Long-Term Safety and Efficacy of Nevirapine-Based Approaches in HIV Type 1-Infected Patients

Abstract

Using a multicenter, cross-sectional, observation study, the long-term safety, metabolic profile, and viral efficacy of nevirapine (NVP)-based approaches in HIV-1-infected patients treated for at least 2 years were assessed. For 4 months, all consecutive HIV-1-infected patients who had been receiving an NVP-containing regimen for at least 2 years were recruited. A total of 613 patients were included with a median follow-up period of 43 months (IQR: 31-51). At baseline, 24.5% (150 patients) were treatment naive, 41.5% (254 patients) switched for simplification purposes, and 34% (209 patients) were failing HAART. Increases by five times or more in AST/ALT values were observed in fewer than 2% of patients. Only 5.7% of all adverse events reported during the investigation were attributable to NVP. The percentage of patients with normal HDL cholesterol levels rose from 17.7% at baseline to 35.4% at the last visit. At the latest time point available for analysis, 76% of naive and 74% of those who had switched had HIV-1 RNA loads of <50 copies/ml, while 59% of salvage patients achieved this level of viral suppression. Factors associated with viral suppression at the latest visit were adequate adherence (OR: 2.58, 95% CI: 0.85-7.78, p < 0.001), first-line treatment (OR: 3.02, 95% CI: 1.52-6.00, p = 0.002), and baseline CD4 cells >400 cells/microl (OR: 2.34, 95% CI: 1.22-4.47, p = 0.010). Exposure to nevirapine for up to 4 years is safe. Liver toxicity is infrequent and generally mild. HDL cholesterol levels consistently increase over time and viral suppression is maintained.

Long‐term follow‐up of nevirapine‐treated patients in a single‐centre cohort

“…This outcome may have been influenced by differences in the attitude of the treating clinician and of the patient and may have changed over time based on literature findings and the availability of alternative treatments. All the cited factors complicate the comparison between our results and those observed in other cohorts and in reviews of clinical trials [15][16][17][18][19][20]. In any case, grade 3 or higher liver enzyme elevations were extremely rare (only 1.9%).…”

Risk of side effects associated with the use of nevirapine in treatment‐naïve patients, with respect to gender and CD4 cell count

“…In another multicentre study in which 613 patients treated with NVP were recruited with a median follow-up time of 43 months, fivefold or greater increases in transaminase levels were observed in o2% of cases [16]. One explanation for these differences could be that there were differences in the way researchers defined hepatotoxicity.…”

Valutazione di alcuni parametri di epatotossicità di nevirapina ed efavirenz su oltre 700 pazienti trattati per infezione da HIV. Assenza di connessioni con il sesso femminile ed una conta di linfociti CD4+ elevata

“…Finally, in their recent Cochrane revision of April 2006 (17), Siegfried et al assessed nevirapinebased regimens as providing favorable efficacy and durability, associated with a contained adverse effect profile and potential for drug-drug interactions. In the published series quoted above (1,17), around 40% of treated patients were represented by females, and no significant difference as to toxicity and efficacy was found compared with efavirenz-treated subjects (17).…”

“…As assessed in our study conducted on 742 evaluable patients who received a NNRTI for the first time in different baseline conditions, the female gender and a CD4+ lymphocyte count exceeding 250 cells/µL do not prompt any adjunctive hepatotoxicity risk. In the meantime, also very recent studies and extensive literature revisions underlined the longterm efficacy and safety profile of nevirapine (1,4,15). In particular, a multicentre experience recruited 613 patients treated with nevirapine for at least two years (median follow-up 43 months): increases by 5 times of more in AST/ALT values were observed in less than 2% of cases, while overall viral suppression ranged around 75% of patients (including naïve patients, failing subjects, and those switching for prior toxicity) (1).…”

“…Non-nucleoside reverse transcriptase inhibitors (NNRTI) form a very easy class to be explored, since it presently includes only two major compounds (nevirapine and efavirenz), which share extensive genotypic cross-reaction, so that in the great majority of cases a prior failure with one component precludes the use of the second derivative (3). Although several studies did not underline a remarkable difference in major efficacy parameters compared with efavirenz (1, 13, 17, 19), however since 2002 efavirenz retains its recommendation in antiretroviral-naïve patients due to its superior intrinsic anti-HIV activity (1,3,13), while nevirapine is very often suggested as a part of switch, simplification, or de-intensification regimens in patients who achieved a sustained viral suppression and a complete immune reconstitution (3), but suffered from a broad spectrum of adverse events, or an excessive pill burden (3,9,10,13,15), as well as a component of rescue treatments (13). All these issues, together with a convenient administration and a favorable pharmacoeconomic profile (as represented by 57.12% lower cost Parole chiave: Epatotossicità, nevirapina, efavirenz, sesso, conta dei T-linfociti CD4+, assetto laboratoristico iniziale, pazienti naïve, soggetti pre-trattati, terapia antiretrovirale di salvataggio Assessment of some parameters of liver toxicity of nevirapine and efavirenz on over 700 patients treated for HIV infection.…”