PRELIMINARY RESULTS FROM 232 WEEKS CLINICAL TRIAL USING REMUNE^®, AN IMMUNO-MODULATOR, AS INITIAL TREATMENT FOR HIV INFECTION

W. Sukeepaisarncharoen ¹, W.Chantratita ², S. Kulpradist ³, V. Chandeying ⁴, S. Rugpao ⁵, B. Israngkura Na Ayudhtaya⁶, W. Sirawaraporn⁷, C. Boonshuyar⁸ and V. Churdboonchart⁷

¹Khon Kaen University Khon Kaen, Thailand; ² Ramathibodi Hospital, Bangkok, Thailand; ³ Vajira Hospital, Bangkok, Thailand; ⁴ Prince of Songkla University, Songkla, Thailand; ⁵ Chiang Mai University, Chiang Mai, Thailand;  ⁶ Pramongkutklao Hospital, Bangkok, Thailand; ⁷ Faculty of Science, Mahidol University, Bangkok, Thailand; ⁸Faculty of Public Health, Mahidol University, Bangkok, Thailand

Abstract: The purpose of this extension of P2101B is to determine the immunotherapy that can delay the AIDS progression. The result of 186 volunteers was classified into two groups, responder and non-responder, by Area-Under-the-Curve-Minus Baseline (AUCMB) that determines whether the value of AUCMB is positive or negative respectively. The responders, 51.08%, showed increasing number of CD4+ cells and stabilizing level of HIV-1 RNA copies at week 232. Drug-resistant virus also was not found by genotypic test; therefore, REMUNE^® can be used as an immunomodulator to delay the initiation of antiretroviral treatment and a drug therapy that can be used after immunotherapy failure.

Methodology: This is P2101B Extension Study up to 232 Weeks. Volunteers previously enrolled in the 40-weeks, double-blind, randomized, placebo-controlled P2101B study who continued in the Extended Phase II P2101B study up to 132 weeks were still the same in this open-label REMUNE^® extension study. The remaining 260 volunteers were grouped into nine cohorts from five clinical test sites (Khon Kaen, Pramongkut, Vajira, Chiang Mai and Songkla). These volunteers were administered with 1.0 ml of REMUNE^® through intramuscular injection into the belly or triceps muscle every 12 weeks. Clinical assessment or physical examination, including medications and adverse events, vital signs and body weight were performed. Blood samples were drawn to determine CD4+ and CD8+ cell counts, percent CD4+ and CD8+. Determination for plasma HIV-1 RNA was also done. Genotypic drug resistance testing study was also conducted to determine emergence of drug mutation in volunteers.

Results, Discussion and Conclusion: From the 260 volunteers who started in this extension study, 186 volunteers continued and remained until the 232-week duration. Changes in the number of CD4+ T cells by Area-Under-Curve-Minus-Baseline (AUCMB) determine whether a volunteer is a responder or a non-responder to the REMUNE^® treatment. The responders, 51.08% of the 186 volunteers, showed increasing in the number of CD4+ cells and stabilizing the level of HIV-1 RNA copies at week 232. The mean body weight also increased by 1.04 kg at week 232 compared to day 1. Results in the genotypic-drug resistance testing indicate no evidence of mutation that could lead to resistant strain. Standard treatment suggests of using the antiretroviral when CD4+ cell count is lower than 300 cells/mm³. Therefore REMUNE^® can be used as an immunomodulator before CD4+ cell counts of HIV-1-infected persons decline to the level that the initiation of antiretroviral drugs is recommended. The results also indicate that REMUNE^® can delay the use of antiretroviral drugs, has safety profile, and the absence of drug resistance in REMUNE^®-treated cohort enables the use of any available drug whenever necessary.

Keywords: Immune-based therapy, Immunomodulator, delaying antiretroviral drugs, drug resistance