Lopinavir/ritonavir or 3TC PrEP equally protective against infant HIV infection during breastfeeding

Lopinavir/ritonavir (Kaletra) or 3TC (lamivudine, Epivir) proved equally protective as infant prophylaxis against HIV infection during 12 months of breastfeeding, Dr Chipepo Kankasa, presenting on behalf of the ANRS 12174 trial, told participants at the 21st Conference on Retroviruses and Opportunistic Infections (CROI) last week in Boston.

Both drugs were equally well tolerated with similar safety profiles. Lopinavir, boosted with ritonavir, proved as efficacious as 3TC with transmission rates at 50 weeks of 1.4% (0.7-2.8) and 1.5% (0.8-2.9) p = 0.83, respectively.

HIV transmission through breastfeeding remains a challenge in many resource-limited settings where there are no safe alternatives. The World Health Organization (WHO) now recommends breastfeeding of infants born to mothers living with HIV for 12 months, using either maternal antiretroviral therapy (ART) or peri-exposure prophylaxis (PrEP) to reduce the risk of HIV transmission.

Nevirapine (Viramune) and 3TC have shown similar efficacy and safety as infant prophylaxis during six months of breastfeeding but no studies to date have evaluated the effectiveness of infant prophylaxis over the entire 12-month breastfeeding period. Lopinavir/ritonavir is a good candidate for infant prophylaxis: it has a high genetic barrier to resistance, a good safety profile and is available in a paediatric formulation.

ANRS 12174, a multi-national, open-label, randomised, double-blind controlled study compared the efficacy and safety of prolonged infant prophylaxis with lopinavir/ritonavir (40mg/10mg twice daily if 2 to 4kg and 80mg/20mg if >4kg) to 3TC (7.5mg twice daily if 2 to 4kg, 25mg if weight 4 to 8 kg and 50mg if >8kg) to prevent HIV transmission from day seven until one week after cessation of breastfeeding (for a maximum of 50 weeks) in infants born to mothers with CD4 counts above 350 cells/mm³ and who were therefore not eligible for ART. 

The study recruited infants who were 5 to 9 days old, did not have HIV, were being breastfed and had birth weights over 2000 grams in Ougadougou (Burkina Faso), East London (South Africa), Mbale (Uganda) and Lusaka (Zambia). Overall, 1273 infants were enrolled, 636 in the lopinavir/ritonavir arm and 637 in the 3TC arm, of which 604 and 607 infants, respectively, were included in the analyses.

The primary outcome was HIV infection by week 50 and secondary outcomes included death, HIV-free survival and severe adverse events.

Infants’ baseline characteristics were similar between the two arms of the study, with a median birth weight of 3000 grams. Baseline antenatal maternal median CD4 count was 529 (IQR: 432-669) and median maternal age was 27.4 years. At baseline, the proportion of mothers with undetectable viral load varied between countries ranging from a median of 65.1% in Uganda to 30.3% in Zambia. The median percentage of mothers on a PMTCT (prevention of mother-to-child transmission) regimen during pregnancy and labour was 96.3% and 98%, respectively. Median duration of breastfeeding was 41.1 and 41.4 weeks, p = 0.17 in the lopinavir/ritonavir and 3TC arms, respectively, with considerable variation between countries.

Seventeen HIV infections were diagnosed: eight in the lopinavir/ritonavir arm and nine in the 3TC arm. There were a total of 33 deaths, of which 18 and 15 were in the lopinavir/ritonavir and 3TC arms, respectively; a mortality rate of 3% (1.9-4.8) and 2.5% (1.5-4.1), p = 0.57, respectively. Dr Kankasa noted no death was attributable to HIV but to diarrhoea or pneumonia.

HIV-free survival was similar, 95.6% (93.6-97) and 96.2% (94.3-94.7) in the lopinavir/ritonavir and 3TC arms, respectively. Approximately a third of infants in both arms experienced one or more severe adverse events.

Compared with other studies Dr Kankasa noted these findings report the lowest postnatal transmission rate at 12 months.

Comparison of ANRS 12174 with other studies

Dr Kankasa noted concerns about the efficacy of option B+ (the current WHO recommendation) and cited the results of the Kesho Bora randomised trial as an example in which transmission was only reduced by 50%. She added this is likely related to activated T-cell reservoir in breast milk not affected by maternal ART. In this context, she said, infant PrEP could potentially help further decrease HIV postnatal transmission among women on ART.