Serodeconversion of HIV antibody-positive AIDS patients following treatment with V-1 Immunitor.

It is extremely rare when HIV seropositive adult patients experience spontaneous loss of antibodies, that is, seroreversion. The disappearance of HIV antibodies was occasionally attributed to iatrogenic intervention-serodeconversion. Such interventions include: HAART; oral interferon; Chinese herbal remedies; and therapeutic AIDS vaccines derived from pooled blood. Oral therapeutic, alloimmune AIDS vaccine, V-1 Immunitor (V1), was administered to 60000 HIV-positive Thai patients. The administration of V1 resulted in serodeconversion among 23 individuals. The patient group consisted of 9 females (39%) and 14 males (61%) including two 2-year-old boys. The age range was 2-58 years with mean/median 29/29.3 years. Patients were tested seropositive for HIV at least once before being enrolled on V1. The duration of treatment until discovery of seronegative status ranged between 2 weeks and 15 months with average/median 7.2/8 months. Time to seronegativity was correlated with baseline disease stage (R = 0.62; P = .002). The seronegative status was positively associated with V1-induced undetectable or low viral load (R = 0.65; P = .0008). The odds ratio analysis comparing the outcome of our study with published surveys of diagnostic accuracy of laboratory tests suggested that the probability of HIV antibody testing error was remote (P < .000001). The possible causes responsible for this unusual phenomenon are discussed.

Prolonged survival of end-stage AIDS patients immunized with therapeutic HIV vaccine V-1 Immunitor.

Death, rather than surrogate markers, is a single and most straightforward clinical endpoint, defining unequivocally the merit of a therapeutic intervention. As there is still neither a cure for AIDS nor a vaccine to prevent HIV infection, an AIDS diagnosis remains associated with a death sentence. V-1 Immunitor (V1) is an experimental, oral, therapeutic AIDS vaccine licensed as a dietary supplement. As part of a charity program V1 has been offered at Wat Phra Baht Nam Phu--a Buddhist hospice for end-stage AIDS patients. Out of 117 approached individuals, 53 decided to take V1 and 64 declined the treatment. Patients in both groups did not differ in age, gender, or severity of disease. All patients were in WHO terminal stage 4 at study entry and had received similar palliative care. None of the patients had received conventional antiviral drugs. At 9 weeks the last two patients in the non-V1 group died. In contrast, 56.6% (30/53) in the V1 group remained alive. Kaplan-Meier survival analysis showed that median short-term survival time for non-treated and treated patients was 4 and 10 weeks, respectively. The difference was statistically significant by Wilcoxon signed rank test (P=0.000089). Patients who remained alive were followed until the last patient died at 142 weeks. Based on the main outcome, i.e. time to death, patients on V1 had a 15.8 times longer life expectancy than the control group (P<0.000001). Observed results are encouraging and V1 needs to be tested in controlled clinical trials as a life-saving immunotherapy.

Phase II placebo-controlled study of V-1 Immunitor as a therapeutic modality for treatment of HIV.

BACKGROUND: V-1 Immunitor (V1) is an oral AIDS vaccine containing heat- and chemically-inactivated viral antigens derived from pooled blood of HIV-positive donors. V1 has a pending status as an investigational drug but is currently marketed as a dietary supplement. Earlier published, uncontrolled studies of V1 demonstrated body weight gain, increase in T-lymphocyte numbers, decrease in viral load, and improved survival of end-stage AIDS patients. OBJECTIVES AND STUDY DESIGN: In order to substantiate prior observations we have undertaken a placebo-controlled phase II clinical trial involving 47 antiviral therapy naive, asymptomatic individuals who had over 350 mm(3) CD4 T-cells (mean/median 538/480) at study entry. Both placebo and treatment arms were identical demographically and by every clinical parameter measured at baseline. RESULTS AND CONCLUSIONS: At the end of 6-month follow-up 29 volunteers who received V1 b.i.d. had gained on average 43 CD4 T-cells (540 versus 583). This gain was statistically significant (p=0.01) while changes in T-cell numbers in placebo group failed to reach the significance threshold (p=0.33). The clinical potential of V1 is further supported by an elevation in CD4/CD8 ratio among V1 recipients and decline in CD4/CD8 ratio in patients on placebo (0.575 versus 0.524; p=0.02). The average weight gain among patients on V1 was 1.8 kg while placebo group lost 0.5 kg. These results suggest that V1 may delay or reverse the disease progression without any concurrent toxicity and support our prior open-label studies indicating that V1 confers clinical benefit. A phase III clinical study is required to confirm these findings and to allow us to seek license for V1 as a therapeutic AIDS vaccine.

V-1 Immunitor: oral therapeutic AIDS vaccine with prophylactic potential.

V-1 Immunitor (V1) is a therapeutic vaccine comprising pooled HIV antigens formulated into an oral pill. Recent V1 studies demonstrated body weight gain, increase in CD4 and CD8 cells, decrease in viral load, and improved survival of end-stage AIDS patients. The potential of V1 as a prophylactic vaccine has been evaluated in a phase II placebo-controlled trial on 35 volunteers. Twenty HIV-negative volunteers who received V1 b.i.d. for 4 weeks had gained 28.2 and 17.5% in absolute CD4 (825 versus 1058; P=0.007) and CD8 (597 versus 702; P=0.013) cells, while lymphocytes in placebo group did not increase, suggesting that CD4 and CD8 counts may become an easily measurable immune correlate of the efficacy of AIDS vaccines. V1 does not appear to induce HIV-specific antibodies as orally administered immunogens usually produce cell-mediated but not systemic humoral response. V1 as a preventive oral vaccine targeting cellular and mucosal immunity deserves further evaluation.

Mucosal AIDS vaccines.

Debates are still being waged over what is the best strategy for developing a potent AIDS vaccine. All the obvious approaches to making AIDS vaccines have been tried in the past two decades without much success. It is clear that new thinking and a revision of prevailing dogmas needs to be in place if we really want a vaccine. Conventional envelope-based antibody-inducing vaccines do not appear to hold promise, and broadly-neutralizing antibodies are now being searched as an alternative to the failed approach with subunit vaccines. The current consensus is that cellular immune responses, especially those mediated by CD8 cytotoxic/suppressor (CTL) and CD4 helper T lymphocytes, are needed to control HIV. Vaccines capable of inducing cell-mediated responses are, therefore, considered critical for controlling the spread of HIV. DNA-based vaccines triggering CTL reaction are currently thought to be an answer, but will they fulfill the promise? In the following paragraphs, a critical assessment of the state of the art will be provided in an attempt to analyze what we know and still don't know. The focus of this review is primarily on mucosal vaccines-a relatively new area in AIDS research. The update on V-1 Immunitor, the first mucosal AIDS vaccine available commercially, is provided within this context. Some of the reviewed concepts may be disputable, but without departure from the uninspiring consensus no substantial progress in the AIDS vaccine field can be envisioned.