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

Abstract

Background: Since 2001, anti-retroviral therapy (ART) has been provided to over 75,000 HIV-infected patients at the USAID-Academic Model Providing Access to Healthcare (AMPATH) Partnership in western Kenya. Over 1000 of these patients have switched to second-line ART. We therefore set out to determine factors associated with first-line ART failure amongst these patients. Methods: This case controlled study matched patients (in the ratio 1:2) from the electronic AMPATH Medical Record System on the basis of age, gender, and ART initiation date. Cases were adults (≥18 years) who initiated second-line ART between January 1, 2007 and July 31, 2011 after at least one viral load measurement >5000 copies/ml or satisfying the WHO immunological or clinical failure criteria. Controls were those on non-failing first-line ART with a CD4 count > 400 /ml within the last 12 months, at the time of case incidence. Conditional logistic regression for paired data was used to assess association. We evaluated the strength of association of risk factors using stratified Cox model. Results: Of the 1084 cases and 2149 controls included in the analysis, 62% were female. Median age was 36.5 years (IQR = 30.7 - 43.1); median baseline CD4 cell count was 161 /ml (IQR = 72 - 277); Median time to ART failure was 37 months (IQR = 24 - 47). Low baseline CD4 count < 50 /ml (H.R = 7.07, (95% CI = 4.92 - 10.15); Zidovudine based ART (H.R 1.76, 95% CI = 1.25 - 2.48) and imperfect ART adherence (H.R = 2.77, 95% CI = 2.20 - 3.49) were independently associated with treatment failure. Conclusion: In this setting, low baseline CD4 count, zidovudine-based ART and imperfect adherence are associated with first-line ART treatment failure

Modeling Outcomes of First-Line Antiretroviral Therapy and Rate of CD4 Counts Change among a Cohort of HIV/AIDS Patients in Ethiopia: A Retrospective Cohort Study

“…This was supported by a study conducted in Cameron [36] in which patients initiated with d4t has increased risk of toxicity. However, this finding was contradicted with the results reported by a study conducted in Kenya [37] in which d4t has a decreased risk of treatment failure as compared to AZT. The risk of composite outcomes was not statistically significant on d4t with any of the NNRTI drugs when lost patients were assumed censored.…”

A study of profile of patients failing first line NACO recommended ART

“…17 Studies from Ethopia and Kenya reported that the choice of NRTI (NVP vs EVF) was not associated treatment failure. 30,36 In the present study authors found that 74.1% (40/54) patients who had FLA, had very low baseline CD4 count (<100 cells/mm3) at initiation of ART. These patients might have very high baseline viral load as compared to the patients who had higher CD4 count at initiation.…”

“…30 Present study findings were in contrast with the study by Kowbah CM et al, from Kenya who showed that Zidovidine based regime was associated with more treatment failure. 36 Stavudine is more susceptible to develop drug resistance on prolonged therapy as compare to zidovudine. Resistance to stavudine arise through specific pathways that involve either selection of the 151M mutation or insertion of two serine or serinealanine residues at amino acid residue 69.…”

Adherence and Treatment Change among HIV/AIDS Patients in Ghana – A Nested Case Control Study

“…Kwobah et al [21] identified that non adherence was associated with almost three times the odds of treatment failure and Gonzalez-Serna et al [22] found that an adherence level greater than or equal to 95% independently reduced treatment discontinuation by 61%. Ickovics et al [14] have reported that HIV/AIDS patients whose degree of adherence was less than 95% were 3-5 times more likely to have treatment failure compared to those with adherence levels of 95% or higher and treatment failure is one of the most common reasons to switch therapy [25].…”

“…Many HIV studies [21,22] so far have looked at treatment failure and discontinuation of ART from the perspective of temporal trends or taxonomy of possible determinants. The present study aims to elucidate a possible association between insufficient adherence to ART and treatment change among HIV/AIDS patients at the Korle-Bu Teaching Hospital in Ghana.…”