Reasons for Modification of Generic Highly Active Antiretroviral Therapeutic Regimens Among Patients in Southern India

Brown University, Providence, Rhode Island, United States
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.56). 02/2006; 41(1):53-8. DOI: 10.1097/01.qai.0000188123.15493.43
Source: PubMed


To describe reasons for modification and discontinuation of antiretroviral regimens in association with adverse events (AEs), treatment failure, and cost among patients in southern India.
Secular trends of patients initiating highly active antiretroviral therapy (HAART) between January 1996 and October 2004 at a tertiary HIV referral center in India were analyzed using a previously validated natural history database.
All previously antiretroviral therapy-naive patients who initiated HAART (N = 1443) and had at least 1 follow-up visit were evaluated. The median CD4 count at the time of initiating HAART was 108 cells/microL. The most common first-line regimens were stavudine (d4T) plus lamivudine (3TC) plus nevirapine (NVP) (63%), zidovudine (AZT) plus 3TC plus NVP (19%), d4T plus 3TC plus efavirenz (EFV) (9%), and AZT plus 3TC plus EFV (4%). Twenty percent of patients modified their first-line regimen. The most common reason for modifying therapy was the development of an AE (64%), followed by cost (19%) and treatment failure (14%), with median times to modify therapy being 40, 151, and 406 days, respectively. Common AEs were itching and/or skin rash (66%), hepatotoxicity (27%), and anemia (23%). Nine percent of patients discontinued therapy entirely after a median duration of 124 days, primarily because of cost (64%).
The most common reason for modifying therapy was the occurrence of AEs, whereas cost was the most common reason for discontinuing therapy. Despite increasing access to lower cost generic HAART in India, even less expensive and more tolerable first-line regimens and cost-effective treatment monitoring tools need to be introduced to achieve better treatment outcomes and access in resource-constrained settings.

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    • "Toxicity was the most common reason for cART modification similar to what has been reported in other studies [8], [10]–[14], [27]. Stavudine accounted for majority of toxicity related cART modification with risk increasing with time on treatment. "
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    ABSTRACT: Limited antiretroviral treatment regimens in resource-limited settings require long-term sustainability of patients on the few available options. We evaluated the incidence and predictors of combined antiretroviral treatment (cART) modifications, in an outpatient cohort of 955 patients who initiated cART between January 2009 and January 2011 in western Kenya. cART modification was defined as either first time single drug substitution or switch. Incidence rates were determined by Poisson regression and risk factor analysis assessed using multivariate Cox regression modeling. Over a median follow-up period of 10.7 months, 178 (18.7%) patients modified regimens (incidence rate (IR); 18.6 per 100 person years [95% CI: 16.2-21.8]). Toxicity was the most common cited reason (66.3%). In adjusted multivariate Cox piecewise regression model, WHO disease stage III/IV (aHR; 1.82, 95%CI: 1.25-2.66), stavudine (d4T) use (aHR; 2.21 95%CI: 1.49-3.30) and increase in age (aHR; 1.02, 95%CI: 1.0-1.04) were associated with increased risk of treatment modification within the first year post-cART. Zidovudine (AZT) and tenofovir (TDF) use had a reduced risk for modification (aHR; 0.60 95%CI: 0.38-0.96 and aHR; 0.51 95%CI: 0.29-0.91 respectively). Beyond one year of treatment, d4T use (aHR; 2.75, 95% CI: 1.25-6.05), baseline CD4 counts ≤350 cells/mm3 (aHR; 2.45, 95%CI: 1.14-5.26), increase in age (aHR; 1.05 95%CI: 1.02-1.07) and high baseline weight >60kg aHR; 2.69 95% CI: 1.58-4.59) were associated with risk of cART modification. Early treatment initiation at higher CD4 counts and avoiding d4T use may reduce treatment modification and subsequently improve sustainability of patients on the available limited options.
    PLoS ONE 04/2014; 9(4):e93106. DOI:10.1371/journal.pone.0093106 · 3.23 Impact Factor
    • "Similar to several other studies,[121617–22] the most predictable cause for ARV switching, in the present study, was toxicity (67.65%), with significant heterogeneity in the distribution of adverse events. The patients were with a more advanced disease at the baseline, which could necessitate higher rates of regimen change/discontinuation due to adverse events. "
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    ABSTRACT: Highly active antiretroviral therapy (HAART) has markedly decreased the morbidity and mortality due to HIV disease. However, toxicities, comorbidity, pregnancy, and treatment failure, among others, would result in frequent initial HAART regimen change. The study was designed to assess the causes of initial highly active antiretroviral therapeutic regimen changes among patients on HAART. The study was conducted using a retrospective institution-based study, by reviewing the patient information sheet and physician diagnosis cards. Patient cards that showed a change in the initial treatment regimen were assessed and analyzed, to identify the common reason that resulted in a change from the initial treatment regimen. The data was analyzed using SPSS version 16.0. A total of 340 patient cards were assessed. The majority of the patients (69.29%) were females. The most common first regimen, before the first switch, was stavudine / lamivudine / nevirapine (D4T/3TC/NVP) (54.70%) and stavudine / lamivudine / Efavirenz (D4T/3TC/EFV) (20.88%). The main reasons for modification were toxicity, comorbidity, pregnancy, and treatment failure. The main types of toxicities observed were peripheral neuropathy (36.52%), rash (17.83%), and anemia (17.39%). Toxicity was the main reason for the modification of initial HAART among the study population. Efavirenz-based regimens had the lowest hazard for change relatively, except in pregnancy-related cases.
    North American Journal of Medical Sciences 01/2012; 4(1):19-23. DOI:10.4103/1947-2714.92898
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    • "In comparison with patients from low-income countries, those from high-income countries were more likely to change two or more drugs of the failing regimen and to change to a PI-containing regimen (Zhou et al., 2009). For India in particular, previous studies have shown the majority of switches were treatment substitutions within the same class of drugs, driven primarily by concomitant tuberculosis (TB) infection and adverse reactions to antiretroviral agents (Kumarasamy et al., 2006). "
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    ABSTRACT: Early identification and management of treatment failure on highly active antiretroviral therapy (HAART) is crucial in maintaining a sustained response to therapy in HIV infection. However, HIV viral load (VL) and resistance testing, and second-line HAART regimens, are unaffordable to many patients in India, leaving them with limited treatment options. Predictors and reasons for antiretroviral switching, therefore, are likely to differ in settings of varying resources. A one-year, observational study of patients receiving antiretroviral therapy was conducted in a private, non-profit hospital in Bangalore. This paper examines the predictors and consequences of antiretroviral treatment switching in this setting and explores reasons for switching in a subset of patients. Data on demographics, drug regimens, adherence, and physical and psychosocial outcomes were collected quarterly. Tests of VL and CD4 cell counts were performed every six months. One-third of the patients switched therapy during the study period. Baseline predictors of switching included lower CD4 cell counts and more physical symptoms. Contrary to studies in other settings, a high VL did not predict treatment switching, and only a minority of those experiencing drug failure were switched to second-line regimens. Both groups (switchers and non-switchers) improved significantly over time with respect to CD4 counts and psychological well-being, and showed a reduction in physical and depressive symptoms. Any differences between the groups were no longer significant at the end of the study, once we controlled for baseline levels. Clinical, policy, and research implications of these findings are discussed within the context of resource-limited settings.
    AIDS Care 02/2011; 23(5):569-77. DOI:10.1080/09540121.2010.525607 · 1.60 Impact Factor
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