Determinants of health-related quality of life in people with Human Immunodeficiency Virus, failing first-line treatment in Africa.

BACKGROUND: Antiretroviral treatment improves health related quality of life (HRQoL) of people with human immunodeficiency virus (PWH). However, one third initiating first-line treatment experience virological failure and the determinants of HRQoL in this key population are unknown. Our study aims to identify determinants of among PWH failing antiretroviral treatment in sub-Saharan Africa. METHODS: We analysed data from a cohort of PWH having virological failure (> 1,000 copies/mL) on first-line ART in South Africa and Uganda. We measured HRQoL using the EuroQOL EQ-5D-3L and used a two-part regression model to obtain by-country analyses for South Africa and Uganda. The first part identifies risk factors that were associated with the likelihood of participants reporting perfect health (utility = 1) versus non-perfect health (utility < 1). The second part identifies risk factors that were associated with the EQ-5 L-3L utility scores for participants reporting non-perfect health. We performed sensitivity analyses to compare the results between the two-part model using tobit models and ordinary least squares regression. RESULTS: In both countries, males were more likely to report perfect health and participants with at least one comorbidity were less likely to report perfect health. In South Africa, participants with side effects and in Uganda those with opportunistic infections were also less likely to report perfect health. In Uganda, participants with 100% ART adherence were more likely to report perfect health. In South Africa, high HIV viral load, experiencing ART side effects, and the presence of opportunistic infections were each associated with lower HRQoL, whereas participants with 100% ART adherence reported higher HRQoL. In Uganda participants with lower CD4 count had lower HRQoL. CONCLUSION: Markers of advanced disease (opportunistic infection, high viral load, low CD4), side effects, comorbidities and lack of ART adherence negatively impacted HRQoL for PWH experiencing virological failure. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02787499.

Who's slipping through the cracks? A comprehensive individual, clinical and health system characterization of people with virological failure on first-line HIV treatment in Uganda and South Africa.

OBJECTIVES: HIV virological failure remains a major threat to programme success in sub-Saharan Africa. While HIV drug resistance (HIVDR) and inadequate adherence are the main drivers of virological failure, the individual, clinical and health system characteristics that lead to poor outcomes are not well understood. The objective of this paper is to identify those characteristics among people failing first-line antiretroviral therapy (ART). METHODS: We enrolled a cohort of adults in HIV care experiencing virological failure on first-line ART at five sites and used standard statistical methods to characterize them with a focus on three domains: individual/demographic, clinical, and health system, and compared each by country of enrolment. RESULTS: Of 840 participants, 51% were women, the median duration on ART was 3.2 years [interquartile range (IQR) 1.1, 6.4 years] and the median CD4 cell count prior to failure was 281 cells/µL (IQR 121, 457 cells/µL). More than half of participants [53%; 95% confidence interval (CI) 49-56%] stated that they had > 90% adherence and 75% (95% CI 72-77%) took their ART on time all or most of the time. Conversely, the vast majority (90%; 95% CI 86-92%) with a completed genotypic drug resistance test had any HIV drug resistance. This population had high health system use, reporting a median of 3 (IQR 2.6) health care visits and a median of 1 (IQR 1.1) hospitalization in the preceding 6 months. CONCLUSIONS: Patients failing first-line ART in sub-Saharan Africa generally report high rates of adherence to ART, have extremely high rates of HIV drug resistance and utilize significant health care resources. Health systems interventions to promptly detect and manage treatment failure will be a prerequisite to establishing control of the HIV epidemic.

Resistance Testing for Management of HIV Virologic Failure in Sub-Saharan Africa : An Unblinded Randomized Controlled Trial.

BACKGROUND: Virologic failure in HIV predicts the development of drug resistance and mortality. Genotypic resistance testing (GRT), which is the standard of care after virologic failure in high-income settings, is rarely implemented in sub-Saharan Africa. OBJECTIVE: To estimate the effectiveness of GRT for improving virologic suppression rates among people with HIV in sub-Saharan Africa for whom first-line therapy fails. DESIGN: Pragmatic, unblinded, randomized controlled trial. (ClinicalTrials.gov: NCT02787499). SETTING: Ambulatory HIV clinics in the public sector in Uganda and South Africa. PATIENTS: Adults receiving first-line antiretroviral therapy with a recent HIV RNA viral load of 1000 copies/mL or higher. INTERVENTION: Participants were randomly assigned to receive standard of care (SOC), including adherence counseling sessions and repeated viral load testing, or immediate GRT. MEASUREMENTS: The primary outcome of interest was achievement of an HIV RNA viral load below 200 copies/mL 9 months after enrollment. RESULTS: The trial enrolled 840 persons, divided equally between countries. Approximately half (51%) were women. Most (72%) were receiving a regimen of tenofovir, emtricitabine, and efavirenz at enrollment. The rate of virologic suppression did not differ 9 months after enrollment between the GRT group (63% [263 of 417]) and SOC group (61% [256 of 423]; odds ratio [OR], 1.11 [95% CI, 0.83 to 1.49]; P = 0.46). Among participants with persistent failure (HIV RNA viral load ≥1000 copies/mL) at 9 months, the prevalence of drug resistance was higher in the SOC group (76% [78 of 103] vs. 59% [48 of 82]; OR, 2.30 [CI, 1.22 to 4.35]; P = 0.014). Other secondary outcomes, including 9-month survival and retention in care, were similar between groups. LIMITATION: Participants were receiving nonnucleoside reverse transcriptase inhibitor-based therapy at enrollment, limiting the generalizability of the findings. CONCLUSION: The addition of GRT to routine care after first-line virologic failure in Uganda and South Africa did not improve rates of resuppression. PRIMARY FUNDING SOURCE: The President's Emergency Plan for AIDS Relief and the National Institute of Allergy and Infectious Diseases.

The Technology Acceptance Model for Resource-Limited Settings (TAM-RLS): A Novel Framework for Mobile Health Interventions Targeted to Low-Literacy End-Users in Resource-Limited Settings.

Although mobile health (mHealth) technologies have shown promise in improving clinical care in resource-limited settings (RLS), they are infrequently brought to scale. One limitation to the success of many mHealth interventions is inattention to end-user acceptability, which is an important predictor of technology adoption. We conducted in-depth interviews with 43 people living with HIV in rural Uganda who had participated in a clinical trial of a short messaging system (SMS)-based intervention designed to prompt return to clinic after an abnormal laboratory test. Interviews focused on established features of technology acceptance models, including perceived ease of use and perceived usefulness, and included open-ended questions to gain insight into unexplored issues related to the intervention's acceptability. We used conventional (inductive) and direct content analysis to derive categories describing use behaviors and acceptability. Interviews guided development of a proposed conceptual framework, the technology acceptance model for resource-limited settings (TAM-RLS). This framework incorporates both classic technology acceptance model categories as well as novel factors affecting use in this setting. Participants described how SMS message language, phone characteristics, and experience with similar technologies contributed to the system's ease of use. Perceived usefulness was shaped by the perception that the system led to augmented HIV care services and improved access to social support from family and colleagues. Emergent themes specifically related to mHealth acceptance among PLWH in Uganda included (1) the importance of confidentiality, disclosure, and stigma, and (2) the barriers and facilitators downstream from the intervention that impacted achievement of the system's target outcome. The TAM-RLS is a proposed model of mHealth technology acceptance based upon end-user experiences in rural Uganda. Although the proposed model requires validation, the TAM-RLS may serve as a useful tool to guide design and implementation of mHealth interventions.

Behavioral Predictors of Intention to Use a Text Messaging Reminder System Among People Living With HIV in Rural Uganda: Survey Study.

BACKGROUND: The expansion of cellular phones in sub-Saharan Africa spurred the development of SMS text message-based mobile health (mHealth) technology. Numerous SMS text message-based interventions have attempted to increase retention in care for people living with HIV in sub-Saharan Africa. Many of these interventions have failed to scale. Understanding theory-grounded factors leading to mHealth acceptability is needed to create scalable, contextually appropriate, and user-focused interventions to improve longitudinal HIV care for people living with HIV in sub-Saharan Africa. OBJECTIVE: In this study, we aimed to understand the relationship between constructs from the Unified Theory of Acceptance and Use of Technology (UTAUT), constructs identified in previous qualitative research, and behavioral intention to use a novel SMS text message-based mHealth intervention designed to improve care retention among people living with HIV initiating treatment in rural Uganda. METHODS: We conducted a survey of people living with HIV who were newly initiating HIV care in Mbarara, Uganda, and had agreed to use a novel SMS text message-based system that notified them of abnormal laboratory results and reminded them to return to the clinic. Survey items assessed behavioral intention to use the SMS text messaging system; constructs from UTAUT; and demographics, literacy, SMS text messaging experience, HIV status disclosure, and social support. We used factor analysis and logistic regression to estimate the relationships between UTAUT constructs and the behavioral intention to use the SMS text messaging system. RESULTS: A total of 249 participants completed the surveys, of whom 115 (46.2%) expressed high behavioral intention to use the SMS text messaging intervention. In a multivariable analysis, we found that performance expectancy (adjusted odds ratio [aOR] of the scaled factor score 5.69, 95% CI 2.64-12.25; P<.001), effort expectancy (aOR of the scaled factor score 4.87, 95% CI 1.75-13.51; P=.002), and social influence (measured as a 1-unit Likert score increase in the perception that clinical staff have been helpful in the use of the SMS text messaging program; aOR 3.03, 95% CI 1.21-7.54; P=.02) were significantly associated with high behavioral intention to use the SMS text messaging program. SMS text messaging experience (aOR/1-unit increase 1.48, 95% CI 1.11-1.96; P=.008) and age (aOR/1-year increase 1.07, 95% CI 1.03-1.13; P=.003) were also significantly associated with increased odds of high intention to use the system. CONCLUSIONS: Performance expectancy, effort expectancy, and social influence, as well as age and SMS experience, were drivers of high behavioral intention to use an SMS text messaging reminder system among people living with HIV initiating treatment in rural Uganda. These findings highlight salient factors associated with SMS intervention acceptability in this population and indicate attributes that are likely to be key to the successful development and scaling of novel mHealth interventions.

Seemingly Unrelated Regression Analysis of the Cost and Health-Related Quality of Life Outcomes of the REVAMP Randomized Clinical Trial.

OBJECTIVE: This study aimed to evaluate the 9-month cost and health-related quality of life (HRQOL) outcomes of resistance versus viral load testing strategies to manage virological failure in low-middle income countries. METHODS: We analyzed secondary outcomes from the REVAMP clinical trial: a pragmatic, open label, parallel-arm randomized trial investigating resistance versus viral load testing for individuals failing first-line treatment in South Africa and Uganda. We collected resource data, valued according to local cost data and used the 3-level version of EQ-5D to measure HRQOL at baseline and 9 months. We applied seemingly unrelated regression equations to account for the correlation between cost and HRQOL. We conducted intention-to-treat analyses with multiple imputation using chained equations for missing data and performed sensitivity analyses using complete cases. RESULTS: For South Africa, resistance testing and opportunistic infections were associated with statistically significantly higher total costs, and virological suppression was associated with lower total cost. Higher baseline utility, higher cluster of differentiation 4 (CD4) count, and virological suppression were associated with better HRQOL. For Uganda, resistance testing and switching to second-line treatment were associated with higher total cost, and higher CD4 was associated with lower total cost. Higher baseline utility, higher CD4 count, and virological suppression were associated with better HRQOL. Sensitivity analyses of the complete-case analysis confirmed the overall results. CONCLUSION: Resistance testing showed no cost or HRQOL advantage in South Africa or Uganda over the 9-month REVAMP clinical trial.

The REVAMP trial to evaluate HIV resistance testing in sub-Saharan Africa: a case study in clinical trial design in resource limited settings to optimize effectiveness and cost effectiveness estimates.

BACKGROUND: In sub-Saharan Africa, rates of sustained HIV virologic suppression remain below international goals. HIV resistance testing, while common in resource-rich settings, has not gained traction due to concerns about cost and sustainability. OBJECTIVE: We designed a randomized clinical trial to determine the feasibility, effectiveness, and cost-effectiveness of routine HIV resistance testing in sub-Saharan Africa. APPROACH: We describe challenges common to intervention studies in resource-limited settings, and strategies used to address them, including: (1) optimizing generalizability and cost-effectiveness estimates to promote transition from study results to policy; (2) minimizing bias due to patient attrition; and (3) addressing ethical issues related to enrollment of pregnant women. METHODS: The study randomizes people in Uganda and South Africa with virologic failure on first-line therapy to standard of care virologic monitoring or immediate resistance testing. To strengthen external validity, study procedures are conducted within publicly supported laboratory and clinical facilities using local staff. To optimize cost estimates, we collect primary data on quality of life and medical resource utilization. To minimize losses from observation, we collect locally relevant contact information, including Whatsapp account details, for field-based tracking of missing participants. Finally, pregnant women are followed with an adapted protocol which includes an increased visit frequency to minimize risk to them and their fetuses. CONCLUSIONS: REVAMP is a pragammatic randomized clinical trial designed to test the effectiveness and cost-effectiveness of HIV resistance testing versus standard of care in sub-Saharan Africa. We anticipate the results will directly inform HIV policy in sub-Saharan Africa to optimize care for HIV-infected patients.