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.

Gender-specific risk factors for virologic failure in KwaZulu-Natal: automobile ownership and financial insecurity.

We sought to examine which socioeconomic indicators are risk factors for virologic failure among HIV-1 infected patients receiving antiretroviral therapy (ART) in KwaZulu-Natal, South Africa. A case-control study of virologic failure was conducted among patients recruited from the outpatient clinic at McCord Hospital in Durban, South Africa between October 1, 2010 and June 30, 2012. Cases were those failing first-line ART, defined as viral load >1,000 copies/mL. Univariate logistic regression was performed on sociodemographic data for the outcome of virologic failure. Variables found significant (p < 0.05) were used in multivariate models and all models were stratified by gender. Of 158 cases and 300 controls, 35 % were male and median age was 40 years. Gender stratification of models revealed automobile ownership was a risk factor among males, while variables of financial insecurity (unemployment, non-spouse family paying for care, staying with family) were risk factors for women. In this cohort, financial insecurity among women and automobile ownership among men were risk factors for virologic failure. Risk factor differences between genders demonstrate limitations of generalized risk factor analysis.

Early warning indicators for first-line virologic failure independent of adherence measures in a South African urban clinic.

We sought to develop individual-level Early Warning Indicators (EWI) of virologic failure (VF) for clinicians to use during routine care complementing WHO population-level EWI. A case-control study was conducted at a Durban clinic. Patients after ≥ 5 months of first-line antiretroviral therapy (ART) were defined as cases if they had VF [HIV-1 viral load (VL)>1000 copies/mL] and controls (2:1) if they had VL ≤ 1000 copies/mL. Pharmacy refills and pill counts were used as adherence measures. Participants responded to a questionnaire including validated psychosocial and symptom scales. Data were also collected from the medical record. Multivariable logistic regression models of VF included factors associated with VF (p<0.05) in univariable analyses. We enrolled 158 cases and 300 controls. In the final multivariable model, male gender, not having an active religious faith, practicing unsafe sex, having a family member with HIV, not being pleased with the clinic experience, symptoms of depression, fatigue, or rash, low CD4 counts, family recommending HIV care, and using a TV/radio as ART reminders (compared to mobile phones) were associated with VF independent of adherence measures. In this setting, we identified several key individual-level EWI associated with VF including novel psychosocial factors independent of adherence measures.

Antiretroviral therapy-associated toxicities in the resource-poor world: the challenge of a limited formulary.

Toxicities related to antiretroviral therapy make long-term adherence to therapy difficult for patients and present challenges to providers, especially those in the resource-poor world who work with a limited formulary. In resource-poor settings, where limited drug options are the rule, when and how to change therapy are especially difficult problems. Drugs such as stavudine and didanosine are associated with serious metabolic complications, such as lactic acidosis, pancreatitis, and peripheral neuropathy. Antiretroviral agents associated with fewer metabolic effects, such as tenofovir and abacavir, remain widely unavailable. Because the current formulary restrictions appear to be unlikely to change quickly, providers in resource-poor countries must be familiar with the common adverse events-including metabolic complications, hypersensitivity reactions, anemia, and liver enzyme abnormalities-and must understand how to manage them with what is locally available. Most importantly, to avoid drug toxicities, a larger formulary is needed in resource-poor settings, and this must be a high priority for policy makers and health care professionals involved in treating human immunodeficiency virus infection globally.

HIV Online Provider Education (HOPE): the internet as a tool for training in HIV medicine.

Human immunodeficiency virus (HIV) treatment programs in resource-limited areas are expanding rapidly. Providing training and education to health care providers in these programs is a major challenge. We have employed Internet-based conferencing technology to conduct interactive case-based training conferences with health care professionals in Africa, Asia, and the Caribbean. This online program may be a model for other efforts to provide education to health care providers treating HIV-infected patients in the developing world.