Differences between self-reported and electronically monitored adherence among patients receiving antiretroviral therapy in a resource-limited setting

Measurement of adherence to antiretroviral therapy (ART) by patient self-report is common in resource-limited settings but widely believed to overstate actual adherence. The extent to which these measures overstate adherence has not been examined among a large patient population

Enhanced prophylaxis with antiretroviral therapy for advanced HIV in Africa

BACKGROUND In sub-Saharan Africa, among patients with advanced human immunodeficiency virus (HIV) infection, the rate of death from infection (including tuberculosis and cryptococcus) shortly after the initiation of antiretroviral therapy (ART) is approximately 10%. METHODS In this factorial open-label trial conducted in Uganda, Zimbabwe, Malawi, and Kenya, we enrolled HIV-infected adults and children 5 years of age or older who had not received previous ART and were starting ART with a CD4+ count of fewer than 100 cells per cubic millimeter. They underwent simultaneous randomization to receive enhanced antimicrobial prophylaxis or standard prophylaxis, adjunctive raltegravir or no raltegravir, and supplementary food or no supplementary food. Here, we report on the effects of enhanced antimicrobial prophylaxis, which consisted of continuous trimethoprim–sulfamethoxazole plus at least 12 weeks of isoniazid–pyridoxine (coformulated with trimethoprim–sulfamethoxazole in a single fixed-dose combination tablet), 12 weeks of fluconazole, 5 days of azithromycin, and a single dose of albendazole, as compared with standard prophylaxis (trimethoprim– sulfamethoxazole alone). The primary end point was 24-week mortality. RESULTS A total of 1805 patients (1733 adults and 72 children or adolescents) underwent randomization to receive either enhanced prophylaxis (906 patients) or standard prophylaxis (899 patients) and were followed for 48 weeks (loss to follow-up, 3.1%). The median baseline CD4+ count was 37 cells per cubic millimeter, but 854 patients (47.3%) were asymptomatic or mildly symptomatic. In the Kaplan–Meier analysis at 24 weeks, the rate of death with enhanced prophylaxis was lower than that with standard prophylaxis (80 patients [8.9% vs. 108 [12.2%]; hazard ratio, 0.73; 95% confidence interval [CI], 0.55 to 0.98; P=0.03); 98 patients (11.0%) and 127 (14.4%), respectively, had died by 48 weeks (hazard ratio, 0.76; 95% CI, 0.58 to 0.99; P=0.04). Patients in the enhanced-prophylaxis group had significantly lower rates of tuberculosis (P=0.02), cryptococcal infection (P=0.01), oral or esophageal candidiasis (P=0.02), death of unknown cause (P=0.03), and new hospitalization (P=0.03). However, there was no significant between-group difference in the rate of severe bacterial infection (P=0.32). There were nonsignificantly lower rates of serious adverse events and grade 4 adverse events in the enhanced-prophylaxis group (P=0.08 and P=0.09, respectively). Rates of HIV viral suppression and adherence to ART were similar in the two groups. CONCLUSIONS Among HIV-infected patients with advanced immunosuppression, enhanced antimicrobial prophylaxis combined with ART resulted in reduced rates of death at both 24 weeks and 48 weeks without compromising viral suppression or increasing toxic effects

Late Presentation With HIV in Africa: Phenotypes, Risk, and Risk Stratification in the REALITY Trial.

This article has been accepted for publication in Clinical Infectious Diseases Published by Oxford University PressBackground: Severely immunocompromised human immunodeficiency virus (HIV)-infected individuals have high mortality shortly after starting antiretroviral therapy (ART). We investigated predictors of early mortality and "late presenter" phenotypes. Methods: The Reduction of EArly MortaLITY (REALITY) trial enrolled ART-naive adults and children ≥5 years of age with CD4 counts .1). Results: Among 1711 included participants, 203 (12%) died. Mortality was independently higher with older age; lower CD4 count, albumin, hemoglobin, and grip strength; presence of World Health Organization stage 3/4 weight loss, fever, or vomiting; and problems with mobility or self-care at baseline (all P < .04). Receiving enhanced antimicrobial prophylaxis independently reduced mortality (P = .02). Of five late-presenter phenotypes, Group 1 (n = 355) had highest mortality (25%; median CD4 count, 28 cells/µL), with high symptom burden, weight loss, poor mobility, and low albumin and hemoglobin. Group 2 (n = 394; 11% mortality; 43 cells/µL) also had weight loss, with high white cell, platelet, and neutrophil counts suggesting underlying inflammation/infection. Group 3 (n = 218; 10% mortality) had low CD4 counts (27 cells/µL), but low symptom burden and maintained fat mass. The remaining groups had 4%-6% mortality. Conclusions: Clinical and laboratory features identified groups with highest mortality following ART initiation. A screening tool could identify patients with low CD4 counts for prioritizing same-day ART initiation, enhanced prophylaxis, and intensive follow-up. Clinical Trials Registration: ISRCTN43622374.REALITY was funded by the Joint Global Health Trials Scheme (JGHTS) of the UK Department for International Development, the Wellcome Trust, and Medical Research Council (MRC) (grant number G1100693). Additional funding support was provided by the PENTA Foundation and core support to the MRC Clinical Trials Unit at University College London (grant numbers MC_UU_12023/23 and MC_UU_12023/26). Cipla Ltd, Gilead Sciences, ViiV Healthcare/GlaxoSmithKline, and Merck Sharp & Dohme donated drugs for REALITY, and ready-to-use supplementary food was purchased from Valid International. A. J. P. is funded by the Wellcome Trust (grant number 108065/Z/15/Z). J. A. B. is funded by the JGHTS (grant number MR/M007367/1). The Malawi-Liverpool–Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine (grant number 101113/Z/13/Z) and the Kenya Medical Research Institute (KEMRI)/Wellcome Trust Research Programme, Kilifi (grant number 203077/Z/16/Z) are supported by strategic awards from the Wellcome Trust, United Kingdom. Permission to publish was granted by the Director of KEMRI. This supplement was supported by funds from the Bill & Melinda Gates Foundation

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

"I understood…but some parts were confusing and hard to grasp": Patients′ perception of informed consent forms and clinical trials in Eldoret, Kenya

Background: A signed informed consent (IC) form proves voluntary participation in a study. Yet the development of accessible and understandable IC forms comes with its own set of challenges, particularly when conducting international research. Purpose: This study explores understanding by participants in an Eldoret-based clinical trial of IC and its implications as well as whether they will volunteer for future trials. Materials and Methods: In mid-2010, in-depth interviews with trial participants were recorded in audio format. Content analysis provides a description of trial participants′ experiences and thoughts. Results: All participants were informed about the trial and its voluntariness and they consented. However, some were too ill to scrutinize trial details. Thus, they relied on their health care provider′s advice, or on their guardians. In general, participants understood their role and were happy to volunteer or invite others to participate in future trials. They also emphasised the importance of an open on-going dialogue in order for participants to be able to ask questions. Conclusion: Clinical trial participants in Eldoret seem to understand their role, but rely on providers and guardians when consenting. They are very willing to participate in future trials. Evaluation of research participants′ opinions may improve trial protocols, increase comprehension and guard against manipulation of study participants. In addition, this research focus should guide development of consent forms and process that facilitates a truly IC

Factors Associated with First-Line Antiretroviral Therapy Failure amongst HIV-Infected African Patients: A Case-Control Study

This find is registered at Portable Antiquities of the Netherlands with number PAN-0002693

Health facility barriers to HIV linkage and retention in Western Kenya

Abstract Background HIV linkage and retention rates in sub-Saharan Africa remain low. The objective of this study was to explore perceived health facility barriers to linkage and retention in an HIV care program in western Kenya. Methods This qualitative study was conducted July 2012-August 2013. A total of 150 participants including; 59 patients diagnosed with HIV, TB, or hypertension; 16 caregivers; 10 community leaders; and 65 healthcare workers, were purposively sampled from three Academic Model Providing Access to Healthcare (AMPATH) sites. We conducted 16 in-depth interviews and 17 focus group discussions (FGDs) in either, English, Swahili, Kalenjin, Teso, or Luo. All data were audio recorded, transcribed, translated to English, and a content analysis performed. Demographic data was only available for those who participated in the FGDs. Results The mean age of participants in the FGDs was 36 years (SD = 9.24). The majority (87%) were married, (62.7%) had secondary education level and above, and (77.6%) had a source of income. Salient barriers identified reflected on patients’ satisfaction with HIV care. Barriers unique to linkage were reported as quality of post-test counseling and coordination between HIV testing and care. Those unique to retention were frequency of clinic appointments, different appointments for mother and child, lack of HIV care for institutionalized populations including students and prisoners, lack of food support, and inconsistent linkage data. Barriers common to both linkage and retention included access to health facilities, stigma associated with health facilities, service efficiency, poor provider-patient interactions, and lack of patient incentives. Conclusion Our findings revealed that there were similarities and differences between perceived barriers to linkage and retention. The cited barriers reflected on the need for a more patient-centered approach to HIV care. Addressing health facility barriers may ultimately be more efficient and effective than addressing patient related barriers

Health facility barriers to HIV linkage and retention in Western Kenya

BACKGROUND: HIV linkage and retention rates in sub-Saharan Africa remain low. The objective of this study was to explore perceived health facility barriers to linkage and retention in an HIV care program in western Kenya. METHODS: This qualitative study was conducted July 2012-August 2013. A total of 150 participants including; 59 patients diagnosed with HIV, TB, or hypertension; 16 caregivers; 10 community leaders; and 65 healthcare workers, were purposively sampled from three Academic Model Providing Access to Healthcare (AMPATH) sites. We conducted 16 in-depth interviews and 17 focus group discussions (FGDs) in either, English, Swahili, Kalenjin, Teso, or Luo. All data were audio recorded, transcribed, translated to English, and a content analysis performed. Demographic data was only available for those who participated in the FGDs. RESULTS: The mean age of participants in the FGDs was 36 years (SD = 9.24). The majority (87%) were married, (62.7%) had secondary education level and above, and (77.6%) had a source of income. Salient barriers identified reflected on patients' satisfaction with HIV care. Barriers unique to linkage were reported as quality of post-test counseling and coordination between HIV testing and care. Those unique to retention were frequency of clinic appointments, different appointments for mother and child, lack of HIV care for institutionalized populations including students and prisoners, lack of food support, and inconsistent linkage data. Barriers common to both linkage and retention included access to health facilities, stigma associated with health facilities, service efficiency, poor provider-patient interactions, and lack of patient incentives. CONCLUSION: Our findings revealed that there were similarities and differences between perceived barriers to linkage and retention. The cited barriers reflected on the need for a more patient-centered approach to HIV care. Addressing health facility barriers may ultimately be more efficient and effective than addressing patient related barriers