Long‐term assessment of nevirapine‐containing highly active antiretroviral therapy in antiretroviral‐naive HIV‐infected patients: 3‐year follow‐up of the VIRGO study

Abstract

ObjectivesData 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. MethodsThis 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 200 cells/mL and plasma viral loads 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. ResultsOf 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 o500 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. ConclusionAfter 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.Keywords: long-term efficacy, nevirapine, safety IntroductionHighly active antiretroviral therapy (HAART) has led to a dramatic decline in HIV-related morbidity and mortality. Protease inhibitor (PI)-containing regimens were initially considered the best option because of their demonstrated antiviral potency and immunological benefits. However, despite the efficacy of PI-containing regimens, the use of combination therapy including two nucleoside reverse transcriptase inhibitors (NRTIs) and one PI has been associated with a number of problems. In the short term, PI-related adverse effects, including diarrhoea, nausea and even renal colic, can lead to the discontinuation of treatment [1]. Long-term adverse effects are also a source of concern; these include hyperlipidaemia with hypertriglyceridaemia, resistance to insulin or insulin-dependent diabetes, and fat redistribution syndrome, with a possible increased risk of coronary heart disease [1][2][3][4]. HAART including two NRTIs and one nonnucleoside reverse transcriptase inhibitor (NNRTI) is now considered to be the preferred option by many [5][6][7], because, in addition to providing similar results in terms of virological response and immune restoration, this combination is simpler, more convenient, better tolerated and less toxic than PI-based regimens, especially in the mid-term [8][9][10] 431Assessments of durability of antiretroviral therapy (ART) and long-term safety have seldom been reported [11,12] but are of major importance for better selection of initial therapy. Among the NNRTIs, efavirenz (EFV) has been evaluated over a 3-year peri...

Long-Term Assessment of Didanosine, Lamivudine, and Efavirenz in Antiretroviral-Naive Patients: 3-Year Follow-Up

“…Longterm safety was very satisfactory, with no unexpected toxicities. The global percentage of withdrawals due to adverse effects through 36 months is similar to that reported in other studies of combinations of EFV and another backbone, 1,3,5,6 and it was also similar to that in the 5-year follow-up study with 3TC-stavudine (d4T)-lopinavir/ritonavir reported by Abbott. 7 Concerning hepatotoxicity, four cases were seen in the initial cohort 4 but during the extended study period no grade 3-4 hepatotoxicity was detected.…”

“…A SSESSMENTS OF DURABILITY of highly active antiretroviral therapy (HAART) and long-term safety have seldom been reported but are of major importance in order to select the best initial therapy. Among the nonnucleoside reverse transcriptase inhibitors (NNRTI), efavirenz (EFV) and nevirapine have been evaluated over a 2-to 3-year period in naive patients [1][2][3] but never in association with didanosine (ddI) and lamivudine (3TC). We present the 3-year follow-up results of an open-label, noncontrolled, observational, multicenter study of adult naive patients with HIV who started HAART with a once-daily regimen of ddI-3TC-EFV.…”

No increased risk of hepatotoxicity in long‐term use of nonnucleoside reverse transcriptase inhibitors in HIV‐infected patients

“…However, NNRTIs are known for their potential to cause hepatotoxicity, which can lead to morbidity and therapy switches. Different studies have reported a cumulative incidence of severe hepatotoxicity varying from 1.4 to 15.6% in patients treated with NVP and from 1.1 to 10% in patients treated with EFV . However, the follow‐up time in these studies was relatively short, up to 3 years.…”

Nevirapine‐associated hepatotoxicity was not predicted by CD4 count ≥250 cells/μL among women in Zambia, Thailand and Kenya

“…An estimated 2.9 million people in sub‐Saharan Africa and 0.6 million people in Asia were receiving antiretroviral therapy (ART) as of December 2008 [1]. More than 66% of ART regimens in these regions include the nonnucleoside reverse transcriptase inhibitor (NNRTI) nevirapine [1], which is highly effective [2], nonteratogenic [3,4] and has little long‐term toxicity [5,6]. Nevirapine, however, can cause early hepatotoxicity [7,8] and rash [9], including potentially life‐threatening hypersensitivity reactions [10].…”