期刊
AIDS
卷 36, 期 14, 页码 1979-1986出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAD.0000000000003337
关键词
cART; CCR5; combination antiretroviral therapy; CXCR4; HAART; HIV infection in women; HIV-1; HIV-1 coreceptor usage; HIV-1 tropism; immunologic nonresponders
资金
- National Heart, Lung, and Blood Institute (NHLBI)
- Eunice Kennedy Shriver National Institute Of Child Health & Human Development (NICHD)
- National Institute On Aging (NIA)
- National Institute Of Dental & Craniofacial Research (NIDCR)
- National Institute Of Allergy And Infectious Diseases (NIAID)
- National Institute Of Neurological Disorders And Stroke (NINDS)
- National Institute Of Mental Health (NIMH)
- National Institute On Drug Abuse (NIDA)
- National Institute Of Nursing Research (NINR)
- National Cancer Institute (NCI)
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- National Institute on Deafness and Other Communication Disorders (NIDCD)
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- National Institute on Minority Health and Health Disparities (NIMHD)
- National Institutes of Health, Office of AIDS Research (OAR)
- NIAID [R01-AI-52015]
- Health Research, Incorporated
- University of California, Los Angeles (UCLA) Center for AIDS Research [AI-028697]
- UCLA AIDS Institute
- [U01-HL146204]
- [U01-HL146202]
- [U01-HL146193]
Long-term combination antiretroviral therapy (cART) greatly reduces the detrimental effects of X4-tropic HIV-1 on AIDS morbidity and mortality. Duration of viral suppression through at least 10 semiannual cART visits mitigates the harmful effect of X4-tropic strains.
Objective: CXCR4 (X4)-tropic HIV-1 was found previously to herald CD4(+) cell depletion and disease progression in individuals who were antiretroviral-naive or took combination antiretroviral therapy (cART) for less than 5 years. We updated this finding by investigating whether the deleterious effect of X4-tropic strains is mitigated by long-term cART. Design: We examined morbidity and mortality in relation to HIV-1 tropism and cART in 529 participants followed up to 18 years in the Women's Interagency HIV Study; 91% were women of color. Methods: Plasma-derived HIV-1 tropism was determined genotypically. Results: We categorized participants according to the number of visits reported on cART after initiation. Group 1: three or less visits, 74% of these participants reporting no cART; group 2: at least four visits and less than 70% of visits on cART; group 3: at least 70% of visits on cART. AIDS mortality rates for participants in each group with X4 virus compared with those with R5 virus exclusively were, respectively: 62 vs. 40% (P = 0.0088); 23% vs. 22% [nonsignificant (NS)]; 7% vs. 14% (NS). Kaplan-Meier curves showed accelerated progression to AIDS death or AIDS-defining illness in participants with three or less cART visits and X4 viruses (P = 0.0028) but no difference in progression rates stratified by tropism in other groups. Logistic regression found that HIV-1 suppression for at least 10 semiannual visits (>= 5 years total) mitigated X4 tropism's deleterious effect on mortality, controlling for maximal viral load, and CD4(+) nadir. Conclusion: Long-term cART markedly mitigated the deleterious effect of X4 viruses on AIDS morbidity and mortality. Mitigation was correlated with duration of viral suppression, supporting HIV-1 suppression as a crucial goal.
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