HIV-1 tropism and CD4 T lymphocyte recovery in a prospective cohort of patients initiating HAART in Ribeirão Preto, Brazil.
While human immunodeficiency virus (HIV)-1 chemokine co-receptors 5 tropism and the GWGR motif in the envelope third variable region (V3 loop) have been associated with a slower disease progression, their influence on antiretroviral response remains unclear. The impact of baseline V3 characteristics on treatment response was evaluated in a randomised, double blind, prospective cohort study with patients initiating highly active antiretroviral therapy with lopinavir or efavirenz plus azithothymidine/3TC (1:1) over 48 weeks. Similar virological and immunological responses were observed for both treatment regimens. The 43 individuals had a mean baseline CD4 T cell count of 119 cells/mm(3) [standard deviation (SD) = 99] and a mean viral load of 5.09 log(10) copies/mL (SD = 0.49). The GWGR motif was not associated with a CD4 T cell response, but predicted R5 tropism by the geno2pheno([clinical20%]) algorithm correlated with higher CD4 T cell levels at all monitoring points (p < 0.05). Moreover, higher false-positive rates (FPR) values from this analysis revealed a strong correlation with CD4 T cell recovery (p < 0.0001). Transmitted drug resistance mutations, documented in 3/41 (7.3%) cases, were unrelated to the assigned antiretroviral regimen and had no impact on patient outcomes. In conclusion, naÏve HIV-1 R5 infected patients exhibited higher CD4 T cell counts at baseline; this difference was sustained throughout therapy. The geno2pheno([clinical]) option FPR positively correlated with CD4 T cell gain and may be useful in predicting CD4 T cell recovery.
Laboratório de Retrovirus, Centro de Virologia, Instituto Adolfo Lutz, São Paulo, Brasil.
Andre Minhoto
AM
Lanca
Jeova Keny Baima
JK
Collares
João Leandro de Paula
JL
Ferreira
Danielle Malta
DM
Lima
Luis Fernando de Macedo
LF
Brigido
Rosangela
R
Rodrigues
Benedito Antonio Lopes da
BA
Fonseca
D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D003521:Cyclopropanes; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D061466:Lopinavir / Q000627:therapeutic use; D008297:Male; D011446:Prospective Studies; D016896:Treatment Outcome; D019562:Viral Load; D056189:Viral Tropism / Q000187:drug effects*
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D061466:Lopinavir; C098320:efavirenz