The high-dose influenza vaccine (HDIV) demonstrated a 50% reduction in influenza-like illness (ILI) compared with the standard dose in HIV-infected patients, according to research presented atIDWeek, held virtually from October 21 to 25, 2020.

In a retrospective cohort study, conducted at the University of Kansas Medical Center, included 219 patients with HIV during the 2017-2018 influenza season. The median age was 53 years and 197 patients (89.9%) were men. Within the cohort, 13.7% had a HIV viral load greater than 40 copies/mL and 5% had CD4 count less than 200 cells/µL. HDIV and standard dose influenza vaccines (SDIV) were administered to 119 patients (54.3%) and 77 patients (35.2%), respectively, and 23 patients (10.5%) were unvaccinated.

A modified CDC definition of ILI, defined as fever and cough, sore throat, or shortness of breath occurred in 8 patients (10.4%) in the SDIV group compared with 6 patients (5.0%) in the HDIV group (P =.16). A broader protocol-defined ILI, defined as sore throat, cough, or shortness of breath with either fever, chills, headache, or myalgia was reported in 16 patients (20.8%) and 12 patients (10.1%) of the SDIV and HDIV groups, respectively (P =.04). There was no difference in confirmed influenza cases between groups. Vaccine side effects were mild, occurring in 11 patients (14.3%) in the SDIV group compared with 13 patients (10.9%) in the HDIV group (P =.5). Vaccine dose (SDIV odds ratio [OR], 2.34; 95% CI, 1.04-5.37; P =.04) and age in years (OR, 0.97; 95% CI, 0.94-1.0; P =.045) were associated with protocol-defined ILI. HDIV remained protective regardless of age.

The CDC reported an influenza attack rate of 14.7% in US adults and an overall vaccine effectiveness of 38% for the 2017-2018 influenza season. This study “demonstrated a 50% relative reduction in protocol-defined ILI with the HDIV compared [with] standard-dose vaccine our HIV clinic in 2017-2018,” study authors concluded. Investigators, therefore, recommended a larger prospective randomized control trial on the effectiveness of the HDIV in HIV patients.

Disclosure: One study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of author’s disclosures.

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Bioinformatically designed mosaic antigens increase the breadth of HIV vaccine-elicited immunity. This study compared the safety, tolerability, and immunogenicity of a newly developed, tetravalent Ad26 vaccine with the previously tested trivalent formulation.
This randomised, parallel-group, placebo-controlled, double-blind, phase 1/2a study (TRAVERSE) was done at 11 centres in the USA and one centre in Rwanda. Eligible participants were adults aged 18 to 50 years, who were HIV-uninfected, healthy at screening based on their medical history and a physical examination including laboratory assessment and vital sign measurements, and at low risk of HIV infection in the opinion of study staff, who applied a uniform definition of low-risk guidelines that was aligned across sites. Enrolled participants were randomly assigned at a 2:1 ratio to tetravalent and trivalent groups. Participants in tetravalent and trivalent groups were then further randomly assigned at a 5:1 ratio to adenovirus 26 (Ad26)-vectored vaccine and placebo subgroups. Randomisation was stratified by region (USA and Rwanda) and based on a computer-generated schedule using randomly permuted blocks prepared under the sponsor’s supervision. We masked participants and investigators to treatment allocation throughout the study. On day 0, participants received a first injection of tetravalent vaccine (Ad26.Mos4.HIV or placebo) or trivalent vaccine (Ad26.Mos.HIV or placebo), and those injections were repeated 12 weeks later. At week 24, vaccine groups received a third dose of tetravalent or trivalent together with clade C gp140, and this was repeated at week 48, with placebos again administered to the placebo group. All study vaccines and placebo were administered by intramuscular injection in the deltoid muscle. We assessed adverse events in all participants who received at least one study injection (full analysis set) and Env-specific binding antibodies in all participants who received at least the first three vaccinations according to the protocol-specified vaccination schedule, had at least one measured post-dose blood sample collected, and were not diagnosed with HIV during the study (per-protocol set). This study is registered with Clinicaltrials.gov, NCT02788045.
Of 201 participants who were enrolled and randomly assigned, 198 received the first vaccination: 110 were in the tetravalent group, 55 in the trivalent group, and 33 in the placebo group. Overall, 185 (93%) completed two scheduled vaccinations per protocol, 180 (91%) completed three, and 164 (83%) completed four. Solicited, self-limiting local, systemic reactogenicity and unsolicited adverse events were similar in vaccine groups and higher than in placebo groups. All participants in the per-protocol set developed clade C Env binding antibodies after the second vaccination, with higher total IgG titres after the tetravalent vaccine than after the trivalent vaccine (10 413 EU/mL, 95% CI 7284-14 886 in the tetravalent group compared with 5494 EU/mL, 3759-8029 in the trivalent group). Titres further increased after the third and fourth vaccinations, persisting at least through week 72. Other immune responses were also higher with the tetravalent vaccine, including the magnitude and breadth of binding antibodies against a cross-clade panel of Env antigens, and the magnitude of IFNγ ELISPOT responses (median 521 SFU/10 peripheral blood mononuclear cells [PBMCs] in the tetravalent group and median 282 SFU/10 PBMCs in the trivalent group after the fourth vaccination) and Env-specific CD4+ T-cell response rates after the third and fourth vaccinations. No interference by pre-existing Ad26 immunity was identified.
The tetravalent vaccine regimen was generally safe, well-tolerated, and found to elicit higher immune responses than the trivalent regimen. Regimens that use this tetravalent vaccine component are being advanced into field trials to assess efficacy against HIV-1 infection.
National Institutes of Health, Henry M Jackson Foundation for Advancement of Military Medicine and the US Department of Defense, Ragon Institute of MGH, MIT, & Harvard, Bill & Melinda Gates Foundation, and Janssen Vaccines & Prevention.

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In another setback in the long quest to prevent HIV infection, a trial in South Africa has been shut down because an experimental vaccine was not working, federal health officials announced Monday.

The trial, which began in 2016, followed one in Thailand that ended in 2009. That vaccine offered only modest protection against infection. Experts argued over how much, but the vaccine was no more than 30% protective.

Nonetheless, it was the only vaccine that had appeared to work at all.

“We hoped this vaccine candidate would work — regrettably, it does not,” said Dr Anthony S. Fauci, director of the National Institute for Allergy and Infectious Diseases, which conducted the trial.

A vaccine against HIV, the virus that causes AIDS, is sorely needed. Even now, nearly 40 years after the start of the epidemic, 1.7 million people are newly infected each year — most of them in Africa, especially southern Africa, according to UNAIDS, the United Nations’ AIDS-fighting agency.

The trial — known as HVTN 702 but nicknamed Uhambo, which means “journey” in Zulu — included 5,407 young adult men and women in South Africa.

Last month, a safety-monitoring panel looked at early results and found there were 123 infections among participants who got a placebo injection and 129 among those who got the vaccine.

That clearly indicated that the vaccine was not protective but did not mean it was making participants more vulnerable to HIV, scientists said. A difference of just six infections in so large a pool of participants could have been due to chance.

The Uhambo vaccine had to be significantly changed from the one tested in Thailand because South Africa has a different dominant strain of HIV.

The vaccine used canarypox, a bird virus that can infect human cells but cannot multiply in them, to deliver into the body a protein found on the outer envelope of HIV The immune system learns to recognize the protein and to make protective antibodies to it.

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