Quantifying residual HIV-1 replication in patients receiving combination antiretroviral therapy
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.
| Errataetall: |
CommentIn: N Engl J Med. 1999 May 27;340(21):1672-4. - PMID 10341281 |
|---|---|
| Medienart: |
Artikel |
| Erscheinungsjahr: |
1999 |
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| Erschienen: |
1999 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:340 |
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| Enthalten in: |
The New England journal of medicine - 340(1999), 21 vom: 27. Mai, Seite 1605-13 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, L [VerfasserIn] |
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| Themen: |
Anti-HIV Agents |
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| Anmerkungen: |
Date Completed 27.05.1999 Date Revised 14.11.2007 published: Print GENBANK: AF093912, AF094325 CommentIn: N Engl J Med. 1999 May 27;340(21):1672-4. - PMID 10341281 Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM102736332 |
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| 100 | 1 | |a Zhang, L |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Quantifying residual HIV-1 replication in patients receiving combination antiretroviral therapy |
| 264 | 1 | |c 1999 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
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| 500 | |a Date Completed 27.05.1999 | ||
| 500 | |a Date Revised 14.11.2007 | ||
| 500 | |a published: Print | ||
| 500 | |a GENBANK: AF093912, AF094325 | ||
| 500 | |a CommentIn: N Engl J Med. 1999 May 27;340(21):1672-4. - PMID 10341281 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Clinical Trial | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a Research Support, U.S. Gov't, P.H.S. | |
| 650 | 7 | |a Anti-HIV Agents |2 NLM | |
| 650 | 7 | |a RNA, Viral |2 NLM | |
| 700 | 1 | |a Ramratnam, B |e verfasserin |4 aut | |
| 700 | 1 | |a Tenner-Racz, K |e verfasserin |4 aut | |
| 700 | 1 | |a He, Y |e verfasserin |4 aut | |
| 700 | 1 | |a Vesanen, M |e verfasserin |4 aut | |
| 700 | 1 | |a Lewin, S |e verfasserin |4 aut | |
| 700 | 1 | |a Talal, A |e verfasserin |4 aut | |
| 700 | 1 | |a Racz, P |e verfasserin |4 aut | |
| 700 | 1 | |a Perelson, A S |e verfasserin |4 aut | |
| 700 | 1 | |a Korber, B T |e verfasserin |4 aut | |
| 700 | 1 | |a Markowitz, M |e verfasserin |4 aut | |
| 700 | 1 | |a Ho, D D |e verfasserin |4 aut | |
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