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Among 1121 patients (90% Caucasian) infected by the human immunodeficiency virus (HIV), the glomerular filtration rate increased (+0.72 mL/min/1.73 m(2)/month) from treatment initiation to month 16 (the rate increase was lower among men and those with low body mass index, AIDS, or receipt of indinavir), then remained stable up to 7 years. Kidney function should be monitored in patients previously exposed to indinavir.

Background: Zidovudine, the first antiretroviral agent, has short-term haematological toxicity. However, it is unclear whether patients tolerating long-term zidovudine-containing regimens will benefit from a switch to non-zidovudine-containing regimens., Methods: One hundred and fifty-eight patients enrolled in the ALIZE trial receiving zidovudine at baseline were analysed. These patients were randomized to continue their regimen or to switch to a combination of emtricitabine, didanosine and efavirenz for 48 weeks. Changes from baseline in haemoglobin (Hb), neutrophil and platelet counts were compared between arms as well as the occurrence of cardiovascular events, bacterial infections, use of haematopoietic growth factors, blood transfusion and quality of life using the Medical Outcome Study HIV (MOS-HIV) health survey., Results: Eighty-one patients continued their regimen and 77 switched. At 48 weeks, mean change from baseline in Hb were +0.73 and -0.37 g/dL in the switch and maintenance groups, respectively (P < 0.01). Mean neutrophil counts increased by 592 and 51 cells/mm(3) in the switch and maintenance groups, respectively (P = 0.02). The occurrence of cardiovascular events or bacterial infections was similar in both treatment arms with no use of haematopoietic growth factors or blood transfusion. Also, mean change from baseline in MOS-HIV physical and mental health summary scores was similar in both arms., Conclusions: A switch from a long-standing zidovudine- to a non-zidovudine-containing regimen modestly improves haematological parameters and is not associated with obvious clinical benefit.

Objectives: Data on the durability of antiretroviral regimens over a 3-year period have only rarely been reported. The aim of this study was to evaluate the long-term efficacy and safety of one or two daily doses of nevirapine (NVP), in combination with stavudine (d4T) and didanosine (ddI), in HIV-infected patients., Methods: This study was a follow-up of the VIR (amune) Grand Ouest (VIRGO) study, a 12-month open-label trial to assess the safety and immunovirological activity of NVP-d4T-ddI combination therapy in antiretroviral-naive HIV-1-infected adults with baseline CD4 counts > or =200 cells/microL and plasma viral loads > or =5000 HIV-1 RNA copies/mL. Of the 100 patients included in the study, the 67 patients remaining on the initial triple therapy at the end of the study (1 year) were offered an extra 24 months of follow-up., Results: Of the 60 patients who extended follow-up, 46 were still being treated with d4T-ddI-NVP at month 36; 91% (39/43) had a plasma viral load <500 copies/mL (data were missing for three patients). CD4 cell counts increased over 36 months. Safety and tolerance were good with no unexpected long-term toxicity., Conclusion: After 3 years of treatment with NVP-d4T-ddI, nearly half of the patients were still receiving the initial antiretroviral therapy with a sustained and durable immunovirological benefit. Long-term toxicity was mainly related to the nucleoside reverse transcriptase inhibitor components of the regimen.

Background: Efavirenz (EFV) is a highly active antiretroviral drug, use of which is associated with frequent (although transient) neurosensorial adverse reactions. Whether the use of EFV is associated with the risk of depression or suicide remains controversial., Methods: ALIZE-ANRS (Agence Nationale de Recherches sur le SIDA et les Hepatites Virales) 099 was a 48-week randomized trial involving virologically suppressed, human immunodeficiency virus (HIV)-infected patients that compared the maintenance of a treatment regimen that contained protease inhibitors (177 subjects) with a switch to a once-daily combination of EFV, didanosine, and emtricitabine (178 subjects). We used the trial's adverse events reporting system and a self-administered Center for Epidemiologic Studies-Depression Scale questionnaire to assess depressive disorders. Determinants were studied using a multivariate proportional hazards model adjusted for antiretroviral treatment, sex, age, HIV risk factor, history of depression, hepatic disorder, alcohol abuse, and HIV-related or non-HIV-related events., Results: Thirty cases of depressive disorder (26 cases of depression and 4 suicide attempts) occurred during treatment in 27 patients (12 patients [7%] and 15 patients [8%] in the protease inhibitor-based and EFV-based treatment arms, respectively; P = .56). In the proportional hazards model, only age (hazard ratio, 1.6 per 10 years younger; 95% confidence interval, 1.0-2.6) and a history of depressive disorder (hazard ratio, 5.0; 95% confidence interval, 2.1-12.0) were associated with a risk of depressive disorders. The proportion of depressive patients (24%), as determined on the basis of the Center for Epidemiologic Studies-Depression Scale data, was stable during the follow-up period, without difference between treatment groups. Patients with a history of depressive disorder were more frequently depressed (53%) than were those without such history (22%; P = .03)., Conclusions: The frequency of depressive disorders was high in this population, but the disorders were not related to EFV treatment. Younger age and a history of depression are important determinants for depression and should be considered for early detection and case management.

The virological and immunological efficacy of the triple regimen containing nevirapine (once or twice daily), didanosine (once daily) and stavudine, in antiretroviral-naive patients infected with HIV-1, was evaluated in an open-label, prospective, non-randomized, multi-centre, 52-week study. The first 60 patients (VIRGO I) received nevirapine as the standard dose, 200 mg twice daily; the subsequent 40 patients (VIRGO II) received nevirapine at a dose of 400 mg once daily. All patients received 400 mg of didanosine once daily and 40 mg of stavudine twice daily, adjusted for body weight. At baseline, the median CD4 cell count and plasma viral load (pVL) were 414 cells/mm3 and 4.59 log10 copies/ml in VIRGO I, and 412 cells/mm3 and 4.87 log10 copies/ml in VIRGO II. Using an intent-to-treat, 'non-completer equals failure', analysis, 78% (95% CI, 68-88%) of patients in VIRGO I and 68% (95% CI, 53-83%) of those in VIRGO II had a pVL <500 copies/ml at 24 weeks; the proportions achieving a pVL of <50 copies/ml were 62% (95% CI, 50-74%) and 50% (95% CI, 35-65%), respectively. The week 24 median CD4 cell count increase was 168 cells/mm3 (VIRGO I) and 139 cells/mm3 (VIRGO II). At week 52, 39/45 (87%) of VIRGO I patients had pVL <500 copies/ml and 30/45 (67%) <50 copies/ml. Of the 100 patients, 44 experienced grade 2 to 4 adverse events; 20 permanently discontinued study medication because of an adverse event. Combination therapy with the three reverse transcriptase (RT) inhibitors stavudine, once-daily didanosine and either once- or twice-daily nevirapine could be considered as an alternative option for first-line antiretroviral therapy.