New drugs in pregnancy: atazanavir; T20
Polly Clayden, HIV i-Base
Atazanavir use in pregnancy
In the industrialised world, most HAART regimens used in pregnancy include a protease inhibitor (PI). In the UK we have greater experience with nevirapine containing regimens, but practice is changing since the Boehringer Ingelheim hepatoxicity warning for women with >250 CD4 cells/mm3. Some data exist on nelfinavir and several other PIs, but there are little or none to guide use of the newer drugs in pregnancy.
Atazanavir is labeled pregnancy category B. There have been concerns about infant hyperbilirubinaemia with using this drug in pregnancy.
A poster from Morris and co-workers presented findings from a small retrospective observational study of all pregnant women receiving atazanavir in one clinic in Springfield, Massachusetts to June 2005.
The authors recorded infant weights and heights, the presence or absence of hyperbilirubinaemia and infant HIV status. Adverse events were also recorded in both mothers and infants.
To date, nine women have been treated with atazanavir during pregnancy, and six of these women received ritonavir-boosted atazanavir. The womens mean viral load at onset of pregnancy was 31,133 copies/mL for the seven women not on HAART. The two women on HAART at the time of conception had undetectable viral loads <50 copies/mL.
At delivery, seven women had viral loads <100 copies/ml and two women <50 copies/ml. Their mean CD4 count increased from 366 to 450 cell/mm3. Maternal total bilirubin at time of delivery ranged fro 0.3-3.5 mg/dl. No hepatic, renal or pancreatic abnormalities were seen in the women during pregnancy. The authors noted that the women tolerated the treatment well.
All pregnancies were full term. There were eight singleton births and one pair of twins. The highest infant bilirubin was 11.5 mg/dl and three infants were treated briefly with phototherapy. Neonatal hyperbilirubinaemia – ie total serum hyperbilirubin of >/= 5 mg/dl – occurs frequently in the general population with up to 60% of infants experiencing clinical jaundice. The incidence in this cohort is within the range observed amongst the general population. The HIV-DNA PCRs on eight singleton infants are all negative at >/= 4 months, the initial HIV-DNA PCRs of the twins at one week of age are negative. Infants will be followed for a year to confirm HIV status.
The authors write: Atazanavir-based regimens in this cohort of pregnant women were very well tolerated in both the mothers and infants. To date all have had good responses immunologically and virologically and no infant has been infected. They add: Until prospective data are available, this series helps to inform the field.
T20 (enfuvirtide) use in pregnancy
Multi drug resistant HIV will challenge the use of conventional PI or NNRTI based regimens in pregnancy.
Brennan-Benson and co-workers from St Georges Hospital in London presented a poster reporting two case studies of multi drug resistant women receiving the fusion inhibitor T20 (enfuvirtide) in pregnancy.
Both women received care from a multi-disciplinary pregnancy team. Resistance testing was used to guide optimised antiretroviral regimens and both mothers had multiple mutations. Neither mother had an undetectable viral load, and T20 was added at 32 weeks gestation. Both mothers achieved viral load <400 at delivery one to <50 copies/mL and the other to 305 copies/mL. Both had uncomplicated Caesarean deliveries at 39 weeks.
Table 1: Details of both patients
|Case 1: 37 years, RTV intolerant||Case 2: 33 years, poor adherence, LPV intolerant|
|ART||AZT, ddC, d4T, ddI, 3TC, NVP, DLV, IDV, NFV, RTV, SQV, LPV/r, hydroxyurea||3TC, AZT, ddI, d4T, TDF, NVP, NFV, RTV, LPV/r|
|CD4 c/mm3||90 at presentation, 198 at delivery||75 at presentation, 51 at 32 weeks, 135 at delivery|
|HIV RNA cp/mL||8350 at baseline, <50 at 24 wks, 1362 at 32 wks||20,000 at baseline, 31,319 at 32 weeks, 305 at delivery|
|Backbone||ABC, DLV, fosAPV, ATV||NVP, 3TC, TDF, fosAPV, RTV|
|T20||32 weeks||32 weeks|
Both infants received LPV/r plus 3TC. Both infants tested negative on HIV-PCR DNA tests at four weeks of age.
The authors write: Suppression of maternal viraemia is the cornerstone of therapeutic intervention to prevent MTCT of HIV. The increasing prevalence of MDR-HIV makes the use of T20 a useful adjunct to the ARV armoury in such challenging cases, and appears to be safe and efficacious. If enfuvirtide crosses the placenta its mode of action makes it attractive as a part of a PEP regimen for the neonate.
- Morris A, Juethner S and Theroux E. Atazanavir use in pregnancy. 3rd IAS Conference on HIV Pathogenesis and Treatment, Rio de Janeiro, 2005. Abstract TuPe5.2P01.
- Brennan-Benson P, Pakianthan M, Rice P et al. The role of enfuvirtide in the prevention of vertical transmission of multi-drug resistant HIV in pregnancy. IAS Conference on HIV Pathogenesis and Treatment, Rio de Janeiro, 2005. Abstract TuPe52P06.