The effects of short-term zidovudine treatment on mother to child hiv-1Transmission
Rikia, Mwari Kibaya
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Vertical transmission accounts for the majority of pediatrics HIV-1 infections. Immunological, obstetrical, co-infection with other diseases and maternal viral load are some of the factors that influence this mode of transmission. It is not clear which of these factors are important in determining whether a mother will infect her infant. The long-term treatment of mothers with Zidovudine (AZT) during pregnancy reduced the infection rate by 70%. However, drug resistance variants are generated and can be vertically transmitted during long-term treatment. In Kenya, the use of a short-term treatment reduces transmission by 67% but whether this treatment could induce drug but whether this treatment could induce drug resistance is not known. This study investaigated the induction and transmission of drug resistance variants during a short-term treatmen with AZT. part of pol (697bp) region encoding the reverse transcriptase of six HIV-1 isolates from positive mothers (three on AZT adn three untreated) and their infected infants was analyzed. Proviral DNA was amplified by nested PCR, the products cloned, sequenced and phylogenetically analyzed. Some natural points mutations at codons known to confer resistance to AZT were observed in some mothers' but none were transmitted to the infants. However in one case (BU025) of a child whose mother was on AZT, lysine was substituted for serine at codon 70 (K7OS) but, serine is not documented to confer any resistance to AZT. Selective transmission was observed in both treatment and non treatment groups (KSO51,KSOO6,BU025 and KSOO4), supported by high bootstrap values of 914,995,898 and 914 and 995 respectively. However multiple transmissions were also observed where the mothers population was heterogeneous and homogeneous in mother-child pairs KSOO4 ad BUO69 respectively. In mother -child pair KSO12, the infant's viral population clustered away fromthe mothers but the boostsrap value was low (421). Phylogenetic analysis revealed that four mothers were infected with HIV-1 subtype A and remaining two mothers were dually infected. Mother KSO12 was infected with two distinct subtype A viruses and the other mother KSOO4 with subtype A and D. The dually infected mothers trasmitted subtype A virus to their infants. In cases of mixed infection our results suggest that there is selective transmission of genotypes and/or phenotypes. None of the three mothers' on short-term AZT treatment transmitted resistant variants to their infants. In addition, there were no differences in the transmission patterns between the AZT treated and non-term AZT treatment for prevention of vertical transmission of HIV-1 is effective adn safe.