Meta Analysis of Genetic Variants of HIV Mother to Child Transmission

Nearly 80 million people have been infected by HIV, primarily through sexual aquition and 35 million have died from HIV –I and associated diseases (Abrahams MR et al: J Virol 83:3556–3553, 2009; Bal AK, Miller G, Viscarello R, Andiman WA: Pediatr Infect Dis J 15:315–320, 1996; Barin F et al: J Infect Dis 193:1504–1511, 2006; Bashirova AA, Geijtenbeek TB, van Duijnhoven GC, van Vliet SJ, Eilering JB et al: J Exp Med 193:671–678, 2001; Binley JM et al: J Virol 78:13232–13252, 2004; Blish CA, Blay WM, Haigwood NL, Overbaugh J: Curr HIV Res 8(5):578–587, 2007; Boily LG, Zijenah LS, Mbizvo M, Ward BJ, Roger M: Hum Immunol 68:523–530, 2007). HIV infect infants through MTCT and adult through blood born or sexual transmission discussed in Chap. 1. The epidemic has affected sub population in heterozygous fashions, with rates varying by age, sex, predominant mode of exposure and geographic locations. The overall risks of transmission of HIV is thought to be low, roughly to 0.18% per sex act, but varies considerably from 0.02% to 1.6% in previous published mata analysis findings. Similarly, level of viremia during acute HIV infection, set point VL rate of CD4 T-cell depletion, and eventual rates of progression to AIDS all vary widely (Bongertz V et al: Scand J Immunol 53:302–309, 2001). For example, while some individuals have been observed to develop profound CD4 T cells lymphopenia and AIDS within 2 years, others remain AIDS free for up to 15 years following HIV seroconversion. Since the sequencing of the human genome in (Lander et al. 2011) large scale genetic and genomic studies have played an increasingly important role in delineating the pathogensis of human disease. Understanding the variable risk and course of HIV infection in vivo by studying host genetics has been instrumental to understanding the immunopathogensis of HIV. Moreover, it has complemented the invitro understanding of the biology of HIV infection and replication that led to development of ARV drugs, which are cornerstone of HIV prevention and therapy. Studies of host genetic correlates have reflected the wide ranging nature of possible HIV outcome measures over the course of HIV infection, beginning with acquition through disease progression and development of OIs and AIDS (Boniotto M, Crovella S, Pirulli D, Scarlatti G, Spano A et al: Genes Immun 1:346–348, 2000; Bryson YJ, Luzuriaga K, Sullivan JL, Wara DW: N Engl J Med 327:1246–1247, 1992). Similarly, the studies reflects the heterogeneity in population affected by HIV. Hundreds of studies have been conducted into the genetic determinants of HIV aquition and disease progression. Previous studies, referred to as candidate gene studies were locus or gene centric, while larger recent studies have searched for correlates across the genome using genome wide genotypic or whole exome/genome sequencing is an unbiased “agnostic” manner. In total, 5 genome wide association studies of HIV acquisition and the 11 of markers of HIV disease course have been reported at global level. Asper the literature survey GWAS have also been instrumental in generating estimates of the relative contribution of the host and viral genetic variation in HIV. Accordingly, the present study reviewed the relevant literature briefly, and then turns attention to the two well validated genetic correlates of HIV aquition and HIV disease outcome (Chohan B et al: J Virol 79:6528–6531; 2005; Derdeyn CA et al: Science. 2004 303:2019, 2004). We specifically highlight questions or hypothesis, which, in our view remain unanswered with regard to the mechanism of HLA effects in HIV. We anticipate further progress in these areas and discuss additional future prospects in this mata analysis study intervention. Further, the biological mechanisms involved in HIV type –I I Dieltjens T et al: Retrovirology 2009 6:113, 2009; Edmonson PF, Mullins JI: Nucleic Acids Res 20:4933, 1992). Shorter variable loops and fewer PNG sites have separately been shown to correlate with increased viral fitness and greater neutralizing antibody sensitivity. One study suggested that HIV-1C viruses newly transmitted from MTCT were more fit, had significantly fewer PNG sites and were more resistant to autologus maternal serum than non transmitted viruses. For studies that analyzed vertical transmission stratified by timing, viral populations have been reported to have different properties if transmitted inutero (IU) or intrapartum (IP). There is no consensus on the neutralizing antibodies may play in MTCT (Galtier N, Gouy MG et al: Comput Appl Biosci 12:543, 1996; Gardner M et al: AIDS Res Hum Retrovir 11:843–854, 1995). Animal studies have demonstrated that neutralizing antibodies elicited by simian immunodeficiency virus (SIV) vaccine can at least slow disease progression. Ehile direct administration of antibodies matched to the challenge virus can block transmission. Studies of natural MTCT have yielded conflicting results a, although possibly for identifiable reasons. The breadth of the neutralizing antibody response may depend on the sub type of HIV-1 being studied and neutralizing antibody levels may be associated with the timing of transmission. A comprehensive picture of the effect of neutralizing antibodies on MTCT is difficult to obtain because of small sample sizes and different sub types accounting for transmission timing are needed to better understand the transmission mechanisms. There is also uncertainty about the role of antibodies in super infection. In the present chapter we analyzed and formulated the statistical model for describing the HIV sub type C env genes from 25 mothers –infant pairs: 15 transmitting IU and 10 transmitting IP data sets accruded from the meta analysis conducted at global level, and also correlate strong genetic bottle neck associated with vertical transmission. Compared to the maternal viral population, viruses’ transmitted IP tended to have shorter variable loops and fewer PNG sites than viruses transmitted IU however, the present study also formulate env growth models approach to psuedo typed viruses from transmitted infants variants and maternal variants (Gay Cynthia L et al: Diagn Microbiol Infect Dis 66:356, 2010). The recently characterize chemokine receptor gen CCR5 and its most frequent mutation have become the objects of intense interest since their roles in the entry of HIV-I in to target cells were identified. This mata analysis reports the estimation of genotypes distribution of the deletion in children born to HIV I infected mothers, the genotype distribution are in Hardy Weinberg equilibrium HW law suggesting the absence of deleterious genotypes. The δ32 allilic frequency in this populations. Homozygosity for a 32 bp deleted allele in CCR5 gene protects adults from HIV-I infection following blood or sexual exposure. So, it is possible that this mutated allele also has a protective effect in children born to HIV –I seropositive mothers. The present study not evidence may partial resistance to HIV I infection among heterozygous children. Many research cited that, the heterozygous adults are discordant Dean et al., Huang et al., and Zimmeraman et al. (2016) found no protective effect, where as, Samsn et al. (2003) and Micheal et al. (2003) suggested that, the existence of a protective effect as they reported a frequency of the heterozyogous state that was lower in those whose were infected than in the general population of naive group. A major strength of prospective cohorts of children born to HIV I seropositive mothers is that infected and uninfected patients can be compared within single group rather than using reference group comparison. Considerations of the predictive biological factors for the disease in children have mostly addressed the risk of early and severe forms, which are associated with advanced maternal disease and viral replication in utero. Genetic factors have previously been suggested in HIV I infected children, namely the HLA genotype and complement system genotype, but only in analyses of small subgroup population. Those concerning HLA remain controversial due to low sensitivity and specificity.