Nucleoside reverse transcriptase inhibitors (zidovudine and stavudine) side-effects in people living with human immunodeficiency virus/acquired immunodeficiency syndrome attending the antiretroviral treatment center of B.J. Medical College and Civil Hospital at Ahmedabad, Gujarat, India

Abstract

Sir, With the development of highly active antiretroviral therapy (HAART) the survival and quality-of-life of people living with human immunodeficiency virus (PLHIV) has increased dramatically in the recent years. Nucleoside reverse transcriptase inhibitors (NRTIs) in combinations with other anti-retrovirals (HAART) are the cornerstones of acquired immunodeficiency syndrome (AIDS) therapy, turning HIV infection into a manageable chronic illness.[1] NRTIs form the backbone of antiretroviral (ARV) cocktail and zidovudine (ZDV) and stavudine (d4T) are the most preferred NRTIs widely used in the first line management for HIV treatment in the National AIDS Control Organization (NACO) sponsored antiretroviral therapy (ART) program.[2] ZDV as an NRTI has been shown to be associated with hematological toxicity. d4T has been, before sometime, one of the most frequently prescribed NRTIs in initial first line regimens in most resource poor settings. However, there is increasing evidence that d4T is one of the NRTIs most often associated with long-term toxicities including mitochondrial toxicities and it is therefore no longer recommended by World Health Organization as the preferred NRTI. The present study was undertaken to reviews common side-effects experienced by PLHIV/AIDS who were initiated with ZDV or d4T based fixed dose combination (FDC) ART regimen as per Indian National ART Guidelines. All the Integrated Counseling and Testing Centers confirmed HIV positive patients who were eligible for starting ART based on NACO guidelines were registered at our ART center and were initiated with FDC of two NRTIs (ZDV/d4T + lamivudine) and one non-nucleoside reverse transcriptase inhibitors (nevirapine/efavirenz) as per national guidelines in India.[2] A total 4379 patients were registered for taking ART at the center of excellence (COE) B.J. Medical College Ahmedabad from May 2005 to November 2008. Patients taking ARV regimens from outside the government program including those who were previously on monotherapy, dual therapy, expired before starting ARV (n = 237) were excluded from the present study. Furthermore out of 4142 patients initiated on the first line ART from the government program 3355 (81%) were still continuing either ZDV or d4T based ARV and were regular visitors at the ART center while remaining 1024 (24.7%) (lost to follow-uP = 310, expired = 477) were excluded from the present study. Hence, the study sample size was 3355. ZDV based ART regimen was prescribed if the hemoglobin (Hb) level was more than 8 g/dl and d4T based regimen was started if Hb was less than 8 g/dl. Similarly, HIV patient co-infected with tuberculosis were started with efavirenz based ART (ZDV + lamivudine + efavirenz/d4T + lamivudine efavirenz and later shifted to NVP when AKT was completed.[2] A total of 3355 patients initiated on ART during the study period. Out of them, 1538 (45.84%) were initiated on ZDV based regimen while 1817 (54.16%) were initiated on d4T based ARV regimen. Of those initiated on ZDV based regimen 1047 (68.1%) were males, 456 (29.6%) were females, male child 19 (1.2%), female child 07 (0.5%) while 09 (0.6%) patients were transgender/transsexual. Anemia as a side effect of ZDV based ART was observed in 212 (13.78%) cases. Similar study in India by Agarwal et al.,[3] reported anemia in 16.2% of cases. Furthermore, the average time duration for development of ZDV induced anemia was 3 months. Similar study by van Leeuwen et al.[4] reported development of anemia in 14 weeks. In our study, majority 182 out of 212 (89.85%) developed anemia within 6 months, similar study by Agarwal et al.[3] reported time duration for development of anemia within first 6 months of starting ART in 94% cases. This leads to the fact that patients who are initiated on ZDV based ART regimen should be closely monitored for Hb levels during the initial 6 months of start of ART. Those initiated on d4T based ART regimen, peripheral neuropathy was the most common side-effect observed in 220 (12.1%) cases followed by dysipidemias 143 (7.87%), lipoatrophy 108 (5.94%), lactic acidosis, 06 (0.33%) and pancratitis 05 (0.27%). 15 (0.83%) patients had multiple toxicities to d4T. Similar study in Africa by Karara et al.,[5] reported peripheral neuropathy in 20.5% of patients. In the present study, the average time duration for development of d4T induced side-effects was 19 months. A similar study by Agarwal et al.[3] reported mean duration of 14.4 ± 3.8 months in 102 patients started initially with d4T based regimen, but due to either peripheral neuropathy or lipoatrophy regimen was substituted to ZDV. In resource limited settings, the selection of HAART regimens is determined not only by treatment efficacy, but also on the availability and affordability. The most common obse rved side-effects after initiating ART; anemia (ZDV based) and peripheral neuropathy (d4T based) requires regular monitoring for early diagnosis. ZDV still remains the ARV agent of choice in the treatment of HIV disease in the resource limited settings. Although d4T drug has been shown to be associated with long-term toxicities, substitution within the same group can delay side effects. In order to optimize adherence and efficacy, clinicians must closely focus on preventing adverse ARV side-effects and distinguish those that are self-limiting from the potentially serious that can yield overall successfulness to the national program.