HIV-1 genotype and vertical transmission in northern Vietnam

University dissertation from Stockholm : Karolinska Institutet, Department of Microbiology, Tumor and Cell Biology

Abstract: After 18 years from the beginning of the HIV-1/AIDS epidemic in Vietnam, the number of HIV-1 infected individuals is still increasing. Investigations conducted at two distinct time points in two separate groups of HIV-1 infected intravenous drug users (IDUs) and pregnant women in Northern Vietnam indicated that the HIV-1 CRF01_AE genotype is dominating in Northern Vietnam. Our analysis was based on 399 gp120 V3 env sequences comprising HIV-1 strains studied by us and on previously published Vietnamese sequences and on reference sequences from neighboring countries available in the Los Alamos HIV database. By using different softwares to determine the phylogenetic relationship of the different HIV-1 strains, we showed that the HIV-1 CRF01_AE present in Northern Vietnam is closely related with the HIV-1 CRF01_AE sequences from Southern China, whereas HIV-1 CRF01_AE sequences from Southern Vietnam have a closer link with HIV-1 CRF01_AE Thailand sequences. The genetic analysis of the gp120 V3 env sequences obtained from HIV-1 infected IDUs in 2002 and pregnant women in 2006-2007 revealed that HIV-1 is spreading rapidly in Northern Vietnam. The fast spreading epidemic can be identified by the low level of variation noticed in HIV-1 strains infecting IDUs and pregnant women in Northern Vietnam. HIV-1 infection in pregnant women is increasing in Vietnam. Several prevention programs have however been started to control HIV-1 vertical transmission in Northern Vietnam. In my study 182 HIV-1 infected mothers and their children were enrolled. The HIV-1 infection in children was confirmed by the presence of the HIV-1 pol gene in blood cell DNA. The PCR was performed from birth until 12 months and HIV-1 serology from 12 to 18 months. The total HIV-1 transmission rate to the children in our study was 6.7% with a rate of pre-partum transmission of 4.2% and intra-partum transmission of 1.5%. About 60% of the HIV-1 infected mothers received one dose of nevirapine at labor. The children were treated with liquid nevirapine within 48 hours from birth. In addition, ARV combination was provided to 11% of the HIV-1 pregnant women for a few weeks prior to delivery and zidovudine was given to the children one week after birth. Through counselling, the women were convinced to not breast-feed their infants. It was documented that there was no evidence of postpartum transmission. The key for the prevention of HIV-1 transmission from mother to child is counselling and this procedure needs to be further implemented in Vietnam. The different HIV-1 subtypes might have a different response to the anti retroviral treatment. In order to evaluate this possibility we measured the changes of sCD27 levels in plasma in patients infected with HIV-1 subtypes A, or B, or C or D and treated with ART for 12 months. The sCD27 is a marker of immune activation. The data showed that sCD27 is considerably higher (p<0.001) in the HIV-1 infected group than in the control group. After 12 months of treatment, the reduction of sCD27 levels in plasma was significant for all HIV-1 subtypes (p<0.001) with the largest reduction for HIV-1 subtype C. Our results suggest that a significant reduction in immune activation could be measured after 1 year of ART for all the different subtypes; thus sCD27 can be considered as a relevant immune marker to measure response to therapy.

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