Human Immunodeficiency Virus Type 1 Infection in Twin Pairs Infected at Birth

Biggar, Robert J.; Janes, Michelle; Pilon, Richard; Roy, Reena; Broadhead, Robin L.; Kumwenda, Newton; Taha, Taha E.; Cassol, Sharon

doi:10.1086/341453

Cited by 12 publications

(10 citation statements)

References 11 publications

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“…Because different TCR recognizing the same epitope vary in functional properties, such as ligand avidity and recognition of different epitope escape variants (34), important aspects of CTL function are stochastically determined, as reflected by divergent viral sequence evolution in the twins. Our observations are consistent with the findings of Biggar et al, who studied HIV-1 evolution following mother-to-child transmission for 14 fraternal and 5 identical twins (4). Although the period of follow-up was relatively brief (12 to 16 weeks on average), HIV-1 sequences diverged between twins, and there did not appear to be a difference in the divergence rates between identical versus fraternal twins.…”

Section: Discussionsupporting

confidence: 92%

Genetic and Stochastic Influences on the Interaction of Human Immunodeficiency Virus Type 1 and Cytotoxic T Lymphocytes in Identical Twins

Yang

Church

Kitchen

et al. 2005

J Virol

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Human immunodeficiency virus type 1 (HIV-1) evolves in vivo under selective pressure from CD8؉ Tlymphocyte (CTL) responses, which are in turn determined by host and viral genetic factors, such as restricting major histocompatibility complex molecules and the available viral epitope sequences. However, CTL are derived stochastically through the random gene rearrangements to produce T-cell receptors (TCR), and the relative impact of genetic versus stochastic processes on CTL targeting of HIV and immune-driven viral evolution is unclear. Here we evaluate identical twins infected with HIV-1 as neonates from a common blood transfusion, with subsequently similar environmental exposures, thereby allowing controlled comparisons of CTL targeting and viral evolution. Seventeen years after infection, their CTL targeting of HIV-1 was remarkably similar. In contrast, their overall TCR profiles were highly dissimilar, and a dominant epitope was recognized by distinctly different TCR in each twin. Furthermore, their viral epitopes had diverged, and there was ongoing viral phylogenetic divergence between the twins between 12 and 17 years after infection. These results indicate that while CTL targeting is predominately genetically determined, stochastic influences render the interaction of HIV-1 and host immunity, and therefore viral escape and CTL efficacy, unpredictable.

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Section: Discussionsupporting

confidence: 92%

Genetic and Stochastic Influences on the Interaction of Human Immunodeficiency Virus Type 1 and Cytotoxic T Lymphocytes in Identical Twins

Yang

Church

Kitchen

et al. 2005

J Virol

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“…This difference in infection rate between twins can occur despite similar maternal virus, immunologic and genetic factors [58,59]. Of note, the twin association was reported in early US-based studies, however, a recent study in Malawi did not find first-born twins to be at increased risk, perhaps as a result of viral factors or cohort differences [60,61]. To restrict exposure to maternal HIV-1 in blood and mucosal secretions, caesarean section has been utilised effectively in many developed world settings, and is recommended when plasma viral load is > 1000 copies/ml [62].…”

Section: Intrapartum Hiv-1 Transmissionmentioning

confidence: 99%

Biological mechanisms of vertical human immunodeficiency virus (HIV‐1) transmission

Lehman

Farquhar

2007

Reviews in Medical Virology

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In the absence of interventions, 30-45% of exposed infants acquire human immunodeficiency virus type 1 (HIV-1) through mother-to-child transmission. It remains unclear why some infants become infected while others do not, despite significant exposure to HIV-1 in utero, during delivery and while breastfeeding. Here we discuss the correlates of vertical transmission with an emphasis on factors that increase maternal HIV-1 levels, either systemically or locally in genital secretions and breast milk. Immune responses may influence maternal viral load, and data suggest that maternal neutralising antibodies reduce infection rates. In addition, infants may be capable of mounting HIV-specific cellular immune responses. We propose that both humoral and cellular responses are necessary to reduce infection because cell-free as well as cell-associated virus appears to play a role in vertical transmission. These distinct forms of the virus may be targeted most effectively by different components of the immune system. We also discuss the use of antiretrovirals to reduce transmission, focusing on the mechanisms of action of regimens currently used in developing country settings. We conclude that prevention relies not only on reducing maternal HIV-1 levels within blood, genital tract and breast milk, but also on pre- and/or post-exposure prophylaxis to the infant. However, HIV-1 has the capacity to mutate under drug pressure and rapidly acquires mutations conferring antiretroviral resistance. This review concludes with data on persistence of low-level resistance after delivery as well as recent guidelines for maternal and infant regimens designed to limit resistance.

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“…It is however not necessarily true for twin pregnancy to be associated with MTCT more often than singletons. There is a paucity of literature on the risk of MTCT in twins and serodiscordance between second and first born twins [16,17].…”

Section: Prophylaxis or Cart Indicated In Hiv Exposed Infantsmentioning

confidence: 99%

“…Second born twins spend a comparatively shorter time in the birth canal than the first born baby. The latter baby had already dilated the passage and mechanically removed most of the infected material [17][18][19].…”

Section: Prophylaxis or Cart Indicated In Hiv Exposed Infantsmentioning

confidence: 99%

Serodiscordant twins: A case report of vertical HIV transmission during PMTCT option B+ role out

Lion-Cachet¹

2016

Pediatr Dimensions

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Similar factors promote vertical transmission of HIV in singleton pregnancies as in twin pregnancies. MTCT (mother to child transmission) in single pregnancies are associated with viral, maternal, obstetrical, foetal and infant factors. In twin pregnancies factors associated with serodiscordance are not clear. Mechanisms implicated are uterine contractions, mixing mother and foetal blood (2 nd twin), broken skin, exposure in the birth canal (1 st twin). Since Antiretroviral Therapy as Prevention of MTCT (ART PMTCT) the most important factor associated with vertical HIV transmission is the Viral Load (VL). Due to early attainments of NSP goals of 2% 6 weeks and 5% 18 months HIV rates Elimination of MTCT (EMTCT) became a possibility. New challenges en route to eliminate HIV are interventions to reverse HIV latency and to induce an effective anti-HIV immune response. Twin studies could be utilised to improve the understanding of the role of host genetics, co-infections and HIV sub-types in HIV transmission.Correspondence to: Carien Lion-Cachet, Sub-District Family Physician, North West

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Human Immunodeficiency Virus Type 1 Infection in Twin Pairs Infected at Birth

Cited by 12 publications

References 11 publications

Genetic and Stochastic Influences on the Interaction of Human Immunodeficiency Virus Type 1 and Cytotoxic T Lymphocytes in Identical Twins

Genetic and Stochastic Influences on the Interaction of Human Immunodeficiency Virus Type 1 and Cytotoxic T Lymphocytes in Identical Twins

Biological mechanisms of vertical human immunodeficiency virus (HIV‐1) transmission

Serodiscordant twins: A case report of vertical HIV transmission during PMTCT option B+ role out

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