73 Acta virologica 48: 73 – 78, 2004 EFFECT OF AN ORAL THERAPEUTIC HIV-1 VACCINE ON AIDS PATIENTS WITH CD4 COUNT ABOVE 250 CELLS/MM 3 V. JIRATHITIKAL 1 , A.S. BOURINBAIAR 2* 1 Immunitor Corporation, Ltd., 71 Moo 5, Bangpakong Industrial Park, Takarm, Chachoengsao 24130, Thailand; 2 Immunitor USA Inc., College Park, MD 20740, USA Received April 14, 2003; accepted March 16, 2004 Summary. – A simple delivery route, e.g. oral, would greatly facilitate the acceptance of an AIDS vaccine by a large target population. We developed a vaccine that took advantage of inherent properties of mucosal immunity in response to oral antigen challenge, namely the V-1 Immunitor vaccine (V1), which is a polyvalent oral Human immunodeficiency virus 1 (HIV-1) vaccine. The vaccine, currently manufactured in Thailand, contains pooled, inactivated viral antigens. In order to compare this vaccine with HIV-1 therapeutic vaccines reported earlier we analyzed retrospectively 13 HIV-1-positive patients that had the baseline CD4 T-cell counts greater than 250 cells/mm 3 (range 270–605 cells/mm 3 ). The patients self-administered one 850 mg vaccine tablet at breakfast and dinnertime for an average of 32 weeks (median 26 weeks). The treatment was well tolerated without any toxic effect. Twelve of thirteen patients (92%) and 9 of 13 patients (69%) experienced an elevation in CD4 and CD8 cells. The mean increase in absolute CD4 and CD8 cell counts across this group was 98 (22%; P = 0.02) and 324 (26%; P = 0.05) cells/mm 3 , respectively. Viral plasma load was measured by PCR in six patients. The observed viremia reduction was within 1 log unit. Subjective parameters, i.e., appetite, energy, and sense of well-being were reported by patients as being markedly improved, reflected in a mean body weight gain of 2.75 kg (P = 0.0008). Oral administration of HIV-1 immunogens provides compelling clinical response, especially when patients are treated earlier. Key words: antiviral therapy; cellular immunity; clinical trials; gut, immune-based therapy; therapeutic vaccine * Corresponding author. E-mail: info@immunitor.com; fax: +1775- 6406636. Abbreviations: AIDS = acquired immunodeficiency syndrome; ALVAC = recombinant vaccinia virus-based vaccine; CTL = cytotoxic lymphocyte; HIV-1 = Human immunodeficiency virus1; MIP-1 alpha = macrophage inflammatory protein-1 alpha; NYVAC = recombinant vaccinia virus-based vaccine; rgp = recombinant glycoprotein; V1 = V-1 Immunitor; VLP = virus-like particle Introduction Anti-HIV-1 cocktail drugs are toxic and effective for a limited period of time, and, most importantly, they are too expensive for the majority of HIV-1-infected individuals. One of the alternatives in solving this problem is the development of an inexpensive therapeutic vaccine. A great variety of preventive vaccines against HIV-1 are now being developed and many of them have been first tested in clinical trials as a therapeutic modality administered to already infected individuals. There has been a considerable experience with this type of approach, with over 30 clinical trials reported over the last fifteen years. Most, if not all, have demonstrated no clinical benefit and had no effect on CD4 or CD8 T cell counts or viral load (Kinloch-de Loes and Autran, 2002; Lisziewicz et al., 2003). The availability of simple delivery route, i.e., oral, would greatly improve the acceptance of a vaccine by a large population of patients, especially in developing countries. The development of an oral AIDS vaccine is a task fraught with many challenges including the antigen degradation in the stomach. The insight gained from our earlier groundwork dealing with transmucosal transmission of retroviruses has enabled us to develop an oral HIV-1 vaccine (Bourinbaiar