Higher CD4+ T cell counts associated with low viral pol replication capacity among treatment-naive adults in early HIV-1 infection.
BACKGROUND
Infection with primary drug-resistant human immunodeficiency virus type 1 (HIV-1) has been associated with higher CD4(+) T cell counts in drug-naive patients, suggesting that altered viral pol replication capacity (RC) associated with drug resistance diminishes immune injury in vivo, independent of exposure to drugs.


METHODS
Virus replication over a single cycle was measured by use of a viral test vector containing patient-derived HIV-1 protease and reverse transcriptase gene segments.


RESULTS
Among 191 recently infected patients, pol RC ranged widely, with only 6% of the variance explained by drug-resistance mutations. Patients infected with a virus with a low pol RC (</=43% of the reference virus) had significantly higher CD4(+) T cell counts at study entry, independent of drug resistance and plasma HIV-1 RNA level, and over time, both before and during combination antiretroviral therapy.


CONCLUSIONS
Viral pol RC may influence HIV-1 disease progression by affecting the amount and tissue distribution of viral replication. The pol RC value of 43% may represent a threshold below which HIV-1 has lowered virulence and is less able to deplete CD4(+) T cell counts.
Barbour
Jason D
JD
Gladstone Institute of Virology and Immunology, University of California, San Francisco, USA.
Hecht
Frederick M
FM
Wrin
Terri
T
Segal
Mark R
MR
Ramstead
Clarissa A
CA
Liegler
Teri J
TJ
Busch
Michael P
MP
Petropoulos
Christos J
CJ
Hellmann
Nicholas S
NS
Kahn
James O
JO
Grant
Robert M
RM
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D015684:Gene Products, pol / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D008297:Male; D012367:RNA, Viral / Q000097:blood; D014774:Virulence; D014779:Virus Replication
D019380:Anti-HIV Agents; D015684:Gene Products, pol; D012367:RNA, Viral