No abstract

We examined the effect of a human immunodeficiency virus (HIV)-specific immune-based therapy in Thailand, where access to antiviral drug therapy is limited. A 40-week trial was conducted with 297 asymptomatic, HIV-infected Thai subjects with CD4-cell counts greater than 300 l/mm 3 . Subjects were randomized to receive either HIV type 1 (HIV-1) immunogen (Remune; inactivated HIV-1 from which gp120 is depleted in incomplete Freund's adjuvant or adjuvant control at 0, 12, 24, and 36 weeks at five different clinical sites in Thailand. Neither group received antiviral drug therapy. The a priori primary endpoint for the trial was changes in CD4-cell counts with secondary parameters of percent changes in CD8-cell counts (percent CD4, CD8, and CD4/CD8) and body weight. Subsets of subjects were also examined for changes in plasma HIV-1 RNA levels, Western blot immunoreactivity, and HIV-1 delayed-type hypersensitivity (DTH) skin test reactivity. There was a significant difference in changes in CD4-cell counts that favored the HIV-1 immunogen-treated group compared to those for the adjuvant-treated control group (P < 0.05). On average, for HIV-1 immunogentreated subjects CD4-cell counts increased by 84 cells by week 40, whereas the increase for the control group was 38 cells by week 40. This increase in CD4-cell count was associated with increased HIV-specific immunogenicity, as shown by Western blotting and enhanced HIV-1 DTH skin reactivity. No significant differences in adverse events were observed between the groups. The results of this trial suggest that HIV-1 immunogen is safe and significantly increases CD4-cell counts and HIV-specific immunity compared to those achieved with the adjuvant control in asymptomatic HIV-1-infected subjects not taking antiviral drugs.

Objectives To observe the long‐term effects of an immune‐based therapy HIV‐1 Immunogen (REMUNE®; Immune Response Corp., Carlsbad, CA, USA) as a first course of treatment designed to sustain the immune system and thus delay the initiation of therapy with antiretroviral drugs and/or delay disease progression. Methods In this open‐label, multi‐institute extended phase II P2101B study, disease progression, CD4 and CD8 T‐cell counts, HIV‐1 RNA levels, and genotypic antiretroviral drug resistance were examined in 223 asymptomatic HIV‐1‐infected Thai volunteers receiving REMUNE® every 12 weeks over 132 weeks. A subset of subjects was randomly selected by the physicians to receive antiretroviral drugs for 10 months. Results Patients treated with REMUNE® demonstrated a low rate of clinical disease progression (0.72 per 100 person‐years), higher CD4 and CD8 T‐cell counts, higher body weight before and after treatment in the same patient, and stable viral load with no serious adverse events. We found no genotypic evidence of drug resistance in subgroups of patients on REMUNE® monotherapy or REMUNE® plus antiretrovirals (ARTs). Conclusions This Thai study, like previous US and European studies, confirms that therapeutic immunization of HIV‐infected volunteers modifies disease progression, as evidenced by stabilization of CD4 and CD8 T‐cell counts, body weight, and viral load. As the majority of asymptomatic patients demonstrated an objective response to immunization, this study suggests that REMUNE® may be utilized prior to initiation of antiviral drug therapy when CD4 cell counts are still above the current ART guidelines. Further work should be carried out to examine its potential use in combination with ART in order to reduce the increasingly common occurrence of drug resistance.

These results suggest that long-term treatment of HIV-1 infection with Remune monotherapy is safe and results in a stabilization of CD4+ counts. Furthermore, it is likely that HIV-1 therapeutic immunization may show its greatest clinical benefit in participants with higher CD4+ cell counts. Such an approach may have important ramifications in developing countries where access to antiviral drugs is limited and also in early chronic HIV-1 infection when CD4+ cells are still over 300 cells/microL in order to limit the cost and toxicity.