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Risk factors for early and late transmission of HIV via breast-feeding among infants born to HIV-infected women in a randomized clinical trial in Botswana
Global Health Sciences Literature Digest
Published August 4, 2009
Journal Article

Shapiro RL, Smeaton L, Lockman S, et al. Risk factors for early and late transmission of HIV via breast-feeding among infants born to HIV-infected women in a randomized clinical trial in Botswana. J Infect Dis 2009;199:1-5.

In Context

Breast-feeding (BF) has been associated with a 4%-12% absolute risk of HIV transmission from infected mothers to infants through six months of life.(1,2,3,4) Studies have shown, however, that compared to BF, formula-feeding (FF) of infants in under-developed countries is associated with increased mortality.(2,5) The Mashi Study was a clinical trial of the prevention of mother-to-child transmission of HIV (MTCT) that randomized pregnant women and infants to single dose nevirapine (NVP) plus zidovudine (ZDV) prophylaxis or to placebo plus ZDV(6) and also determined whether the provision of ZDV to mothers and infants reduced HIV transmission among BF infants.(2) The study did not examine the specific risks for early and late MTCT. Knowledge of such factors can be used to determine women among whom BF should be recommended over FF.


To determine 1) the contribution of early BF to MTCT between birth and one month, 2) the impact of maternal receipt of single-dose NVP on early and late MTCT via BF, and 3) the risk factors for late MTCT.


Southern Botswana

Study Design

Secondary analysis from the Mashi Study


1200 pregnant women at four sites (one city, one town, and two large villages)


MTCT of HIV and predictors of late MCTC


HIV-infected pregnant mothers were referred from antenatal clinics to study centers. Study arms are described above. ZDV was given to mothers from 34 weeks gestation and intrapartum NVP or placebo. In October 2003, combination antiretroviral therapy (ART) became available and was offered to women with CD4 counts <200 cells/mm3 or with AIDS. Infants initially received single-dose NVP or placebo at birth and ZDV prophylaxis for one month (FF arm) or six months (BF arm). Based upon efficacy data from another clinical trial, the study protocol changed and after 17 months of enrollment all infants received single-dose NVP.

Intrapartum or early BF transmission was defined as infants with a negative DNA PCR test result at or within 15 days of birth and a positive DNA PCR test result at one month. Late transmission was defined as infants with a negative DNA PCR at birth and one month and a positive DNA PCR at anytime thereafter.

Data on demographics, CD4 cell count, and plasma viral load were collected at 34 weeks gestation. Infant DNA PCR testing for HIV was conducted at birth and at one, four, seven, nine, and 12 months. ELISA testing for HIV was done at 18 months. HIV-RNA levels were tested in breast milk samples collected at two weeks and at two and five months post-partum.

BF women were counseled at each visit to BF exclusively for five to six months and then to wean children to FF and solids. Mothers of HIV-infected infants were encouraged to continue BF.

Comparison of infant HIV infection rates at one month in the groups was done using the Fisher exact test and after one month using the Kaplan-Meier method. Predictors of transmission were done using Cox proportional hazards regression models.


Baseline characteristics of participants in the two groups were similar. PCR testing within four days of birth was available for 96% of infants and for 92% of infants up to seven months of age. Intrapartum or early BF transmission of HIV infection occurred in six (1.1%) FF infants and in seven (1.3%) BF infants (P=0.99). The mothers of the six infected children in the FF arm did not report any BF. Maternal NVP did not predict early transmission in the BF group (P=0.45). Late transmission occurred in 24 (4.4%) of the 547 at-risk infants; 15 infections occurred before four months, six between four and six months, and three between seven and 24 months. The independent predictors of reduced transmission were the presence of electricity in the home (adjusted hazards ratio [AHR] 0.14, 95% confidence intervals [CI]: 0.02-1.02) and maternal CD4 count at baseline (AHR 0.88, 95% CI: 0.77-1.01) while viral load was associated with increased risk of transmission (AHR 2.6, 95% CI: 1.3-5.0). Breast milk HIV RNA levels also were associated with increased transmission in the bivariate analysis but co-linearity and missing data prevented its inclusion in the multivariable analysis.


BF, in the presence of maternal and infant ART, is safe up to one month.

Quality Rating

The quality rating of this study is based upon the methods described in the initial report from the study;(6) the study summarized here is comprised solely of data analysis. The clinical trial was of high quality because it was randomized centrally and double-blinded, because loss to follow-up was described and acceptable, and because an intention-to-treat analysis was performed. The randomization of feeding allowed analysis of the isolated risk of MTCT from early BF. In most situations, this is difficult to separate from intrapartum transmission.

Programmatic Implications

This study identified higher levels of HIV RNA (in plasma and breast milk) as the main risk factors for transmission from BF. The availability of combination ART for HIV-infected pregnant women allows for maintaining low viral loads. In areas where FF has been associated with high rates of infant mortality, these findings provide evidence for the safety of BF in the presence of NVP-prophylaxis and MTCT programs.


  1. The Breastfeeding and HIV International Transmission Study Group et al. Late postnatal transmission of HIV-1 in breast-fed children: an individual patient data meta-analysis. J Infect Dis 2004;189:2154-66.
  2. Thior I, Lockman S, Smeaton LM, et al. Breastfeeding plus infant zidovudine prophylaxis for 6 months vs formula feeding plus infant zidovudine for 1 month to reduce mother-to-child HIV transmission in Botswana: a randomized trial: the Mashi Study. JAMA 2006;296:794-805.
  3. Miotti PG, Taha TE, Kumwenda NI, et al. HIV transmission through breastfeeding: a study in Malawi. JAMA 1999;282:744-9.
  4. Coutsoudis A, Pillay K, Kuhn L, Spooner E, Tsai WY, Coovadia HM. Method of feeding and transmission of HIV-1 from mothers to children by 15 months of age: prospective cohort study from Durban, South Africa. AIDS 2001; 15:379-87.
  5. Coovadia HM, Rollins NC, Bland RM, et al. Mother-to-child transmission of HIV-1 infection during exclusive breastfeeding in the first 6 months of life: an intervention cohort study. Lancet 2007;369:1107-16.
  6. Shapiro RL, Thior I, Gilbert PB, et al. Maternal single-dose nevirapine versus placebo as part of an antiretroviral strategy to prevent mother-to-child HIV transmission in Botswana. AIDS 2006;20:1281-8.