Delayed progression to AIDS in volunteers treated with long‐term HIV‐1 Immunogen (REMUNE®) therapy in Thailand

Abstract

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.

Therapeutic HIV vaccines: An update

“…Overall, the results showed a trend suggesting a delay in the time to reach virologic failure in the Remune arm versus the IFA placebo arm (logrank test: P=0.056). In another open label phase II P2101B study conducted in Thailand in 223 asymptomatic patients, a stabilization of CD4+ and CD8+ T-cell counts, viral load and body weight was noted [33]. However, the results of this open trial were also difficult to interpret since a subgroup of patients was selected by physicians to receive antivirals, whereas the majority of patients remained naïve of antivirals.…”

“…Therefore, a clear demonstration of the proof of concept of the potential benefit of therapeutic immunization in HIV infection is needed. In the last years, besides studies evaluating the immunogenicity of candidate vaccines [21][22][23][24][25][26], studies were designed in order to demonstrate the immunologic efficacy and also the capability of therapeutic immunization to control virus replication either after antiviral discontinuation [27][28][29][30]31•], or during the follow up [32][33][34]. This review highlights the results of some of these recent studies conducted in patients treated early after the primary infection (PHI) or during the chronic phase of the infection.…”

HIV-1 Immunogen: an overview of almost 30 years of clinical testing of a candidate therapeutic vaccine

“…These 223 participants, some of whom had originally been in the IFA placebocontrol group in the parent study, received HIV-1 Immunogen at week 48 (8 weeks following the end of the original study), with repeated immunizations every 12 weeks until week 132. Two reports were published based on this extended phase study; one report considered the participants as a single cohort [35], while the other report subdivided the participants into non-responders and responders based on the latter group's increased CD4 T-cell counts at the end of the 132 weeks compared to baseline (day 1 of the parent study) [36].…”

“…It should be noted that in the report by Chantratita et al in which participants were subdivided into responders (n = 135) and non-responders (n = 88) based on the CD4 T-cell count at the end of the 132 weeks relative to baseline, the controversial AUCMB metric (discussed below), was used for this analysis [36]. According to the study, responders experienced an average increase of 177 CD4 T-cells/μl from baseline, in contrast to the non-responders who experienced an average loss of 180 CD4 T-cells/μl; the mean CD4 T-cell counts at week 132 was significantly different between the two groups (669.54 vs. 414.24 cells/μl for responders and non-responders, respectively; p < 0.001) [36].…”

“…This phase 2 study was followed by a 132-week (from baseline of the parent study) open label, multi-institute, extended, phase 2 study that examined safety, disease progression, and virologic and immunological endpoints in 223 of the original 297 participants [35,36] (Table 1). These 223 participants, some of whom had originally been in the IFA placebocontrol group in the parent study, received HIV-1 Immunogen at week 48 (8 weeks following the end of the original study), with repeated immunizations every 12 weeks until week 132.…”