BACKGROUND: Mother-child human leukocyte antigen (HLA) concordance and maternal HLA homozygosity may increase the risk of vertical transmission of human immunodeficiency virus type 1 (HIV-1) risk by reducing infant immune responses. METHODS: We analyzed mother-child HLA concordance and maternal HLA homozygosity in a Kenyan perinatal cohort receiving antenatal zidovudine. HLA concordance was scored as the number of shared class I alleles, and relative risk estimates were adjusted for maternal HIV-1 load. RESULTS: Among 277 mother-infant pairs, HIV-1 transmission occurred in 58 infants (21%), with in utero transmission in 21 (36%), peripartum transmission in 26 (45%), and transmission via breast-feeding in 11 (19%). With increased concordance, we observed a significant increase in the risk of transmission overall (adjusted hazard ratio [aHR], 1.3 [95% confidence interval {CI}, 1.0-1.7]; P = .04 in utero (adjusted odds ratio, 1.72 [95% CI, 1.0-1.7]; P = .04), and via breast-feeding (aHR, 1.6 [95% CI, 1.0-2.5]; P = .04). Women with homozygosity had higher plasma HIV-1 RNA levels at 32 weeks of gestation (5.1 vs. 4.8 log(10) copies/mL; P = .03) and an increased risk of transmission overall (aHR, 1.7 [95% CI, 1.1-2.7]; P = .03) and via breast-feeding (aHR, 5.8 [95% CI, 1.9-17.7]; P = .002). CONCLUSION: The risks of overall, in utero, and breast milk HIV-1 transmission increased with HLA concordance and homozygosity. The increased risk may be due to reduced alloimmunity or less diverse protective immune responses.
BACKGROUND: Mother-childhuman leukocyte antigen (HLA) concordance and maternal HLA homozygosity may increase the risk of vertical transmission of humanimmunodeficiency virus type 1 (HIV-1) risk by reducing infant immune responses. METHODS: We analyzed mother-child HLA concordance and maternal HLA homozygosity in a Kenyan perinatal cohort receiving antenatal zidovudine. HLA concordance was scored as the number of shared class I alleles, and relative risk estimates were adjusted for maternal HIV-1 load. RESULTS: Among 277 mother-infant pairs, HIV-1 transmission occurred in 58 infants (21%), with in utero transmission in 21 (36%), peripartum transmission in 26 (45%), and transmission via breast-feeding in 11 (19%). With increased concordance, we observed a significant increase in the risk of transmission overall (adjusted hazard ratio [aHR], 1.3 [95% confidence interval {CI}, 1.0-1.7]; P = .04 in utero (adjusted odds ratio, 1.72 [95% CI, 1.0-1.7]; P = .04), and via breast-feeding (aHR, 1.6 [95% CI, 1.0-2.5]; P = .04). Women with homozygosity had higher plasma HIV-1 RNA levels at 32 weeks of gestation (5.1 vs. 4.8 log(10) copies/mL; P = .03) and an increased risk of transmission overall (aHR, 1.7 [95% CI, 1.1-2.7]; P = .03) and via breast-feeding (aHR, 5.8 [95% CI, 1.9-17.7]; P = .002). CONCLUSION: The risks of overall, in utero, and breast milk HIV-1 transmission increased with HLA concordance and homozygosity. The increased risk may be due to reduced alloimmunity or less diverse protective immune responses.
Authors: Photini Kiepiela; Alasdair J Leslie; Isobella Honeyborne; Danni Ramduth; Christina Thobakgale; Senica Chetty; Prinisha Rathnavalu; Corey Moore; Katja J Pfafferott; Louise Hilton; Peter Zimbwa; Sarah Moore; Todd Allen; Christian Brander; Marylyn M Addo; Marcus Altfeld; Ian James; Simon Mallal; Michael Bunce; Linda D Barber; James Szinger; Cheryl Day; Paul Klenerman; James Mullins; Bette Korber; Hoosen M Coovadia; Bruce D Walker; Philip J R Goulder Journal: Nature Date: 2004-12-09 Impact factor: 49.962
Authors: V Thaineua; P Sirinirund; A Tanbanjong; M Lallemant; A Soucat; J L Lamboray Journal: Southeast Asian J Trop Med Public Health Date: 1998-09 Impact factor: 0.267
Authors: J Tang; C Costello; I P Keet; C Rivers; S Leblanc; E Karita; S Allen; R A Kaslow Journal: AIDS Res Hum Retroviruses Date: 1999-03-01 Impact factor: 2.205
Authors: K S MacDonald; J Embree; S Njenga; N J Nagelkerke; I Ngatia; Z Mohammed; B H Barber; J Ndinya-Achola; J Bwayo; F A Plummer Journal: J Infect Dis Date: 1998-03 Impact factor: 5.226
Authors: M Carrington; G W Nelson; M P Martin; T Kissner; D Vlahov; J J Goedert; R Kaslow; S Buchbinder; K Hoots; S J O'Brien Journal: Science Date: 1999-03-12 Impact factor: 47.728
Authors: D D Panteleeff; G John; R Nduati; D Mbori-Ngacha; B Richardson; J Kreiss; J Overbaugh Journal: J Clin Microbiol Date: 1999-02 Impact factor: 5.948
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