Antiretroviral Therapy for Prevention of Mother-to-Child HIV Transmission

Carlo Giaquinto; Osvalda Rampon; Anita De Rossi


Clin Drug Invest. 2006;26(11):611-627. 

In This Article

Abstract and Introduction


Administration of potent antiretroviral combination therapy in the second and third trimester of pregnancy and during delivery, and for 6 weeks postpartum to the infant, may reduce HIV transmission from the mother to the child to <2% in formula-fed infants. In resource-constrained settings where women have limited access to antenatal care, use of shorter and more practical regimens, including nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs) commenced later in pregnancy, has demonstrated efficacies ranging from 18% to 70% in breast- and bottle-fed populations. Because shorter interventions include regimens such as single-dose nevirapine or zidovudine monotherapy, which do not provide maximal suppression of viral replication, emergence of resistant mutations in mother and infant occurs frequently, primarily after exposure to drugs with low genetic barriers (i.e. those requiring only one genotypic mutation to develop resistance), such as nevirapine.

Different studies have reported nevirapine resistance rates ranging from 25% to 69% in mothers receiving single-dose nevirapine alone. Because NNRTI-based combinations of antiretroviral agents are recommended as first-line therapy in countries where single-dose nevirapine is the main option for preventing mother-to-child transmission of HIV, concerns have been raised as to whether single-dose nevirapine prophylaxis can compromise the efficacy of subsequent NNRTI-based antiretroviral therapy regimens. However, although some studies have shown that nevirapine exposure may impact on short-term virological outcome, the clinical relevance of nevirapine resistance remains unclear, especially in women who start treatment >6 months after delivery or in those who are not severely immunocompromised. Furthermore, studies have shown that adding short-course (up to 7 days) zidovudine or zidovudine/lamivudine prophylaxis after delivery may dramatically reduce the occurrence of nevirapine resistance in both mothers and infants.

Until data are available that allow a better understanding of the relevance of antiretroviral drug resistance acquired as a result of mother-to-child HIV transmission prophylaxis, women and children who have previously received single- dose nevirapine as part of a mother-to-child transmission prevention strategy should be considered eligible for NNRTI-based regimens and should not be denied access to antiretroviral therapy.

1. Introduction

According to WHO estimates, 17.5 million women worldwide were infected with HIV as at the end of 2005, and about 92% of these women lived in sub-Saharan Africa, South and South East Asia, Latin America and the Caribbean.[1] In the year 2005 alone, about 700000 children acquired HIV infection, almost always through mother-to-child transmission before, during or after delivery. In some settings in Africa, the prevalence of HIV infection in childbearing women is as high as 57% and vertically acquired HIV infection is now reversing the positive downward trend in infant and child mortality previously seen in sub-Saharan Africa.[1]

HIV transmission from mother to infant can occur antepartum (in utero), intrapartum (during labour or delivery) or postpartum (through breastfeeding). Estimates suggest that in the absence of breast feeding, 30% of infant HIV infections occur in utero and 70% during labour and delivery.[2] Where formula feeding is not available, breastfeeding contributes substantially to the overall risk of transmission, accounting for approximately one-third of cases.[3] Furthermore, the cumulative probability of HIV transmission increases with the duration of breastfeeding.[3] In the absence of any intervention, the estimated rate of mother-to-child transmission of HIV ranges from 15% to 30% in the non-breastfeeding population and from 25% to 45% in breastfed children,[2] which means that even without intervention, over half of children born to HIV-infected women are not infected. Even when antiretroviral prophylaxis successfully reduces the risk of mother-to-child transmission late in pregnancy and during delivery, postnatal transmission through breastfeeding remains an important risk.[2,3]


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