AEGiS-13IAC: Short term post-exposure treatment with non-nucleosidic drug allows generation of HIV-specific virus-containing immunity lead into long--term non-progressor status.

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

Short term post-exposure treatment with non-nucleosidic drug allows generation of HIV-specific virus-containing immunity lead into long--term non-progressor status.

Int Conf AIDS 2000 Jul 9-14; 13:37 (abstract no.. LbPeA7020)

Ruebsamen-Waigmann H, Mori K, Yasutomi Y, Sawada S, Villinger F, Sugama K, Rosenwirth B, Uberla K, Ansari A
Buyer AG, Wuppertal, Germany. Fax: +49 202 364 162, E-mail: helga.ruebsamen-waigmann.hr@bayer-ag.de.

ISSUES: In most patients HAART therapy has resulted in a significant restoration of immunocompetence against other infections but an insufficient immunological suppression of HIV resulting in a rebound of HIV after cessation of therapy. As this suggests that HIV-specific T-cell clones are lost at earlier stages of infection, short-term post exposition therapy with a nonnucleosidic drug was given to monkeys to suppress primary viraemia. The animals were then observed over 2 years and monitored for viraemia and SIV-specific immune responses.

DESCRIPTION: Post-exposure prophylaxis (PEP) was carried out for 4 weeks with a non-nucleoside reverse transcriptase (RT) inhibitor GW420867 (HBY 1293) in rhesus macaques infected for 8 and 24h with SHIV-RT. The animals were observed up to 2 years p.i. with regular determination of viraemia, SIV-specific antibodies, SIV-specific proliferative cellular responses and general health.

CONCLUSIONS: While the 4 week post-exposure therapy led to undetectable plasma viraemia in half of the treated monkeys after infection, a transient plasma viraemia was noted in the other half at 2 to 4 wks following cessation of therapy. Following this transient viraemia all drug treated animals showed low or undetectable levels of plasma viraemia up to 2 years pi. The magnitude and kinetics of virus specific humoral responses appeared to follow the detection of viraemia. In contrast, virus specific ctl and env-specific T cell proliferative responses were generated in both drug-treated and mock treated animals as early as 3 wks pi. However, the anti-viral immune responses were maintained in the drug-treated animals but declined in the untreated monkeys, which were viraemic. We conclude that short-term PEP permits the generation and maintenance of long lasting virus specific cellular immune responses likely leading to long-term disease protection. These results encourage similar treatment paradigms in humans whenever possible.

Keywords: AEGIS, HIV, SIV, HIV Infections, Viremia, Antiretroviral Therapy, Highly Active, HIV Seropositivity, Macaca mulatta, HIV Antibodies, HIV-1 Reverse Transcriptase, Anti-HIV Agents, HIV Envelope Protein gp120, HIV Envelope Protein gp41, Animal, Human, therapy, immunology, drug therapy, AIDS
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