Kinetics of nevirapine and its impact on HIV-1 RNA levels in maternal plasma and breast milk over time after perinatal single-dose nevirapine

J Acquir Immune Defic Syndr. 2012 Aug 15;60(5):483-8. doi: 10.1097/QAI.0b013e318246bf9e.

Abstract

Objective: To determine kinetics after single-dose nevirapine and the impact on HIV RNA [viral load (VL)] in maternal plasma and breast milk (BM).

Methods: Cohort of 120 HIV-1-infected pregnant Ugandan women received perinatal single-dose nevirapine alone and followed up with their infants through 24 weeks postdelivery. We assessed the relationship of nevirapine concentration (tandem mass spectroscopy) and HIV-1 VL (Roche AMPLICOR HIV-1 Kit, version 1.5) in maternal plasma and BM over time.

Results: At week 1 postpartum, NVP (≥10 ng/mL) was detected in all 53 plasma and 47 of 51 (92.2%) BM samples with median (interquartile ranges) of, respectively, 171 (78-214) ng/mL and 112 (64-158) ng/mL, P = 0.075, which decreased subsequently with traces persisting through week 4 in plasma. Plasma and BM VL dropped by week 1 and were highly correlated at delivery (R = 0.71, P < 0.001) and week 1 (R = 0.69, P < 0.001) but not thereafter. At week 1, VL correlated inversely with NVP concentration in plasma (R = 0.39, P = 0.004) and BM (R = 0.48, P = 0.013). There was a VL rebound in both compartments, which peaked at week 4 to levels greater than those at week 1 [significantly in plasma (P < 0.001) but not in BM] and remained stable thereafter. Median VL was consistently greater (11- to 50-fold) in plasma than BM at all time points (all P < 0.001).

Conclusions: After single-dose nevirapine, NVP concentration was comparably high through week 1, accompanied by suppression of plasma and BM VL. A longer "tail" (>1 week) of potent postnatal antiretroviral drugs is warranted to minimize the observed VL rebound and potential for NVP resistance as a result of persistent NVP traces.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / pharmacokinetics*
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / prevention & control*
  • HIV Infections / virology
  • HIV-1 / isolation & purification*
  • Humans
  • Infant
  • Infant, Newborn
  • Infectious Disease Transmission, Vertical / prevention & control
  • Male
  • Milk, Human / chemistry*
  • Nevirapine / administration & dosage
  • Nevirapine / pharmacokinetics*
  • Plasma / chemistry*
  • Pregnancy
  • RNA, Viral / blood
  • Tandem Mass Spectrometry
  • Time Factors
  • Uganda
  • Viral Load*
  • Young Adult

Substances

  • Anti-HIV Agents
  • RNA, Viral
  • Nevirapine