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Retention in care is a major challenge for pregnant and postpartum women living with HIV (PPHIV) in the prevention of mother-to-child HIV transmission (PMTCT) continuum. However, the factors influencing retention from the perspectives of women who have become lost to follow-up (LTFU) are not well described. We explored these factors within an enhanced sub-cohort of the East Africa International Epidemiology Databases to Evaluate AIDS Consortium. From 2018–2019, a purposeful sample of PPHIV ≥18 years of age were recruited from five maternal and child health clinics providing integrated PMTCT services in Kenya. Women retained in care were recruited at the facility; women who had become LTFU (last visit >90 days) were recruited through community tracking. Interview transcripts were analyzed thematically using a social-ecological framework. Forty-one PPHIV were interviewed. The median age was 27 years, 71% were pregnant, and 39% had become LTFU. In the individual domain, prior PMTCT experience and desires to safeguard infants’ health enhanced retention but were offset by perceived lack of value in PMTCT services following infants’ immunizations. In the peer/family domain, male-partner financial and motivational support enhanced retention. In the community/society domain, some women perceived social pressure to attend clinic while others perceived pressure to utilize traditional birth attendants. In the healthcare environment, long queues and negative provider attitudes were prominent barriers. HIV-related stigma and fear of disclosure crossed multiple domains, particularly for LTFU women, and were driven by perceptions of HIV as a fatal disease and fear of partner abandonment and abuse. Both retained and LTFU women perceived that integrated HIV services increased the risk of disclosure. Retention was influenced by multiple factors for PPHIV. Stigma and fear of disclosure were prominent barriers for LTFU women. Multicomponent interventions and refining the structure and efficiency of PMTCT services may enhance retention for PPHIV.

ObjectivesAlmost 13 million people are estimated to be on antiretroviral therapy in Eastern and Southern Africa, and their disease course and program effectiveness could be significantly affected by the concurrent use of alcohol. Screening for alcohol use may be important to assess the prevalence of alcohol consumption and its impact on patient and programmatic outcomes.MethodsAs part of this observational study, data on patient characteristics and alcohol consumption were collected on a cohort of 765 adult patients enrolling in HIV care in East Africa. Alcohol consumption was assessed with the AUDIT questionnaire at enrollment. Subjects were classified as consuming any alcohol (AUDIT score >0), hazardous drinkers (AUDIT score ≥8) and hyper drinkers (AUDIT score ≥16). The effects of alcohol consumption on retention in care, death and delays in antiretroviral therapy (ART) initiation were assessed through competing risk (Fine & Gray) models.ResultsOf all study participants, 41.6% consumed alcohol, 26.7% were classified as hazardous drinkers, and 16.0% as hyper drinkers. Depending on alcohol consumption classification, men were 3-4 times more likely to consume alcohol compared to women. Hazardous drinkers (median age 32.8 years) and hyper drinkers (32.7 years) were slightly older compared to non-hazardous drinkers (30.7 years) and non-hyper drinkers (30.8 years), (p-values = 0.014 and 0.053 respectively). Median CD4 at enrollment was 330 cells/μl and 16% were classified World Health Organization (WHO) stage 3 or 4. There was no association between alcohol consumption and CD4 count or WHO stage at enrollment. Alcohol consumption was associated with significantly lower probability of ART initiation (adjusted sub-distribution hazard ratio aSHR = 0.77 between alcohol consumers versus non-consumers; p-value = 0.008), and higher patient non-retention in care (aSHR = 1.77, p-value = 0.023).DiscussionAlcohol consumption is associated with significant delays in ART initiation and reduced retention in care for patients enrolling in HIV care and treatment programs in East Africa. Consequently, interventions that target alcohol consumption may have a significant impact on the HIV care cascade.

ObjectivesWe extend the method of Significant Zero Crossings of Derivatives (SiZer) to address within-subject correlations of repeatedly collected longitudinal biomarker data and the computational aspects of the methodology when analyzing massive biomarker databases. SiZer is a powerful visualization tool for exploring structures in curves by mapping areas where the first derivative is increasing, decreasing or does not change (plateau) thus exploring changes and normalization of biomarkers in the presence of therapy.MethodsWe propose a penalized spline SiZer (PS-SiZer) which can be expressed as a linear mixed model of the longitudinal biomarker process to account for irregularly collected data and within-subject correlations. Through simulations we show how sensitive PS-SiZer is in detecting existing features in longitudinal data versus existing versions of SiZer. In a real-world data analysis PS-SiZer maps are used to map areas where the first derivative of weight change after antiretroviral therapy (ART) start is significantly increasing, decreasing or does not change, thus exploring the durability of weight increase after the start of therapy. We use weight data repeatedly collected from persons living with HIV initiating ART in five regions in the International Epidemiologic Databases to Evaluate AIDS (IeDEA) worldwide collaboration and compare the durability of weight gain between ART regimens containing and not containing the drug stavudine (d4T), which has been associated with shorter durability of weight gain.ResultsThrough simulations we show that the PS-SiZer is more accurate in detecting relevant features in longitudinal data than existing SiZer variants such as the local linear smoother (LL) SiZer and the SiZer with smoothing splines (SS-SiZer). In the illustration we include data from 185,010 persons living with HIV who started ART with a d4T (53.1%) versus non-d4T (46.9%) containing regimen. The largest difference in durability of weight gain identified by the SiZer maps was observed in Southern Africa where weight gain in patients treated with d4T-containing regimens lasted 59.9 weeks compared to 133.8 weeks for those with non-d4T-containing regimens. In the other regions, persons receiving d4T-containing regimens experienced weight gains lasting 38-62 weeks versus 55-93 weeks in those receiving non-d4T-based regimens.DiscussionPS-SiZer, a SiZer variant, can handle irregularly collected longitudinal data and within-subject correlations and is sensitive in detecting even subtle features in biomarker curves.

Author(s): Vreeman, Rachel C; Ayaya, Samuel O; Musick, Beverly S; Yiannoutsos, Constantin T; Cohen, Craig R; Nash, Denis; Wabwire, Deo; Wools-Kaloustian, Kara; Wiehe, Sarah E | Abstract: ObjectiveTo describe antiretroviral therapy (ART) adherence and associated factors for a large HIV-infected pediatric cohort followed by sites of the East Africa International Epidemiologic Databases to Evaluate AIDS (IeDEA) consortium.MethodsThis study utilized prospectively collected clinical data from HIV-infected children less than 13 years of age who initiated ART within 4 clinical care programs (with 26 clinical sites) in Kenya, Uganda, and Tanzania and were followed for up to 6 years. Programs used one of 3 adherence measures, including 7-day quantitative recall, 7-day categorical recall, and clinician pill assessments. We fit a hierarchical, three-level, logistic-regression model to examine adherence, with observations nested within patient, and patients within the 26 sites providing pediatric HIV data to this analysis.ResultsIn East Africa, 3,304 children, 52.0% male, were enrolled in care and were subsequently observed for a median of 92 weeks (inter-quartile range [IQR] 50.3-145.0 weeks). Median age at ART initiation was 5.5 years ([IQR] 3.0-8.5 years). "Good" adherence, as reported by each clinic's measures, was extremely high, remaining on average above 90% throughout all years of follow-up. Longer time on ART was associated with higher adherence (adjusted Odds Ratio-aOR-per log-transformed week on ART: 1.095, 95% Confidence Interval-CI-[1.052-1.150].) Patients enrolled in higher-volume programs exhibited higher rates of clinician-assessed adherence (aOR per log-500 patients: 1.174, 95% CI [1.108-1.245]). Significant site-level variability in reported adherence was observed (0.28), with even higher variability among patients (0.71). In a sub-analysis, being an orphan at the start of ART was strongly associated with lower ART adherence rates (aOR: 0.919, 95% CI [0.864-0.976]).ConclusionsSelf-reported adherence remained high over a median of 1.8 years in HIV care, but varied according to patient-level and site-level factors. Consistent adherence monitoring with validated measures and attention to vulnerable groups is recommended.

Objective This cohort study utilized data from a large HIV treatment program in western Kenya to describe the impact of active tuberculosis (TB) on clinical outcomes among African patients on antiretroviral therapy (ART). Design We included all patients initiating ART between March 2004 and November 2007. Clinical (signs and symptoms), radiological (chest radiographs) and laboratory (mycobacterial smears, culture and tissue histology) criteria were used to record the diagnosis of TB disease in the program’s electronic medical record system. Methods We assessed the impact of TB disease on mortality, loss to follow-up (LTFU) and incident AIDS-defining events (ADEs) through Cox models and CD4 cell and weight response to ART by non-linear mixed models. Results We studied 21,242 patients initiating ART–5,186 (24%) with TB; 62% female; median age 37 years. There were proportionately more men in the active TB (46%) than in the non-TB (35%) group. Adjusting for baseline HIV-disease severity, TB patients were more likely to die (hazard ratio – HR = 1.32, 95% CI 1.18–1.47) or have incident ADEs (HR = 1.31, 95% CI: 1.19–1.45). They had lower median CD4 cell counts (77 versus 109), weight (52.5 versus 55.0 kg) and higher ADE risk at baseline (CD4-adjusted odds ratio = 1.55, 95% CI: 1.31–1.85). ART adherence was similarly good in both groups. Adjusting for gender and baseline CD4 cell count, TB patients experienced virtually identical rise in CD4 counts after ART initiation as those without. However, the overall CD4 count at one year was lower among patients with TB (251 versus 269 cells/µl). Conclusions Clinically detected TB disease is associated with greater mortality and morbidity despite salutary response to ART. Data suggest that identifying HIV patients co-infected with TB earlier in the HIV-disease trajectory may not fully address TB-related morbidity and mortality.