Safety and immunogenicity of a monovalent 2009 influenza A/H1N1v vaccine adjuvanted with AS03A or unadjuvanted in HIV-infected adults: a randomized, controlled trial

Abstract

Background: Human immunodeficiency virus (HIV)-infected patients have decreased immune response to vaccines. Few data are available about pandemic flu vaccination in this population.

Methods: We conducted a multicenter, patient-blinded, randomized trial in a cohort of HIV-infected adults. Patients received 2 injections 21 days apart of a AS03(A)-adjuvanted H1N1v vaccine containing 3.75 μg hemagglutinin (HA) or a nonadjuvanted H1N1v vaccine containing 15 μg HA to assess hemagglutination inhibition (HI) response and safety.

Results: A total of 309 patients were randomized, and 306 were vaccinated. After the first vaccine dose, HI titers ≥1:40 were observed in 93.4% of the patients in the adjuvanted group (A group) (n = 155) and in 75.5% in the nonadjuvanted group (B group) (n = 151) (P < .001); seroconversion rates were 88.8% and 71.2%, and factor increases in geometric mean titers (GMT) of 21.9 and 15.1, respectively. After 2 injections, 98.6% of patients of the A group and 92.1% of the B group demonstrated HI titers ≥1:40 (P = .018); seroconversion rates were 96.5% and 87.1%, respectively, and factor increases in GMT were 45.5 and 21.2, respectively. The majority of adverse events were mild to moderate in severity; no impact on CD4+ cell count or viral load has been detected.

Conclusions: In HIV-1-infected adults, the AS03(A)-adjuvanted H1N1v vaccine yielded a higher immune response than did the nonadjuvanted one, with no impact on HIV infection.

Figure 1.

Participant disposition of the HIFLUVAC (HIV InFLUenza VACcine) trial. HIV, human immunodeficiency virus.

Figure 2.

Solicited reports of adverse events 21 days after the first dose and second dose of the H1N1 vaccine. Patients with at least 1 vaccine-related adverse event are reported. Severity of vaccine-related adverse events was graded as mild (mild or transient discomfort, without limitation of normal daily activities, and no medical intervention or corrective treatment required), moderate (mild to moderate limitation of normal daily activities and minimal medical intervention or corrective treatment required), or severe (marked limitation of normal daily activities, medical intervention and corrective treatment required, and possible hospitalization), except for erythema and edema at the injection site, which was graded on the basis of a measurement of the diameter of the local reaction (mild, 0–50 mm; moderate, 50–100 mm; severe, >100 mm). ^*Other severe systemic reactions in the adjuvanted vaccine group after receipt of the first dose: oral herpes, rhinorrhea, and arthralgia, with 1 patient who reported multiple events (arthralgia, shivering, rhinorrhea, back pain, abdominal pain, cough, dyspnea, nasal congestion, and pharyngolaryngeal pain; day 1 to day 10); other severe systemic reactions in the nonadjuvanted vaccine group: arthralgia, cough, and hot flash. †Other severe systemic reactions in the adjuvanted vaccine group after receipt of the second dose: arthralgia in 2 patients, shivering; other severe systemic reactions in the nonadjuvanted vaccine group: shivering. Adj, AS03_A-adjuvanted vaccine group; N, nonadjuvanted-vaccine group; NA, not available.