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Antiretroviral therapy during primary immunodeficiency virus infection can induce persistent suppression of virus load and protection from heterologous challenge in rhesus macaques.
- Source :
-
Journal of virology [J Virol] 2000 Feb; Vol. 74 (4), pp. 1704-11. - Publication Year :
- 2000
-
Abstract
- A limited period of chemotherapy during primary immunodeficiency virus infection might provide a long-term clinical benefit even if treatment is initiated at a time point when virus is already detectable in plasma. To evaluate this strategy, we infected rhesus macaques with the pathogenic simian/human immunodeficiency virus RT-SHIV and treated them with the antiretroviral drug (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA) for 8 weeks starting 7 or 14 days postinfection. PMPA treatment suppressed viral replication efficiently in all of the monkeys. After chemotherapy ended, virus replication rebounded and viral RNA in plasma reached levels comparable to that of the controls in four of the six monkeys. However, in the other two animals, virus loads peaked only moderately after withdrawal of the drug and then declined to low or even undetectable levels. These low levels of viremia remained stable for at least 31 weeks after cessation of therapy. At this time point, these two monkeys were challenged with SIV(8980) to evaluate whether the host responses which were able to keep RT-SHIV replication under control were also sufficient to protect against infection with a highly pathogenic heterologous virus. Both monkeys proved to be protected against the heterologous virus. In one of the two animals, low levels of SIV(8980) replication were detected. Thus, by chemotherapy during the acute phase of pathogenic virus replication, we could achieve not only persistent virus load suppression in two out of six monkeys but also protection from subsequent heterologous challenge. By this chemotherapeutic attenuation, the replication kinetics of attenuated viruses could be mimicked and a vaccination effect similar to that induced by live attenuated simian immunodeficiency virus vaccines was achieved.
- Subjects :
- Adenine adverse effects
Adenine therapeutic use
Animals
Anti-HIV Agents adverse effects
Cells, Cultured
HIV Envelope Protein gp120 immunology
HIV Reverse Transcriptase antagonists & inhibitors
HIV Reverse Transcriptase genetics
Humans
Lymphocyte Subsets
Macaca mulatta
Organophosphorus Compounds adverse effects
RNA, Viral blood
Recombination, Genetic
Reverse Transcriptase Inhibitors adverse effects
Simian Acquired Immunodeficiency Syndrome immunology
Simian Acquired Immunodeficiency Syndrome physiopathology
Simian Acquired Immunodeficiency Syndrome virology
Tenofovir
Adenine analogs & derivatives
Anti-HIV Agents therapeutic use
HIV-1 enzymology
HIV-1 genetics
Membrane Glycoproteins
Organophosphonates
Organophosphorus Compounds therapeutic use
Reverse Transcriptase Inhibitors therapeutic use
Simian Acquired Immunodeficiency Syndrome drug therapy
Simian Immunodeficiency Virus enzymology
Simian Immunodeficiency Virus genetics
Simian Immunodeficiency Virus immunology
Viral Envelope Proteins
Viral Load
Subjects
Details
- Language :
- English
- ISSN :
- 0022-538X
- Volume :
- 74
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 10644340
- Full Text :
- https://doi.org/10.1128/jvi.74.4.1704-1711.2000