Timing of mother to child transmission may be dependent on HIV-1 subtype

The risk of transmission of HIV-1 from mother to child in the womb may be dependent on the viral subtype. A higher proportion of HIV-1 subtype C was transmitted in utero than subtypes A and D, according to a new study published in the August 20th edition of AIDS.

The findings suggest that in regions where subtype C is the dominant form of HIV-1, such as southern Africa, short course antiretroviral treatment given during labour may not lead to the same reduction in mother to child transmission as in trials carried out in regions where other subtypes are dominant. The findings also add to a growing body of research suggesting that HIV-1 subtype C has different characteristics from other HIV-1 subtypes that may go some way to explaining the greater severity of the epidemic in southern Africa.

Mother-to-child transmission (MTCT) of HIV-1 can occur in the womb, during delivery and postnatally through breastfeeding. Estimates of the risk of MTCT range from 16% to 50%, with the highest rates reported in Africa. Viruses involved in the HIV/AIDS epidemic show extensive genetic variability, the widest range of genetic difference is seen between HIV-1 and HIV-2, with the rates of MTCT being much lower for HIV-2 infected women than HIV-1. Although HIV-1 subtypes A, C and D are all responsible for the epidemic in Africa, subtype C has become the most prevalent.

Dr Renjifo and colleagues determined HIV-1 subtype among 253 HIV-1 infected infants enrolled in a vitamin trial in Dar es Salaam, Tanzania. They found significant differences in the distribution of mother to child transmission time (i.e. during pregnancy, birth or postnatally through breastfeeding) according to HIV-1 subtype.

In Dar es Salaam a high prevalence of infection occurs with three HIV-1 subtypes (A, C and D), allowing a comparison between the major African HIV-1 genotypes in the same population. Of the 253 HIV-1 infected infants in this study, 101 infections were caused by HIV-1 subtype A (39%), 73 by subtype C (29%) and 53 by subtype D (21%). Fifty nine infants were infected during pregnancy, 64 during delivery and 70 through breastfeeding, with a further 8 infected either during pregnancy or delivery and 38 infected either during delivery or through breastfeeding. In 14 of the infants the precise timing of infection was unknown.

Transmission of the different HIV-1 subtypes to the infants during pregnancy, birth and in the postpartum period was compared. After allowing for maternal HIV-1 viral load and CD4 counts, both of which significantly increased the risk of transmission to the infants, there was a significant difference in transmission rates between in utero, and intra partum and breastfeeding periods dependent on maternal HIV-1 subtypes. The transmission times of subtypes A and D occurred mostly in the intra partum and postnatal period, whereas subtype C infected mothers were more likely to transmit in utero than at any other time point (OR 2.54 vs subtypes A and D, p = 0.026). The effect was most pronounced when comparing in utero vs intra partum transmission (OR 4.96 vs A and D, p = 0.004).

No significant difference in maternal viral load by subtype could be detected, suggesting that a biological factor such as greater ability of subtype C HIV to infect placental cells could be to blame.

Several short term treatments for prevention of transmission, centred on the time of delivery, are currently being implemented in many HIV affected countries with limited resources. The most widely used is short course treatment with nevirapine for mothers and their infants during labour and at delivery.

The results of this study suggest that in regions with a predominantly HIV-1 subtype C epidemic, treatment may need to begin earlier in order to achieve the same degree of reduction in mother to child transmission, and that comparisons of the efficacy of short course regimens tested in regions where HIV-1 C is the predominant subtype with regimens previously tested in populations infected with other subtypes need to take subtype characteristics into account.