A randomized, dose-finding study with didanosine plus stavudine versus didanosine alone in antiviral-naive, HIV-infected Thai patients

Ruxrungtham, Kiat; Kroon, Eugène; Ungsedhapand, Chaiwat; Teeratakulpisarn, Somsong; Ubolyam, Sasiwimol; Buranapraditkun, Supranee; Leeuwen, Remko van; Weverling, G. J.; Kunanusont, Chaiyos; Lange, Joep M. A.; Cooper, David A.; Phanuphak, Praphan

doi:10.1097/00002030-200007070-00010

Cited by 29 publications

(16 citation statements)

References 22 publications

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“…52 53 55 – 62 66 77 79 80 Double therapy resulted in significantly better clinical outcomes than monotherapy did (fig 6) (odds ratio for disease progression/death was 0.6, 0.5 to 0.7). There was some heterogeneity, but this seemed to be largely accounted for by one large trial of protease inhibitors 79.…”

Section: Resultsmentioning

confidence: 99%

Systematic review and meta-analysis of evidence for increasing numbers of drugs in antiretroviral combination therapy

Jordan

Gold²,

Cummins³

et al. 2002

BMJ

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Objective To assess the evidence for the effectiveness of increasing numbers of drugs in antiretroviral combination therapy. Design Systematic review, meta-analysis, and meta-regression of fully reported randomised controlled trials. Results 54 randomised controlled trials, most of good quality, with 66 comparison groups were included in the analysis. For both the clinical outcomes and surrogate markers, combinations with up to and including three (triple therapy) were progressively and significantly more effective. The odds ratio for disease progression or death for triple therapy compared with double therapy was 0.6 (95% confidence interval 0.5 to 0.8). Heterogeneity in effect sizes was present in many outcomes but was largely related to the drugs used and trial quality. Conclusions Evidence from randomised controlled trials supports the use of triple therapy. Research is needed on the effectiveness of quadruple therapies and the relative effectiveness of specific combinations of drugs.

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Section: Resultsmentioning

confidence: 99%

Systematic review and meta-analysis of evidence for increasing numbers of drugs in antiretroviral combination therapy

Jordan

Gold²,

Cummins³

et al. 2002

BMJ

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“…Although the data on a lower dose of stavudine are scarce, there is evidence that patients can maintain virologic suppression, improve immunologic response and decrease stavudine-related adverse events while on ART [34–37]. One study reported that a switch to a half dose of stavudine (15 or 20 mg) modestly improved mitochondrial function and lessened the loss of bone mineral density [35].…”

Section: Discussionmentioning

confidence: 99%

Increases in regimen durability associated with the introduction of tenofovir at a large public‐sector clinic in Johannesburg, South Africa

Brennan

Maskew

Ive

et al. 2013

Journal of the International AIDS Society

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IntroductionIn April 2010, tenofovir replaced stavudine in public-sector first-line antiretroviral therapy (ART) in South Africa. The association of tenofovir with fewer side effects and toxicities compared to stavudine could translate to increased durability of tenofovir-based regimens. We evaluated changes over time in regimen durability at the Themba Lethu Clinic, Johannesburg, South Africa.MethodsThis was a cohort analysis of treatment-naïve, non-pregnant adult patients initiated on ART between April 2004 and December 2011. First-line ART regimens before April 2010 consisted of stavudine or zidovudine with lamivudine and either efavirenz or nevirapine. Tenofovir was substituted for stavudine after April 2010. We evaluated the frequency and type of single-drug substitutions (excluding switches to second-line therapy). Cox models were used to evaluate the association of ART initiation year and antiretroviral drug type with single-drug substitutions in the first 12 months on treatment.ResultsOne thousand nine hundred and sixty-four (10%) substitutions occurred amongst 19,699 patients. Excluding 2004 (year of treatment roll-out), before 2010 one-year single-drug substitutions ranged from 10.0 to 13.1%. In 2011, well after integration of tenofovir, substitutions decreased to 5.6%. Single-drug substitution was lowest amongst patients on tenofovir (5.1%) versus zidovudine (11.3%), 30 mg stavudine (10.5%) or 40 mg stavudine (14.4%). Adjusted Cox models showed that patients initiating treatment between 2005 and 2010 (vs. 2011) had a twofold increased hazard of single-drug substitution, while those on zidovudine or stavudine had a two to threefold increase in single-drug substitution versus tenofovir patients in the first 12 months on ART.ConclusionsThe decline in single-drug substitutions is associated with the introduction of tenofovir. Tenofovir use could improve regimen durability and treatment outcomes in resource-limited settings.

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“…Dose reduction of d4T to 20 mg twice daily for patients with body weight less than 60 kg and 30 mg twice daily for patients with body weight more than 60 kg has been shown to be effective, with a more favorable toxicity profile [22,33]. Furthermore, AZT 300 mg twice daily, which is the recommended dosage, results in a 5-fold increases in plasma AZT concentrations in Thais [34].…”

Section: Introductionmentioning

confidence: 99%

Generic and low dose antiretroviral therapy in adults and children: implication for scaling up treatment in resource limited settings

Ramautarsing

Ananworanich

2010

AIDS Res Ther

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Although access to antiretroviral therapy (ART) for the treatment of HIV has increased during the last decade, many patients are still in need of treatment. With limited funds to provide ART to millions of patients worldwide, there is a need for alternative ways to scale up ART in resource limited settings. This review provides an overview of pharmacokinetic, safety and efficacy studies of generic and reduced dose ART. The production of generic ART has greatly influenced the decline in drug prices and the increased in ART access. Generic ART has good pharmacokinetic profile, safety and efficacy. Toxicity is however the main cause for ART discontinuation. Several dose reduction studies have shown adequate pharmacokinetic parameters and short term efficacy with reduced dose ART. Ethnicity may affect drug metabolism; several pharmacokinetic studies have confirmed higher plasma ART concentration in Asians. Randomized efficacy trial of reduced versus standard ART is warranted.

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A randomized, dose-finding study with didanosine plus stavudine versus didanosine alone in antiviral-naive, HIV-infected Thai patients

Abstract: The d4T/ddI combination was superior to ddI alone in producing HIV-1 viral suppression. At week 48, > 60% of patients treated with this combination reached HIV-1 RNA levels < 500 copies/ml. Receiving high dose ddI but not d4T may correlate with a better viral suppression.

Cited by 29 publications

References 22 publications

Systematic review and meta-analysis of evidence for increasing numbers of drugs in antiretroviral combination therapy

Systematic review and meta-analysis of evidence for increasing numbers of drugs in antiretroviral combination therapy

Increases in regimen durability associated with the introduction of tenofovir at a large public‐sector clinic in Johannesburg, South Africa

Generic and low dose antiretroviral therapy in adults and children: implication for scaling up treatment in resource limited settings

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