Search

Despite declines in morbidity and mortality with the use of combination antiretroviral therapy, its effectiveness is limited by adverse events, problems with adherence, and resistance of the human immunodeficiency virus (HIV).We randomly assigned persons infected with HIV who had a CD4+ cell count of more than 350 per cubic millimeter to the continuous use of antiretroviral therapy (the viral suppression group) or the episodic use of antiretroviral therapy (the drug conservation group). Episodic use involved the deferral of therapy until the CD4+ count decreased to less than 250 per cubic millimeter and then the use of therapy until the CD4+ count increased to more than 350 per cubic millimeter. The primary end point was the development of an opportunistic disease or death from any cause. An important secondary end point was major cardiovascular, renal, or hepatic disease.A total of 5472 participants (2720 assigned to drug conservation and 2752 to viral suppression) were followed for an average of 16 months before the protocol was modified for the drug conservation group. At baseline, the median and nadir CD4+ counts were 597 per cubic millimeter and 250 per cubic millimeter, respectively, and 71.7% of participants had plasma HIV RNA levels of 400 copies or less per milliliter. Opportunistic disease or death from any cause occurred in 120 participants (3.3 events per 100 person-years) in the drug conservation group and 47 participants (1.3 per 100 person-years) in the viral suppression group (hazard ratio for the drug conservation group vs. the viral suppression group, 2.6; 95% confidence interval [CI], 1.9 to 3.7; P0.001). Hazard ratios for death from any cause and for major cardiovascular, renal, and hepatic disease were 1.8 (95% CI, 1.2 to 2.9; P=0.007) and 1.7 (95% CI, 1.1 to 2.5; P=0.009), respectively. Adjustment for the latest CD4+ count and HIV RNA level (as time-updated covariates) reduced the hazard ratio for the primary end point from 2.6 to 1.5 (95% CI, 1.0 to 2.1).Episodic antiretroviral therapy guided by the CD4+ count, as used in our study, significantly increased the risk of opportunistic disease or death from any cause, as compared with continuous antiretroviral therapy, largely as a consequence of lowering the CD4+ cell count and increasing the viral load. Episodic antiretroviral therapy does not reduce the risk of adverse events that have been associated with antiretroviral therapy. (ClinicalTrials.gov number, NCT00027352 [ClinicalTrials.gov].).

Background Several agents are effective in preventing Mycobacterium avium complex disease in patients with advanced human immunodeficiency virus (HIV) infection. However, there is uncertainty about whether prophylaxis should be continued in patients whose CD4+ cell counts have increased substantially with antiviral therapy. Methods We conducted a multicenter, double-blind, randomized trial of treatment with azithromycin (1200 mg weekly) as compared with placebo in HIV-infected patients whose CD4+ cell counts had increased from less than 50 to more than 100 per cubic millimeter in response to antiretroviral therapy. The primary end point was M. avium complex disease or bacterial pneumonia. Results A total of 520 patients entered the study; the median CD4+ cell count at entry was 230 per cubic millimeter. In 48 percent of the patients, the HIV RNA value was below the level of quantification. The median prior nadir CD4+ cell count was 23 per cubic millimeter, and 65 percent of the patients had had an acquire...

Background Disseminated Mycobacterium avium complex infection eventually develops in most patients with the acquired immunodeficiency syndrome (AIDS). This infection results in substantial morbidity and reduces survival by about six months. Methods We conducted two randomized, double-blind, multicenter trials of daily prophylactic treatment with either rifabutin (300 mg) or placebo. All the patients had AIDS and CD4 cell counts ≤ 200 per cubic millimeter. The primary end point was M. avium complex bacteremia as assessed monthly by blood culture. The secondary end points were signs and symptoms associated with disseminated M. avium complex infection, adverse events, hospitalization, and survival. Results In the first trial, M. avium complex bacteremia developed in 51 of 298 patients (17 percent) assigned to placebo and 24 of 292 patients (8 percent) assigned to rifabutin (P

Background. Zidovudine is recommended for asymptomatic and early symptomatic human immunodeficiency virus (HIV) infection. The best time to initiate zidovudine treatment remains uncertain, however, and whether early treatment improves survival has not been established. Methods. We conducted a multicenter, randomized, double-blind trial that compared early zidovudine therapy (beginning at 1500 mg per day) with late therapy in HIV-infected patients who were symptomatic and had CD4+ counts between 0.2×109 and 0.5×109 cells per liter (200 to 500 per cubic millimeter) at entry. Those assigned to late therapy initially received placebo and began zidovudine when their CD4+ counts fell below 0.2×109 per liter (200 per cubic millimeter) or when the acquired immunodeficiency syndrome (AIDS) developed. Results. During a mean follow-up period of more than two years, there were 23 deaths in the early-therapy group (n = 170) and 20 deaths in the late-therapy group (n = 168) (P = 0.48; relative risk [late vs. e...