Structural equation modelling of viral tropism reveals its impact on achieving viral suppression within 6 months in treatment-naive HIV-1-infected patients after combination antiretroviral therapy.
To evaluate the role of pre-treatment co-receptor tropism of plasma HIV on the achievement of viral suppression (plasma HIV RNA 1.69 log10copies/mL) at the sixth month of combination antiretroviral therapy (cART) in a cohort of naive patients using, for the first time in this context, a path analysis (PA) approach.



Adult patients with chronic infection by subtype B HIV-1 were consecutively enrolled from the start of first-line cART (T0). Genotypic analysis of viral tropism was performed on plasma and interpreted using the bioinformatic tool Geno2pheno, with a false positive rate of 10%. A Bayesian network starting from the viro-immunological data at T0 and at the sixth month of treatment (T1) was set up and this model was evaluated using a PA approach.



A total of 262 patients (22.1% bearing an X4 virus) were included; 178 subjects (67.9%) achieved viral suppression. A significant positive indirect effect of bearing X4 virus in plasma at T0 on log10HIV RNA at T1 was detected (P = 0.009), the magnitude of this effect was, however, over 10-fold lower than the direct effect of log10HIV RNA at T0 on log10HIV RNA at T1 (P = 0.000). Moreover, a significant positive indirect effect of bearing an X4 virus on log10HIV RNA at T0 (P = 0.003) was apparent.



PA overcame the limitations implicit in common multiple regression analysis and showed the possible role of pre-treatment viral tropism at the recommended threshold on the outcome of plasma viraemia in naive patients after 6 months of therapy.
Department of Molecular Medicine, University of Padova, Padova, Italy.
Carlo
C
Mengoli
Department of Molecular Medicine, University of Padova, Padova, Italy.
Samantha
S
Andreis
Infectious Disease Unit, Padova Hospital, Padova, Italy.
Renzo
R
Scaggiante
Center of Diffusive Diseases, Verona, Italy.
Mario
M
Cruciani
ULSS-20, Verona, Italy.
Oliviero
O
Bosco
Clinical Infectious Diseases, Schio Hospital, Schio, Italy.
Roberto
R
Ferretto
Clinical Infectious Diseases, Tor Vergata University, Rome, Italy.
Davide
D
Leoni
Department of Systems Medicine, Tor Vergata University, Rome, Italy.
Gaetano
G
Maffongelli
Department of Molecular Medicine, University of Padova, Padova, Italy.
Monica
M
Basso
Unit of Infectious Diseases, University 'Magna Graecia', Catanzaro, Italy.
Carlo
C
Torti
Clinical Infectious Diseases, Tor Vergata University, Rome, Italy.
Loredana
L
Sarmati
Clinical Infectious Diseases, Tor Vergata University, Rome, Italy.
Massimo
M
Andreoni
Department of Molecular Medicine, University of Padova, Padova, Italy.
Giorgio
G
Palù
Department of Molecular Medicine, University of Padova, Padova, Italy saverio.parisi@unipd.it.
Saverio Giuseppe
SG
Parisi
D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D060005:Genotyping Techniques; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000235:genetics; D000072230:Sustained Virologic Response; D016896:Treatment Outcome; D056189:Viral Tropism
D044966:Anti-Retroviral Agents; D012367:RNA, Viral