Risk of Discontinuation of Nevirapine due to Toxicities in Antiretroviral-Naive and -Experienced HIV-Infected patients with High and Low CD4 + T-cell Counts
Free accessResearch articleFirst published online April, 2007
Risk of Discontinuation of Nevirapine due to Toxicities in Antiretroviral-Naive and -Experienced HIV-Infected patients with High and Low CD4 + T-cell Counts
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 cART-experienced patients.
Patients and 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], ≤400/mm3 or ≤250/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 antiretro-viral-experienced than in antiretroviral-naive patients with high CD4+T-cell counts.
References
1.
Panel on Antiretroviral Guidelines for Adult and Adolescents.Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents.Washington, DC: Department of Health and Human Services; 10 October 2006. [Cited 6 November 2006]. Available at http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentsGL.pdf.
2.
Viramune.Package insert. Revised 22 December 2003. Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
3.
CattelanA.M., ErneE., SalatinoA.Severe hepatic failure related to nevirapine treatment (letter).Clin Inf Dis1999; 29: 455–456.
4.
BoxwellD., HaverkosH., KukichS.Serious adverse events attributed to nevirapine regimens for post exposure prophylaxis after HIV exposures - worldwide, 1997–2000.MMWR2001; 49: 1153–1156.
5.
BaylorM.S., Johann-LiangR.Hepatotoxicity associated with nevirapine use (letter).JAIDS2004; 35: 538–539.
6.
AnanworanichJ., MoorZ., SiangphoeU.Incidence and risk factors for rash in Thai patients randomised to regimens with nevirapine, efavirenz or both drugs.AIDS2005; 19: 185–192.
7.
BartlettJ.Severe liver toxicity in patients receiving two nucleoside analogues and a non-nucleoside reverse transcriptase inhibitor. 8th Conference on Retroviruses and Opportunistic Infections. 4–8 February 2001, Chicago, IL, USA. Abstract 19.
8.
MocroftA., LedergerberB., KatlamaC.Decline in the AIDS and death rates in the EuroSIDA study: an observational study.Lancet2003; 362: 22–29.
9.
MocroftA., RockstrohJ., SorianoV.Are specific anti-retrovirals associated with an increased risk of discontinuation due to toxicities or patient/physician choice in patients with hepatitis C virus coinfection?Antivir Ther2005; 10: 779–790.
10.
SternJ.O., RobinsonP.A., LoveJ., LanesS., ImperialeM.S., MayersD.L.A comprehensive hepatic safety analysis of nevirapine in different populations of HIV infected patients.JAIDS2003; 34Suppl 1: S21–S33.
11.
DietrichD.T., RobinsonP.A., LoveJ., SternJ.O.Drug-induced liver injury associated with the use of nonucleoside reverse-transcriptase inhibitors.Clin Inf Dis2004; 38Suppl 2: S80–S89.
12.
US Food and Drug Administration Center for Drug Evaluation and Research.FDA Public Health Advisory for nevirapine (Viramune). 11 January 2005. [Cited 31 May 2006]. Rockville MD: US Food and Drug Administration. Available from: http://www.fda.gov/cder/drug/advisory/nevirapine.htm.
13.
Van LethF., PhanuphakP., RuxrungthamK.Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomised open-label trial, the 2NN study.Lancet2004; 363: 1253–1263.
14.
StorferS., LeithJ., RobinsonP., PilieroP., HallD.Analysis of hepatic events within the 2NN study: Controlling for geographic region and CD4+ cell count at initiation of nevirapine therapy. 45th Interscience Conference on Antimicrobial Agents and Chemotherapy. 16–19 December 2005, Washington, DC, USA. Abstract LB-13.
15.
MontanerJ.S., CahP., ZalaC.Randomised, controlled study of the effects of a short course of prednisone on the incidence of rash associated with nevirapine in patients infected with HIV-1.JAIDS2003; 33: 41–46.
16.
MartinA.M., NolanD., JamesI.Predisposition to nevirapine hypersensitivity associated with HLA-DRB1*0101 and abrogated by low CD4 T-cell counts (letter).AIDS2005; 19: 97–99.
17.
AntinoriA., BaldiniF., GirardiE.Female sex and the use of anti-allergic agents increase the risk of developing cutaneous rash associated with nevirapine therapy.AIDS2001; 15: 1579–1581.
18.
FloridiaM., BucciardiniR., FragolaV.Risk factors and occurrence of rash in HIV-positive patients not receiving non-nucleoside reverse transcriptase inhibitor: Data from a randomized study evaluating use of protease inhibitors in nucleoside-experienced patients with very low CD4 levels (<50 cells/microl.).HIV Med2004; 5: 1–10.
19.
GrabarS., Le MoingV., GoujardC.Clinical outcome of patients with HIV-1 infection according to immunologic and virologic response after 6 months of highly active antiretroviral therapy.Ann Intern Med2000; 133: 401–410.
20.
The Antiretroviral Therapy in Lower Income Countries (ARTLINC) and ART Cohort Collaboration (ART-CC) groups. Mortality of HIV-1 infected patients in the first year of antiretroviral therapy: Comparisons between low-income and high-income countries.Lancet2006; 367: 817–824.
