Antiretroviral therapy during primary immunodeficiency virus infection caninduce persistent suppression of virus load and protection from heterologous challenge in rhesus macaques

A limited period of chemotherapy during primary immunodeficiency virus infe ction might provide a longterm clinical benefit even if treatment is initia ted at a time point when virus is already detectable in plasma. To evaluate this strategy, we infected rhesus macaques with the pathogenic simian/huma n immunodeficiency virus RT-SHIV and treated them with the antiretroviral d rug (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA) for 8 weeks starting 7 or 14 days postinfection. PMPA treatment suppressed viral replication effic iently in all of the monkeys. After chemotherapy ended, virus replication r ebounded and viral RNA in plasma reached levels comparable to that of the c ontrols in four of the six monkeys. However, in the other two animals, viru s loads peaked only moderately after withdrawal of the drug and then declin ed 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 poin t, these two monkeys mere challenged with SIV8980 to evaluate whether the h ost responses which were able to keep RT-SHIV replication under control wer e also sufficient to protect against infection with a highly pathogenic het erologous virus. Both monkeys proved to be protected against the heterologo us virus. In one of the two animals, low levels of SIV8980 replication were detected. Thus, by chemotherapy during the acute phase of pathogenic virus replication, we could achieve not only persistent virus load suppression i n two out of six monkeys but also protection from subsequent heterologous c hallenge. By this chemotherapeutic attenuation, the replication kinetics of attenuated viruses could be mimicked and a vaccination effect similar to t hat induced by live attenuated simian immunodeficiency virus vaccines was a chieved.