Association of host genetic risk factors with the course of cytomegalovirus retinitis in patients infected with human immunodeficiency virus

Efe Sezgin, Mark L Van Natta, Alka Ahuja, Alice Lyon, Sunil Srivastava, Jennifer L. Troyer, Stephen J. O'Brien, Douglas Jabs

Research output: Contribution to journalArticle

Abstract

• Purpose: To evaluate the effects of previously reported host genetics factors that influence cytomegalovirus (CMV) retinitis incidence, progression to acquired immune deficiency syndrome (AIDS), and efficacy of highly active antiretroviral therapy (HAART) for mortality, retinitis progression, and retinal detachment in patients with CMV retinitis and AIDS in the era of HAART. • Design: Prospective, multicenter, observational study. • Methods: Cox proportional hazards model based genetic association tests examined the influence of IL-10R1-S420L, CCR5-Δ32, CCR2-V64I, CCR5 promoter, and SDF-3′A polymorphisms among patients with mortality, retinitis progression, and retinal detachment. Participants were 203 European-American and 117 African-American patients with AIDS and CMV retinitis. • Results: European-American patients with the CCR5 +.P1.+ promoter haplotype showed increased risk for mortality (hazard ratio [HR] = 1.83; 95% confidence interval [CI]: 1.00-3.40; P = .05). Although the same haplotype also trended for increased risk for mortality in African-American patients, the result was not significant (HR = 2.28; 95% CI: 0.93-5.60; P = .07). However, this haplotype was associated with faster retinitis progression in African Americans (HR = 5.22; 95% CI: 1.54-17.71; P = .007). Increased risk of retinitis progression was also evident for African-American patients with the SDF1-3′A variant (HR = 3.89; 95% CI: 1.42-10.60; P = .008). In addition, the SDF1-3′A variant increased the retinal detachment risk in this patient group (HR = 3.05; 95% CI: 1.01-9.16; P = .05). • Conclusion: Besides overall immune health, host genetic factors influence mortality, retinitis progression, and retinal detachment in patients with AIDS and CMV retinitis that are receiving HAART.

Original languageEnglish (US)
JournalAmerican Journal of Ophthalmology
Volume151
Issue number6
DOIs
StatePublished - Jun 2011

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Cytomegalovirus Retinitis
Retinitis
HIV
Retinal Detachment
African Americans
Confidence Intervals
Highly Active Antiretroviral Therapy
Acquired Immunodeficiency Syndrome
Mortality
Haplotypes
Proportional Hazards Models
Multicenter Studies
Observational Studies

ASJC Scopus subject areas

  • Ophthalmology

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Association of host genetic risk factors with the course of cytomegalovirus retinitis in patients infected with human immunodeficiency virus. / Sezgin, Efe; Van Natta, Mark L; Ahuja, Alka; Lyon, Alice; Srivastava, Sunil; Troyer, Jennifer L.; O'Brien, Stephen J.; Jabs, Douglas.

In: American Journal of Ophthalmology, Vol. 151, No. 6, 06.2011.

Research output: Contribution to journalArticle

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abstract = "• Purpose: To evaluate the effects of previously reported host genetics factors that influence cytomegalovirus (CMV) retinitis incidence, progression to acquired immune deficiency syndrome (AIDS), and efficacy of highly active antiretroviral therapy (HAART) for mortality, retinitis progression, and retinal detachment in patients with CMV retinitis and AIDS in the era of HAART. • Design: Prospective, multicenter, observational study. • Methods: Cox proportional hazards model based genetic association tests examined the influence of IL-10R1-S420L, CCR5-Δ32, CCR2-V64I, CCR5 promoter, and SDF-3′A polymorphisms among patients with mortality, retinitis progression, and retinal detachment. Participants were 203 European-American and 117 African-American patients with AIDS and CMV retinitis. • Results: European-American patients with the CCR5 +.P1.+ promoter haplotype showed increased risk for mortality (hazard ratio [HR] = 1.83; 95{\%} confidence interval [CI]: 1.00-3.40; P = .05). Although the same haplotype also trended for increased risk for mortality in African-American patients, the result was not significant (HR = 2.28; 95{\%} CI: 0.93-5.60; P = .07). However, this haplotype was associated with faster retinitis progression in African Americans (HR = 5.22; 95{\%} CI: 1.54-17.71; P = .007). Increased risk of retinitis progression was also evident for African-American patients with the SDF1-3′A variant (HR = 3.89; 95{\%} CI: 1.42-10.60; P = .008). In addition, the SDF1-3′A variant increased the retinal detachment risk in this patient group (HR = 3.05; 95{\%} CI: 1.01-9.16; P = .05). • Conclusion: Besides overall immune health, host genetic factors influence mortality, retinitis progression, and retinal detachment in patients with AIDS and CMV retinitis that are receiving HAART.",
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AU - O'Brien, Stephen J.

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