AEGiS-13IAC: CCR5 promoter polymorphisms in a Kenyan perinatal HIV-1 cohort: association with maternal 2-year mortality.

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

CCR5 promoter polymorphisms in a Kenyan perinatal HIV-1 cohort: association with maternal 2-year mortality.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. TuOrB352)

John G, Bird T, Overbaugh J, Nduati R, Mbori-Ngacha D, Dong T, Rostron T, Kostrikis L, Kreiss J, Rowland-Jones S
G. John, University of Washington and University of Nairobi, University of Washington, Box 359909, Seattle, WA 98195, United States, Tel.: +1 206 731 28 22, Fax: +1 206 731 24 27, E-mail: gjohn@u.washington.edu

BACKGROUND: Macrophage-tropic strains of HIV-1 utilize the CCR5 coreceptor for infection of cells. Mutations in the promoter region of CCR5 may result in effects on HIV-1 pathogenesis and transmission.

METHODS: We evaluated the effect of 4 polymorphisms in the CCR5 promoter region on maternal HIV-1 plasma viral load, mucosal HIV-1 shedding, and disease progression, and on mother-to-child transmission of HIV-1 in a perinatal HIV-1 cohort in Nairobi Kenya. Assays for CCR5 promoter polymorphisms were conducted using the ARMS-PCR technique, plasma viral HIV-1 RNA levels were determined using the Gen-Probe TMA assay, and cervical, vaginal, and breastmilk HIV-1 DNA detected using qualitative PCR. Mother-infant pairs were followed for 2 years following delivery and effect on mortality assessed using Kaplan-Meier survival analysis.

RESULTS: Among 258 mothers, the allele frequency for CCR5 promoter polymorphisms was 0.40 for 353 "t", 0.13 for 356 "t", 0.12 for 402 "a", and 0.19 for 59029 "a". Women heterozygous for 356 "t" had a 3.2-fold increased risk of mortality during the 2-year postpartum follow-up period (95% CI 1.0-10.4). Vaginal shedding of HIV-1 DNA was significantly increased in women with this mutation (OR 2.3, 95% CI 1.2-5.0). Plasma HIV-1 RNA levels, and cervical and breastmilk HIV-1 DNA shedding did not differ significantly in women with the 356 mutation from those with wildtype. Mother-to-child transmission of HIV-1 was not increased among mothers with the 356 mutation. Mutations at 353, 402, or 59029 were not associated with effects on maternal mortality, mucosal shedding or vertical transmission in the cohort.

CONCLUSIONS: A mutation at position 356 of the CCR5 promoter appears to have clinical importance with effects both on disease progression and genital shedding of virus.

Keywords: AEGIS, HIV-1, Viral Load, Disease Transmission, Vertical, Polymorphism (Genetics), Promoter Regions (Genetics), Maternal Mortality, HIV-1 Reverse Transcriptase, Mutation, Gene Frequency, Kenya, Human, Female, Child, Infant, transmission, genetics
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