AEGiS-15IAC: Duration of nevirapine (NVP) postpartum exposure in women who received single dose NVP during labor in addition to standard zidovudine (ZDV) prophylaxis for the prevention of mother-to-child transmission of HIV-1 in Thailand.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Duration of nevirapine (NVP) postpartum exposure in women who received single dose NVP during labor in addition to standard zidovudine (ZDV) prophylaxis for the prevention of mother-to-child transmission of HIV-1 in Thailand.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. ThOrB1352)

Cressey TR, Kunkeaw S, Ruttana-Aroongorn PN, Jungpichanvanich S, Techapalokul S, Gomuthbutra V, Atthakorn W, Seubmongkolchai S, Jourdain G, Lallemant MJ
Harvard School of Public Health/IRD054/Chiang Mai University, Chiang Mai, Thailand

BACKGROUND: A single 200 mg dose of NVP during labor has been shown to be effective for the prevention of mother-to-child transmission of HIV, but HIV resistance mutations to NVP are observed in the following weeks to months in a significant number of women. This study aimed to determining the length of time during which nevirapine is detectable in human plasma in order to define the period where there is a high risk of developing NVP resistance following a single a dose at the onset of labor.

METHOD: Plasma samples were obtained from patients enrolled in PHPT-2, a perinatal HIV prevention trial assessing the efficacy of a single dose NVP given to women at onset of labor and to their infant 48-72 hours after birth in addition to ZDV. Blood samples available to measure NVP plasma levels had been obtained at delivery and up to 24 days postpartum. NVP levels were measured by HPLC on a minimum of 2 samples, with the sample at delivery being at least 5 hours after NVP intake, i.e. after Tmax. The sensitivity of the NVP assay used was 50 ng/ml, which is slightly higher than the NVP IC50 of 10-100 nM.

RESULTS: Sixty-one patients were studied with a total of 142 samples analyzed. The median NVP plasma level at delivery was 1740 ng/ml (Range: 337-3737, N=61). Median postpartum NVP levels between 8 - Pound 11 days was 83 ng/ml (<50-224, N=21), 72 ng/ml (<50-228, N=20) between 11- Pound13 days and 58 ng/ml (<50-166, N=21) between 13-21 days. At 8-11, 11-13 and 13-21 days postpartum, 14%, 20% and 33% of the samples had< 50 ng/ml NVP, respectively. The longest detectable NVP level was found at 19 days postpartum. The median T1/2 was 58.3 hours (22.9 - 160.0). Conclusion The duration of NVP in the plasma following a single dose is variable but drug levels where resistance could be selected can occur up to 3-4 weeks. If antiretroviral post partum interventions to reduce the incidence of NVP resistance mutations are envisioned, the duration of treatment should cover at least this period.

Keywords: AEGIS, Nevirapine, Zidovudine, HIV-1, Single Person, Labor, Obstetric, Acquired Immunodeficiency Syndrome, HIV-1 Reverse Transcriptase, Mothers, HIV Seropositivity, Thailand, Antiretroviral Therapy, Highly Active, Delivery, Obstetric, Child, Humans, Female, Pregnancy, Infant, transmission, prevention & control, surgery, therapy, drug therapy

040711
ThOrB1352