Combination Therapy in Pregnant HIV-infected Women and Their Newborns

Katjia Wolf, from the University Children’s Hospital in Basel, reported on this study at Lisbon whose aim is to assess the safety of combination therapy in pregnant HIV infected women and their newborns. Women received 2 or more anti-retroviral drugs and their newborns.

By October 1999, there were 103 pregnancies, 95 children born, and there is complete data on 85 mother-child pairs. 6 pregnancies are ongoing, there was 1 induced abortion, 1 extrauterine pregnancy.

About 40% of women diagnosed with HIV during pregnancy. Most women (67%) were at CDC stage A, 22% at stage B (See Table 3):   

The women were prone to use drugs which may effect newborns: i.v. drug use (5), methadone (6), cigarette smoking (22), alcohol (5),  benzos/barbituates (3). Women were also receiving concomittant therapy: cotrimoxazole (13), antimycotics (10), antiemetics (6), psychotropes (3),  ciprofloxacin (1), pentamidine (1), other (6).

At some time during pregnancy 100% were on NRTIs, 62% on PI therapy and 1% on hydroxyurea. During the first trimester 39% were on treatment and 26% on PI therapy. At delivery all were receiving treatment and 88% received i.v. AZT according to 076 protocol. One women received a single dose of NVP at delivery. Median viral load at delivery was 2.26 log (below 400 copies/ml in 64%).

Nelfinavir (27) was most commonly used PI: IDV (19), RTV (8), SQV (7). AZT and 3TC were used by 77, d4T (16), ddI (8), NVP (2).

Mild anemia was the most frequently experienced lab abnormality: grade 1 or 2 (n=81)- 15 on RTIs and 26 on RTIs + PIs. Other abnormalities,  such as thrombopenia, LFT elevations, amylase elevation and cholesterol were generally not severe nor associated with clinical symptoms.

Clinical Adverse Events for Newborns. 

As previously reported they found a high prematurity  (<37 weeks) birth rate in this study (11 receiving RTIs and 13 receiving RTIs+PI). 6 experienced neurologic symptoms but 3 were on drug withdrawal. (See Table 4):  

  So far there have been two perinatal transmissions. One was receiving AZT+3TC, had a vaginal delivery with 3077 copies/ml of viral load. The other was receiving AZT+3TC+NFV, had a secondary C-section and had 10,000 copies/ml viral load. Delivery was not optimal for these two women and both women had a detectable viral load. All other children have negative HIV test results at about 4 months.

Investigators compared pre-maturity rate of children in this study to those of the Swiss Neonatal HIV Study exposed to AZT only or to no HIV therapy at all and found it to be higher in children on combination therapy when compared to children receiving no therapy  during pregnancy (p=0.001) (See Table 5):    

In summary, adverse events occurred in 72% of women but were not unexpected and were not life threatening. And in 55% of newborns with 3 unexpected findings: high pre-maturity rate, CNS hemorrhage in a term born baby, 1 case of extrahepatic biliary atresia. Wolf concluded there was no clear evidence of a major risk of intrauterine exposure to combination therapy. But there was a high rate of prematurity and 1 major malformation which demand further inquiry. Therefore, a long term observation of large group is necessary. When asked by panel what she thought a pregnant women should do in terms of treatment, Wolf said it should be women’s decision based on an informed consent about the risk of therapy and for her own health if she’s not taking combination therapy during pregnancy. If the patient asked for Wolf’s recommendation, she said she would recommend combination anti-retroviral therapy during pregnancy.