Triple-nucleoside regimens versus efavirenz-containing regimens for the initial treatment of HIV-1 infection. Antiretroviral regimens in pregnancy and breast-feeding in Botswana. A prospective, 96-week study of the impact of Trizivir, Combivir/nelfinavir, and lamivudine/stavudine/nelfinavir on lipids, metabolic parameters and efficacy in antiretroviral-naive patients: effect of sex and ethnicity.
Regimens containing three nucleoside reverse-transcriptase inhibitors offer an alternative to regimens containing nonnucleoside reverse-transcriptase inhibitors or protease inhibitors for the initial treatment of human immunodeficiency virus type 1 (HIV-1) infection, but data from direct comparisons are limited.
                This randomized, double-blind study involved three antiretroviral regimens for the initial treatment of subjects infected with HIV-1: zidovudine-lamivudine-abacavir, zidovudine-lamivudine plus efavirenz, and zidovudine-lamivudine-abacavir plus efavirenz.
                We enrolled a total of 1147 subjects with a mean baseline HIV-1 RNA level of 4.85 log10 (71,434) copies per milliliter and a mean CD4 cell count of 238 per cubic millimeter were enrolled. A scheduled review by the data and safety monitoring board with the use of prespecified stopping boundaries led to a recommendation to stop the triple-nucleoside group and to present the results in the triple-nucleoside group in comparison with pooled data from the efavirenz groups. After a median follow-up of 32 weeks, 82 of 382 subjects in the triple-nucleoside group (21 percent) and 85 of 765 of those in the combined efavirenz groups (11 percent) had virologic failure; the time to virologic failure was significantly shorter in the triple-nucleoside group (P<0.001). This difference was observed regardless of the pretreatment HIV-1 RNA stratum (at least 100,000 copies per milliliter or below this level; P< or =0.001 for both comparisons). Changes in the CD4 cell count and the incidence of grade 3 or grade 4 adverse events did not differ significantly between the groups.
                In this trial of the initial treatment of HIV-1 infection, the triple-nucleoside combination of abacavir, zidovudine, and lamivudine was virologically inferior to a regimen containing efavirenz and two or three nucleosides.
                Copyright 2004 Massachusetts Medical Society The most effective highly active antiretroviral therapy (HAART) to prevent mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) in pregnancy and its efficacy during breast-feeding are unknown.
                We randomly assigned 560 HIV-1-infected pregnant women (CD4+ count, > or = 200 cells per cubic millimeter) to receive coformulated abacavir, zidovudine, and lamivudine (the nucleoside reverse-transcriptase inhibitor [NRTI] group) or lopinavir-ritonavir plus zidovudine-lamivudine (the protease-inhibitor group) from 26 to 34 weeks' gestation through planned weaning by 6 months post partum. A total of 170 women with CD4+ counts of less than 200 cells per cubic millimeter received nevirapine plus zidovudine-lamivudine (the observational group). Infants received single-dose nevirapine and 4 weeks of zidovudine.
                The rate of virologic suppression to less than 400 copies per milliliter was high and did not differ significantly among the three groups at delivery (96% in the NRTI group, 93% in the protease-inhibitor group, and 94% in the observational group) or throughout the breast-feeding period (92% in the NRTI group, 93% in the protease-inhibitor group, and 95% in the observational group). By 6 months of age, 8 of 709 live-born infants (1.1%) were infected (95% confidence interval [CI], 0.5 to 2.2): 6 were infected in utero (4 in the NRTI group, 1 in the protease-inhibitor group, and 1 in the observational group), and 2 were infected during the breast-feeding period (in the NRTI group). Treatment-limiting adverse events occurred in 2% of women in the NRTI group, 2% of women in the protease-inhibitor group, and 11% of women in the observational group.
                All regimens of HAART from pregnancy through 6 months post partum resulted in high rates of virologic suppression, with an overall rate of mother-to-child transmission of 1.1%. (ClinicalTrials.gov number, NCT00270296.)
                2010 Massachusetts Medical Society To compare the lipid and metabolic effects, efficacy, and safety of twice-daily regimens of Trizivir (abacavir 300 mg/lamivudine 150 mg/zidovudine 300 mg triple nucleoside tablet; TZV), Combivir (lamivudine 150 mg/zidovudine 300 mg combination tablet; COM)+nelfinavir (NFV), and stavudine (d4 T)+lamivudine (3TC)+NFV.
                An international, phase 4, open-label, parallel-group, 34-centre study was conducted in 254 non-diabetic, antiretroviral-naive, HIV-infected out-patients with an HIV-1 RNA level of >1000 HIV-1 RNA copies/mL and < or =200,000 copies/mL and a CD4 cell count of >50 cells/microL.
                Patients were randomized 1 : 1 : 1 to TZV twice daily (n = 85), COM/NFV 1250 mg twice daily (n = 88), or d4T 40 mg+3TC 150 mg+NFV 1250 mg twice daily (n = 81) for 96 weeks. Treatments were compared using analysis of covariance (ANCOVA) with regard to changes from baseline in fasting lipids in the total population and in sex and ethnic subgroups. The proportions of patients achieving HIV-1 RNA <50 and <400 copies/mL were compared using a 95% confidence interval (CI) on the difference between proportions.
                The study population was diverse (50% female, 40% black and 37% Hispanic). Mean baseline low-density lipoprotein (LDL) cholesterol was 99 mg/dL, HIV-1 RNA was 4.43 log10 copies/mL and CD4 cell count was 355 cells/microL. At week 96, fasting LDL cholesterol changed minimally in the TZV group [least square mean (LSM) change from baseline, -8 mg/dL], but increased with d4T/3TC/NFV and COM/NFV (+29 and +19 mg/dL, respectively; P < 0.001 versus TZV). Week 96 LDL-cholesterol levels were significantly lower in the TZV group than in the other two treatment groups in women and men and lower than in the d4T/3TC/NFV group in Hispanic and black patients. In black patients, the week-96 LSM change from baseline in LDL cholesterol was significantly less with TZV than with d4T/3TC/NFV (+1 vs+39 mg/dL; P = 0.003). Total cholesterol >200 mg/dL occurred in a smaller proportion of patients receiving TZV (30%) compared with COM/NFV (50%) or d4T/3TC/NFV (60%; P = 0.005 vs TZV). High-density lipoprotein (HDL) cholesterol did not change markedly with any treatment. Although triglycerides increased, they changed least in women and Hispanic patients receiving TZV. Virological and CD4 responses to the treatments were similar in the total population and in the subgroups. Diarrhoea was reported more often in the NFV arms and nausea in the ZDV arms.
                Over 96 weeks, TZV twice daily has significantly less effect on LDL cholesterol than COM/NFV or d4T/3TC/NFV twice daily, especially in women and black patients, and is associated with similar virological and CD4 responses.
This review provides evidence that co-formulated abacavir-lamivudine-zidovudine remains a viable option for initiating antiretroviral therapy, especially in HIV-infected patients with pre-existing hyperlipidaemia. The varied geographical locations of the included trials augment the external validity of these findings. We are moderately confident in our estimate of the treatment effects of the triple NRTI regimen as initial therapy for HIV infection. In the context of the GRADE approach, such moderate quality of evidence implies that the true effects of the regimen are likely to be close to the estimate of effects found in this review; but there is a possibility that they could be substantially different.  Further research should be geared towards defining the subgroup of HIV patients for whom this regimen will be most beneficial.