Nelfinavir and nevirapine well tolerated during pregnancy

HAART regimens containing either the protease inhibitor nelfinavir or the NNRTI nevirapine are well tolerated during pregnancy, according to a Dutch study published in the May 20^th edition of AIDS. The investigators found, however, that side-effects associated with either nelfinavir (such as gastrointestinal problems) or nevirapine (hepatitis) occurred more frequently in pregnant women than non-pregnant women.

The risk of mother-to-baby transmission of HIV is significantly reduced by the appropriate use of HAART. There are concerns, however, that the physiological changes associated with pregnancy may change the body’s ability to process anti-HIV therapy. Studies have suggested that HIV-positive pregnant women have lower levels of the protease inhibitor nelfinavir in the blood, increasing the risk of virological failure. In addition, pregnancy is also thought to increase the risk of side-effects including vomiting, liver inflammation and increased blood lipids, which may in turn increase the likelihood of non-adherence to anti-HIV therapy.

Dutch investigators therefore wished to assess the efficacy, tolerability and safety of two alternative HAART regimens used by HIV-positive women. One regimen was based on the protease inhibitor nelfinavir, the other based on the NNRTI nevirapine.

A total of 186 pregnant women and 186 HIV-positive non-pregnant women were included in the investigators’ retrospective analysis. All the women were aged under 45 and first took a nelfinavir or nevirapine-containing regimen between 1997 and 2003.

Data were gathered on patient characteristis (including age, HIV transmission group, country of birth and ethnicity), HIV treatment regimen, side-effects and CD4 and viral load at baseline and at months three and six.

Information was also gathered on the duration of pregnancy, mode of delivery and the HIV status of the newborns. Data on prematurity and the weight of infants were also collected.

The outcomes of the study were:

• Tolerability, defined as side-effects leading to a switch of therapy.
• Safety, indicated by liver toxicity or glucose intolerance.
• Efficacy, indicated by virological response.

At baseline, pregnant women were younger (27 versus 34 years), had a higher CD4 cell count (300 cells/mm³ versus 219 cells/mm³), lower viral load (6,200 copies/ml versus 64,000 copies/ml), and were more likely to be taking nelfinavir (69% versus 49%).

In general, pregnancy was associated with more side-effects caused by HAART. Pregnant women taking nevirapine were significantly more likely to experience hepatotoxicity than non-pregnant women taking this drug (19% versus 4%, p = 0.003). Pregnant women taking nelfinavir were more likely to experience gastrointestinal side-effects than non-pregnant women taking the drug (30% versus 7%, p = 0.001). The investigators also found that pregnant women taking either of the two study drugs were more likely to develop hyperglycaemia than non-pregnant women (nevirapine, 9% versus 1%, p = 0.019; nelfinavir, 16% versus 2%, p = 0.001).

Rash occurred with equal frequency in pregnant and non-pregnant women taking nevirapine (9% versus 10%).

Investigators noted a difference in treatment response between pregnant and non-pregnant women. Prior to delivery 82% of pregnant women had an undetectable viral load. Six months after baseline, only 70% of non-pregnant women had an undetectable viral load, a statistically significant difference (p = 0.009).

There were a total of 23 (13%) premature deliveries. There were equally distributed between the women taking nelfinavir (12%) and nevirapine (14%). There were no significant differences in the birth weight of babies between the two arms of the study or in the rate of low birth weight.

Two infants were infected with HIV. One mother had a viral load of almost 30,000 copies/ml at the time of delivery and was delivered by elective caesarean section. The other infant’s mother had a viral load below 50 copies/ml at the time of delivery, and the mother opted for a managed vaginal birth. However, an emergency caesarean was performed because of prolonged rupture of the membranes.

“HAART was well tolerated in…pregnant women, although the rate of manageable side-effects was higher than in non-pregnant women,” write the investigators. They also note that the response to HAART amongst pregnant women was “comparable to the results in non-pregnant women”. The investigators also emphasise that the rates of prematurity were comparable in the nelfinavir and nevirapine arms and that the number of low birth-weight children did not differ between the two study arms.