Adherence challenges and opportunities for optimizing care through enhanced adherence counseling for adolescents with suspected HIV treatment failure in Kenya.

BACKGROUND: Adolescents living with HIV (ALHIV) experience higher mortality and are more likely to have poor antiretroviral therapy (ART) adherence and unsuppressed viral load (VL) compared to adults. Enhanced adherence counseling (EAC) is a client-centered counseling strategy that aims to identify and address barriers to optimal ART use and can be tailored to the unique needs of adolescents. This study aimed to better understand adherence barriers among ALHIV with suspected treatment failure and their experience with EAC to inform future programming. METHODS: A qualitative study was conducted in Homa Bay and Turkana counties, Kenya in 2019 with adolescents and caregivers of children and adolescents living with HIV with suspected treatment failure after ≥6 months on ART and who had received ≥1 EAC sessions. Sixteen focus group discussions (FGDs) were conducted; five FGDs each were held with adolescents 12-14 years (n = 48) and 15-19 years (n = 36). Caregivers (n = 52) participated in six FGDs. Additionally, 17 healthcare workers providing pediatric/adolescent HIV services participated in in-depth interviews. Audio recordings were transcribed and translated from Kiswahili or Dholuo into English and coded using MAXQDA software. Data were thematically analyzed by participant group. RESULTS: Participants identified adolescents' fear of being stigmatized due to their HIV status and their relationship with and level of support provided by caregivers. This underpinned and often undermined adolescents' ART-taking behavior and progress towards more independent medication management. Adolescents were generally satisfied with EAC and perceived it to be important in improving adherence and reducing VL. However, problems were noted with facility-based, individual EAC counseling, including judgmental attitudes of providers and difficulties traveling to and keeping EAC clinic appointments. Participant-suggested improvements to EAC included peer support groups in addition to individual counseling, allowing for greater flexibility in the timing and location of sessions and greater caregiver involvement. CONCLUSIONS: The findings provide opportunities to better tailor EAC interventions to promote improved ALHIV adherence and caregiver-supported disease management. Multi-prong EAC interventions that include peer-led and community approaches and target adolescent and caregiver treatment literacy may improve EAC delivery, address issues contributing to poor adherence, and position adolescents to achieve viral suppression. TRIAL REGISTRATION: ClinicalTrials.gov : NCT04915469.

"When you have a high life, and you like sex, you will be afraid": a qualitative evaluation of adolescents' decision to test for HIV in Zambia and Kenya using the health belief model.

BACKGROUND: HIV testing among adolescents is significantly lower than among adults and many adolescents living with HIV do not know their status. Adolescent perceptions of HIV testing are poorly understood and may negatively affect testing uptake. Using a qualitative design, this study sought to explore perceptions about HIV testing and treatment among adolescents living with HIV and adolescents of unknown HIV status in Lusaka, Zambia and Kenya. METHODS: Study participants were adolescents aged 15-19 years old. The adolescents living with HIV were recruited from HIV support groups at health facilities. Adolescents of unknown HIV status were recruited from existing adolescent groups within the community. In both Zambia and Kenya, four focus group discussions (FGDs) were conducted with adolescents living with HIV and four FGDs were conducted with adolescents whose HIV status was unknown, for a total of 16 FDGs. FGDs consisted of 6-12 participants, a moderator, and a note-taker. FGDs were audio-recorded, transcribed, and translated into transcripts. Transcripts were coded in the qualitative analysis software program MAXQDA v. 12. Data reduction and summary tables were generated to help identify themes across the two study population groups. Data were interpreted within the health belief model. RESULTS: Adolescents discussed the challenges of facing a positive HIV test result, including fear of a positive result and need to change their lifestyle, fear of social isolation, and perception of the lost opportunity to achieve future dreams. Most adolescents of unknown status were not as aware of the benefits of learning their HIV status, nor were they aware of the ability to live a long and healthy life on ART. HIV-positive adolescents reported that the messages targeted towards adolescents focus on the need to remain HIV-negative, as opposed to the benefits of knowing one's status. Adolescents described age and requirements for parental permission as a significant limitation in their ability to access HIV testing. CONCLUSIONS: Adolescents require more information about the benefits of testing early and the ability to live a long and healthy life on ART. Educating adolescents that HIV testing is a normative behavior among their peers could strengthen HIV testing among adolescents.

Integrating pediatric TB services into child healthcare services in Africa: study protocol for the INPUT cluster-randomized stepped wedge trial.

BACKGROUND: Tuberculosis is among the top-10 causes of mortality in children with more than 1 million children suffering from TB disease annually worldwide. The main challenge in young children is the difficulty in establishing an accurate diagnosis of active TB. The INPUT study is a stepped-wedge cluster-randomized intervention study aiming to assess the effectiveness of integrating TB services into child healthcare services on TB diagnosis capacities in children under 5 years of age. METHODS: Two strategies will be compared: i) The standard of care, offering pediatric TB services based on national standard of care; ii) The intervention, with pediatric TB services integrated into child healthcare services: it consists of a package of training, supportive supervision, job aids, and logistical support to the integration of TB screening and diagnosis activities into pediatric services. The design is a cluster-randomized stepped-wedge of 12 study clusters in Cameroon and Kenya. The sites start enrolling participants under standard-of-care and will transition to the intervention at randomly assigned time points. We enroll children aged less than 5 years with a presumptive diagnosis of TB after obtaining caregiver written informed consent. The participants are followed through TB diagnosis and treatment, with clinical information prospectively abstracted from their medical records. The primary outcome is the proportion of TB cases diagnosed among children < 5 years old attending the child healthcare services. Secondary outcomes include: number of children screened for presumptive active TB; diagnosed; initiated on TB treatment; and completing treatment. We will also assess the cost-effectiveness of the intervention, its acceptability among health care providers and users, and fidelity of implementation. DISCUSSION: Study enrolments started in May 2019, enrolments will be completed in October 2020 and follow up will be completed by June 2021. The study findings will be disseminated to national, regional and international audiences and will inform innovative approaches to integration of TB screening, diagnosis, and treatment initiation into child health care services. TRIAL RESISTRATION: NCT03862261, initial release 12 February 2019.

Anaemia in HIV-infected pregnant women receiving triple antiretroviral combination therapy for prevention of mother-to-child transmission: a secondary analysis of the Kisumu breastfeeding study (KiBS).

OBJECTIVE: The prevalence of anaemia during pregnancy is estimated to be 35-75% in sub-Saharan Africa and is associated with an increased risk of maternal mortality. We evaluated the frequency and factors associated with anaemia in HIV-infected women undergoing antiretroviral (ARV) therapy for prevention of mother-to-child transmission (PMTCT) enrolled in The Kisumu Breastfeeding Study 2003-2009. METHODS: Maternal haematological parameters were monitored from 32 to 34 weeks of gestation to 2 years post-delivery among 522 enrolled women. Clinical and laboratory assessments for causes of anaemia were performed, and appropriate management was initiated. Anaemia was graded using the National Institutes of Health Division of AIDS 1994 Adult Toxicity Tables. Data were analysed using SAS software, v 9.2. The Wilcoxon two-sample rank test was used to compare groups. A logistic regression model was fitted to describe the trend in anaemia over time. RESULTS: At enrolment, the prevalence of any grade anaemia (Hb < 9.4 g/dl) was 61.8%, but fell during ARV therapy, reaching a nadir (7.4%) by 6 months post-partum. A total of 41 women (8%) developed severe anaemia (Hb < 7 g/dl) during follow-up; 2 (4.9%) were hospitalised for blood transfusion, whereas 3 (7.3%) were transfused while hospitalised (for delivery). The greatest proportion of severe anaemia events occurred around delivery (48.8%; n = 20). Anaemia (Hb ≥ 7 and < 9.4 g/dl) at enrolment was associated with severe anaemia at delivery (OR 5.87; 95% CI: 4.48, 7.68, P < 0.01). Few cases of severe anaemia coincided with clinical malaria (24.4%; n = 10) and helminth (7.3%; n = 3) infections. CONCLUSION: Resolution of anaemia among most participants during study follow-up was likely related to receipt of ARV therapy. Efforts should be geared towards addressing common causes of anaemia in HIV-infected pregnant women, prioritising initiation of ARV therapy and management of peripartum blood loss.

Post-abortion care services for youth and adult clients in Kenya: a comparison of services, client satisfaction and provider attitudes.

Unsafe abortion accounts for 35% of maternal mortality in Kenya. Post-abortion care (PAC) reduces maternal death and provides an opportunity to prevent unwanted pregnancies. Few studies have documented how the receipt of PAC services varies by client age. In this study, descriptive data were collected from clients, providers and eight health facilities in Kenya's Central and Nairobi provinces to examine receipt of PAC services by client age, client satisfaction and provider attitudes. Delivery of PAC treatment, pain management, HIV and STI services and violence screening did not vary by age. However, fewer youth between the ages of 15 and 24 received a contraceptive method compared with adult clients (35% versus 48%; p=0.02). Forty-nine per cent of youth reported not using a family planning method due to fears of infertility, side-effects or lack of knowledge compared with 22% of adults. Additional efforts are needed in Kenya to bolster the family planning services that young PAC clients receive and increase the uptake of contraception.

Experiences of adolescents and youth with HIV testing and linkage to care through the Red Carpet Program (RCP) in Kenya.

Adolescents and youth living with HIV (AYLHIV) experience worse health outcomes compared to adults. We aimed to understand the experiences of AYLHIV in care in the youth-focused Red-Carpet program in Kenya to assess the quality of service provision and identify programmatic areas for optimization. We conducted focus group discussions among 39 AYLHIV (15-24 years) and structured analysis into four thematic areas. Within the HIV testing theme, participants cited fear of positive results, confidentiality and stigma concerns, and suggested engaging the community and youth in HIV testing opportunities. Within the HIV treatment adherence theme, participants cited forgetfulness, stigma, adverse side effects, lack of family support, and treatment illiteracy as barriers to adherence. Most participants reported positive experiences with healthcare providers and peer support. In terms of the HIV status disclosure theme, AYLHIV cited concerns about their future capacity to conceive children and start families and discussed challenges with understanding HIV health implications and sharing their status with friends and partners. Youth voices informing service implementation are essential in strengthening our capacity to optimize the support for AYLHIV within the community, at schools and healthcare facilities.

Follow-up Outcomes of Children, Adolescents and Young People on Darunavir-Based Third-line Antiretroviral Therapy - Observational Cohort from Nine African Countries.

BACKGROUND: We assessed clinical outcomes among children, adolescents and young people (< 25 years) on darunavir-based antiretroviral therapy (ART) in nine sub-Saharan African countries. SETTING: Third-line ART centers in Cameroon, Eswatini, Kenya, Lesotho, Nigeria, Rwanda, Uganda, Zambia and Zimbabwe. METHODS: From January 2019 to December 2022, we collected data from a cohort of children, adolescents and young people receiving third-line ART from 9 sub-Saharan African countries. Data on treatment continuity, viral suppression, death and clinic transfers were extracted from medical records and summarized. Cox proportional hazards models were used to identify factors independently associated with retention in care. RESULTS: Of 871 participants enrolled, median age 14.8 (range: 0.2 - 24.7) years, 488 (56.0%) male; 809 (92.9%) [median duration of follow-up of 28.3 months (IQR:17.5 - 45.2)] had final outcomes after initiating third-line ART. Of these, 711 (87.9%) were alive and in care at the end of study follow-up, 29 (3.6%) died, 30 (3.7%) transferred to other facilities, and 39 (4.8%) were lost to follow-up. Retention in care was less likely among males compared to females (aHR: 0.85, 95%CI 0.72-1.0), and in 10-14-year-olds compared to younger children. Adolescents (15-19 years) had higher mortality compared to children <10 years of age (aSHR: 4.20, 95% CI 1.37-12.87). Viral suppression was seen in 345/433 (79.7%), 249/320 (77.8%), and 546/674 (81.0%) patients with results at 6, 12 months and study end, respectively. CONCLUSION: A high proportion of children and young people receiving third-line ART in Sub-Saharan Africa, remain in care, and attain viral suppression during follow-up.

Effect of COVID-19 on paediatric TB service delivery and patients' comfort receiving TB services in Cameroon and Kenya during COVID: a qualitative assessment.

BACKGROUND: The outbreak of COVID-19 has caused a setback to the gains achieved in tuberculosis (TB) control by impairing TB diagnosis, delaying treatment initiation and aggravating TB deaths. This study explored the effect of COVID-19 on paediatric TB services provided through the Catalysing Paediatric TB Innovations (CaP-TB) project among caregivers of children receiving TB services and healthcare workers (HCWs) providing TB services in Cameroon and Kenya. METHODS: From March to September 2021, in-depth interviews (44) were conducted with caregivers whose children under 5 years had gone through TB services and programme managers (10) overseeing the CaP-TB project. Focus group discussions were conducted with HCWs (07) and community health workers (04) supporting TB care services. Transcripts were coded and analysed by using MAXQDA V.12. RESULTS: The COVID-19 pandemic has caused fear and anxiety among HCWs and caregivers. This fear was motivated by stigma related to COVID-19 and affected the ability to screen patients for TB due to the similarity of symptoms with COVID-19. The health-seeking behaviour of patients was affected, as many caregivers avoided hospitals and those accessing the facilities concealed their sickness due to fear of testing positive or being vaccinated. In addition, COVID-19 mitigation strategies implemented by both government and health facilities to curb the spread of the virus limited patient access to paediatric healthcare services. These included temporary closure of health facilities due to COVID-19 infections among staff, transfer of services to other spaces, spacing out patient appointments and reduced time spent with patients. CONCLUSIONS: The outbreak of COVID-19 has induced fear and stigma that affected patients' health-seeking behaviour and provider attitudes towards paediatric TB service delivery. In addition, facility and governmental measures put in place to mitigate COVID-19 impact negatively affected paediatric service delivery. Training for health personnel, timely provision of personal protective equipments and appropriate communication strategies could help mitigate COVID-19 impact on paediatric TB service delivery.

Operational Research to Support Rapid Evidence-Based Responses to Outbreaks: Learnings from COVID-19.

During the COVID-19 pandemic, the need for making testing readily available was recognized as an important factor for individuals to help make informed decisions, including to isolate or seek care, and for policymakers to control transmission. Toward this end, FIND and the Access to COVID-19 Tools Accelerator funded 16 rapid operational research studies and one implementation project in Africa, the Caribbean, and Asia evaluating the utility, acceptability, and feasibility of different community-based SARS-CoV-2 testing approaches. Here, we discuss common factors and challenges encountered during study implementation. We note six key factors essential for success: 1) collaboration and partnerships; 2) buy-in of local stakeholders, including communities; 3) access to affordable supplies; 4) flexible financing; 5) effective approval systems; and 6) a skilled and motivated workforce. We also note various challenges that must be addressed to fully capitalize on these success factors. In particular, ethics committees are often not well equipped to assess operational research during outbreaks. Outbreaks, especially of novel pathogens, are unpredictable, and transmission dynamics are even more likely to change if the pathogen is prone to frequent mutations, such as SARS-CoV-2. Research that aims to evaluate strategies for curbing transmission must hence be easily and swiftly adaptable. This requires flexibility from researchers, funders, staff conducting the studies, and ethics and other approval committees. International guidelines for evaluating operational research protocols in outbreaks are needed to provide timely evidence to enable informed decisions by individuals, communities, and policymakers, thereby reducing both the human and the economic impact of outbreaks.

Antiretroviral treatment failure and associated factors among people living with HIV on therapy in Homa Bay, Kenya: A retrospective study.

Despite large numbers of patients accessing antiretroviral treatment (ART) in Kenya, few studies have explored factors associated with virologic failure in Western Kenya, specifically. We undertook a study in Homa Bay County, Kenya to assess the extent of virologic treatment failure and factors associated with it. This was an observational retrospective study conducted from September 2020 to January 2021. Data were abstracted from the records of patients who had been on ART for at least six months at the time of data collection after systematic sampling stratified by age group at ART initiation (0-14 and 15+ years), using probability proportion to the numbers of patients attending the facility. Confirmed viral treatment failure was defined as viral load ≥1000 copies/ml based on two consecutive viral load measurements after at least three months of enhanced adherence counseling. Data were analyzed using descriptive statistics and Cox regression modeling. Of the 2,007 patients sampled, 160 (8.0%) had confirmed virologic treatment failure. Significantly higher virologic treatment failure rates were identified among male patients 78/830 (9.4%) and children 115/782 (14.7%). Factors associated with virologic treatment failure (VTF), were age 0-14 years, adjusted hazard ratio (AHR) 4.42, (95% Confidence Interval [CI], 3.12, 6.32), experience of treatment side effects AHD: 2.43, (95% CI, 1.76, 3.37), attending level 2/3 health facility, AHR: 1.87, (95% CI: 1.29, 2,72), and history of opportunistic infections (OIs), AHR: 1.81, (95% CI, 1.76, 3.37). Children, attendees of level 2/3 health facilities, patients with a history of OIs, and those experiencing treatment side-effects are at risk of VTF. Increased focus on children and adolescents on screening for drug resistance, administration of and adherence to medication, and on effective information and education on side-effects is critical. Additionally, there is need for increased training and support for health care workers at primary level care facilities.

Advanced HIV disease in Homa Bay County, Kenya: Characteristics of newly-diagnosed and antiretroviral therapy-experienced clients.

Advanced HIV disease (AHD) remains a significant burden, despite the widespread use of antiretroviral therapy (ART) programs. Individuals with AHD are at a high risk of death even after starting ART. We characterized treatment naïve and treatment experienced clients presenting with AHD in western Kenya to inform service delivery and program improvement. We conducted a retrospective study using routinely collected program data from October 2016 to September 2019 for AHD clients in eight facilities in Homa Bay County, Kenya. Demographic and clinical data were abstracted from the medical records of AHD clients, defined as HIV-positive clients aged ≥ 5 years with documented CD4 count < 200 cells/mm3 and/or WHO clinical stage II/IV. Associations were assessed using Pearson's chi-square and Mann-Whitney Rank-Sum tests at 5% level of significance. Of the 19,427 HIV clients at the eight facilities, 6649 (34%) had a CD4 count < 200 cells/mm3 or a WHO III/IV stage. Of these, 1845 were randomly selected for analysis. Over half (991) of participants were aged 45 + years and 1040 (56%) were female. The median age was 46.0 years (interquartile range: 39.2-54.5); 1553 (84%) were in care at county and sub-county hospitals; and 1460 (79%) were WHO stage III/IV at enrollment. At ART initiation, 241 (13%) had tuberculosis, 192 (10%) had chronic diarrhea, and 94 (5%) had Pneumocystis jiroveci pneumonia. At the time of data collection, 89 (5%) participants had died and 140 (8%) were lost to follow-up. Eighteen percent (330) of participants were ART-experienced (on ART for ≥ 3 months). The proportions of ART-experienced and -naïve clients regarding age, sex and marital status were similar. However, a higher proportion of ART-experienced clients received care at primary care facilities, (93(28%) vs. 199 (13%); P < .001); were WHO stage 3/4 at AHD diagnosis, 273 (84%) vs. 1187 (79%) (P = .041); and had died or been LTFU, (124 (38%) vs. 105 (7%); P < .001). With increasing prevalence of patients on ART, the proportion of AHD treatment-experienced clients may increase without effective interventions to ensure that these patients remain in care.

Service delivery characteristics associated with contraceptive use among youth clients in integrated voluntary counseling and HIV testing clinics in Kenya.

Youth attending voluntary counseling and HIV testing (VCT) services often have unmet need for contraception. Integrated family planning (FP) and HIV services can address dual HIV and unintended pregnancy prevention needs. However, little is known about which VCT service characteristics, such as quality of care, strength of FP-HIV service integration, and youth-friendliness, affect contraceptive behavior. This study explores the facility- and provider-level characteristics that may be associated with same day uptake or intention to use contraception after a VCT visit, and contraceptive use three months later among youth clients, controlling for client characteristics. This was a descriptive study conducted in 20 integrated VCT clinics across Kenya. Data collection included 20 structured clinic observations, 349 baseline interviews with male and female clients aged 15-24 after their VCT visit plus 277 follow-up interviews with clients three months later, and interviews with 46 providers who served the clients at the study clinics. Client, provider, and structured observation data were linked and multi-level logistic path models were used for analyses. Results revealed little evidence of specific service characteristics being associated with contraceptive behavior. However, VCT providers were not routinely screening for risk of unintended pregnancy or counseling on contraception. Results are likely a reflection of suboptimal integrated services. The clinics were serving youth with unmet contraceptive need and therefore integrated services should be strengthened overall to ensure no missed opportunities.

Nevirapine-associated hepatotoxicity and rash among HIV-infected pregnant women in Kenya.

BACKGROUND: Few studies have evaluated the risk of nevirapine (NVP)-associated hepatotoxicity among HIV-infected pregnant women with a CD4 count ≥250 cells/mm(3). METHODS: We enrolled HIV-infected pregnant Kenyan women who initiated triple antiretroviral therapy (ART) at 34 weeks gestation. We compared the rates of severe hepatotoxicity (grades 3-4 hepatotoxicity) and rash-associated hepatotoxicity (rash with ≥grade 2 hepatotoxicity) with NVP and nelfinavir (NFV), respectively. RESULTS: We initiated triple ART in 522 pregnant women; severe hepatotoxicity and rash-associated hepatotoxicity occurred in 14 (3%) and 9 (2%) women, respectively. Women who initiated NVP had higher rates of severe hepatotoxicity (5% vs 1%; P = .03) and rash-associated hepatotoxicity (4% vs 0%; P = .003) when compared with NFV. Among women who initiated NVP (n = 254), a baseline CD4 count ≥250 cells/mm(3) was not associated with severe hepatotoxicity (5% vs 3%; P = .52) or rash-associated hepatotoxicity (4% vs 3%; P = .69). CONCLUSION: Nevirapine use but not CD4 count ≥250 cells/mm(3) was associated with hepatotoxicity.

Standardized enhanced adherence counseling for improved HIV viral suppression among children and adolescents in Homa Bay and Turkana Counties, Kenya.

Viral suppression is suboptimal among children and adolescents on antiretroviral therapy (ART) in Kenya. We implemented and evaluated a standardized enhanced adherence counseling (SEAC) package to improve viral suppression in children and adolescents with suspected treatment failure in Homa Bay and Turkana. The SEAC package, implemented from February 2019 to September 2020, included: standard procedures operationalizing the enhanced adherence counseling (EAC) process; provider training on psychosocial support and communication skills for children living with HIV and their caregivers; mentorship to providers and peer educators on EAC processes; and individualized case management. We enrolled children and adolescents aged 0 to 19 years with suspected treatment failure (viral load [VL] >1000 copies/mL) who received EAC before standardization as well as those who received SEAC in a pre-post evaluation of the SEAC package conducted in 6 high-volume facilities. Pre-post standardization comparisons were performed using Wilcoxon-Mann-Whitney and Pearson's chi-square tests at a 5% level of significance. Multivariate logistic regression was performed to identify factors associated with viral resuppression. The study enrolled 741 participants, 595 pre- and 146 post-SEAC implementation. All post-SEAC participants attended at least 1 EAC session, while 17% (n = 98) of pre-SEAC clients had no record of EAC attendance. Time to EAC following the detection of high VL was reduced by a median of 8 days, from 49 (interquartile range [IQR]: 23.0-102.5) to 41 (IQR: 20.0-67.0) days pre- versus post-SEAC (P = .006). Time to completion of at least 3 sessions was reduced by a median of 12 days, from 59.0 (IQR: 36.0-91.0) to 47.5 (IQR: 33.0-63.0) days pre- versus post-SEAC (P = .002). A greater percentage of clients completed the recommended minimum 3 EAC sessions at post-SEAC, 88.4% (n = 129) versus 61.1% (n = 363) pre-SEAC, P < .001. Among participants with a repeat VL within 3 months following the high VL, SEAC increased viral suppression from 34.6% (n = 76) to 52.5% (n = 45), P = .004. Implementation of the SEAC package significantly reduced the time to initiate EAC and time to completion of at least 3 EAC sessions, and was significantly associated with viral suppression in children and adolescents with suspected treatment failure.

HIV-1 drug resistance emergence among breastfeeding infants born to HIV-infected mothers during a single-arm trial of triple-antiretroviral prophylaxis for prevention of mother-to-child transmission: a secondary analysis.

BACKGROUND: Nevirapine and lamivudine given to mothers are transmitted to infants via breastfeeding in quantities sufficient to have biologic effects on the virus; this may lead to an increased risk of a breastfed infant's development of resistance to maternal antiretrovirals. The Kisumu Breastfeeding Study (KiBS), a single-arm open-label prevention of mother-to-child HIV transmission (PMTCT) trial, assessed the safety and efficacy of zidovudine, lamivudine, and either nevirapine or nelfinavir given to HIV-infected women from 34 wk gestation through 6 mo of breastfeeding. Here, we present findings from a KiBS trial secondary analysis that evaluated the emergence of maternal ARV-associated resistance among 32 HIV-infected breastfed infants. METHODS AND FINDINGS: All infants in the cohort were tested for HIV infection using DNA PCR at multiple study visits during the 24 mo of the study, and plasma RNA viral load for all HIV-PCR-positive infants was evaluated retrospectively. Specimens from mothers and infants with viral load >1,000 copies/ml were tested for HIV drug resistance mutations. Overall, 32 infants were HIV infected by 24 mo of age, and of this group, 24 (75%) infants were HIV infected by 6 mo of age. Of the 24 infants infected by 6 mo, nine were born to mothers on a nelfinavir-based regimen, whereas the remaining 15 were born to mothers on a nevirapine-based regimen. All infants were also given single-dose nevirapine within 48 hours of birth. We detected genotypic resistance mutations in none of eight infants who were HIV-PCR positive by 2 wk of age (specimens from six infants were not amplifiable), for 30% (6/20) at 6 wk, 63% (14/22) positive at 14 wk, and 67% (16/24) at 6 mo post partum. Among the 16 infants with resistance mutations by 6 mo post partum, the common mutations were M184V and K103N, conferring resistance to lamivudine and nevirapine, respectively. Genotypic resistance was detected among 9/9 (100%) and 7/15 (47%) infected infants whose mothers were on nelfinavir and nevirapine, respectively. No mutations were detected among the eight infants infected after the breastfeeding period (age 6 mo). CONCLUSIONS: Emergence of HIV drug resistance mutations in HIV-infected infants occurred between 2 wk and 6 mo post partum, most likely because of exposure to maternal ARV drugs through breast milk. Our findings may impact the choice of regimen for ARV treatment of HIV-infected breastfeeding mothers and their infected infants.

Triple-antiretroviral prophylaxis to prevent mother-to-child HIV transmission through breastfeeding--the Kisumu Breastfeeding Study, Kenya: a clinical trial.

BACKGROUND: Effective strategies are needed for the prevention of mother-to-child HIV transmission (PMTCT) in resource-limited settings. The Kisumu Breastfeeding Study was a single-arm open label trial conducted between July 2003 and February 2009. The overall aim was to investigate whether a maternal triple-antiretroviral regimen that was designed to maximally suppress viral load in late pregnancy and the first 6 mo of lactation was a safe, well-tolerated, and effective PMTCT intervention. METHODS AND FINDINGS: HIV-infected pregnant women took zidovudine, lamivudine, and either nevirapine or nelfinavir from 34-36 weeks' gestation to 6 mo post partum. Infants received single-dose nevirapine at birth. Women were advised to breastfeed exclusively and wean rapidly just before 6 mo. Using Kaplan-Meier methods we estimated HIV-transmission and death rates from delivery to 24 mo. We compared HIV-transmission rates among subgroups defined by maternal risk factors, including baseline CD4 cell count and viral load. Among 487 live-born, singleton, or first-born infants, cumulative HIV-transmission rates at birth, 6 weeks, and 6, 12, and 24 mo were 2.5%, 4.2%, 5.0%, 5.7%, and 7.0%, respectively. The 24-mo HIV-transmission rates stratified by baseline maternal CD4 cell count <500 and ≥500 cells/mm(3) were 8.4% (95% confidence interval [CI] 5.8%-12.0%) and 4.1% (1.8%-8.8%), respectively (p = 0.06); the corresponding rates stratified by baseline maternal viral load <10,000 and ≥10,000 copies/ml were 3.0% (1.1%-7.8%) and 8.7% (6.1%-12.3%), respectively (p = 0.01). None of the 12 maternal and 51 infant deaths (including two second-born infants) were attributed to antiretrovirals. The cumulative HIV-transmission or death rate at 24 mo was 15.7% (95% CI 12.7%-19.4%). CONCLUSIONS: This trial shows that a maternal triple-antiretroviral regimen from late pregnancy through 6 months of breastfeeding for PMTCT is safe and feasible in a resource-limited setting. These findings are consistent with those from other trials using maternal triple-antiretroviral regimens during breastfeeding in comparable settings.

Supporting adolescents living with HIV within boarding schools in Kenya.

Adolescents and youth living with HIV (AYLHIV) are a uniquely vulnerable population facing challenges around adherence, disclosure of HIV status and stigma. Providing school-based support for AYLHIV offers an opportunity to optimize their health and wellbeing. The purpose of this study was to evaluate the feasibility of school-based supportive interventions for AYLHIV in Kenya. From 2016-2019, with funding from ViiV Healthcare, the Elizabeth Glaser Pediatric AIDS Foundation implemented the innovative Red Carpet Program (RCP) for AYLHIV in participating public healthcare facilities and boarding schools in Homa Bay and Turkana Counties in Kenya. In this analysis, we report the implementation of the school-based interventions for AYLHIV in schools, which included: a) capacity building for overall in-school HIV, stigma and sexual and reproductive health education; b) HIV care and treatment support; c) bi-directional linkages with healthcare facilities; and d) psychosocial support (PSS). Overall, 561 school staff and 476 school adolescent health advocates received training to facilitate supportive environments for AYLHIV and school-wide education on HIV, stigma, and sexual and reproductive health. All 87 boarding schools inter-linked to 66 regional healthcare facilities to support care and treatment of AYLHIV. Across all RCP schools, 546 AYLHIV had their HIV status disclosed to school staff and received supportive care within schools, including treatment literacy and adherence counselling, confidential storage and access to HIV medications. School-based interventions to optimize care and treatment support for AYLHIV are feasible and contribute to advancing sexual and reproductive health within schools.

Factors affecting breastfeeding cessation after discontinuation of antiretroviral therapy to prevent mother-to-child transmission of HIV.

In the Kisumu Breastfeeding Study (KiBS), prevention of mother-to-child HIV transmission study, highly active antiretroviral therapy (HAART) is provided from 34 weeks gestation, through delivery to six months postpartum. The study recommends that women practice exclusive breastfeeding for six months, then wean abruptly. We sought to explore factors such as, education, family support, cultural norms, and sources of information about perinatal HIV transmission, which may influence a mother's decision to comply or not comply with the study's recommendation to stop breastfeeding when HAART is discontinued. We used semi-structured interviews of a purposive sample of 18 mothers participating in the KiBS. By interviewing 10 mothers who stopped breastfeeding and eight mothers who continued, it was possible to examine how different factors may have affected the groups of participants. All participants stated that it was not traditional to stop breastfeeding at six months. Participants who stopped breastfeeding reported more family support, were more educated, and were more likely to disclose their HIV status. Participants who continued breastfeeding more often expressed concern about stigma. Participants learned about mother-to-child transmission from clinics, churches, community groups, and other HIV-positive mothers. This substudy suggests that family support, education, and cultural norms are important factors that may influence a mother's decision regarding breastfeeding cessation. Thus, counseling and family support may play integral roles in the promotion of early breastfeeding cessation.

Effect of a point-of-use water treatment and safe water storage intervention on diarrhea in infants of HIV-infected mothers.

To reduce mother-to-child transmission of human immunodeficiency virus (HIV) in resource-poor settings, the World Health Organization recommends exclusive breast-feeding for 6 months, followed by rapid weaning if replacement feeding is affordable, feasible, available, safe, and sustainable. In the Kisumu Breastfeeding Study (trial registration: Clinicaltrials.gov identifier NCT00146380), infants of HIV-infected mothers who received antiretroviral therapy experienced high rates of diarrhea at weaning. To address this problem, mothers in the Kisumu Breastfeeding Study were given safe water storage vessels, hygiene education, and bleach for household water treatment. We compared the incidence of diarrhea in infants enrolled before (cohort A) and after (cohort B) implementation of the intervention. Cohort B infants experienced less diarrhea than cohort A infants, before and after weaning (P < .001 and P = .047, respectively); however, during the weaning period, there were no differences in the frequency of diarrhea between cohorts (P = 0.89). Testing of stored water in cohort B homes indicated high adherence (monthly range, 80%-95%) to recommended chlorination practices. Among infants who were weaned early, provision of safe water may be insufficient to prevent weaning-associated diarrhea.

Active pediatric HIV case finding in Kenya and Uganda: A look at missed opportunities along the prevention of mother-to-child transmission of HIV (PMTCT) cascade.

BACKGROUND: Children living with HIV remain undiagnosed due to missed opportunities along the prevention of mother-to-child HIV transmission cascade. This study addresses programmatic gaps in the cascade by describing pregnancy and HIV-related services received by mothers of children newly identified as HIV-positive through active case finding. METHODS: This was a prospective observational cohort (2017-2018) of HIV-positive children <15 years of age newly diagnosed at study facilities and/or surrounding communities in Kenya and Uganda. At enrollment, caregivers were interviewed about maternal and child health and HIV history. Child medical and laboratory information was abstracted at two months post-diagnosis. Descriptive summary statistics were calculated; associations between selected factors and child age at HIV diagnosis were evaluated using generalized estimating equations. RESULTS: 174 HIV-positive children (median age 2.4 years) were enrolled. Among maternal caregivers, 110/132 (83.3%) attended antenatal care and 60 (45.5%) reported testing HIV-negative in antenatal care. Of 41 and 56 women known to be HIV-positive during pregnancy and breastfeeding respectively, 17 (41.5%) and 15 (26.8%) did not receive antiretroviral drugs. Despite known maternal HIV-positive status during pregnancy, 39% of these children were not diagnosed until after two years of age; children were diagnosed at younger ages in Uganda (p = 0.0074) and if mother was the caregiver (p<0.0001). The most common HIV testing points identifying children were outpatient (44.3%) and maternal/child health departments (29.9%). Nearly all children initiated antiretroviral therapy within two weeks of diagnosis. CONCLUSIONS: Multiple missed opportunities for HIV prevention and delays in HIV testing of HIV-exposed children were identified in newly diagnosed children. Findings support critical prevention messaging and retesting of HIV-negative women during pregnancy and breastfeeding, strengthening HIV treatment initiation and follow-up systems and interventions to ensure HIV-positive women receive lifelong antiretroviral therapy throughout the cascade, and broader implementation of community case finding so children not engaged in care receive testing services.