Acceptability and Feasibility of Providing Adherence Feedback Based on Tenofovir Diphosphate in Dried Blood Spots: Results from a Pilot Study Among Patients and Providers in Cape Town, South Africa.

Tenofovir diphosphate (TFV-DP) concentrations in dried blood spots (DBS) predict viral breakthrough, but their use remains understudied in real-world clinic settings. This pilot study examined acceptability, feasibility, and initial adherence outcomes of providing adherence feedback using TFV-DP concentrations on patient- and provider-levels in Cape Town, South Africa. We enrolled 60 persons with HIV (PWH) receiving tenofovir-containing ART attending a primary health clinic. They were randomized 1:1 to an intervention receiving TFV-DP concentration feedback by research staff vs. no feedback at monthly visits for 4 months. Acceptability among medical providers and level of clinical follow-up of TFV-DP results was examined. Patient acceptability was assessed descriptively. Mean electronic adherence (EA), as measured by WisePill device, and TFV-DP in DBS were compared between the two arms. All participants in the intervention group (100%) reported finding TFV-DP feedback helpful and 86% reported changing adherence behaviors. Medical providers indicated high acceptability of incorporating TFV-DP concentration feedback into the clinic, yet among 29 results < 1000 fmol/punch, only 2 were reviewed with no follow-up actions performed. In the intervention arm, mean TFV-DP concentrations were significantly higher (t = 2.5, p < .01) during follow-up and EA in upper quartile (96-100%) was greater compared to controls (x2 = 7.8, p ≤ .05). This study found high acceptability among patients for receiving adherence feedback based on TFV-DP concentrations. TFV-DP and EA data demonstrated greater adherence in the intervention group. Providers indicated high acceptability of incorporating TFV-DP feedback into the clinic, but few providers reviewed results, which could impact clinic-level feasibility.

Immune Activation Is Associated With Neurocognitive Performance in Ugandan Adolescents Living With HIV.

ABSTRACT: We examined relationships between neurocognition and immune activation in Ugandan adolescents with perinatally acquired HIV (PHIV). Eighty-nine adolescents in Kampala, Uganda (32 virally suppressed [<400 copies/mL] PHIV and 57 sociodemographically matched HIV-negative controls), completed a tablet-based neurocognitive test battery. Control-derived z-scores for 12 individual tests and a global/overall z-score were calculated. We measured plasma (soluble CD14 and CD163), monocyte (proportions of monocyte subsets), and T-cell (expression of CD38 and HLA-DR on CD4 + and CD8 + ) activation and gut markers. Spearman rank correlations and median regressions examined associations between test performance and immune activation. The median [IQR] age was 15 [13-16] years, and 40% were girls. The median time on antiretroviral therapy was 10 years [7-11] for PHIV; 87% had viral load <50 copies/mL. Compared with controls, global z-scores were lower among PHIV ( P = 0.05) and significantly worse on tests of executive functioning and delayed recall ( P 's ≤ 0.05). Overall, monocyte activation significantly correlated with worse test performance on global z-score (r = 0.21, P = 0.04), attention, processing speed, and motor speed (r = 0.2-0.3, P ≤ 0.01). T-cell activation was significantly correlated with worse performance on tests of learning, executive functioning, and working memory (r = 0.2-0.4, P ≤ 0.04). In PHIV, after adjusting for age, sex, and antiretroviral therapy duration, activated CD4 T cells remained associated with worse memory (ß-0.3, 95% CI: -0.55 to -0.07, P = 0.01). PHIV with virologic suppression on antiretroviral therapy shows evidence of worse neurocognitive test performance compared with controls. Monocyte and T-cell activation is correlated with worse neurocognition in Ugandan youth with and without HIV, which has not been previously investigated in this setting.

Acceptability and Feasibility of Genetic Testing to Assess Risk of HIV-Associated Neurocognitive Impairment Among Thai Adolescents and Young Adults.

Host genetic factors may modify the risk of developing HIV-associated neurocognitive impairment (HIV-NCI), and genetic research has the potential to inform novel treatments for HIV-NCI. However, there is a need to better understand the acceptability of genetic testing among distinct populations of people living with HIV at increased risk for HIV-NCI, such as young people living with perinatally acquired HIV (PHIV) in low- and middle-income countries, to gauge the feasibility of genetic research within these populations. This pilot study evaluated the acceptability and feasibility of genetic testing to assess risk of future neurocognitive problems in 50 Thai adolescents and young adults (13-24 years; Meanage = 19.16 [standard deviation = 3.09]; 52% female) with PHIV and demographically similar HIV-negative controls. Participants (25 PHIV; 25 controls) completed a survey assessing acceptability of and concerns about genetic testing and were asked to provide blood samples for genetic testing. Descriptive statistics and blood draw completion rates were produced and calculated. Reported concerns about genetic testing were grouped thematically and tallied. Independent t tests and chi-squares explored demographic differences between participants who reported concerns and peers. Results indicated 46 participants (92%) rated genetic testing as "acceptable" or "completely acceptable." Eight participants (16%) reported concerns about genetic testing. The most common concerns were related to genetic information being shared or misused. Compared with participants without concerns, participants who reported concerns had more years of education and were more likely to have postsecondary schooling. Regarding completion rates, 49 participants (98%) agreed to genetic testing and provided blood samples. Overall, results support the acceptability and feasibility of incorporating genetic testing into research investigating HIV-NCI among adolescents and young adults in Thailand. Findings provide important considerations for planning future genetic studies among young people in Thailand.

Evaluating construct and criterion validity of NeuroScreen in assessing neurocognition among hospitalized Ugandan first-episode psychosis patients.

Introduction: Neurocognitive impairment (NCI) is commonly exhibited among patients experiencing their first episode of psychosis. However, there are few resources in many low-income countries, such as Uganda, that allow for the administration of extensive neurocognitive test batteries for the detection of NCI. NeuroScreen is a brief tablet-based neurocognitive assessment battery that can be administered by all levels of healthcare staff. We examined the validity of NeuroScreen to assess neurocognition and detect NCI in first-episode psychosis (FEP) patients in Uganda. Methods: We enrolled 112 participants FEP patients and matched controls at Butabika Mental Referral Hospital. Each participant completed NeuroScreen and a traditionally administered neurocognitive battery: the MATRIC Consensus Cognitive Battery (MCCB). We examined correlations between participant performance on NeuroScreen and the MCCB. A ROC curve determined sensitivity and specificity of NeuroScreen to detect NCI as determined by MCCB criterion. Results: There was a large, statistically significant correlation between overall performance on NeuroScreen and the MCCB [r(112) = 0.64, p < .001]. Small to large correlations were found between tests in the MCCB and NeuroScreen batteries. The ROC curve of NeuroScreen performance to detect MCCB-defined NCI had an area under curve of 0.80 and optimal sensitivity and specificity of 83 % and 60 %, respectively. Conclusion: There was a moderate positive correlation between overall performance on both batteries. NeuroScreen shows promise as a valid assessment battery to assess neurocognition and detect NCI in FEP patients in Uganda. Further studies of NeuroScreen in healthy individuals and in a range of mental disorders are recommended.

Comparing Predictive Ability of Two Objective Adherence Measures in a Community-Based Cohort on Antiretroviral Therapy in South Africa: Tenofovir Diphosphate Concentrations and Electronic Adherence Monitors.

BACKGROUND: Electronic adherence (EA) and tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) are objective measures of antiretroviral therapy (ART) adherence. We characterized the association between these measures in a prospective cohort of persons with HIV (PWH) on ART. SETTING: Four primary health clinics in Cape Town, South Africa. METHODS: We enrolled 250 virally suppressed PWH receiving tenofovir-based ART. We collected EA data, monthly viral load, and TFV-DP in DBS for 12 months. We used logistic regression to estimate the adjusted odds ratio (aOR) and 95% confidence intervals (CIs) for future viral breakthrough (VB) (>400 copies/mL) for each adherence measure. Receiver operating characteristics (ROCs) provided the predictive power of these measures. RESULTS: Participants had a median (IQR) age of 34 (27-42); 78% were women. Twenty-one (8%) developed VB. Logistic regression showed that when percent EA and TFV-DP concentrations increased, the odds of VB decreased. This relationship was consistent at the time of VB (aOR of 0.41 [95% CI: 0.25 to 0.66] for TFV-DP and aOR of 0.64 [95% CI: 0.54 to 0.76] for EA) and for up to 2 months before VB. Both adherence measures predicted future VB at both 1 month and 2 months before viral load measurement. CONCLUSION: We established that 2 objective adherence measures, EA and TFV-DP in DBS, have a positive association with, and are both strongly predictive of, VB in a community-based South African cohort on ART. Future research is needed to determine the feasibility of implementing these adherence measures in resource-limited settings to facilitate adherence interventions.