[pronut-hiv] Aidsmap: Mma Bana study: MTCT reduced below 1% in BF mothers who receive ART

["ProNut-HIV" <pronut-hiv@healthnet.org>]

Keith Alcorn & Michael Carter, Friday, July 24, 2009
 
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 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 take 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 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 9,100 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 one, three and six 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 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. 

Reference 

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.