Efficacy and Safety of Tenofovir DF vs Stavudine in Combination Therapy in Antiretroviral-Naive Patients<SUBTITLE>A 3-Year Randomized Trial</SUBTITLE>

Abstract

753 patients infected with HIV who were antiretroviral naive were screened and 602 patients entered the study. Intervention Patients were randomized to receive either tenofovir DF (n=299) or stavudine (n=303), with placebo, in combination with lamivudine and efavirenz. Main Outcome Measure Proportion of patients with HIV RNA levels of less than 400 copies/mL at week 48. Results In the primary intent-to-treat analysis in which patients with missing data or who added or switched antiretroviral medications before week 48 were considered as failures, the proportion of patients with HIV RNA of less than 400 copies/mL at week 48 was 239 (80%) of 299 in patients receiving tenofovir DF and 253 (84%) of 301 in patients receiving stavudine (95% confidence interval, −10.4% to 1.5%), exceeding the predefined −10% limit for equivalence. However, equivalence was demonstrated in the secondary analyses (HIV RNA Ͻ50 copies/ mL) at week 48 and through 144 weeks. Virologic failure was associated most frequently with efavirenz and lamivudine resistance. Through 144 weeks, the K65R mutation emerged in 8 and 2 patients in the tenofovir DF and stavudine groups, respectively (P = .06). A more favorable mean change from baseline in fasting lipid profile was noted in the tenofovir DF group at week 144: for triglyceride levels (+1 mg/dL for tenofovir DF [n=170] vs +134 mg/dL for stavudine [n=162], PϽ.001), total cholesterol (+30 mg/dL [n=170] vs +58 mg/dL [n=162], PϽ.001), direct lowdensity lipoprotein cholesterol (+14 mg/dL [n = 169] vs +26 mg/dL [n = 161], PϽ.001), and high-density lipoprotein cholesterol (+9 mg/dL [n=168] vs +6 mg/dL [n = 154], P = .003). Investigator-reported lipodystrophy was less common in the tenofovir DF group compared with the stavudine group (9 [3%] of 299 vs 58 [19%] of 301, PϽ.001). The number of bone fractures and the renal safety profile were similar between the 2 groups. Conclusions Through 144 weeks, the combination of tenofovir DF, lamivudine, and efavirenz was highly effective and comparable with stavudine, lamivudine, and efavirenz in antiretroviral-naive patients. However, tenofovir DF appeared to be associated with better lipid profiles and less lipodystrophy.

Weight loss after the first year of stavudine-containing antiretroviral therapy and its association with lipoatrophy, virological failure, adherence and CD4 counts at primary health care level in Kigali, Rwanda

“…25 The association of weight loss, body fat changes and stavudine use was also observed in a large randomized trial, comparing stavudine with tenofovir-based ART. 18 This study reported that, after an initial increase, the average body weight of the study population returned to baseline levels by three years of stavudine intake, paralleled by a gradual peripheral fat loss. Although the difference did not reach statistical significance, patients with poor treatment adherence appeared to have less weight loss after the first year of ART in our study.…”

“…[14][15][16] Although never specifically addressed, several studies suggest a potential association of lipoatrophy with weight loss. 15,17,18 We conducted a study on patients on stavudinecontaining ART to (a) determine the proportion who manifest weight loss after one year of ART, (b) examine the association between such weight loss and a number of variables namely: lipoatrophy, virological failure, adherence and on-treatment CD4 count and (c) assess the validity and predictive values of weight loss to identify patients with lipoatrophy.…”

HIV infection, bone metabolism, and fractures

“…concluded that the probability of osteopenia and osteoporosis would be over 6-fold and almost 4-fold higher in HIV-infected than in uninfected populations respectively (23). In line with these data, in a clinical trial that evaluated BMD before starting ART, the prevalence of osteopenia at the start of ART was in a range of 23 to 28%, clearly higher than that in the general population (24).…”

“…The authors reported a relative risk of 2.5 for osteopenia in patients with ART compared with untreated patients. In fact, other longitudinal studies and clinical trials conducted to date also suggest that ART is associated with low bone mass (24,27).…”

Study of lipid profile in HIV/AIDS patients on antiretroviral therapy

“…They cause increases in total cholesterol, triglycerides and LDL. Among that category of drugs Stavudine is the drug associated with severe dyslipidemia [8]. The presence of an atherogenic lipid profile in HIV patients on antiretroviral therapy makes these patients more susceptible to cardiovascular events.…”