Therapeutics
IIV3 reduced flu in HIVⴚ pregnant women and infants, and in HIV+ pregnant women but not their infants 多多多多多多夞
Clinical impact ratings:
多多多多多夞夞
Madhi SA, Cutland CL, Kuwanda L, et al; Maternal Flu Trial (Matflu) Team. Influenza vaccination of pregnant women and protection of their infants. N Engl J Med. 2014;371:918-31.
多多多多多夞夞
Question
Conclusion
In HIV+ and HIV⫺ pregnant women, is the trivalent inactivated influenza vaccine (IIV3) effective and safe?
Trivalent inactivated influenza vaccine (IIV3) reduced confirmed influenza in HIV⫺ mothers and their infants, and HIV+ mothers but not their infants.
Methods Design: 2 randomized placebo-controlled trials (Influenza Vaccine Trial in HIV Uninfected Pregnant Women [MatfluHIVneg] and Influenza Vaccination of HIV Infected Pregnant Women: Safety and Immunogenicity [MatfluHIVpos]). ClinicalTrials.gov NCT01306669 and NCT01306682. Allocation: {Concealed}*.† Blinding: Blinded† (patients, clinicians, data collectors, outcome assessors, and {data safety committee}*). Follow-up period: 24 weeks after birth. Setting: 4 antenatal clinics in Soweto, South Africa. Patients: Black African pregnant women 18 to 38 years of age who were at 20 to 36 weeks of gestation. Exclusion criteria included receipt of IIV3 during the current influenza season or licensed vaccine or unlicensed agent in the past 28 days; acute illness or fever in the past day; use of steroids or immune mediators, immunoglobulin or other blood products, or anticancer systemic chemotherapy or radiation therapy within specified periods; uncontrolled major psychiatric disorder; or pregnancy complications. 194 HIV+ women (mean age 28 y) who did not have World Health Organization clinical AIDS category 3 or 4, and 2116 HIV⫺ women (mean age 26 y) met the selection criteria. Intervention: IIV3 (n = 1062 HIV⫺, 100 HIV+) or placebo (n = 1054 HIV⫺, 94 HIV+). Outcomes: Primary outcome was confirmed influenza in the HIV⫺ study. Secondary outcomes included influenza-like illness (ILI) and adverse events. Immunogenicity outcomes (primary outcome in the HIV+ study) are not reported here because follow-up for these outcomes was < 80%. Patient follow-up: 92% of HIV⫺ mothers and infants and {84% of HIV+ mothers and infants}* for confirmed influenza and ILI (intention-to-treat analysis).
Main results IIV3 reduced confirmed influenza, but not ILI, compared with placebo in HIV⫺ women and their infants (Table). IIV3 reduced risk for confirmed influenza in HIV+ women (relative risk reduction 58%, 95% CI 0.2 to 82), but not in their infants (P = 0.60). In both studies, the IIV3 group had more injection-site reactions than the placebo group, but groups did not differ for miscarriage, stillbirth, or premature birth.
*Information provided by author. †See Glossary. Sources of funding: Bill and Melinda Gates Foundation and 3 other agencies. For correspondence: Dr. S.A. Madhi, e-mail [email protected]; or Dr. M.C. Nunes, e-mail [email protected].
Commentary The randomized controlled trial (RCT) by Madhi and colleagues shows that vaccination for seasonal influenza is as effective for second- and third-trimester pregnant HIV⫺ women and their infants as it is in the general adult population: about 50% (1, 2). The flu shot was protective in HIV+ mothers, but the study was not powered to address efficacy in their infants. Seroconversion rates are about 2 times higher in HIV⫺ women and infants than in HIV+ women and their infants. 56 HIV⫺ pregnant women would need to be vaccinated to prevent 1 additional mother from becoming infected with influenza through 24 weeks postpartum. Whether 56 is “too many” is a value-based judgment, which only a patient can make; it is not an ethical question. This study supports our clinical practice of emphasizing respiratory hygiene, with optional flu vaccination for our HIV− women. 11 HIV+ pregnant women would need to be vaccinated to prevent 1 additional woman from being infected with influenza, but whether vaccination would benefit her infant remains to be established. In developing countries, the decision to offer influenza vaccination to pregnant HIV⫺ women depends on the cost-effectiveness ratio (CER): If the CER is < 3 times a country's gross domestic product per capita, it could be considered cost-effective (3). With the cost of the vaccine at half of the cost charged in the USA (4), vaccine efficacy of about 50%, and seroconversion rates for the 3 strains in HIV⫺ women < 100%, a CER is unlikely to be favorable. The double-blind RCT by Madhi and colleagues, with confirmed reverse transcriptase PCR identification of influenza outcomes in pregnant women, supports the findings of previous studies (2, 5). Luz M. Fernandez, MD Renee V. Girdler, MD R. Brent Wright, MD, MMM Diane M. Harper, MD, MPH, MS University of Louisville Louisville, Kentucky, USA
Trivalent inactivated influenza vaccine (IIV3) vs placebo during pregnancy in HIVⴚ women‡
References
Group
1. Jackson LA, Gaglani MJ, Keyserling HL, et al. Safety, efficacy, and immunogenicity of an inactivated influenza vaccine in healthy adults: a randomized, placebo-controlled trial over two influenza seasons. BMC Infect Dis. 2010;10:71.
Women
Outcomes
Influenza§ Influenza-like illness
Infants
Influenza§
Event rates IIV3
Placebo
1.8%
3.6%
16.5%
17.2%
1.9%
3.6%
At 24 wk after birth RRR (95% CI) 50% (15 to 71)
58%
57%
56 (31 to 223)
4% (⫺16 to 21) Not significant 49% (12 to 70)
RRI (CI) Influenza-like illness
NNT (CI)
1.6% (⫺6 to 9)
57 (31 to 275)
NNH Not significant
‡Abbreviations defined in Glossary. NNT and CI calculated from event rates in article.
2. Jefferson T, Di Pietrantonj C, Rivetti A, et al. Vaccines for preventing influenza in healthy adults. Cochrane Database Syst Rev. 2014;3:CD001269. 3. WHO (2001) Macroeconomics and health: investing in health for economic development. Report of the Commission on Macroeconomics and Health. http://whqlibdoc.who.int/publications/2001/924154550x.pdf (accessed 4 Dec 2014). 4. Vaccines for Children Program (VFC).www.cdc.gov/vaccines/programs/vfc/ awardees/vaccine-management/price-list/ (accessed 4 Dec 2014). 5. Mak TK, Mangtani P, Leese J, Watson JM, Pfeifer D. Influenza vaccination in pregnancy: current evidence and selected national policies. Lancet Infect Dis. 2008;8:44-52.
§Confirmed by reverse transcriptase polymerase chain reaction.
姝 2015 American College of Physicians JC6 ACP Journal Club Downloaded From: http://annals.org/ by a Penn State University Hershey User on 05/27/2015
Annals of Internal Medicine
17 February 2015
IIV3 reduced flu in HIVⴚ pregnant women and infants, and in HIV+ pregnant women but not their infants 多多多多多多夞
Clinical impact ratings:
多多多多多夞夞
Madhi SA, Cutland CL, Kuwanda L, et al; Maternal Flu Trial (Matflu) Team. Influenza vaccination of pregnant women and protection of their infants. N Engl J Med. 2014;371:918-31.
多多多多多夞夞
Question
Conclusion
In HIV+ and HIV⫺ pregnant women, is the trivalent inactivated influenza vaccine (IIV3) effective and safe?
Trivalent inactivated influenza vaccine (IIV3) reduced confirmed influenza in HIV⫺ mothers and their infants, and HIV+ mothers but not their infants.
Methods Design: 2 randomized placebo-controlled trials (Influenza Vaccine Trial in HIV Uninfected Pregnant Women [MatfluHIVneg] and Influenza Vaccination of HIV Infected Pregnant Women: Safety and Immunogenicity [MatfluHIVpos]). ClinicalTrials.gov NCT01306669 and NCT01306682. Allocation: {Concealed}*.† Blinding: Blinded† (patients, clinicians, data collectors, outcome assessors, and {data safety committee}*). Follow-up period: 24 weeks after birth. Setting: 4 antenatal clinics in Soweto, South Africa. Patients: Black African pregnant women 18 to 38 years of age who were at 20 to 36 weeks of gestation. Exclusion criteria included receipt of IIV3 during the current influenza season or licensed vaccine or unlicensed agent in the past 28 days; acute illness or fever in the past day; use of steroids or immune mediators, immunoglobulin or other blood products, or anticancer systemic chemotherapy or radiation therapy within specified periods; uncontrolled major psychiatric disorder; or pregnancy complications. 194 HIV+ women (mean age 28 y) who did not have World Health Organization clinical AIDS category 3 or 4, and 2116 HIV⫺ women (mean age 26 y) met the selection criteria. Intervention: IIV3 (n = 1062 HIV⫺, 100 HIV+) or placebo (n = 1054 HIV⫺, 94 HIV+). Outcomes: Primary outcome was confirmed influenza in the HIV⫺ study. Secondary outcomes included influenza-like illness (ILI) and adverse events. Immunogenicity outcomes (primary outcome in the HIV+ study) are not reported here because follow-up for these outcomes was < 80%. Patient follow-up: 92% of HIV⫺ mothers and infants and {84% of HIV+ mothers and infants}* for confirmed influenza and ILI (intention-to-treat analysis).
Main results IIV3 reduced confirmed influenza, but not ILI, compared with placebo in HIV⫺ women and their infants (Table). IIV3 reduced risk for confirmed influenza in HIV+ women (relative risk reduction 58%, 95% CI 0.2 to 82), but not in their infants (P = 0.60). In both studies, the IIV3 group had more injection-site reactions than the placebo group, but groups did not differ for miscarriage, stillbirth, or premature birth.
*Information provided by author. †See Glossary. Sources of funding: Bill and Melinda Gates Foundation and 3 other agencies. For correspondence: Dr. S.A. Madhi, e-mail [email protected]; or Dr. M.C. Nunes, e-mail [email protected].
Commentary The randomized controlled trial (RCT) by Madhi and colleagues shows that vaccination for seasonal influenza is as effective for second- and third-trimester pregnant HIV⫺ women and their infants as it is in the general adult population: about 50% (1, 2). The flu shot was protective in HIV+ mothers, but the study was not powered to address efficacy in their infants. Seroconversion rates are about 2 times higher in HIV⫺ women and infants than in HIV+ women and their infants. 56 HIV⫺ pregnant women would need to be vaccinated to prevent 1 additional mother from becoming infected with influenza through 24 weeks postpartum. Whether 56 is “too many” is a value-based judgment, which only a patient can make; it is not an ethical question. This study supports our clinical practice of emphasizing respiratory hygiene, with optional flu vaccination for our HIV− women. 11 HIV+ pregnant women would need to be vaccinated to prevent 1 additional woman from being infected with influenza, but whether vaccination would benefit her infant remains to be established. In developing countries, the decision to offer influenza vaccination to pregnant HIV⫺ women depends on the cost-effectiveness ratio (CER): If the CER is < 3 times a country's gross domestic product per capita, it could be considered cost-effective (3). With the cost of the vaccine at half of the cost charged in the USA (4), vaccine efficacy of about 50%, and seroconversion rates for the 3 strains in HIV⫺ women < 100%, a CER is unlikely to be favorable. The double-blind RCT by Madhi and colleagues, with confirmed reverse transcriptase PCR identification of influenza outcomes in pregnant women, supports the findings of previous studies (2, 5). Luz M. Fernandez, MD Renee V. Girdler, MD R. Brent Wright, MD, MMM Diane M. Harper, MD, MPH, MS University of Louisville Louisville, Kentucky, USA
Trivalent inactivated influenza vaccine (IIV3) vs placebo during pregnancy in HIVⴚ women‡
References
Group
1. Jackson LA, Gaglani MJ, Keyserling HL, et al. Safety, efficacy, and immunogenicity of an inactivated influenza vaccine in healthy adults: a randomized, placebo-controlled trial over two influenza seasons. BMC Infect Dis. 2010;10:71.
Women
Outcomes
Influenza§ Influenza-like illness
Infants
Influenza§
Event rates IIV3
Placebo
1.8%
3.6%
16.5%
17.2%
1.9%
3.6%
At 24 wk after birth RRR (95% CI) 50% (15 to 71)
58%
57%
56 (31 to 223)
4% (⫺16 to 21) Not significant 49% (12 to 70)
RRI (CI) Influenza-like illness
NNT (CI)
1.6% (⫺6 to 9)
57 (31 to 275)
NNH Not significant
‡Abbreviations defined in Glossary. NNT and CI calculated from event rates in article.
2. Jefferson T, Di Pietrantonj C, Rivetti A, et al. Vaccines for preventing influenza in healthy adults. Cochrane Database Syst Rev. 2014;3:CD001269. 3. WHO (2001) Macroeconomics and health: investing in health for economic development. Report of the Commission on Macroeconomics and Health. http://whqlibdoc.who.int/publications/2001/924154550x.pdf (accessed 4 Dec 2014). 4. Vaccines for Children Program (VFC).www.cdc.gov/vaccines/programs/vfc/ awardees/vaccine-management/price-list/ (accessed 4 Dec 2014). 5. Mak TK, Mangtani P, Leese J, Watson JM, Pfeifer D. Influenza vaccination in pregnancy: current evidence and selected national policies. Lancet Infect Dis. 2008;8:44-52.
§Confirmed by reverse transcriptase polymerase chain reaction.
姝 2015 American College of Physicians JC6 ACP Journal Club Downloaded From: http://annals.org/ by a Penn State University Hershey User on 05/27/2015
Annals of Internal Medicine
17 February 2015
