Cervicovaginal HIV-1 Shedding in Pregnant Women near Delivery

Most perinatal HIV-1 infections occur during labour and delivery, suggesting that newborn exposure to HIV in the birth canal is an important determinant of mother-to-child transmission [1]. Detectable levels of HIV RNA have been measured in cervicovaginal secretions of pregnant HIV-infected women and it appears that the amount of virus in both plasma and cervicovaginal secretions can influence the transmission rate [2–3]. Zidovudine administration to women during pregnancy and labour, and to the infant at birth, reduces perinatal HIV transmission, and therefore should be included as a component of the antenatal therapeutic regimen. However, the treatment of pregnant infected women needs to focus not only on fetal protection but also on the health of the mother. As zidovudine monotherapy is no longer considered acceptable for HIV control, combination antiretroviral therapy is recommended to achieve a durable viral suppression which might further reduce perinatal HIV transmission [4–6]. Nevertheless, data regarding the safety of most antiretrovirals in pregnancy are lacking and their potential long-term hazards for children are unknown [7–9]. We evaluated HIV-1 shedding in cervicovaginal secretions collected shortly before delivery from HIV-1 infected pregnant women who were receiving different antiretroviral regimens. The study was in part retrospective and included 13 HIV-1-infected women from whom blood and cervicovaginal samples had been collected at 34±4 weeks of gestation (1–30 days before delivery). At the time of sampling, all women were receiving antiretroviral therapy. In order to collect cervicovaginal fluid, a speculum was introduced and cervicovaginal lavages (CVLs) were performed by irrigating the vaginal wall and fornix with a sterile pipette containing 3 ml of sterile PBS. The samples were centrifuged within 2 h of collection, and cell-free CVLs were aliquoted and stored at –70°C together with paired plasma samples until use. HIV-1 RNA levels in plasma and CVL were measured with the use of the Amplicor Kit (Roche Diagnostic Systems, Nutley, N.J., USA) according to manufacturer’s instructions. The main patient characteristics are shown in Table 1 along with the results of CVL and plasma viral loads. At the time of sample collection, three patients were receiving zidovudine monotherapy (patients 1, 2 and 3) and an additional six (patients 4–9) women were treated with a combination of zidovudine plus lamivudine. Therapy was initiated during the second trimester of pregnancy for eight of these women, whilst one (patient 6) was already on treatment before pregnancy. Moreover, zidovudine was intravenously administered during the intrapartum period and to the newborn for the first 6 weeks of life. The remaining four women (patients 10–13) received a combination regimen including a protease inhibitor (PI), which had been initiated before, and was continued throughout pregnancy. Moreover, zidovudine was intravenously administered during the intrapartum period to all women except patients 10, 12 and 13 for whom the use of zidovudine was contraindicated, and to all newborns for the first 6 weeks of life. As the use of zidovudine was contraindicated in patients 10, 12 and 13, it was not administered during labour, but only to the newborn. All women were adherent to therapy and no discontinuation was recorded. The women were randomly assigned to delivery by spontaneous vaginal delivery (four patients) or by caesarean section (four patients) [10] and an additional five women underwent a caesarean section due to obstetrical indications. Plasma viral loads were below the detection limit of the assay in 6/13 (46.1%) patients; in the remaining, plasma HIV RNA levels ranged from 5000 to 466635