- French healthy volunteers participating in 17 clinical trials, to assess preventive HIV vaccine candidates, had a sustained high commitment to research, a high retention rate but no increase in risky behaviours in the post-vaccination period.
- HIV vaccine candidates are well tolerated, with no increased incidence of breast cancer, herpes zoster infection, or mortality and no deaths due to clinical adverse events (AEs) were classified as probably related to the vaccines.
- Vaccine-induced seropositivity may persist for more than 23 years after receiving recombinant HIV-1 envelope protein (rgp160).
Safety and immunogenicity of preventive HIV vaccine candidates have been evaluated by different phase I/II trials worldwide. Seventeen trials assessing HIV envelope protein, canarypox vectors, lipopeptides and other vaccines, conducted by the French National Agency for Research on AIDS and Viral Hepatitis (ANRS), evidenced one case of uveitis and one of a neurological symptom. Thus, authors of this study wanted to investigate the occurrence of AEs in the ANRS COV1-COHVAC cohort, a long-term safety cohort of 496 healthy volunteers who received at least one dose of a vaccine candidate (1992-2007).
Between 2008 and 2013, 488 volunteers were included (median age at baseline was 41 years for men and 45.5 years for women): 355 (72.7%) and 133 (27.3%) consented to the prospective/retrospective and to the retrospective collection of data, respectively.
270 (76%) participants completed the follow-up. In 2016, due to the absence of a safety signal, the study was terminated. The total follow-up after the first vaccination was 4,934 person-years and the median duration was 9.6 years (interquartile ranges 5.4-14.2).
Investigation of grade 3/4 AEs and all grade AEs suggestive of neurological, ophthalmological and immune disorders (including migraine, sciatica, carpal tunnel syndrome, cervical radiculopathy, cataract, and glaucoma) showed that none of the relevant AEs was considered as possibly related to the vaccine.
Breast cancer incidence (the most common cancer in women in France) and female mortality did not differ from those of the general French population (Standardised Incidence Ratio=1.47, P=0.45, and Standardised Mortality Ratio=0.65, P=0.28) while male mortality was significantly lower (Standardised Mortality Ratio=0.26, P=0.0003). No increased incidence rates of herpes zoster infection were observed in participants (male or female) compared to the French population.
At the last follow-up visit, only participants who received rgp160 had a positive HIV serology: 21/29 (72%) volunteers still showed vaccine-induced seropositivity after a median follow-up of 23.6 years (range 17.6-24.3).
Only one case of HIV infection occurred during the follow-up and few volunteers reported risky sexual practices (men: 20/192, women: 2/162).
Limitations: absence of control subjects; potential vaccine-associated AEs are rare; vaccine-induced antibodies were not characterised.