A Randomized, Double-blind Trial Comparing Combinations of Nevirapine, Didanosine, and Zidovudine for HIV-Infected Patients

Abstract

; for the INCAS Study Group Context.-Current guidelines recommend that individuals infected with the human immunodeficiency virus type 1 (HIV-1) be treated using combinations of antiretroviral agents to achieve sustained suppression of viral replication as measured by the plasma HIV-1 RNA assay, in the hopes of achieving prolonged remission of the disease. However, until recently, many drug combinations have not led to sustained suppression of HIV-1 RNA. Objective.-To compare the virologic effects of various combinations of nevirapine, didanosine, and zidovudine. Design.-Double-blind, controlled, randomized trial. Setting.-University-affiliated ambulatory research clinics in Italy, the Netherlands, Canada, and Australia (INCAS). Patients.-Antiretroviral therapy-naive adults free of the acquired immunodeficiency syndrome with CD4 cell counts between 0.20 and 0.60ϫ10 9 /L (200-600/µL). Intervention.-Patients received zidovudine plus nevirapine (plus didanosine placebo), zidovudine plus didanosine (plus nevirapine placebo), or zidovudine plus didanosine plus nevirapine. Main Outcome Measure.-Plasma HIV-1 RNA. Results.-Of the 153 enrolled patients, 151 were evaluable. At week 8, plasma HIV-1 RNA levels had decreased by log 2.18, 1.55, and 0.90 in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively (PϽ.05). The proportions of patients with plasma HIV-1 RNA levels below 20 copies per milliliter at week 52 were 51%, 12%, and 0% in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively (PϽ.001). Viral amplification was attempted in 59 patients at 6 months. Viral isolation was unsuccessful in 19 (79%) of 24, 10 (53%) of 19, and 5 (31%) of 16 patients in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively. Among patients from whom virus could be amplified, resistance to nevirapine was found in all 11 patients receiving zidovudine plus nevirapine and in all 5 patients receiving triple drug therapy. Rates of disease progression or death were 23% (11/47), 25% (13/53), and 12% (6/51) for the zidovudine plus nevirapine, zidovudine plus didanosine, and triple drug therapy groups, respectively (P=.08). Conclusions.-Triple drug therapy with zidovudine, didanosine, and nevirapine led to a substantially greater and sustained decrease in plasma viral load than the 2-drug regimens studied. Our results also suggest that suppression of viral replication, as demonstrated by a decrease in the plasma HIV-1 RNA load below the level of quantitation of the most sensitive test available, may at least forestall the development of resistance.

Treatment Outcomes in Patients Receiving Combination Antiretroviral Therapy in Central Hospital, Benin City, Nigeria

“…Adherence to medication and lifestyle changes is a key factor to positive treatment outcome in the therapy of HIV/AIDS and this presents a challenge to both patients and healthcare providers [11][12][13][14][15][16]. The patients' knowledge of the benefits of ART and consequences of non-adherence of a majority was found to be high and that might have enhanced medication adherence and possibly the survival of patients on ART.…”

“…Misconceptions, cultural beliefs, poor socio-economic indices and ignorance are among the factors that could constitute the greatest challenge to wide acceptance and adherence to ART in Africa. Since adherence is the cornerstone of successful ART [11][12][13][14][15][16], there is a need to appraise the treatment outcomes of ART interventions against these factors which are considered as obstacles to mounting concerted ART programmes in Nigeria.…”

Hepatotoxicity associated with nevirapine or efavirenz-containing antiretroviral therapy: Role of hepatitis C and B infections

“…Accordingly, the United States Food and Drug Administration has issued warnings regarding the risk of NVP-related hepatotoxicity. 5,15,[18][19][20][21][22][23][24][25][26][27][28] Conversely, although reported, little published information is available regarding the risk of hepatotoxicity among patients receiving efavirenz. [29][30][31] Furthermore, most data regarding NNRTI-associated hepatotoxicity are derived from anecdotal reports, which may focus attention on exceptional cases or high-risk populations, or from clinical trials, which are frequently restricted to persons at low risk for adverse events.…”

HIV-1 Genotypic Resistance Patterns Predict Response to saquinavir–ritonavir Therapy in Patients in Whom Previous Protease Inhibitor Therapy Had Failed

“…C ombination antiretroviral therapy for HIV-1 infection has resulted in profound control of HIV replication in vivo, improved immune function, and significant decreases in AIDS-related morbidity and mortality (1)(2)(3)(4)(5)(6)(7)(8)(9). For many persons, however, this therapy does not provide sustained viral suppression or durable clinical benefit (10,11).…”