Virological Response Following Anti-Retroviral Therapy Employing Once-A-Day 30 mg of Stavudine in HIV-Infected Patients: A 24- Week Randomized Controlled Study in Dar Es Salaam, Tanzania (original) (raw)
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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.
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2002
To identify the level of phenotypic susceptibility for stavudine (d4T) that is associated with a diminished virologic response to d4T therapy, phenotyping was performed on archived baseline HIV isolates from 26 subjects who received d4T monotherapy in AIDS Clinical Trials Group (ACTG) 302 who had received >3 years of prior zidovudine (ZDV) monotherapy. Seven of 26 subjects achieved a virologic response of >0.3-log 10 copies/mL reduction in plasma HIV RNA after 8 weeks of d4T. Responders had lower fold changes in susceptibility to d4T (1.0 vs. 1.6, p ס .003), lower baseline viral loads (4.26 vs. 4.74 log 10 copies/mL, p ס .004), and fewer thymidine analog mutations (TAMS) (1 vs. 2, p ס .059). Lower baseline d4T fold change in susceptibility predicted greater reductions in HIV RNA from baseline to week 8 after adjusting for baseline HIV RNA, ZDV fold change in susceptibility, and number of TAMS. Using the same phenotypic assay, drug susceptibility among 240 antiretroviral-naive patients found all HIV isolates to have d4T susceptibility Յ1.4fold change. Using Յ1.4 as the d4T cutoff, the positive predictive value for a virologic response in this study was 44%, and the negative predictive value was 100%. d4T susceptibility greater than 1.4-fold change was associated with failure to achieve significant viral load reduction after 8 weeks of d4T monotherapy.
HIV Medicine, 2008
Stavudine (d4T) is a potent but potentially toxic nucleoside reverse transcriptase inhibitor that is still widely used in developing countries. This study's aim was to determine the efficacy and safety profile of lower-dose d4T. -centre, open-label, single-arm, pilot, 48-week study in French patients weighing 460 kg with viral load o400 HIV-1 RNA copies/mL who were receiving d4T 40 mg twice daily and then switched to 30 mg twice daily. The primary endpoint was the proportion with plasma viral load o400 copies/mL at week 24. Secondary endpoints included the proportion with o50 copies/mL at weeks 24 and 48, changes in mitochondrial DNA, CD4 cell count and pharmacokinetics, and clinical and laboratory safety.
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
AIDS, 2009
HIV suppression with stavudine 30mg versus 40mg in adults over 60kg on antiretroviral therapy in South Africa Christopher J Hoffmann (1),(2) , Salome Charalambous (1) , Katherine L Fielding (4) , Craig Innes (1) , Richard E Chaisson (2) , Alison D Grant (4) , and Gavin J Churchyard (1),(3),(4)
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.
Antiretroviral therapy in resource-limited settings: is there still a role for stavudine?
Antiviral Therapy, 2012
Phanuphak et al. compared three strategies for first-line antiretroviral therapy in 150 Thai patients: initiating therapy with zidovudine (AZT), tenofovir disoproxil fumarate (TDF), or a 24-week lead-in phase with stavudine (d4T) followed by a switch to AZT. Those taking d4T had higher haemoglobin levels and CD4 + T-cell counts without an increase in neuropathic symptoms, peripheral neuropathy or lipoatrophy compared with those on AZT. Because AZT is associated with more short-term side effects and toxicity than d4T, and because most d4T toxicity occurs only after long-term use, this approach may have advantages over initial use of AZT. However, TDF-based regimens, while more expensive, are more effective, better tolerated, less toxic, less likely to lead to cross-resistance, and possibly more cost-effective. The goal in resource-limited settings should be to move away from use of thymidine analogues in first-line regimens.