Cellular proviral HIV-DNA decline and viral isolation in naïve subjects with <5000 copies/ml of HIV-RNA and >500 x 10(6)/l CD4 cells treated with highly active antiretroviral therapy.
OBJECTIVE
To evaluate the decay rate of cellular proviral HIV-DNA and viral replication in patients receiving highly active antiretroviral therapy (HAART) in the very early phase of infection.


METHODS
Thirty-four patients treated with HAART and retrospectively selected for progressive decline of plasma viraemia up to undetectable levels (< 20 copies/ml), were stratified according to CD4+ cell count and plasma viraemia at base line: > 500 x 10(6) cells/l with < 5000 copies/ml (group 1) or with > 5000 copies/ml (group 2), > 5000 copies/ml with 300-500 x 10(6) cells/l (group 3) or with < 300 x 10(6) cells/l (group 4). Plasma HIV-RNA and proviral HIV-DNA were analysed at baseline and after 1, 2, 3, 6, 9 and 12 months of treatment.


RESULTS
After 1 year of treatment, a significant decrease of proviral DNA titre was observed in all patients and a decrease > 1 log was achieved in 24 of 29 subjects of the first three groups. The more pronounced decay of HIV-DNA (half-life 28 weeks) up to < 50 HIV-DNA copies/10(6) CD4+ cells was detected in patients of group 1. At the year's endpoint, five patients (four in group 1 and one in group 2) had < 20 HIV-DNA copies. However, HIV strains sensitive to antiretroviral drugs were isolated from peripheral lymphocytes of 16 out of 34 patients.


CONCLUSIONS
In patients with undetectable plasma viraemia after 1 year of HAART, the highest reduction of proviral DNA up to < 50 copies/10(6) CD4+ cells was obtained only in subjects in the early asymptomatic phase of infection. Nevertheless, a replication-competent virus can be detected in all phases of antiretroviral therapy.
Andreoni
M
M
Department of Public Health, University of Rome Tor Vergata, Italy. andreoni@uniroma2.it
Parisi
S G
SG
Sarmati
L
L
Nicastri
E
E
Ercoli
L
L
Mancino
G
G
Sotgiu
G
G
Mannazzu
M
M
Trevenzoli
M
M
Tridente
G
G
Concia
E
E
Aceti
A
A
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004279:DNA, Viral / Q000097:blood*; D016049:Didanosine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000254:growth & development* / Q000378:metabolism; D006801:Humans; D019469:Indinavir / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011533:Proviruses / Q000254:growth & development* / Q000378:metabolism; D012367:RNA, Viral / Q000097:blood*; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018119:Stavudine / Q000627:therapeutic use; D014766:Viremia / Q000188:drug therapy*
D019380:Anti-HIV Agents; D004279:DNA, Viral; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019469:Indinavir; D018119:Stavudine; D016049:Didanosine