Risk of discontinuation of nevirapine due to toxicities in antiretroviral-naive and -experienced HIV-infected patients with high and low CD4+ T-cell counts.
BACKGROUND
It is unknown whether the increased risk of toxicities in antiretroviral-naive HIV-infected patients initiating nevirapine-based (NVPc) combination antiretroviral therapy (cART) with high CD4+ T-cell counts is also observed when NVPc is initiated in cARTexperienced patients.


METHODS
1,571 EuroSIDA patients started NVPc after 1/1/1999, with CD4+ T-cell counts and viral load measured in the 6 months before starting treatment, and were stratified into four groups based on CD4+ T-cell counts at initiation of NVPc (high [H], > 400/mm3 or > 250/mm3 for male or female, respectively, or low [L], < or = 400/mm3 or 5250/mm3 for male or female) and prior antiretroviral experience (antiretroviral-naive [N] or -experienced [E]). Cox proportional hazards models compared the risks of discontinuation of nevirapine due to toxicities or patient/physician choice (TOXPC).


RESULTS
After adjustment, there was a significantly lower risk of discontinuation of nevirapine due to TOXPC in the HE group (n = 588; proportion discontinued by 3/12 months: 10/17%, respectively) than in HN (n = 62; 21/32% respectively; overall relative hazard [RH]: 0.56; 95% confidence interval [CI]: 0.34-0.94; P = 0.027). This difference was most pronounced during the first 3 months of NVPc (RH: 0.44; 95% CI: 0.23-0.87; P = 0.017). There were no deaths in the 6 months after starting NVPc resulting from exposure to < 3 months of NVPc exposure within the HE group (incidence: 0; per 1,000 person-years follow up; 95% CI: 0-6.9). After adjustment, there were no differences between the HE and HN groups in discontinuation due to TOXPC in patients starting efavirenz-based cART (RH: 0.91; 95% CI: 0.60-1.38; P = 0.66) or protease-inhibitor-based cART (RH: 1.13; 95% CI: 0.77-1.66; P = 0.52).


CONCLUSIONS
Results from this non-randomized study suggest that NVPc might be safer to initiate in antiretroviral-experienced than in antiretroviral-naive patients with high CD4+ T-cell counts.
Mocroft
Amanda
A
Royal Free and University College Medical School, London, UK. a.mocroft@pcps.ucl.ac.uk
Staszewski
Schlomo
S
Weber
Rainer
R
Gatell
José
J
Rockstroh
Jurgen
J
Gasiorowski
Jacek
J
Panos
George
G
Monforte
Antonella d'Arminio
Ad
Rakhmanova
Aza
A
Phillips
Andrew N
AN
Lundgren
Jens D
JD
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D001118:Argentina; D018791:CD4 Lymphocyte Count; D056486:Chemical and Drug Induced Liver Injury; D005060:Europe; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1; D006801:Humans; D007557:Israel; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000009:adverse effects / Q000627:therapeutic use; D016016:Proportional Hazards Models; D012307:Risk Factors; D016896:Treatment Outcome; D028761:Withholding Treatment
D019380:Anti-HIV Agents; D044966:Anti-Retroviral Agents; D019829:Nevirapine