title: Non-R5-tropic HIV-1 in subtype A1 and D infections were associated with lower pretherapy CD4+ cell count but not with PI/(N)NRTI therapy outcomes in Mbarara, Uganda.
abstract: Previous studies suggest that infection with non-R5-tropic subtype B HIV-1, compared with R5, is associated with a more rapid decline in CD4 cell count, but does not affect PI/(N)NRTI therapy outcome. Here, we explored clinical correlates associated with viral tropism in subtype A1 and D infections.
  
  
  
  HIV-1 subtype A1 (n = 196) and D (n = 143) pretherapy plasma samples and up to 7.5 years of posttherapy virologic and CD4 data were collected from a cross-sectional cohort in Mbarara, Uganda. Tropism and subtype were inferred using env V3 (geno2pheno) and gp41 (RIP) Sanger sequences. For each subtype, R5 infection was compared with non-R5 in terms of: pretherapy viral load and CD4 cell count (Mann-Whitney tests), and therapy outcomes, including time to virologic suppression, postsuppression virologic rebound, CD4 decline and CD4 recovery (log-rank tests).
  
  
  
  A 94% of all patients in this study achieved virologic suppression within median 3 months posttherapy. In both subtypes, non-R5 infection was associated with lower pretherapy CD4 cell count (non-R5 vs. R5; A: median 57 vs. 147 cells/μl P = 0.005; D: 80 vs. 128 cells/μl P = 0.006). Multivariable linear regression confirmed that tropism, not subtype nor the interaction between subtype and tropism, was a significant predictor of pretherapy CD4 cell count (P < 0.0001). None of pretherapy viral load, time to virologic suppression, virologic rebound, CD4 decline nor CD4 recovery was significantly different (all P > 0.09).
  
  
  
  Regardless of HIV-1 subtype or tropism, the majority of patients in this Ugandan cohort responded to therapy, even though non-R5 infection was associated with lower pretherapy CD4 cell count.
authors.affiliation: aBC Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada bMbarara University of Science and Technology, Mbarara, Uganda cUniversity of California, San Francisco, California dHarvard Medical School eHarvard School of Public Health fMassachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Guinevere Q
authors.initials: GQ
authors.lastname: Lee
authors.forename: Chris
authors.initials: C
authors.lastname: Lachowski
authors.forename: Eric
authors.initials: E
authors.lastname: Cai
authors.forename: Viviane D
authors.initials: VD
authors.lastname: Lima
authors.forename: Yap
authors.initials: Y
authors.lastname: Boum
authors.forename: Conrad
authors.initials: C
authors.lastname: Muzoora
authors.forename: Adrienne Rain
authors.initials: AR
authors.lastname: Mocello
authors.forename: Peter W
authors.initials: PW
authors.lastname: Hunt
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Martin
authors.forename: David R
authors.initials: DR
authors.lastname: Bangsberg
authors.forename: P Richard
authors.initials: PR
authors.lastname: Harrigan
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D008297:Male; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D014454:Uganda; D056189:Viral Tropism; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D044966:Anti-Retroviral Agents; D054299:env Gene Products, Human Immunodeficiency Virus