Vertical Transmission of HIV‐1 in Mid‐trimester Gestation

EDITORIAL COMMENT: Because of the importance of zidovudine therapy in the reduction of HTV transmission from HIV‐infected pregnant women to their babies we print below the following Abstract from the Journal of the Physicians Association for AIDS care prepared by Mr Paul Drinkwater, Director of Pharmacy, Mercy Hospital for Women. Zidovudine Reduces Maternal‐Fetal Transmission of HTV According to an interim analysis of the ACTG076 trial, zidovudine (ZDV) therapy reduced HIV transmission from HIV‐infected pregnant women to their babies by about two‐thirds. Eligible participants in the ACTG076 trial were HIV‐infected pregnant women who had received no antiretroviral treatment during the current pregnancy, had no clinical indications for maternal antepartum ZDV therapy and had base‐line CD4 lymphocyte counts greater than 200 cells/mm 3 . Patients were randomized to either an active arm containing ZDV or a control arm containing placebo. The ZDV regimen consisted of antepartum ZDV (100 mg orally 5 times a day) initiated between 14 and 34 weeks' gestation and continued throughout the remainder of the pregnancy, followed by intrapartum intravenous ZDV (loading dose 2 mg/kg, starting in labour followed by continuous infusion 1 mg/kg/hour until delivery), followed by oral administration of ZDV (syrup 2 mg/kg every 6 hours for 6 weeks beginning 8 to 12 hours after birth) to the infant. The primary study end point, HTV infection of the infant, was defined by one positive viral culture obtained from peripheral blood, specimens taken at birth, 12, 24 and 78 weeks postpartum. To date, 421 babies have been born to subjects of the trial. Three hundred and sixty four of these infants had sufficient data to be included in the analysis, 180 in the ZDV group and 184 in the placebo group. Thirteen babies in the ZDV group and 40 in the placebo group were HIV infected (i.e. at least one positive culture). This corresponded to a 67.5% relative reduction in transmission risk. Reported maternal and infant side‐effects were balanced between the 2 randomized groups with the one exception that haemoglobin levels were lower for infants in the ZDV group. The mean decrease in haemoglobin value was less than 1 g/dL, did not require transfusion, and resolved within several weeks after completion of ZDV therapy. There was no difference in the incidence of birth defects between the 2 arms and the incidence reflected the baseline rate within the population. There was no apparent adverse effect of the treatment regimen on the health of the women in the study or on the progression of their HTV disease. This study currently provides no information regarding any late effect of ZDV on infants, including those who do not become infected with HIV. Continued long‐term follow‐up of the infants in this trial, and of those who may subsequently be treated in a similar fashion, is a high priority. These data strengthen the case for routine screening for HIV‐infection during pregnancy because of the provision of the opportunity to minimize the risk of maternal‐fetal transmission with treatment and improve the prognosis for the fetus. The recognition of the HIV‐infected pregnant woman also gives her information that may be relevant to her decision on whether to opt for termination of pregnancy, and provides a warning for her health care attendants ‐ the latter important consideration is seldom mentioned when this topic is discussed in the media. Summary: Between July, 1994 and March, 1995, 23 heart blood samples from fresh abortuses of HIV‐1 seropositive pregnant women after elective termination of pregnancy between 18 and 25 weeks of gestation by prostaglandin El analogue vaginal administration were examined for polymerase chain reaction (PCR) of HIV‐1 genome and p24 antigen to investigate the transplacental transfer of HIV‐1 infection. All samples of fetal heart blood were positive for HIV‐1 antibody (ELISA), but negative for PCR and HIV‐1 p24 antigen assay. These negative results could be due to the lack of the virus in the peripheral blood or to a viral load low enough to be undetectable by PCR method at mid‐trimester gestation and suggest that HIV‐1 vertical transmission occurs mostly during the last trimester of pregnancy and/or at delivery.