Antiretroviral treatment during pregnancy and breastfeeding resulted in a mother-to-child transmission rate of less than 1% in a large randomised comparison of two triple combinations in women with CD4 counts above 200 cells/mm3, the Mma Bana study, presented this week at the Fifth International AIDS Society conference in Cape Town.
The study also showed that a triple-nucleoside analogue regimen containing abacavir is just as effective as a protease inhibitor-based regimen in a population of women with relatively low viral load (Trizivir has previously shown itself to be less effective than efavirenz-based ART in people with viral loads above 100,000 copies/ml, leading to its withdrawal from the list of recommended first-line regimens in the United States and Europe).
However it should be noted that women in this study were followed for a little less than nine months, which may not be long enough to evaluate the suitability of Trizivir as a long-term regimen for women in sub-Saharan Africa.
The Mma Bana study was a randomised comparison of the virologic efficacy and PMTCT (prevention of mother-to-child transmission) efficacy of two antiretroviral regimens taken during pregnancy and breastfeeding by women with CD4 counts above 200 cells/mm3.
The investigators randomised 560 HIV-positive pregnant women with CD4 cell counts above 200 cells/mm3 to start one of two antiretroviral regimens between weeks 26 and 34 of pregnancy. This treatment was continued until weaning six months after giving birth.
Women in the first arm were provided with a combination of drugs that comprised the three nucleoside reverse transcriptase inhibitors (NRTIs) 3TC, abacavir and AZT, dosed as Trizivir. Nevirapine-based ART is unsuitable for women with CD4 counts above 250 cells/mm3 due to an increased risk of liver toxicity, so alternative regimens need to be identified to enable treatment in pregnancy to be extended to women with higher CD4 counts.
Women in the other arm were treated with the protease inhibitor lopinavir/ritonavir (Kaletra) in combination with 3TC and AZT (dosed as Combivir).
Also included in the study were 170 women with a CD4 cell count below 200 cells/mm3. In accordance with treatment guidelines at that time, to protect their own health they started a combination of anti-HIV drugs consisting of nevirapine with 3TC and AZT between weeks 18 and 34 of pregnancy.
All mothers received supplemental AZT (zidovudine) during labour.
Infants received single dose nevirapine after delivery and one month of treatment with AZT (zidovudine).
Women in the randomisation arms had median CD4 counts of approximately 400 cells/mm3, and were enrolled to the study around week 27 of their pregnancy. Median viral loads were relatively low in the randomisation arm; 13,300 and 9100 copies in the Trizivir and Kaletra arms respectively, with only 15% of women having a baseline viral load above 100,000 copies/ml.
In the observational group receiving nevirapine-based ART the median CD4 cell count was 147 cells/mm3 and the median viral load 51,000 copies/ml. Thirty-seven per cent had baseline viral load above 100,000 copies/ml.
There were two main study outcomes: the proportion of women with a viral load below 400 copies/ml at delivery and throughout breastfeeding at months 1, 3 and 6; and the rate of mother-to-child transmission of HIV assessed at birth and then months 1, 3 and 6 of feeding. Data were also gathered on adverse events, including still births and the number of babies born prematurely or with a low birth weight.
At the time of birth, equal proportions of women taking triple NRTI treatment (96%), protease inhibitor-based therapy (93%) and treatment that included nevirapine (94%) had a viral load below 400 copies/ml. The median duration of treatment was 11 weeks in the randomisation arm, and 13 weeks in the observational arm.
Moreover, similar proportions of women maintained viral suppression throughout breastfeeding, regardless of the HIV treatment they were taking (92% vs 93% vs 95%).
The cumulative rates of mother-to-child transmission of HIV were equally low in all three groups of women (2% in the triple NRTI arm vs below 0.4% in the Kaletra group and 0.6% in the nevirapine group). This difference was not statistically significant.
The very small number of transmissions in the study occurred almost entirely in utero, in women who had high baseline viral loads and shorter than average periods on ART prior to delivery, and in some cases, a history of self-reported adherence problems. Insufficient viral suppression is likely to explain these cases of transmission, and indicates the need for ART to be initiated promptly in pregnancy in order to achieve rapid viral suppression before delivery.
Only two transmissions occurred during the breastfeeding period, in one case from a mother who had viral load below 50 copies/ml at months 1 and 3 and no evidence of adherence problems.
There was no difference in the number of babies born with a low birth weight between the arms of the study, although babies born to mothers in the Kaletra arm were more likely to be premature (p = 0.04).
Furthermore, there was a comparable rate of still births amongst the women treated with three NRTIs (3%) and those receiving a protease inhibitor (2%). However, 7% of the babies of mothers taking nevirapine were still births.
Side-effects causing a change of treatment were recorded in 2% of women taking both the triple NRTI treatment or the protease inhibitor-based treatment. Nevirapine-based treatment was associated with a much higher rate of treatment changes, with 11% changing because of side-effects.
Approximately 75% of women breastfed for over five months. Nearly all infants had been weaned six months after birth. Infant mortality during breastfeeding was 2% amongst women who took triple NRTI treatment, 3% amongst those taking a protease inhibitor, and 4% amongst those who started nevirapine-based therapy because they had a low CD4 cell count.
The mother-to-child transmission rate in the Mma Bana study is the lowest yet seen in any randomised study of antiretroviral treatment during pregnancy and breastfeeding, and despite the higher rate of drug substitution in the nevirapine arm, shows that in mothers with higher viral load and low CD4 counts, nevirapine-based ART is remarkably effective in preventing mother-to-child transmission.
Shapiro R et al. A randomized trial comparing highly active antiretroviral therapy regimens for virologic efficacy and the prevention of mother-to-child transmission among breastfeeding women in Botswana (The Mma Bana Study). 5th IAS Conference on HIV Treatment, Pathogenesis and Prevention, Cape Town, abstract WeLLB101, 2009.