Antiretroviral therapy in resource-limited settings: is there still a role for stavudine? (original) (raw)
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PLoS ONE, 2013
Background: Tenofovir (TDF) is part of the WHO recommended first-line antiretroviral therapy (ART); however, there are limited data comparing TDF to other nucleoside reverse transcriptase inhibitors in resource-limited-settings. Using a routine workplace and community-based ART cohort in South Africa, we assessed single drug substitution, HIV RNA suppression, CD4 count increase, loss-from-care, and mortality between TDF, stavudine (d4T) 30 mg dose, and zidovudine (AZT). Methods: In a prospective cohort study we included ART naïve patients aged $17 years-old who initiated ART containing TDF, d4T, or AZT between 2007 and 2009. For analysis of single drug substitutions we used a competing-risks time-to-event analysis; for loss-from-care, mixed-effect Poisson modeling; for HIV RNA suppression, competing-risks logistic regression; for CD4 count slope, mixed-effects linear regression; and for mortality, proportional hazards modeling. Results: Of 6,196 patients, the initial drug was TDF for 665 (11%), d4T for 4,179 (68%), and AZT for 1,352 (22%). During the first 6 months of ART, the adjusted hazard ratio for a single drug substitution was 2.3 for d4T (95% confidence interval [CI]: 0.27, 19) and 5.2 for AZT (95% CI: 1.1, 23), compared to TDF; whereas, after 6 months, it was 10 (95% CI: 5.8, 18) and 4.4 (95% CI: 2.5, 7.8) for d4T and AZT, respectively. Virologic suppression was similar by agent; however, CD4 count rise was lowest for AZT. The adjusted hazard ratio for loss-from-care, when compared to TDF, was 1.5 (95% CI: 1.1, 1.9) for d4T and 1.2 (95% CI: 1.1, 1.4) for AZT. The adjusted hazard ratio for mortality, when compared to TDF, was 2.7 (95% CI: 2.0, 3.5) and 1.4 (95% CI: 1.3, 1.5) and for d4T and AZT, respectively. Discussion: In routine care, TDF appeared to perform better than either d4T or AZT, most notably with less drug substitution and mortality than for either other agent.
Journal of HIV and AIDS ( ISSN 2380-5536 ), 2015
Objectives: To compare the immunological and clinical effects of a further reduction of stavudine dose to 30 mg once-daily with that of a standard zidovudine containing antiretroviral therapy (ART) regimen in a prospective, open-label randomized controlled study. Methods: Naïve HIV infected patients were equally randomized to receive either stavudine 30 mg once-daily or a standard dose zidovudine containing regimen. CD4+ T-cell counts, Haemoglobin (Hb), alanine aminotransferase (ALT), Body Mass Index (BMI), WHO stage and patients' morbidity at baseline, three and six months were determined. Changes between baseline and three as well as six months follow-up were compared within-and between-groups. Results: Five hundred and twenty patients aged ≥ 18 years were included. Males were 159 (30.6%), with the mean (SD) age of 39 (9) years. Within group comparison indicated that there were statistically significant increases in mean CD4+ cell counts, BMI, and Hb (p<0.0001) at 3 and 6 months from the values at baseline in both groups, but there were not significantly different between groups. Furthermore, there was no statistically significant difference between groups in terms of occurrence of opportunistic infections (OIs) however, there was significant decrease of OIs for subsequent follow up time points compared to baseline status. The overall median adherence rate was 94% (IQR 94%, 98%) in both groups, but patients in the stavudine group had better adherence compared to those in the zidovudine group, p<0.0001. Additionally, liver damage at 6 months, as indicated by elevated ALT, was more likely with the zidovudine based regimen, p <0.0001. There was no statistically significant difference in ALT elevations between the groups at 3 months. Conclusion: The immunological and clinical outcomes following a regimen employing a reduced dose of stavudine to 30 mg once-daily were similar to those of a standard zidovudine-based antiretroviral regimen.
Journal of Virology and Emerging Diseases ( ISSN 2471-822X ), 2016
Stavudine at a dose of 30mg has been in use for more Thana decade. Its toxicity remains a challenge and phase out has picked up. However, the information about viral load suppression (VLS) at once-a-day dosing is lacking. A prospective open-label randomized controlled study was conducted. Methods: Naïve HIV infected patients were equally randomized either to receive stavudine 30mg once-daily or zidovudine standard dose regimens. Viral load, hemoglobin (Hb), alanine amino transferase (ALT), Body Mass Index (BMI), opportunistic infections (OIs) at baseline and six months were determined. Changes at baseline and six months were compared within and between-groups. Our outcome was the proportion of patients who attained VLS< 400 copies/mL at six months. Results: Four hundred and eighty three patients aged ≥ 18 years were analyzed. The overall mean standard deviation (SD) age was of 39 (9) years, 41 (9) and 38 (9) for males and females respectively. The two groups were similar in demographic, clinical and other laboratory indices at baseline. At six months, VLS< 400 copies/mL was 73.2%, there was no statistically significant differences been groups. There was no statistically significant differences been males and females. Patients with age >40 years were more likely to have VLS by 8% compared to young ones, risk ratio (95% CI) being 0.921 (0.829, 1.023; p=0.1275) Conclusion: Viral load suppression for stavudine 30 mg once-a-day was similar to zidovudine standard regimen. However, long follow up period is recommended to determine efficacy and long term side effects at our recommended dose.
Stavudine plus Lamivudine in Advanced Human Immunodeficiency Virus Disease: A Short‐Term Pilot Study
The Journal of Infectious Diseases, 1997
The short-term effects of stavudine (d4T) plus lamivudine (3TC) were evaluated among 48 human immunodeficiency virus-infected patients for whom zidovudine therapy had failed or who could not tolerate zidovudine. Patients were followed for 8 weeks after initiation of open-label d4T plus 3TC. Four patients discontinued therapy, because of neutropenia (1), hepatitis (1), or neuropathy (2). Reduction in virus load was 00.86 (/0.3 to 03.4) log 10 copies/mL and CD4 cell increase was 30 (0100 to /290) cells/mm 3. Virologic response was associated with a higher CD4 cell count, no prior exposure to d4T and 3TC, and no previous AIDS-defining illness. Virus load reduction for patients naive to 3TC and d4T was 01.47 (00.14 to 03.37) log 10 copies/mL. Short-term use of d4T plus 3TC is safe, well-tolerated, and associated with virologic and substantial immunologic benefits. Further evaluation of d4T and 3TC in combination is warranted. A number of controlled trials have now demonstrated that untested combinations. Despite the lack of controlled clinical data, stavudine (d4T) and lamivudine (3TC) have often been combination antiretroviral therapy is generally more effective that monotherapy for the treatment of human immunodefi-combined under these circumstances on the basis of their wellcharacterized antiviral effect, nonoverlapping toxicities, and ciency virus (HIV) infection [1-6]. Survival benefit and improvement of clinical outcomes have been correlated with favorable safety and pharmacokinetic profiles [14-24]. We report here the results of a pilot open-label study of the short-term changes in surrogate markers of HIV disease progression [7-9]. In particular, recent evidence suggests that short-term tolerability and antiviral effect of d4T and 3TC combination therapy in the setting of advanced HIV infection changes in plasma virus load within the first 2 months of therapy are predictive of long-term clinical outcome [10-12]. among patients who were zidovudine-intolerant or no longer benefiting from zidovudine therapy. These developments have led to a substantial revision of our therapeutic approach based on the use of combination antiretroviral therapy regimens and ongoing monitoring of plasma Methods virus load and CD4 cell counts [13]. The effect of specific therapeutic regimens on clinical out-Study design. This was an open-label pilot study conducted comes and survival is currently being assessed in long-term within the frame of the 3TC (NUCA 3004) and the d4T (BMS clinical trials. Unfortunately, the realities of HIV management A1455-903) open-label programs. Eligible patients had documented HIV infection and were either zidovudine-intolerant or cannot wait for definitive answers and often rely on preliminary clinically progressing despite zidovudine therapy. Clinical progresresults to guide therapeutic decisions [13]. In the recent past, sion was defined by a lack of CD4 cell response to antiretroviral patients who could not tolerate or who could no longer benefit therapy, clinical disease progression, or both. Patients were §18 from zidovudine therapy have often received treatment with years old and had the following: CD4 cell count õ400 cells/mm 3 , hemoglobin concentration §80 g/L, absolute neutrophil count ú0.6 1 10 9 /L, platelet count ú25 1 10 9 /L, liver function tests õ5 times the upper limit of normal, and serum creatinine level
Journal of AIDS and …, 2010
This study compared the efficacy and tolerability of stavudine at two dose levels in patients attending a HIV Comprehensive Care Centre in Kenya. Data were collected retrospectively from the records of 810 adult patients. Fewer stavudine related adverse effects were seen in patients 60 kg treated with 30 mg stavudine compared to those who received 40 mg (4.2 vs 16.7%, p < 0.001). Patients < 60 kg were more likely to experience drug toxicity than those 60 kg when given 30 mg stavudine (12.8 vs 4.2%, p < 0.001). Occurrence of any adverse drug reaction was significantly associated with severe immunosuppression (HR =1.45, CI: 0.86 -2.45, p < 0.001), co-morbidities (HR = 2.16, CI: 1.06 -4.38, p < 0.001) and treatment with isoniazid (HR = 2.07, CI: 1.09 -3.96, p < 0.001). The onset of drug related toxicities was principally in the first year of commencing therapy. Similar immunologic outcomes were demonstrated across all the treatment groups with median CD4 cell counts after 12 months of treatment more than doubling for patients in all the study cohorts. The findings support the use of combination antiretroviral therapy regimens containing low dose stavudine in Kenya.