Quantifying residual HIV-1 replication in patients receiving combination antiretroviral therapy.
N Engl J Med
; 340(21): 1605-13, 1999 May 27.
Article
in En
| MEDLINE
| ID: mdl-10341272
ABSTRACT
BACKGROUND:
In patients infected with human immunodeficiency virus type 1 (HIV-1), combination antiretroviral therapy can result in sustained suppression of plasma levels of the virus. However, replication-competent virus can still be recovered from latently infected resting memory CD4 lymphocytes; this finding raises serious doubts about whether antiviral treatment can eradicate HIV-1.METHODS:
We looked for evidence of residual HIV-1 replication in eight patients who began treatment soon after infection and in whom plasma levels of HIV-1 RNA were undetectable after two to three years of antiretroviral therapy. We examined whether there had been changes over time in HIV-1 proviral sequences in peripheral-blood mononuclear cells, which would indicate residual viral replication. We also performed in situ hybridization studies on tissues from one patient to identify cells actively expressing HIV-1 RNA. We estimated the rate of decrease of latent, replication-competent HIV-1 in resting CD4 lymphocytes on the basis of the decrease in the numbers of proviral sequences identified during primary infection and direct sequential measurements of the size of the latent reservoir.RESULTS:
Six of the eight patients had no significant variations in proviral sequences during treatment. However, in two patients there was sequence evolution but no evidence of drug-resistant viral genotypes. In one patient, extensive in situ studies provided additional evidence of persistent viral replication in lymphoid tissues. Using two independent approaches, we estimated that the half-life of the latent, replication-competent virus in resting CD4 lymphocytes was approximately six months.CONCLUSIONS:
These findings suggest that combination antiretroviral regimens suppress HIV-1 replication in some but not all patients. Given the half-life of latently infected CD4 lymphocytes of about six months, it may require many years of effective antiretroviral treatment to eliminate this reservoir of HIV-1.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Virus Replication
/
HIV Infections
/
HIV-1
/
Anti-HIV Agents
Type of study:
Prognostic_studies
Limits:
Adult
/
Humans
/
Male
Language:
En
Journal:
N Engl J Med
Year:
1999
Document type:
Article
Affiliation country:
United States