Background:  Since 1994, the French National Agency for AIDS Research (ANRS) has developed HIV-1 lipopeptides for use as candidate vaccine against HIV. A case of myelitis occurring in 1 volunteer of HVTN042/ANRS VAC019 trial and previously reported uveitis in 2 French volunteers triggered the need of a global review of clinical safety of HIV lipopeptides.

Methods:  A meta-analysis to examine clinical safety data collected during the 10 ANRS clinical trials using HIV-1 lipopeptides (8 preventive and 2 therapeutic trials) conducted in France between 1996 and 2005. Five different lipopeptide constructs were tested alone or in combination with recombinant canarypox HIV vaccines or with an immunological adjuvant (QS21) and with different diluents. Specific focus on events that could constitute symptoms of an ophthalmological or neurological complication of lipopeptide vaccination.

Results:  Of 248 trial participants, only 7 did not complete follow-up among the 200 healthy volunteers (3 refusals, 1 for local reaction, 1 for arthralgia, and 2 for health changes not related to vaccination) and 1 among the 48 HIV-1-infected patients. During the 354 person-years of follow-up, 860 lipopeptide injections were administered. Local reactions were common. However, without adjuvant and with an appropriate diluent, none of the vaccinees experienced severe local response. Systemic reactions were mild and transient. The most common systemic adverse effects were asthenia (21.1%), fever (16.9%), and headache (21.5%). No grade 4 reaction was reported, and only 18 subjects experienced grade 3 systemic events related to the vaccination mainly asthenia, fever, headache, and arthralgia. Multivariate analysis showed that female gender, number of injections, and diluent (more reactions in 5% glucose alone than in combination with Tris-HCl buffer) increased significantly systemic reactions related to the vaccination. Specific review of ophthalmological events (23 in 19 volunteers; 6 in 4 patients) and neurological events (89 in 50 volunteers; 15 in 13 patients) showed that, except 1 case of anterior uveitis for which a relationship could not be eliminated, there was no other symptom suggestive of an ophthalmological or neurological complication attributable to lipopeptide vaccination.

Conclusions:  These data support that reactogenicity and systemic safety of HIV lipopeptide vaccines are acceptable both in healthy volunteers and HIV-infected adults.