Back HIV Populations Pregnancy & MTCT CROI 2014: Lopinavir or Lamivudine Equally Protective Against HIV During Breast-feeding

CROI 2014: Lopinavir or Lamivudine Equally Protective Against HIV During Breast-feeding

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Peri-exposure prophylaxis using either lopinavir/ritonavir (Kaletra) or lamivudine (3TC, Epivir) proved equally protective as infant prophylaxis against HIV infection during 12 months of breast-feeding, according to a report at the 21st Conference on Retroviruses and Opportunistic Infections (CROI 2014) this month in Boston.

[Produced in collaboration with Aidsmap.com]

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

Nevirapine (Viramune) and lamivudine have shown similar efficacy and safety as infant prophylaxis during 6 months of breast-feeding, but no studies to date have evaluated the effectiveness of infant prophylaxis over the entire 12-month recommended breast-feeding 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 pediatric formulation.

Chipepo Kankasa of University Teaching Hospitalin Lusaka, Zambia, reported findings from ANRS 12174, a multi-national, open-label, randomized, double-blind controlled study, compared the efficacy and safety of prolonged infant prophylaxis with lopinavir/ritonavir (40 mg/10 mg twice-daily if weight 2 to 4 kg and 80 mg/20 mg if >4kg) versus lamivudine (7.5 mg twice daily if 2 to 4 kg, 25 mg if 4 to 8 kg, and 50 mg if >8kg) to prevent HIV transmission from day 7 until 1 week after cessation of breast-feeding (for a maximum of 50 weeks).

The study recruited infants who were 5 to 9 days old, did not have HIV infection detected after delivery, were being breast-fed, 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 lamivudine arm, of which 604 and 607 infants, respectively, were included in the analyses.

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

Infants' baseline characteristics were similar between the 2 arms of the study, with a median birth weight of 3000 grams. Baseline median maternal age was 27.4 years and antenatal median CD4 T-cell count was 529 cells/mm3. The mothers with CD4 counts above 350 cells/mm3 and therefore were not eligible for ART according to guidelines in effect at the time.

At baseline, the proportion of mothers with undetectable viral load varied between countries, ranging from 65.1% in Uganda to 30.3% in Zambia. Almost all mothers (96%-98%) were on a PMTCT (prevention of mother-to-child transmission) regimen during pregnancy and labor. The median duration of breast-feeding was about 41 weeks in both arms, with considerable variation between countries.

A total of 17 new infant HIV infections were diagnosed: 8 in the lopinavir/ritonavir arm and 9 in the lamivudine arm. Lopinavir/ritonavir proved as efficacious as lamivudine, with transmission rates at 50 weeks of 1.4% and 1.5%, respectively.

There were a total of 33 deaths, of which 18 and 15 were in the lopinavir/ritonavir and lamivudine arms, for mortality rates of 3.0% and 2.5%, respectively -- not a significant difference. Kankasa noted that no deaths were attributable to HIV, but mainly to diarrhea or pneumonia.

HIV-free survival was similar, 95.6% and 96.2% in the lopinavir/ritonavir and lamivudine arms, respectively. Both drugs were equally well tolerated with similar safety profiles. Approximately one-third of infants in both arms experienced 1 or more severe adverse events.

Compared with other studies, Kankasa noted these findings report the lowest postnatal transmission rate at 12 months. Other studies, mostly using nevirapine and with peri-exposure prophylaxis durations of 14 weeks to 6 months, reported postnatal transmission rates ranging from 1.1% (at 6 months) to 6.3% (at 9 months).

Comparison of ANRS 12174 with other studies

Study

Maternal CD4 count

PrEP drug

PrEP duration

Duration of exposure

Postnatal transmission

PEPI

(Malawi)

>200 Median >400

NVP

Max 14W

13% still exposed at M18

W6-M9: 5.2%

PEPI (Malawi)

>200 Median >400

NVP+AZT

Max 14W

13% still exposed at M18

W6-M9: 6.3%

SWEN (Uganda, Ethiopia, India)

>200 Median >400

NVP

Max 6W

32% still exposed at M6

W6-M9: 4.3%

MITRA (Tanzania)

269-611 Median 411

Lamivudine

Max 6M

Median 18W

W6-M6: 1.1%

BAN (Malawi)

>250 Median 440

NVP

Max 6M

96% stopped before W32

W2-M6: 1.7%

W2-W48:

4%

HPTN 046 (South Africa)

>350 Median 530

NVP

Max 6M

Beyond 6M

W6-M12: 1.7%

ANRS 12174

>350 Median 578

Lopinavir/r or 3TC

Max 12M

Max 12M

D7-M12:1.4%

D7-M6: 0.7%

(NVP = nevirapine, AZT = zidovudine)

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

3/18/14

Reference

C Kankasa, N Nagot, N Meda, et al. Infant Lopinavir/r Versus 3TC To Prevent Postnatal HIV-1 Transmission: The ANRS 12174 Trial. 21st Conference on Retroviruses and Opportunistic Infections (CROI 2014). Boston, March 3-6, 2014. Abstract 70.