Diagnosis of antiretroviral therapy failure in Malawi: poor performance of clinical and immunological WHO criteria.

OBJECTIVES: In antiretroviral therapy (ART) scale-up programmes in sub-Saharan Africa viral load monitoring is not recommended. We wanted to study the impact of only using clinical and immunological monitoring on the diagnosis of virological ART failure under routine circumstances. METHODS: Clinicians in two urban ART clinics in Malawi used clinical and immunological monitoring to identify adult patients for switching to second-line ART. If patients met clinical and/or immunological failure criteria of WHO guidelines and had a viral load <400 copies/ml there was misclassification of virological ART failure. RESULTS: Between January 2006 and July 2007, we identified 155 patients with WHO criteria for immunological and/or clinical failure. Virological ART failure had been misclassified in 66 (43%) patients. Misclassification was significantly higher in patients meeting clinical failure criteria (57%) than in those with immunological criteria (30%). On multivariate analysis, misclassification was associated with being on ART <2 years [OR = 7.42 (2.63, 20.95)] and CD4 > 200 cells/microl [OR = 5.03 (2.05, 12.34)]. Active tuberculosis and Kaposi's sarcoma were the most common conditions causing misclassification of virological ART failure. CONCLUSION: Misclassification of virological ART failure occurs frequently using WHO clinical and immunological criteria of ART failure for poor settings. A viral load test confirming virological ART failure is therefore advised to avoid unnecessary switching to second-line regimens.

Comparisons of anemia, thrombocytopenia, and neutropenia at initiation of HIV antiretroviral therapy in Africa, Asia, and the Americas.

BACKGROUND: Hematological abnormalities are common manifestations of advanced HIV-1 infection that could affect the outcomes of highly-active antiretroviral therapy (HAART). Although most HIV-1-infected individuals live in resource-constrained countries, there is little information about the frequency of hematological abnormalities such as anemia, neutropenia, and thrombocytopenia among individuals with advanced HIV-1 disease. METHODS: This study compared the prevalence of pre-antiretroviral therapy hematological abnormalities among 1571 participants in a randomized trial of antiretroviral efficacy in Africa, Asia, South America, the Caribbean, and the USA. Potential covariates for anemia, neutropenia, and thrombocytopenia were identified in univariate analyses and evaluated in separate multivariable models for each hematological condition. RESULTS: The frequencies of neutropenia (absolute neutrophil count ≤1.3×109/l), anemia (hemoglobin ≤10g/dl), and thrombocytopenia (platelets ≤125×109/l) at initiation of antiretroviral therapy were 14%, 12%, and 7%, respectively, and varied by country (p<0.0001 for each). In multivariable models, anemia was associated with gender, platelet count, and country; neutropenia was associated with CD4+ lymphocyte and platelet counts; and thrombocytopenia was associated with country, gender, and chronic hepatitis B infection. CONCLUSIONS: Differences in the frequency of pretreatment hematological abnormalities could have important implications for the choice of antiretroviral regimen in resource-constrained settings.