HIV vaccine fails in first large trial; may protect Blacks, Asians only

The long awaited results of the first phase III HIV vaccine study released today show that Vaxgen’s AIDSVax offered no significant protection against HIV infection in the study population as a whole. However the study did show a statistically significant reduction in HIV infections among black and Asian volunteers, which correlated with a higher level of vaccine-induced neutralising antibodies.

AIDSVax was tested in 5,417 volunteers in North America and the Netherlands in a 36 month randomised placebo controlled study. 5,009 volunteers received at least three of the seven scheduled vaccinations.

Study

Demographics

Number of volunteers to complete three immunizations: 5,009
Placebo recipients:  1,679
White volunteers:  4,185
Hispanic volunteers:  326
Non-white volunteers (Black, Asian, Other):  498
Black volunteers:  314
Annual study infection rate  2.7%
Approximate Efficacy (after at least 3 primary doses)
All volunteers:  3.8% (p-value = 0.76; confidence interval: -23% to 24%)
Non-white volunteers: 67% (p-value

Black volunteers:  78% (p-value

Glossary

placebo

A pill or liquid which looks and tastes exactly like a real drug, but contains no active substance.

statistical significance

Statistical tests are used to judge whether the results of a study could be due to chance and would not be confirmed if the study was repeated. If result is probably not due to chance, the results are ‘statistically significant’. 

p-value

The result of a statistical test which tells us whether the results of a study are likely to be due to chance and would not be confirmed if the study was repeated. All p-values are between 0 and 1; the most reliable studies have p-values very close to 0. A p-value of 0.001 means that there is a 1 in 1000 probability that the results are due to chance and do not reflect a real difference. A p-value of 0.05 means there is a 1 in 20 probability that the results are due to chance. When a p-value is 0.05 or below, the result is considered to be ‘statistically significant’. Confidence intervals give similar information to p-values but are easier to interpret. 

sample

Studies aim to give information that will be applicable to a large group of people (e.g. adults with diagnosed HIV in the UK). Because it is impractical to conduct a study with such a large group, only a sub-group (a sample) takes part in a study. This isn’t a problem as long as the characteristics of the sample are similar to those of the wider group (e.g. in terms of age, gender, CD4 count and years since diagnosis).

subtype

In HIV, different strains which can be grouped according to their genes. HIV-1 is classified into three ‘groups,’ M, N, and O. Most HIV-1 is in group M which is further divided into subtypes, A, B, C and D etc. Subtype B is most common in Europe and North America, whilst A, C and D are most important worldwide.

The results appear to suggest that AIDSVax may be more effective in individuals of African origin. All participants were infected with HIV-1 subtype B, so this result does not imply that AIDSVax is more effective against subtypes of HIV found in Africa, Asia and Latin America.

However, Seth Berkley, President of the International AIDS Vaccine Initiative, highlighted the limitations of this finding.

"The results on AIDSVAX must be further analyzed, and independently reviewed. For example, VaxGen's preliminary analysis of the small number of nonwhite volunteers suggests that there were fewer infections among black volunteers who received AIDSVAX than blacks who received the placebo. However, it is difficult to draw conclusions about what this means, given that the number of blacks in the study was so small (VaxGen's analysis is based on just 13 infections among black volunteers, 4 in the vaccine group and 9 in the placebo group).”

Vaxgen says that although the subgroup sample sizes were relatively small compared to the entire study sample, the results are statistically significant.

With regard to ethnic minorities in the trial, there is less than a 1% possibility that the observed difference in infection rates could have occurred by chance”, the company said in its press release. “There is less than a 2% possibility that the observed difference in infection rates among black volunteers could have occurred by chance. In addition to the results in those receiving three doses, the reduction in infection in individuals who received at least one dose of vaccine or placebo were similar and also statistically significant.”