ) were compared among HEU infants with and without TDF exposure using t-tests and multivariate linear regression models. RESULTS: Among 277 mothers who received ART during pregnancy, 63% initiated ART before pregnancy, of which 89 (32%) used TDF. No differences in birth weight (3.0 kg versus 3.1 kg, p = 0.21) or gestational age (38 weeks versus 38 weeks, p = 0.16) were detected between TDF-exposed and TDF-unexposed infants. At 6 weeks, unadjusted mean WAZ was lower among TDF-exposed infants (-0.8 versus -0.4, p = 0.03), with a trend towards association in adjusted analyses (p = 0.06). There were no associations between prenatal TDF use and WLZ, LAZ, and HCAZ in 6-week or 9-month infant cohorts. CONCLUSION: Maternal TDF use did not adversely affect infant growth compared to other regimens.

Intermittent preventive treatment of malaria in pregnancy with mefloquine in HIV-infected women receiving cotrimoxazole prophylaxis: a multicenter randomized placebo-controlled trial.

BACKGROUND: Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended for malaria prevention in HIV-negative pregnant women, but it is contraindicated in HIV-infected women taking daily cotrimoxazole prophylaxis (CTXp) because of potential added risk of adverse effects associated with taking two antifolate drugs simultaneously. We studied the safety and efficacy of mefloquine (MQ) in women receiving CTXp and long-lasting insecticide treated nets (LLITNs). METHODS AND FINDINGS: A total of 1,071 HIV-infected women from Kenya, Mozambique, and Tanzania were randomized to receive either three doses of IPTp-MQ (15 mg/kg) or placebo given at least one month apart; all received CTXp and a LLITN. IPTp-MQ was associated with reduced rates of maternal parasitemia (risk ratio [RR], 0.47 [95% CI 0.27-0.82]; p=0.008), placental malaria (RR, 0.52 [95% CI 0.29-0.90]; p=0.021), and reduced incidence of non-obstetric hospital admissions (RR, 0.59 [95% CI 0.37-0.95]; p=0.031) in the intention to treat (ITT) analysis. There were no differences in the prevalence of adverse pregnancy outcomes between groups. Drug tolerability was poorer in the MQ group compared to the control group (29.6% referred dizziness and 23.9% vomiting after the first IPTp-MQ administration). HIV viral load at delivery was higher in the MQ group compared to the control group (p=0.048) in the ATP analysis. The frequency of perinatal mother to child transmission of HIV was increased in women who received MQ (RR, 1.95 [95% CI 1.14-3.33]; p=0.015). The main limitation of the latter finding relates to the exploratory nature of this part of the analysis. CONCLUSIONS: An effective antimalarial added to CTXp and LLITNs in HIV-infected pregnant women can improve malaria prevention, as well as maternal health through reduction in hospital admissions. However, MQ was not well tolerated, limiting its potential for IPTp and indicating the need to find alternatives with better tolerability to reduce malaria in this particularly vulnerable group. MQ was associated with an increased risk of mother to child transmission of HIV, which warrants a better understanding of the pharmacological interactions between antimalarials and antiretroviral drugs. TRIAL REGISTRATION: ClinicalTrials.gov NCT 00811421; Pan African Clinical Trials Registry PACTR 2010020001813440 Please see later in the article for the Editors' Summary.

Higher prevalence of stunting and poor growth outcomes in HIV-exposed uninfected than HIV-unexposed infants in Kenya.

BACKGROUND: With the growing population of HIV-exposed uninfected (HEU) children globally, it is important to determine population-level growth differences between HEU and HIV-unexposed uninfected (HUU) children. METHODS: We analyzed data from a population-level survey enrolling mother-infant pairs attending 6-week and 9-month immunizations in 140 clinics across Kenya. Weight-for-age (WAZ), length-for-age (LAZ), head circumference-for-age (HCAZ) z-scores and underweight (WAZ < -2), stunting (LAZ < -2), and microcephaly (HCAZ < -2), were compared between HEU and HUU. Correlates of growth faltering and poor growth were assessed using generalized Poisson and linear regression models. RESULTS: Among 2457 infants, 456 (19%) were HEU. Among mothers living with HIV, 64% received antiretroviral therapy (ART) and 22% were on antiretroviral prophylaxis during pregnancy. At 9 months, 72% of HEU and 98% of HUU were breastfeeding. At 6 weeks, HEU had lower mean WAZ (-0.41 vs. -0.09; P < 0.001) and LAZ (-0.99 vs. -0.31; P = 0.001) than HUU. Stunting was higher in HEU than HUU at 6 weeks (34% vs. 18%, P < 0.001) and 9 months (20% vs. 10%, P < 0.001). In multivariable analyses, HEU had lower mean LAZ at 6 weeks (-0.67, 95% confidence interval [CI]: -1.07, -0.26) and 9 months (-0.57, 95% CI: -0.92, -0.21) and HEU had higher stunting prevalence (week-6 adjusted prevalence ratio [aPR]: 1.88, 95% CI: 1.35, 2.63; month-9 aPR: 2.10, 95% CI: 1.41, 3.13). HEU had lower mean head circumference (-0.49, 95% CI: -0.91, -0.07) and higher prevalence of microcephaly (aPR: 2.21, 95% CI: 1.11, 4.41) at 9 months. CONCLUSION: Despite high maternal ART coverage, HEU had poorer growth than HUU in this large population-level comparison. Optimizing breastfeeding practices in HEU may be useful to improve growth.

A national household survey on HIV prevalence and clinical cascade among children aged ≤15 years in Kenya (2018).

We analyzed data from the 2018 Kenya Population-Based HIV Impact Assessment (KENPHIA), a cross-sectional, nationally representative survey, to estimate the burden and prevalence of pediatric HIV infection, identify associated factors, and describe the clinical cascade among children aged < 15 years in Kenya. Interviewers collected information from caregivers or guardians on child's demographics, HIV testing, and treatment history. Blood specimens were collected for HIV serology and if HIV-positive, the samples were tested for viral load and antiretrovirals (ARV). For participants <18 months TNA PCR is performed. We computed weighted proportions with 95% confidence intervals (CI), accounting for the complex survey design. We used bivariable and multivariable logistic regression to assess factors associated with HIV prevalence. Separate survey weights were developed for interview responses and for biomarker testing to account for the survey design and non-response. HIV burden was estimated by multiplying HIV prevalence by the national population projection by age for 2018. Of 9072 survey participants (< 15 years), 87% (7865) had blood drawn with valid HIV test results. KENPHIA identified 57 HIV-positive children, translating to an HIV prevalence of 0.7%, (95% CI: 0.4%-1.0%) and an estimated 138,900 (95% CI: 84,000-193,800) of HIV among children in Kenya. Specifically, children who were orphaned had about 2 times higher odds of HIV-infection compared to those not orphaned, adjusted Odds Ratio (aOR) 2.2 (95% CI:1.0-4.8). Additionally, children whose caregivers had no knowledge of their HIV status also had 2 times higher odds of HIV-infection compared to whose caregivers had knowledge of their HIV status, aOR 2.4 (95% CI: 1.1-5.4)". From the unconditional analysis; population level estimates, 78.9% of HIV-positive children had known HIV status (95% CI: 67.1%-90.2%), 73.6% (95% CI: 60.9%-86.2%) were receiving ART, and 49% (95% CI: 32.1%-66.7%) were virally suppressed. However, in the clinical cascade for HIV infected children, 92% (95% CI: 84.4%-100%) were receiving ART, and of these, 67.1% (95% CI: 45.1%-89.2%) were virally suppressed. The KENPHIA survey confirms a substantial HIV burden among children in Kenya, especially among orphans.

Associations of Sociodemographic and Clinical Factors with Late Presentation for Early Infant HIV Diagnosis (EID) Services in Kenya.

BACKGROUND: Understanding the missed opportunities in early infant HIV testing within the PMTCT program is essential to address any gaps. The study set out to describe the clinical and sociodemographic characteristics of the infants presenting late for early infant diagnosis in Kenya. METHODS: We abstracted routinely collected clinical and sociodemographic characteristics, in a cross-sectional study, on all HIV-infected infants with a positive polymerase chain reaction (PCR) test from 1,346 President's Emergency Plan for AIDS Relief (PEPFAR) supported health facilities for the period October 2016 to September 2018. We used multivariate logistic regression to examine the association of sociodemographic and clinical characteristics with late (>2 months after birth) presentation for infant HIV testing. RESULTS: Of the 4,011 HIV-infected infants identified, the median infant age at HIV diagnosis was 3 months [interquartile range (IQR), 1-16 months], and two-thirds [2,669 (66.5%)] presented late for infant HIV testing. Factors that were associated with late presentation for infant testing were: maternal ANC non-attendance, adjusted odds ratio (aOR) 1.41 (95% confidence interval (CI) 1.18 -1.69); new maternal HIV diagnosis, aOR 1.45, (95%CI 1.24 -1.7); and lack of maternal antiretroviral therapy(ART), aOR 1.94, (95% CI 1.64 - 2.30). There was a high likelihood of identifying HIV-infected infants among infants who presented for medical services in the outpatient setting (aOR 18.9; 95% CI 10.2 - 34.9) and inpatient setting (aOR 12.2; 95% CI 6.23-23.9) compared to the infants who presented late in maternity. CONCLUSION AND GLOBAL HEALTH IMPLICATIONS: Gaps in early infant HIV testing suggest the need to increase maternal pre-pregnancy HIV diagnosis, timely antenatal care, early infant diagnosis services, early identification of mothers who seroconvert during pregnancy or breastfeeding and improved HIV screening in outpatient and inpatient settings. Early referral from the community and access to health facilities should be strengthened by the implementation of national PMTCT guidelines.

Factors Associated with Loss to Follow-Up Among Patients Receiving HIV Treatment in Nairobi, Kenya.

We investigated factors associated with loss to follow-up (LTFU) in 24 urban health facilities in Nairobi, Kenya. We conducted a retrospective analysis of routinely collected data to assess factors associated with LTFU in the period October 1, 2016, to June 30, 2017. LTFU was defined as no antiretroviral therapy (ART) refill for ≥90 days and no documentation of transfer, death, or treatment cessation in the patient chart, and if no lapse of ≥90 days between ART refills, patients were considered retained in care. Multivariable logistic regression modeling was used to compute odds ratios and 95% confidence interval (CI) for LTFU. Our analysis included 633 individuals who were LTFU and 13,098 individuals retained in care. Most participants (69.6%) were women, and median age was 33.0 years (interquartile range, 27.2-38.3 years). Median ART duration was shorter among those LTFU (0.4 years) than retained patients (2.5 years, p < .0001). Being male [adjusted odds ratio (aOR) 1.30; 95% CI: 1.04-1.63, p = .02], transferring into facilities while already receiving ART (aOR 11.58; 95% CI: 8.23-16.29, p < .0001), and having a shorter ART duration (<6 months) were associated with increased odds of LTFU. Patients who transferred into a facility while already receiving ART had the highest adjusted odds of being LTFU compared with those retained in care. In this urban and highly mobile population, transferring into facilities while already receiving ART was strongly associated with LTFU. Focusing programming efforts on patients transferring between urban clinics to identify reasons for transfer and potential barriers to treatment adherence could help improve patient outcomes. Supplementary case management and support may be needed to promote a seamless transition and ensure uninterrupted engagement in HIV care and treatment.

"They Just Tell Me to Abstain:" Variable Access to and Uptake of Sexual and Reproductive Health Services Among Adolescents Living With HIV in Kenya.

Background: To improve holistic care for adolescents living with HIV (ALHIV), including integration of sexual and reproductive health services (SRHS), the Kenya Ministry of Health implemented an adolescent package of care (APOC). To inform optimized SRH service delivery, we sought to understand the experiences with SRHS for ALHIV, their primary caregivers, and health care workers (HCWs) following APOC implementation. Methods: We completed a mixed methods evaluation to characterize SRHS provided and personal experiences with access and uptake using surveys conducted with facility managers from 102 randomly selected large HIV treatment facilities throughout Kenya. Among a subset of 4 APOC-trained facilities in a high burden county, we conducted in-depth interviews (IDIs) with 40 ALHIV and 40 caregivers of ALHIV, and 4 focus group discussions (FGDs) with HCWs. Qualitative data was analyzed using thematic analysis. Facility survey data was analyzed using descriptive statistics. Results: Of 102 surveyed facilities, only 56% reported training in APOC and 12% reported receiving additional adolescent-related SRHS training outside of APOC. Frequency of condom provision to ALHIV varied, with 65% of facilities providing condoms daily and 11% never providing condoms to ALHIV. Family planning (FP) was provided to ALHIV daily in 60% of facilities, whereas 14% of facilities reported not providing any FP services to ALHIV. Screening and treatment for STIs for adolescents were provided at all clinics, with 67% providing STI services daily. Three key themes emerged characterizing experiences with adolescent SRHS access and uptake: (1) HCWs were the preferred source for SRH information, (2) greater adolescent autonomy was a facilitator of SRH discussions with HCWs, and (3) ALHIV had variable access to and limited uptake of SRHS within APOC-trained health facilities. The primary SRHS reported available to ALHIV were abstinence and condom use education. There was variable access to FP, condoms, pregnancy and STI testing, and partner services. Adolescents reported limited utilization of SRHS beyond education. Conclusions: Our results indicate a gap in SRHS offered within APOC trained facilities and highlight the importance of adolescent autonomy when providing SRHS and further HCW training to improve SRHS integration within HIV care for ALHIV.

Disclosure and Clinical Outcomes Among Young Adolescents Living With HIV in Kenya.

PURPOSE: Informing adolescents of their own HIV infection is critical as the number of adolescents living with HIV increases. We assessed the association between HIV disclosure and retention in care and mortality among adolescents aged 10-14 years in Kenya's national program. METHODS: We abstracted routinely collected patient-level data for adolescents enrolled into HIV care in 50 health facilities from November 1, 2004, through March 31, 2010. We defined disclosure as any documentation that the adolescent had been fully or partially made aware of his or her HIV status. We compared weighted proportions for categorical variables using χ2 and weighted logistic regression to identify predictors of HIV disclosure; we estimated the probability of LTFU using Kaplan-Meier methods and dying using Cox regression-based test for equality of survival curves. RESULTS: Of the 710 adolescents aged 10-14 years analyzed; 51.3% had severe immunosuppression, 60.3% were in WHO stage 3 or 4, and 36.6% were aware of their HIV status. Adolescents with HIV-infected parents, histories of opportunistic infections (OIs), and enrolled in support groups were more likely to be disclosed to. At 36 months, disclosure was associated with lower mortality [1.5% (95% CI .6%-4.1%) versus 5.4% (95% CI 3.6.6%-8.0%, p < .001)] and lower LTFU [6.2% (95% CI 3.0%-12.6%) versus 33.9% (95% CI 27.3%-41.1%) p < .001]. CONCLUSIONS: Only one third of HIV-infected Kenyan adolescents in treatment programs had been told they were infected, and knowing their HIV status was associated with reduced LTFU and mortality. The disclosure process should be systematically encouraged and organized for HIV-infected adolescents.

Short Communication: Reduced Nevirapine Concentrations Among HIV-Positive Women Receiving Mefloquine for Intermittent Preventive Treatment for Malaria Control During Pregnancy.

Clinical trials demonstrated intermittent preventive treatment in pregnancy with mefloquine (MQ) reduced malaria rates among pregnant women, yet an unexpected higher risk of mother-to-child transmission (MTCT) of HIV among HIV-positive women receiving MQ has also been observed. To determine if interactions between antiretroviral drugs (ARVs) and MQ could contribute to the increased MTCT observed in women receiving MQ, we performed a retrospective cross-sectional analysis of ARV plasma concentrations in peripheral blood (maternal plasma) and cord blood (cord plasma) collected at delivery from 186 mothers participating in a randomized clinical trial of MQ (n = 102) compared with placebo (n = 84) in Kenya. Plasma zidovudine (AZT), lamivudine (3TC), and nevirapine (NVP) concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry. Although only 4% (7/186) reported not using these ARVs, AZT, 3TC, and NVP were all below the limit of detection in 44% of maternal plasma and 42% of cord plasma samples, and proportions were similar between the two study arms. Median concentrations of AZT and 3TC were not significantly lower in the MQ arm compared with the placebo arm for maternal plasma and cord plasma (p > .05). However, median NVP concentrations were significantly lower in the MQ study arm compared with the placebo study arm in both maternal plasma (1,597 ng/mL vs. 2,353 ng/mL, Mann-Whitney Rank Sum, p = .023) and cord plasma (2,038 ng/mL vs. 2,434 ng/mL, p = .048). Reduced NVP concentrations in maternal and cord plasma of women receiving MQ suggest MQ may affect NVP metabolism for both mother and infant. These results highlight the need to evaluate potential drug-drug interactions between candidate antimalarials and ARVs for use in pregnant women.