Long-term antiretroviral therapy mitigates mortality and morbidity independent of HIV tropism: 18 years follow-up in a women's cohort

Barbara Weiser, Binshan Shi, Kimdar Kemal, Harold Burger, Howard Minkoff, Qiuhu Shi, Wei Gao, Esther Robison, Susan Holman, Tamara Schroeder, Alissa Gormley, Kathryn Anastos, Christina Ramirez

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)1979-1986
Number of pages8
Issue number14
StatePublished - Nov 15 2022


  • CCR5
  • CXCR4
  • HIV infection in women
  • HIV-1
  • HIV-1 coreceptor usage
  • HIV-1 tropism
  • cART
  • combination antiretroviral therapy
  • immunologic nonresponders

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases


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