Pregnancy studies at EACS
Polly Clayden, HIV i-Base
Triple antiretroviral regimens in pregnancy
Three posters looked at triple antiretroviral regimens in pregnancy. The majority of the women studied had higher CD4 counts and received treatment for mother to child transmission.
Historically in the UK, pregnant women with higher CD4 counts would generally receive nevirapine-containing regimens, but following the hepatic toxicity warning from Boehringer Ingelheim, alternative strategies are needed. BHIVA pregnancy guidelines recommend short course protease inhibitor containing regimens for women in this situation Two posters looked at saquinavir-containing (SQV) regimens and another at triple nucleosides. Saquinavir, tenofovir and FTC are all FDA pregnancy category B drugs.
Short course boosted saquinavir
David Hawkins group at Chelsea and Westminster Hospital in London presented results from an observational study on the use of boosted saquinavir in pregnancy from December 2002 to July 2005 .
Data were available for 13 women (15 pregnancies). Following the BHIVA START (Short Term Triple Antiretroviral Therapy) protocol, women received SQV hard gel-capsules (hgc)/ritonavir (1000/100mg BID) plus Combivir from a median of 21 weeks (range 13-25 weeks) until delivery.
The median age of the women was 32 years (range 19-39 years); the median CD4 count at initiation of therapy was 437 cells/mm3 (range 237-637 cells/mm3) and viral load 7901 copies/mL (range 117-55460 copies/mL). Seven women had received HAART previously in pregnancy. One woman was switched from nevirapine/Combivir due to nevirapine-associated hepatic toxicity.
All women had a CD4 count of <50 copies/mL at delivery. The median period of gestation was 37 weeks and 73% of women had a caesarean delivery.
Sixteen HIV negative infants including one set of twins were born during the study period. The investigators noted no additional resistance mutations from baseline were detected on stopping therapy post delivery.
Low dose boosted saquinavir once-daily (QD)
Luis Lopez-Cortes and co-workers from Seville, Spain reported data from a cohort of pregnant women receiving therapeutic drug monitoring (TDM) guided boosted saquinavir containing therapy .
Women received an initial SQV/r dose of 1200/100 mg QD. TDM was used to maintain a SQV Cmin of 100ng/mL (24 +/- 5 hours post dose).
Data were available for 38 women. Their median age was 31 years (range 21-38 years). At inclusion 15 (44.1%) women were drug naive, 33 (86.8%) had no prior PI failure and 11 (32.3%) were already on treatment. Their median CD4 was 508 cells/mm3 (range 42-1158 cells/mm3) and viral load 3,905 copies/mL (range <50-181,000 copies/mL). Therapy was initiated at a median of 20 weeks (range 0-35 weeks) of pregnancy and 30 (78.9%) women received AZT and 3TC as their nucleosides.
SQV Cmin from 24-39 weeks of pregnancy (n=72); 34 women: 239ng/mL (range 80-2235 ng/mL). The SQV dose was increased to 1600 mg QD in two women.
After a median of 17 weeks (range 3-39 weeks), 29 people had undetectable viral load at delivery. Three women had viral loads of 110 copies/mL, 400 copies/mL and no data respectively after only 3-4 weeks of therapy. Mode of delivery was vaginal in 16 pregnancies and 16 by caesarean section (11 of these were for gynaecological reasons). The authors reported no mother to child transmissions.
They wrote: Although SQV plasma levels are lower, low dose SQV/r is an effective and low risk therapeutic option in HIV-infected pregnant women with no prior or limited experience on PIs. TDM is advisable to maintain appropriate levels throughout pregnancy.
Annette Haberi and co-workers reported data from 10 women receiving AZT plus tenofovir with either FTC or 3TC in pregnancy who had CD4 counts >250 cells/mm3 or a history of adherence problems. Of this group, three women received Combivir plus tenofovir, three women tenofovir+FTC (Truvada) plus AZT and four women received tenofovir, FTC and AZT as single drugs.
The median age of the women was 31 years (range 25-43 years) at baseline and 6 women were treatment- naive. Initiation of therapy was at a median of 32 weeks (range 14-33 weeks); the median CD4 count and viral load was 335 cells/mm3 (range 45-605 cells/mm3) and 48,200 copies/mL (range 60-229,000 copies/mL) respectively.
All ten women in this group delivered by caesarean section. The median CD4 count at delivery was 424 cells/mm3 (range 74-652 cells/mm3) and viral load was 25 copies/mL (range 19-50 copies/mL). The median time to </= 50 copies/mL was 4.6 weeks (range 2-12 weeks). There were no cases of mother to child transmission.
The authors wrote: Further evaluations should be implemented to make this regimen an addition to current recommendations for MTCT prophylaxis.
Luis Lopez-Cortes et al report that most women (36/38) taking saquinavir during pregnancy have adequate (>100ng/ml) plasma concentrations when prescribed saquinavir/ritonavir 1200mg/100mg bd. This is a higher dose than routinely recommended and it is of interest to note that despite this 2/36 mothers had a TDM-driven dose increase to 1600mg bd.
Tung MY et al report on 13 mothers taking a more conventional boosted saquinavir/r regimen and note effective viral suspression. It would be interesting to know how many mothers might have had apparently sub-optimal trough plasma concentrations at this lower dose, and whether dose adjustment is required on the basis of total (free and bound) concentrations. The data, whilst not conclusive, adds to the body of evidence that boosted saquinavir is a reasonable option in pregnancy, especially for Short-Term ART. It should be noted that in both studies the median CD4 counts and viral loads were favourable for a good response to ART.
Habert A et al, report their findings treating ten women with a more controversial (triple NRTI) regimen. Clearly a much larger study is required to assess the long-term impact on viral suppression, and there are still few data on the safety of tenofovir in this setting.
- Tung MY, Khan W, Hawkins DA. The clinical outcome of using saquinavir hard-gel capsules/ritonavir (SQV/r) with two nucleosides (NRTIs) in HIV-infected pregnant women. 10th European AIDS Conference. November 2005, Dublin, Ireland. Abstract PE14.2/2.
- Lopez-Cortes R, Ruiz-Valderas R, Rivero A et al. Therapeutic drug monitorization and efficacy of low-dose saquinavir/ritonavir QD in HIV-infected pregnant women. 10th European AIDS Conference. November 2005, Dublin, Ireland. Abstract PE14.4.1.
- Habert A, Linde R, Faul-Burbes C et al. Effective MTCT-prophylaxis with AZT, TDF plus FTC or 3TC. 10th European AIDS Conference. November 2005, Dublin, Ireland. Abstract PE14.2/3.