H1N1 in people with HIV: severity of disease generally unaffected, vaccine responses may be blunted

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Several studies on H1N1 vaccines and clinical outcomes in people with HIV were presented as posters and in a discussion session Friday at the 17th Conference on Retroviruses and Opportunistic Infections (CROI). The H1N1 vaccine studies have found them to be generally safe but not always fully protective in patients with HIV. Patients with HIV who contract swine flu generally appear to fare comparably to HIV-negatives, but the impact may be worse in those with low CD4 counts or who have other opportunistic infections.

Does HIV worsen H1N1 infection?

Two studies presented here found that HIV status generally had little impact on the severity or outcome of H1N1 infection, although low CD4 counts may increase the risk of worse outcomes and opportunistic infections may complicate diagnosis.

Esteban Martinez and researchers at the IDIBAPS hospital clinic in Barcelona compared 56 HIV-positive adults with 168 randomly chosen HIV-negative controls, all diagnosed with H1N1 at their clinic. The patients with HIV had comparable or better symptoms and outcomes, with fewer diagnoses of pneumonia (9% vs 25%, p=.01) and lung failure (9% vs 21%, p=.03), fewer day-or-longer hospital stays (27% vs 42%, p=.047), greater chance of receiving oseltamivir treatment (95% vs 71%, p=.0003), and greater rate of clinical recovery within a week (77% vs 56%, p=.0056). There was no difference in mortality or in risk of other complications during admission.

Gustavo Reyes-Terán and team at a Mexico City respiratory diseases hospital analysed records of 22 HIV-positive patients with H1N1, finding more serious outcomes in HIV-positive patients with low CD4 cell counts, with opportunistic infections (OIs), or who were not on ART. The chance of requiring hospitalisation was much higher in those with an OI (OR>24.5, p=0.0004) and lower with successful ART (OR=0.1, p=0.03). The researchers noted that overlapping H1N1 and respiratory OI symptoms could complicate diagnosis and delay the start of appropriate treatment.

Glossary

opportunistic infection (OI)

An infection that occurs more frequently or is more severe in people with weakened immune systems, such as people with low CD4 counts, than in people with healthy immune systems. Opportunistic infections common in people with advanced HIV disease include Pneumocystis jiroveci pneumonia; Kaposi sarcoma; cryptosporidiosis; histoplasmosis; other parasitic, viral, and fungal infections; and some types of cancer. 

adjuvant

A substance used in conjunction with another to enhance its activity. For example, a substance administered with a vaccine that increases the effectiveness of the vaccine.

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. 

titre

A laboratory measurement of the amount, or concentration, of a given component in solution.

 

immune response

The immune response is how your body recognises and defends itself against bacteria, viruses and substances that appear foreign and harmful, and even dysfunctional cells.

In patients with HIV, H1N1 disease appeared to take longer to develop after infection, and H1N1 virus continued to shed for a longer time during treatment with oseltamivir.

How effective is the H1N1 vaccine?

Several studies investigated the effectiveness of various formulations of H1N1 vaccine in individuals with HIV infection. The vaccine was generally safe, but the immune responses were not always strong enough to protect against infection.

Odele Launay presented positive findings from a French trial which tested a single dose of influenza A H1N1v 2009 vaccine in 300 HIV-positive patients on or off ART, randomised to receive vaccine with or without the adjuvant AS03A. (An adjuvant is a substance sometimes added to vaccines to trigger a stronger immune response.) Three weeks after vaccination, the unadjuvanted vaccine generated protective responses (antibody titres of 1:40 or above) in 77%, and the adjuvanted vaccine in 95.3%. (The threshold required for meeting European regulatory acceptance is 70%.) Side effects were mostly mild to moderate, with no effect on CD4 cell count or viral load.

However, several other studies found lower rates of protective response. In a US trial (Tebas), the H1N1 2009 vaccine was tested in 120 HIV-positive individuals, most of whom were on suppressive therapy with undetectable viral loads. Three weeks after vaccination, 69% had developed a protective response (titres ≥ 1:40). However, roughly one in four already had protective levels of H1N1 antibody before the vaccine was administered, presumably due to prior exposure to the virus. When these were excluded, the response rate dropped to 61% in those who did not have protective antibodies pre-vaccination.

A newly developed split-virion vaccine (A/California/7/2009) was protective in 69% of 160 HIV-positive people vaccinated in a study by Bickel et al. Patients with protective responses had higher median CD4 cell counts (532 vs 475 cells/mm3, p=.03), slightly younger (median 45.1 vs 45.8, p=.04), and had more likely received the 2009 H5N1 flu (not seasonal flu) vaccination (25% vs. 8%, p=.009).

Investigators in the above studies concluded that higher doses, additional doses, or different formulations might be needed to induce protection in enough vaccine recipients.

Several other trials conducted by the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) found good safety responses in HIV-positive pregnant women (Nachman) after two doses of the Novartis inactivated H1N1 vaccine, and in perinatally infected children and adolescents (Flynn) after two doses of Novartis Influenza A (H1N1) 2009 vaccine. No cases of Guillain-Barré syndrome were reported in either study; two possibly vaccine-related Grade 3 adverse events were seen in 155 vaccinated children. Effectiveness data will be presented as the studies continue.

Further information

You can view the abstracts from this session on the official conference website.

You can also view a webcast and slides of this session on the official conference website.

References

Martinez E et al. 2009 H1N1 virus infection in HIV+ adults. 17th Conference on Retroviruses and Opportunistic Infections, poster abstract 802LB. San Francisco, 2010.

Reyes-Terán G et al. Clinical features of subjects infected with HIV and H1N1 influenza virus. 17th Conference on Retroviruses and Opportunistic Infections, poster abstract 803LB. San Francisco, 2010.

Launay O et al. Immunogenicity of one dose of influenza A H1N1v 2009 vaccine formulated with and without AS03A-adjuvant in HIV+ adults: preliminary report of the ANRS 151 randomized HIFLUVAC trial. 17th Conference on Retroviruses and Opportunistic Infections, poster abstract 804LB. San Francisco, 2010.

Bickel M et al. Low rate of immunoresponse to the novel split virion, inactivated, adjuvanted pandemic H1N1 influenza vaccine in HIV-1-infected patients. 17th Conference on Retroviruses and Opportunistic Infections, poster abstract 805LB. San Francisco, 2010.

Tebas P et al. Poor immunogenicity of the H1N1 2009 vaccine in well controlled HIV-infected individuals: interim results of an immunogenicity trial. . 17th Conference on Retroviruses and Opportunistic Infections, poster abstract 806LB. San Francisco, 2010.

Nachman S et al. Safety of an inactivated H1N1 2009 H1N1 vaccine in HIV-1-infected pregnant women, IMPAACT P1086.17th Conference on Retroviruses and Opportunistic Infections, poster abstract 808LB. San Francisco, 2010.

Flynn P et al. 2009 H1N1 immunization in HIV-1 perinatally infected children and youth .17th Conference on Retroviruses and Opportunistic Infections, poster abstract 809LB. San Francisco, 2010.