Maternal breastfeeding prophylaxis
Polly Clayden, HIV i-Base
The Kisumu Breastfeeding Study (KiBS), a phase IIB single-arm study evaluating maternal HAART for PMTCT in breastfeeding mothers in Kenya. In an oral presentation Timothy Thomas presented preliminary findings from KiBS. 
In this study, pregnant women received AZT/3TC and NVP (later changed to nelfinavir (NFV) for women with CD4 >250 cells/mm3) from 34 weeks gestation to 6 months postpartum. The mothers treatment was continued after the breastfeeding period where indicated for their own health. Women were counselled to exclusively breastfeed and to wean rapidly at 6 months. Infants received single-dose NVP at birth.
522 women were enrolled in the study of which 500 delivered 502 live born infants. The mothers median CD4 was 382 cells/mm3 and median viral load was 4.5 log copies/mL. HIV infection data were available for 497 infants live born: 27 (11 males, 16 females) became HIV-positive, 3 after 6 months.
Cumulative infant HIV infection rates per 100 infants and by maternal CD4 count and regimen are shown in the table. There was no difference in transmission rates by maternal CD4 (p=0.89) or by regimen (p=0.83). The overall rate at 12 months for female infants was 7.4 (95%CI 4.6 to 11.9) and male infants 4.5 (95%CI 2.5 to 8.1), p=0.15).
Only 3.5% of transmissions were attributed to breastfeeding at 12 months. The investigators noted that transmissions occurred after 6 months when weaning was recommended.
Table 1: Cumulative MTCT to 12 months, overall, by CD4 and NVP vs NVP
|Age||0-7 days||6 wks||3 mo||6 mo||12 mo|
|Overall (n=497)||2.4 (1.2-4.2)||3.9 (2.5-6.0)||4.1 (2.7-6.0)||5.0 (3.4-7.3)||5.9 (4.0-8.5)|
|CD4 =250 (n=118)||3.4 (1.3-8.8)||4.3 (1.8-10.0)||5.2 (2.4-11.2)||5.2 (2.4-11.2)||6.7 (3.2-13.9)|
|CD4 =250 (n=379)||2.1 (1.1-4.2)||3.8 (2.2-6.3)||3.8 (2.2-6.3)||4.9 (3.1-7.7)||5.5 (3.6-8.4)|
|Nevirapine (n=178)||1.1 (0.3-4.4)||3.4 (1.6-7.5)||3.4 (1.6-7.5)||5.2 (3.1-7.7)||5.9 (3.6-8.4)|
|Nelfinavir (n=201)||3.0 (1.4-6.5)||4.0 (2.0-7.9)||4.0 (2.0-7.9)||4.6 (2.0-7.9)||5.2 (2.8-9.5)|
The investigators wrote: Further assessmentadherence to antiretrovirals, the optimal timing for breastfeeding cessation, HIV-free survival, and drug resistance in maternal and infant HIV isolatesis necessary to determine whether HAART is a feasible, acceptable, safe, and efficacious strategy for PMTCT among breastfeeding women, particularly those not meeting WHO treatment criteria.
In a previous analysis this group have reported that maternal NVP and 3TC are transmitted to the infant via breastfeeding in sufficient quantities to have biologic effect.
In a poster authored by Clement Zeh and coworkers, they showed findings from a study evaluating whether infants could acquire resistance in this way .
29/502 infants in this study (5.8%) were HIV-positive. In 24/29 (83%) the first positive HIV PCR was before 24 weeks ie during the period of maternal prophylaxis. Of these 24 infants, 14 (58%) of their mothers received NVP mothers and 10 (42%) received NFV.
The investigators found detectable genotypic resistance in16 infants (see table 2). 6/14(43%) of infants of mothers receiving NVP and 10/10 (100%) of infants of mothers receiving NFV (p = 0.006).
Genotypic NRTI resistance mutations were: M184V (n=13), K65R (n=4), D67N (n=2), and T215Y (n=2), and NNRTI mutations were: Y181C (n=3), K103N (n=2), G190A (n=2), and K101E (n=1).
Of the infants exposed to maternal NVP, 4/6 (67%) of infants with resistance had a NRTI mutation and 6/6 (100%) had an NNRTI mutation. Of those exposed to maternal NFV, 10 (100%) of 10 infants had a NRTI mutation, but none had a major protease inhibitor mutation.
Table 2. Resistance in breastfed infants in KiBS
|Week post-partum||n||First PCR-positive specimen||Week 14 and/or 24 specimen|
|Not amplifiedCI||n resistant / n tested||n resistant / n tested|
The investigators noted that when they evaluated infants who became HIV-positive before 6 weeks of life, they did not initially detect genotypic resistance, suggesting resistant virus may not have been transmitted from the mother in utero or during labour. But they found resistance emerged during the breastfeeding period, likely due to the transfer of ARV from breast-milk.
They wrote: Differing HIV resistance patterns depending on the mothers treatment may have implications for the choice of ARV for mothers during the breastfeeding period and for subsequent treatment of infants who become HIV-infected.
- Thomas T, Masaba R, Ndivo R et al. Prevention of mother-to-child transmission of HIV-1 among breastfeeding mothers using HAART: The Kisumu Breastfeeding Study, Kisumu, Kenya, 20032007. 15th CROI, February 2008, Boston, USA. Oral abstract 45aLB.
- Zeh C, Weidle W, Nafisa L et al. Emergence of HIV-1 drug resistance among breastfeeding infants born to HIV-infected mothers taking antiretrovirals for prevention of mother-to-child transmission of HIV: The Kisumu Breastfeeding Study, Kenya. 15th CROI, February 2008, Boston, USA. Poster abstract 84LB.