Multiple Measures Reveal Antiretroviral Adherence Successes and Challenges in HIV-Infected Ugandan Children

Background: Adherence to HIV antiretroviral therapy (ART) among children in developing settings is poorly understood. Methodology/Principal Findings: To understand the level, distribution, and correlates of ART adherence behavior, we prospectively determined monthly ART adherence through multiple measures and six-monthly HIV RNA levels among 121 Ugandan children aged 2–10 years for one year. Median adherence levels were 100% by three-day recall, 97.4% by 30-day visual analog scale, 97.3% by unannounced pill count/liquid formulation weights, and 96.3% by medication event monitors (MEMS). Interruptions in MEMS adherence of $\geq$48 hours were seen in 57.0% of children; 36.3% had detectable HIV RNA at one year. Only MEMS correlated significantly with HIV RNA levels (r = −0.25, p = 0.04). Multivariable regression found the following to be associated with <90% MEMS adherence: hospitalization of child (adjusted odds ratio [AOR] 3.0, 95% confidence interval [CI] 1.6–5.5; p = 0.001), liquid formulation use (AOR 1.4, 95%CI 1.0–2.0; p = 0.04), and caregiver’s alcohol use (AOR 3.1, 95%CI 1.8–5.2; p<0.0001). Child’s use of co-trimoxazole (AOR 0.5, 95%CI 0.4–0.9; p = 0.009), caregiver’s use of ART (AOR 0.6, 95%CI 0.4–0.9; p = 0.03), possible caregiver depression (AOR 0.6, 95%CI 0.4–0.8; p = 0.001), and caregiver feeling ashamed of child’s HIV status (AOR 0.5, 95%CI 0.3–0.6; p<0.0001) were protective against <90% MEMS adherence. Change in drug manufacturer (AOR 4.1, 95%CI 1.5–11.5; p = 0.009) and caregiver’s alcohol use (AOR 5.5, 95%CI 2.8–10.7; p<0.0001) were associated with $\geq$48-hour interruptions by MEMS, while second-line ART (AOR 0.3, 95%CI 0.1–0.99; p = 0.049) and increasing assets (AOR 0.7, 95%CI 0.6–0.9; p = 0.0007) were protective against these interruptions. Conclusions/Significance: Adherence success depends on a well-established medication taking routine, including caregiver support and adequate education on medication changes. Caregiver-reported depression and shame may reflect fear of poor outcomes, functioning as motivation for the child to adhere. Further research is needed to better understand and build on these key influential factors for adherence intervention development

How informal healthcare providers improve uptake of HIV testing: qualitative results from a randomized controlled trial

ObjectiveUganda is HIV-endemic with a prevalence of 5.7%. Lack of epidemic control has been attributed to low engagement with HIV testing. Collaborating with informal healthcare providers, such as traditional healers, has been proposed as a strategy to increase testing uptake. We explored acceptability and implementation of an HIV testing program where traditional healers delivered point-of-care testing and counseling to adults of unknown serostatus (clinicaltrials.gov NCT#03718871).MethodsThis study was conducted in rural, southwestern Uganda. We interviewed participating traditional healers ( N  = 17) and a purposive sample of trial participants ( N  = 107). Healers were practicing within 10 km of Mbarara township, and 18+ years old. Participants were 18+ years old; sexually active; had received care from participating healers; self-reported not receiving an HIV test in prior 12 months; and not previously diagnosed with HIV infection. Interviews explored perceptions of a healer-delivered HIV testing model and were analyzed following a content-analysis approach.ResultsMost participants were female individuals ( N  = 68, 55%). Healer-delivered HIV testing overcame structural barriers, such as underlying poverty and rural locations that limited use, as transportation was costly and often prohibitive. Additionally, healers were located in villages and communities, which made services more accessible compared with facility-based testing. Participants also considered healers trustworthy and 'confidential'. These qualities explain some preference for healer-delivered HIV testing, in contrast to 'stigmatizing' biomedical settings.ConclusionTraditional healer-delivered HIV testing was considered more confidential and easily accessible compared with clinic-based testing. Offering services through traditional healers may improve uptake of HIV testing services in rural, medically pluralistic communities

Adaption and pilot testing of a lay HIV supporter program for traditional healers: a mixed methods study in rural Uganda

Abstract Background Half of people living with HIV (PLWH) in sub-Saharan Africa default from care within two years. In Uganda, and across sub-Saharan Africa, traditional healers (TH) are ubiquitous and often serve as the first line of health care. We hypothesized that with lay support training, TH could support relinkage to HIV care and ART adherence among rural Ugandan PLWH who have defaulted from HIV care. Methods Following the ADAPT-ITT framework, we adapted an evidence-based layperson HIV support program from South Africa for delivery by Ugandan TH. The ADAPT-ITT framework consists of (1) Assessment of needs; (2) Deciding which evidence-based interventions to adapt; (3) Adaptation of interventions; (4) Production of drafted adapted interventions; (5) Topical expert feedback; (6) Integration of expert feedback; (7) Training personnel; and (8) Testing the adapted intervention. The Testing phase was completed via a pilot mixed methods prospective cohort study. The study population included 12 TH practicing in Mbarara Township and 20 adult PLWH with suboptimal ART adherence (CASE adherence index score < 10) who received care from a participating TH and who resided in Mbarara Township. Primary outcome was re-linkage to HIV care within 14 days. Secondary outcomes were ART re-initiation, ART adherence, retention in care after 9 months, and implementation measures. Qualitative interviews were conducted with all participants. Results Data from the Assessment phase indicated that logistical challenges played an important role in disengagement from care among PLWH who receive care from TH, notably geographical distance to clinics and transportation costs. Additionally, HIV-related stigma and lack of social support were identified as barriers to entering and remaining in HIV care. Two core elements of the intervention were identified during the Production phase: (1) TH facilitating rapid re-linkage to HIV care and (2) TH provision of psychosocial support. In the pilot study phase, baseline median CASE adherence score was 3; only 5% of PLWH were adherent to ART via 4-day recall. The TH-delivered support achieved 100% linkage and ART initiation within 14 days, 95% ART adherence, and 100% of PLWH were retained in HIV care after 9 months. Conclusions The ADAPT-ITT framework successfully guided the adaption of a community health worker-delivered intervention for delivery by TH. TH successfully facilitated re-linkage to HIV care, support ART adherence, and retention in care for PLWH when trained as part of a lay support person program. Future studies are needed to evaluate scale-up and long-term impact

Traditional healer-delivered point-of-care HIV testing versus referral to clinical facilities for adults of unknown serostatus in rural Uganda: a mixed-methods, cluster-randomised trial

BackgroundHIV counselling and testing are essential to control the HIV epidemic. However, HIV testing uptake is low in sub-Saharan Africa, where many people use informal health-care resources such as traditional healers. We hypothesised that uptake of HIV tests would increase if provided by traditional healers. We aimed to determine the effectiveness of traditional healers delivering HIV testing at point of care compared with referral to local clinics for HIV testing in rural southwestern Uganda.MethodsWe did a mixed-methods study that included a cluster-randomised trial followed by individual qualitative interviews among a sample of participants in Mbarara, Uganda. Traditional healers aged 18 years or older who were located within 8 km of the Mbarara District HIV clinic, were identified in the 2018 population-level census of traditional healers in Mbarara District, and delivered care to at least seven clients per week were randomly assigned (1:1) as clusters to an intervention or a control group. Healers screened their clients for eligibility, and research assistants confirmed eligibility and enrolled clients who were aged 18 years or older, were receiving care from a participating healer, were sexually active (ever had intercourse), self-reported not having received an HIV test in the previous 12 months (and therefore considered to be of unknown serostatus), and had not previously been diagnosed with HIV infection. Intervention group healers provided counselling and offered point-of-care HIV tests to adult clients. Control group healers provided referral for HIV testing at nearby clinics. The primary outcome was the individual receipt of an HIV test within 90 days of study enrolment. Safety and adverse events were recorded and defined on the basis of prespecified criteria. This study is registered with ClinicalTrials.gov, NCT03718871.FindingsBetween Aug 2, 2019, and Feb 7, 2020, 17 traditional healers were randomly assigned as clusters (nine to intervention and eight to control), with 500 clients of unknown HIV serostatus enrolled (250 per group). In the intervention group, 250 clients (100%) received an HIV test compared with 57 (23%) in the control group, a 77% (95% CI 73-82) increase in testing uptake, after adjusting for the effect of clustering (p&lt;0·0001). Ten (4%) of 250 clients in the intervention group tested HIV positive, seven of whom self-reported linkage to HIV care. No new HIV cases were identified in the control group. Qualitative interviews revealed that HIV testing delivered by traditional healers was highly acceptable among both providers and clients. No safety or adverse events were reported.InterpretationDelivery of point-of-care HIV tests by traditional healers to adults of unknown serostatus significantly increased rates of HIV testing in rural Uganda. Given the ubiquity of healers in Africa, this approach holds promise as a new pathway to provide community-based HIV testing, and could have a dramatic effect on uptake of HIV testing in sub-Saharan Africa.FundingUS National Institute of Mental Health, National Institutes of Health

Predictors of ≥48-hour interruptions MEMS adherence included in the multivariable model.

<p>Values indicate odds ratios with 95% confidence intervals in parentheses.</p>*<p>Could not be estimated in the multivariate model due to inadequate variation in values.</p><p>Bold indicates p<0.05.</p

Figure 2

<p>Detectable HIV RNA by ART history at enrollment.</p

Characteristics of the child, regimen, caregiver, and household/community.

*<p>N = sample used for determining each characteristic, IQR = interquartile range, FDC = fixed drug combination, UgSh = Ugandan Shillings.</p>1<p>Most common symptoms were cough, weakness/tiredness, and skin problems.</p>2<p>Co-trimoxazole was prescribed to all children on enrollment for prevention of opportunistic and other infections regardless of ARV use.</p>3<p>The most common and consistently endorsed symptom on this scale was “worrying too much about things”.</p>4<p>Defined as >5 drinks (1 glass wine, 333 ml beer, or 40 ml hard liquor).</p>5<p>4000 UgSh equals approximately US$1.60.</p

Correlation among adherence measures and with HIV RNA.

<p>Adherence measures are compared with each other as means for all participants over the duration of the study. Comparisons between mean adherence measures and log HIV RNA reflect adherence in the month prior to the HIV RNA measurement. The first set of values in each box indicates the Spearman correlation coefficient (r).</p><p>VAS  =  visual analog scale.</p><p>Bold indicates p<0.05.</p

Distribution of median adherence by participant using multiple measures.

<p>VAS  =  visual analog scale.</p

Median adherence for the cohort by multiple measures.

<p>The interquartile range is shown in parentheses.</p><p>VAS  =  visual analog scale.</p