A comparison of 3 regimens to prevent nevirapine resistance mutations in HIV-infected pregnant women receiving a single intrapartum dose of nevirapine.

Abstract

BACKGROUND:

Intrapartum single-dose (SD) nevirapine (NVP) reduces perinatal transmission of human immunodeficiency virus (HIV) infection but selects for NVP-resistant virus, which compromises subsequent NVP-based therapy. A 1-week "tail" of lamivudine and zidovudine after SD-NVP decreases the risk of resistance. We hypothesized that increasing the duration or potency of the tail would further reduce this risk to <10%, using a sensitive assay to measure resistance.

METHODS:

HIV-infected pregnant Thai women with a CD4 cell count >250 cells/μL, most receiving zidovudine, were randomized at 28-38 weeks gestation to receive 1 of 3 intrapartum and postpartum regimens: (A) zidovudine plus enteric-coated didanosine plus lopinavir and ritonavir for 7 days, (B) zidovudine plus enteric-coated didanosine for 30 days, or (C) regimen 1 for 30 days. The incidence of NVP resistance mutations at day 10 or week 6 post partum in each arm was compared with that of a historical comparison group who received prenatal zidovudine and SD-NVP. NVP resistance was identified by consensus sequencing and a sensitive oligonucleotide ligation assay (OLA).

RESULTS:

At entry, the 169 participants had a median CD4 cell count of 456 cells/μL and an HIV load of 3.49 log(10) copies/mL. The incidence of mutations in each of the 3 P1032 arms was 0% by sequencing and 1.8%, 7.1%, and 5.3% by OLA in arms A, B, and C, respectively, compared with 13.4% by sequencing and 29.4% by OLA in the comparison group (P < .001 for each study arm vs comparison group). Grade 4 anemia developed in 1 woman.

CONCLUSIONS:

A 7-day tail of highly active combination therapy or 1 month of dual therapy after SD-NVP prevents most NVP resistance to minimal toxicity.

CLINICAL TRIALS REGISTRATION:

The IMPAACT P1032 Clinical Trial is NCT00109590, and the PHPT-2 Clinical Trial is NCT00398684.

• Authors: Russell B Van Dyke, Nicole Ngo-Giang-Huong, David E Shapiro, Lisa Frenkel, Paula Britto, Anuvat Roongpisuthipong, Ingrid A Beck, Praparb Yuthavisuthi, Sinart Prommas, Thanyawee Puthanakit, Jullapong Achalapong, Nantasak Chotivanich, Wirawan Rasri, Tim R Cressey, Robert Maupin, Mark Mirochnick, Gonzague Jourdain, IMPAACT P1032 Protocol Team
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 54 Issue 2 Pg. 285-93 (Jan 15 2012) ISSN: 1537-6591 [Electronic] United States
• PMID: 22144539 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-HIV Agents
• Zidovudine
• Nevirapine

Topics

• Adolescent
• Adult
• Anti-HIV Agents (administration & dosage)
• Drug Administration Schedule
• Drug Resistance, Viral (genetics)
• Female
• HIV (drug effects, genetics)
• HIV Infections (drug therapy, prevention & control, virology)
• Humans
• Infectious Disease Transmission, Vertical (prevention & control)
• Middle Aged
• Mutation
• Nevirapine (administration & dosage)
• Pregnancy
• Pregnancy Complications, Infectious (drug therapy, virology)
• Treatment Outcome
• Viral Load
• Zidovudine (administration & dosage)