Immune response after two doses of the novel split virion, adjuvanted pandemic H1N1 influenza A vaccine in HIV-1-infected patients. Influenzavirus infection is a primary cause of febrile respiratory illness in HIV-infected adults, despite vaccination. H1N1pdm09 Adjuvanted Vaccination in HIV-Infected Adults: A Randomized Trial of Two Single versus Two Double Doses HIV virological suppression influences response to the AS03-adjuvanted monovalent pandemic influenza A H1N1 vaccine in HIV-infected children Cross-reactivity to highly pathogenic avian influenza H5N1 viruses after vaccination with nonadjuvanted and MF59-adjuvanted influenza A/Duck/Singapore/97 (H5N3) vaccine: a potential priming strategy. Efficacy of Influenza Vaccination in HIV-Infected Persons Antibody responses and HIV-1 viral load in HIV-1-seropositive subjects immunised with either the MF59-adjuvanted influenza vaccine or a conventional non-adjuvanted subunit vaccine during highly active antiretroviral therapy. Long-term immunogenicity of two doses of 2009 A/H1N1v vaccine with and without AS03A adjuvant in HIV-1-infected adults Safety and Immunogenicity of Conventional Subunit and MF59-adjuvanted Influenza Vaccines in Human Immunodeficiency Virus-1-seropositive Patients Safety and Immunogenicity of Two Influenza Virus Subunit Vaccines, with or without MF59 Adjuvant, Administered to Human Immunodeficiency Virus Type 1-Seropositive and -Seronegative Adults Safety and immunogenicity of a monovalent 2009 influenza A/H1N1v vaccine adjuvanted with AS03A or unadjuvanted in HIV-infected adults: a randomized, controlled trial. Pandemic influenza A/H1N1 vaccine administered sequentially or simultaneously with seasonal influenza vaccine to HIV-infected children and adolescents. Safety and immunogenicity of a monovalent MF59®-adjuvanted A/H1N1 vaccine in HIV-infected children and young adults.
BACKGROUND To determine the rate of seroconversion after 2 doses of a novel split virion , inactivated , adjuvanted p and emic H1N1 influenza vaccine ( A/California/7/2009 ) in human immunodeficiency virus type 1 (HIV-1)-infected patients ( Clinical Trials.gov NCT01017172 ) . METHODS Diagnostic study of adult HIV-1-infected patients scheduled for H1N1 influenza A vaccination .  Blood sample s where taken before and 21 days after the first dose and 21 days after the second dose of the vaccine . Antibody ( AB ) titers were determined by hemagglutination inhibition assay . Seroconversion was defined by either an AB titer ≤ 1:10 before and ≥ 1:40 after or ≥ 1:10 before and a ≥ 4-fold increase in AB titer 21 days after vaccination . RESULTS One hundred thirty-five patients received 2 doses of the H1N1 vaccine and were analyzed . The rate of seroconversion was 68.2 % ( 95 % confidence interval , 59.6 - 75.9 ) after the first dose and 91.9 % ( 95 % confidence interval , 85.9 - 95.9 ) after the second dose . Patients who did not seroconvert had a lower mean nadir CD4 cell count ( ± st and ard deviation ; 81 ± 99 vs 190 ± 148 cells/μL ; P = .006 ) , had a longer duration of HIV infection ( ± st and ard deviation ; 13.1 ± 5.9 vs 8.8 ± 6.8 years ; P = .04 ) , and were more likely to have an AB titer ≥ 1:40 before vaccination ( 4 % vs 55 % ; P < .001 ) when compared with patients with seroconversion . No other differences were found between the 2 groups , including AIDS status , highly active antiretroviral therapy status , HIV RNA - polymerase chain reaction load < 50 copies/mL , CD4 cell count , sex , body mass index , and chronic hepatitis . CONCLUSION Among HIV-infected patients , the rate of seroconversion after the first dose of an adjuvanted H1N1 influenza A vaccine was 68 % and increased to 92 % after a second doses BACKGROUND There are , to our knowledge , no prospect i ve studies of respiratory tract infections in human immunodeficiency virus (HIV)-infected adults in the highly active antiretroviral therapy ( HAART ) era . We performed a surveillance study of out patients who presented with fever and respiratory symptoms to examine the role of viral pathogens in these patients . METHODS Consecutive patients with a temperature of > 38.0 degrees C and respiratory symptoms were recruited from a tertiary care HIV clinic during the period 2003 - 2006 . Nasal pharyngeal sample s were tested for influenzavirus A and B , respiratory syncytial virus , and human metapneumovirus using real-time multiplex polymerase chain reaction assays . Paired acute- and convalescent-phase serum sample s were tested for respiratory viruses by complement fixation . RESULTS Fifty patients ( 90 % of whom were receiving HAART ) were included in the study ( median CD4(+ ) T cell count , 325 cells/microL ; median HIV RNA level , < 50 copies/mL ) . A causative pathogen was identified in 25 patients ( 50 % ) . Even though 76 % of subjects had received influenza vaccine , viral infections were diagnosed in 21 patients ( 42 % ) , as follows : influenza A , 10 patients ; influenza B , 10 ; and parainfluenza virus type 3 infection , 1 . Patients with and those without viral infection had similar demographic characteristics and HIV statuses . No patients with influenza and 23 % of patients with other conditions had radiography-confirmed pneumonia ( P=.07 ) . Antibiotic prescriptions were common : 70 % of patients received antibiotics . No patients with influenza required hospitalization , compared with 21 % of other patients ( P=.03 ) . CONCLUSIONS Although illness was mild , influenza accounted for a large proportion of unscheduled visits to a health care provider for respiratory illness and was associated with unnecessary antibiotic prescriptions that may contribute to antimicrobial resistance . Vaccination alone was insufficient to prevent infection . Thus , specific identification and management of influenza should be performed in HIV-infected out patients who present with fever and respiratory symptoms Background Since human immunodeficiency virus (HIV)-infected individuals are at increased risk of severe disease from p and emic influenza A ( H1N1pdm09 ) , vaccination was recommended as a prevention strategy . The aim of the present study was to evaluate the safety , immunogenicity and persistence of the immune response after vaccination against p and emic influenza A ( H1N1pdm09 ) with an adjuvanted vaccine in human immunodeficiency virus (HIV)-infected adults using two single and two double doses . Methodology /Principal Findings Open label , r and omized trial to evaluate the immune response following H1N1pdm09 vaccination in HIV-infected participants compared to HIV-negative controls ( NCT01155037 ) . HIV-infected participants were r and omized to receive 2 single ( 3.75 µg hemagglutinin ) or 2 double ( 7.5 µg hemagglutinin ) doses of the vaccine , 21 days apart . Controls received one dose of the vaccine . The primary endpoint was seroconversion as measured by hemagglutination inhibition assay . Two hundred fifty six HIV-infected participants ( 129 and 127 r and omized to single and double doses , respectively ) and 71 HIV-negative controls were enrolled . Among HIV-infected participants , seroconversion increased from 46.7 % and 51.7 % after the first dose to 77.2 % and 83.8 % after the second dose of the vaccine using single and double doses , respectively . Participants aged > 40 years showed higher seroconversion compared to younger participants . Seroconversion among HIV-infected women and those with nadir CD4<200 cells/mm3 was significantly higher with double doses . Persistence of protective antibodies six months after vaccination was achieved by 80 % and 89.9 % of the HIV-infected participants who received single and double doses , respectively . Conclusions / Significance Our results support the recommendation of two double doses of adjuvanted H1N1pdm09 vaccine for HIV-infected individuals , particularly women , and those aged > 40 years or with nadir CD4<200 cells/mm3 , to achieve antibody levels that are both higher and more sustained . Trial Registration Clinical Trials.gov Design Children with HIV are especially susceptible to complications from influenza infection , and effective vaccines are central to reducing disease burden in this population . We undertook a prospect i ve , observational study to investigate the safety and immunogenicity of the inactivated split-virion AS03-adjuvanted p and emic H1N1(2009 ) vaccine in children with HIV . Setting National referral centre for Paediatric HIV in Irel and . Sample Twenty four children with HIV were recruited consecutively and received two doses of the vaccine . The serological response was measured before each vaccine dose ( Day 0 and Day 28 ) and 2 months after the booster dose . Antibody titres were measured using a haemagglutination inhibition ( HAI ) assay . Seroprotection was defined as a HAI titre ≥ 1:40 ; seroconversion was defined as a ≥ fourfold increase in antibody titre and a postvaccination titre ≥ 1:40 . Main outcome measures The seroconversion rates after prime and booster doses were 75 % and 71 % , respectively . HIV virological suppression at the time of immunization was associated with a significantly increased seroconversion rate ( P = 0·009 ) , magnitude of serological response ( P = 0·02 ) and presence of seroprotective HAI titres ( P = 0·017 ) two months after the booster dose . No other factor was significantly associated with the seroconversion/seroprotection rate . No serious adverse effects were reported . Vaccination had no impact on HIV disease progression  . The AS03-adjuvanted p and emic H1N1 vaccine appears to be safe and immunogenic among HIV-infected children . A robust serological response appears to be optimized by adherence to a HAART regimen delivering virological suppression Antigenically well-matched vaccines against highly pathogenic avian influenza H5N1 viruses are urgently required . Human serum sample s after immunization with MF59 or nonadjuvanted A/duck/Singapore/97 ( H5N3 ) vaccine were tested for antibody to 1997 - 2004 human H5N1 viruses . Antibody responses to 3 doses of nonadjuvanted vaccine were poor and were higher after MF59-adjuvanted vaccine , with seroconversion rates to A/HongKong/156/97 , A/HongKong/213/03 , A/Thail and /16/04 , and A/Vietnam/1203/04 of 100 % ( P < .0001 ) , 100 % ( P < .0001 ) , 71 % ( P = .0004 ) , and 43 % ( P = .0128 ) in 14 subjects , respectively , compared with 27 % , 27 % , 0 % , and 0 % in 11 who received nonadjuvanted vaccine . These findings have implication s for the rational design of p and emic vaccines against influenza H5 Influenza vaccination is recommended for patients with HIV-1 infection ( 1 ) , but no studies have measured its efficacy in this population . Patients infected with HIV-1 , especially those with low CD4 + cell counts , often have minimal antibody responses to influenza vaccine ( 2 , 3 ) , leading some research ers to conclude that vaccination is not cost-effective ( 4 ) . In addition , vaccination has been associated with transient increases in HIV replication ( 5 - 8 ) and small decreases in percentage of CD4 cells ( 8) ; both of these findings are of undetermined clinical relevance . To better estimate the potential benefit of routine influenza vaccination in persons infected with HIV , we conducted a r and omized , controlled trial of influenza vaccine in a sample of HIV-1-infected patients during one influenza season . Methods Study Design The study site , a hospital-based clinic affiliated with the U.S. military , provides care to 400 to 500 patients infected with HIV-1 . Posters invited patients who visited the clinic from October to December 1995 to refer themselves for enrollment . All HIV-infected patients who had not yet received their annual influenza vaccine were eligible to participate . All patients gave informed consent , and the hospital 's institutional review board approved the study . Blood was drawn for measurement of CD4 + cell counts , influenza antibody titers , and plasma quantitative HIV-1 RNA level . Using a r and om computer-generated sequence , which was kept sealed until the end of the study , pharmacy staff prepared syringes that were filled with saline or with influenza vaccine purchased by the hospital for clinical use ( whole virion containing 15 g each of A/Johannesburg/33/94 [ H3N2 ] , A/Texas/36/91 [ H1N1 ] , and B/Harbin/07/94 [ Pasteur Mrieux Connaught , Lyon , France ] . Clinic staff could not distinguish vaccine from placebo . At 1 and 3 months after vaccination , patients returned for follow-up measurement of CD4 + cell count and HIV-1 RNA level and for serologic examination for influenza . Patients returned for viral cultures only if respiratory symptoms developed . At the conclusion of the study , all patients were interviewed about respiratory illness ( broadly defined as any rhinitis , pharyngitis , or cough ) experienced during the study period . Laboratory Assays Sample s for T-cell subset analysis were processed according to st and ard methods . The variation of percentage of CD4 cells on replicate testing was 1 % . Plasma sample s for measurement of HIV-1 RNA level were drawn in acid citrate-dextrose tubes , separated at 2000 rpm for 15 minutes , and stored at 70 C. Serum sample s were stored similarly . Quantitative HIV RNA reverse transcriptase polymerase chain reaction assays ( Amplicor Monitor , Roche , Nutley , New Jersey ) were done in batches by Quest Diagnostics at Nichols Institute , San Juan Capistrano , California ; all specimens from individual patients were tested simultaneously . The lower limits of quantification were 400 RNA copies per mL of plasma , and the intra-assay coefficient of variation of 32.3 % to 45.3 % . Serum sample s taken before and 1 month after vaccination were tested for antibody responses to each of the three individual vaccine components by microtiter hemagglutination inhibition ; egg-grown virus antigens starting at a dilution of 1:4 were used ( 9 ) . Sample s below this threshold were assigned a value of 1:2 . Serum sample s obtained 1 month and 3 months after vaccination were tested against the A/Johannesburg/33/94 and A/Nanchang/33/95 ( H3N2 ) virus strains ; the latter is antigenically similar to the A/Wuhan/95-like viruses that were circulating in the United States in 1995 and 1996 . All of the patients who responded to A/Johannesburg/94 ( those who demonstrated a fourfold or greater increase in titer ) also responded to A/Nanchang/95 . Because both A/Johannesburg-like and A/Wuhan-like viruses circulated in the study sample , an antibody response to A/Nanchang/95 occurring between 1 and 3 months after vaccination was defined as evidence of influenza A infection . Viral cultures were performed by using st and ard laboratory methods . Statistical Analysis Statistical analysis was done by using Statview 4.5 software ( Abacus Concepts , Inc. , Berkeley , California ) . Changes in antibody titer , plasma HIV-1 RNA level , and CD4 + cell count were analyzed by using the unpaired t-test to compare vaccine and placebo recipients . Illness rates were compared by using the chi-square test . The percentage of protective efficacy of vaccination was calculated as 1 ( risk ratio comparing vaccine and placebo recipients ) 100 . Results Characteristics of the Study Group A total of 102 patients enrolled in the study . Fifty-five patients were r and omly assigned to receive vaccine , and 47 patients were r and omly assigned to receive placebo .  Table 1 summarizes the participants ' characteristics . Because the study was conducted in fall 1995 , antiretroviral regimens were limited to single or double reverse transcriptase inhibitor combinations . No patients were taking protease inhibitors .  All patients had received at least one previous influenza vaccination .  Table 1 . Baseline Characteristics of the Study Sample Serologic Response to Vaccination Prevaccination and postvaccination paired serum sample s from 49 vaccine recipients and 43 placebo recipients were tested against the three vaccine constituents ( Table 2 ) . Although the aggregate responses to vaccination were statistically significant , only 12 % , 29 % , and 36 % of vaccine recipients had a fourfold or greater response to the A/H1N1 , A/H3N2 , and B components , respectively . Table 2 . Antibody Response to Influenza Vaccination  Protective Efficacy of Influenza Vaccination Peak influenza activity in San Diego County in 1995 and 1996 occurred from mid-January through early February and was predominately caused by the A/Johannesburg ( H3N2 ) virus strain ; some A/Wuhan ( H3N2 ) virus was also present ( San Diego Public Health Department . Personal communication ) . Sixteen of 55 vaccine recipients ( 29 % ) , compared with 23 of 47 placebo recipients ( 49 % ) , reported symptoms of respiratory illness during the fall and winter of 1995 and 1996 ( P=0.04 ) . No patients were hospitalized or treated for pneumonia during the study period . Twenty of 39 patients ( 12 placebo recipients and 8 vaccine recipients ) who reported respiratory illness returned to the clinic for viral respiratory culture . Influenza A ( H3N2 ) virus was isolated from 3 patients , and influenza B virus was isolated from 2 patients , all of whom received placebo . Serum sample s taken 1 and 3 months after vaccination were available for 86 patients ( 43 vaccine recipients and 43 placebo recipients ) . One vaccine recipient and 10 placebo recipients had serologic evidence of influenza A infection ( P=0.004 ) . During the 1995 - 1996 influenza season , 13 of 47 placebo recipients had laboratory-documented influenza A infection ( by culture or serologic examination ) compared with only 1 of 55 vaccine recipients ( P<0.001 ) ( calculated protective efficacy , 93 % [ CI , 69 % to 100 % ] ) . The one vaccinated patient who had serologic evidence of influenza infection had advanced HIV infection with a CD4 + count of 36 cells/mm3 at baseline . Although our study included too few patients with CD4 + cell counts less than 200 cells/mm3 to make firm conclusions , only one of five vaccine recipients ( 20 % ) reported respiratory symptoms during the study period compared with four of eight placebo recipients ( 50 % ) ( P>0.2 ) . The one vaccinated patient with serologic evidence of infection did not report symptoms of respiratory illness during the study period . Ten placebo recipients and no vaccine recipients had symptomatic laboratory-confirmed influenza A ( protective efficacy , 100 % [ CI , 73 % to 100 % ] ) . Effect of Vaccination and Influenza on Plasma HIV-1 RNA Level and CD4 Cell Count No significant differences were seen in changes in the percentage of CD4 cells or plasma HIV-1 RNA levels between the vaccine and placebo groups or between patients with and those without documented influenza infection . At 1 month , the plasma HIV RNA level increased 0.03 log ( CI , 0.12 log to 0.18 log ) in vaccinated patients , a value that is well within the anticipated variability ( 0.3 to 0.5 log ) of the plasma HIV RNA level ( 10 ) . Twenty-six percent of the study patients ( 14 vaccine recipients and 13 placebo recipients ) changed their antiretroviral regimens during the study period . Discussion Our results indicate that influenza vaccine is highly effective in HIV-infected patients . Calculated protective efficacy was 100 % for symptomatic influenza A , and the lower bound of the CI around this estimate was 73 % . This protection is comparable to the 70 % efficacy described in immunocompetent adults ( 1 ) . Although patients with AIDS were underrepresented , the subset of such patients showed nonstatistically significant decreases in respiratory illness that were nearly identical to those of the group as a whole . Our use of serodiagnosis may have missed influenza infections in vaccinated patients who did not have follow-up titers or had antibody titers that were already high before the influenza season . However , the protective efficacy , as measured by serodiagnosis , was supported by a similar decrease in culture-positive illness and significant reductions in respiratory symptoms . Although excellent protection was seen against H3N2 influenza , which was circulating in 1995 and 1996 , an inherent limitation of study ing influenza is that other vaccine components may not be as efficacious against future epidemic influenza strains . Although our study is the first to examine the efficacy of influenza vaccine in persons infected with HIV-1 , many studies have measured the immunogenicity of influenza vaccine in this population ( 2 , 3 , 7 , 11 - 16 ) . Reported response rates range from 0 % to 85 % . The wide variation reflects host factors , such as stage of illness , and variable antigenicity of different vaccine strains . Although the patients in our sample were relatively healthy , OBJECTIVE To study immunological and virological parameters in HIV-1-seropositive adults treated with highly active antiretroviral therapy ( HAART ) for at least 7 months after immunisation with MF59-adjuvanted ( FLUAD , Chiron , Siena , Italy ) or with non-adjuvanted ( AGRIPPAL , Chiron ) trivalent influenza vaccine .  DESIGN Blood sample s , collected before and after vaccination , were analysed for the presence of antibodies against the vaccine antigens , for number of CD4 + T lymphocytes and HIV-1 RNA levels . RESULTS Forty-four volunteers received FLUAD and 40 AGRIPPAL influenza vaccine .  Thirty days after vaccination both adjuvanted and non-adjuvanted vaccines induced significant increases of anti-influenza virus antibodies . However , antibody titres found in volunteers receiving adjuvanted vaccine were in general significantly higher when compared with those found in the non-adjuvanted vaccine group . The requirements of the European Commission of influenza vaccine for a non-elderly adult population were always met by recipients of the adjuvanted vaccine , even in those with the lowest CD4 + cell counts ( < 200 cells/mmc ) . The subjects receiving the non-adjuvanted vaccine failed to met these requirements . The CD4 + T lymphocytes and plasma HIV-1 RNA levels remained stable in the long term , both in people receiving adjuvanted or non-adjuvanted vaccine . CONCLUSION MF59-adjuvanted influenza induced a significant higher immune responses as compared with conventional vaccine in HIV-seropositive HAART-treated patients . Both vaccines were safe regarding HIV RNA viral replication and loss of CD4 + T lymphocytes Objective : In immunocompromised patients , alternative schedules more immunogenic than the st and ard influenza vaccine regimen are necessary to enhance and prolong vaccine efficacy . We previously reported that the AS03A-adjuvanted 2009 A/H1N1v vaccine yielded a higher short-term immune response than the nonadjuvanted one in HIV-1-infected adults . This study reports the long-term persistence of the immune response . Design and methods : In a prospect i ve , multicenter , r and omized , patient-blinded trial , two doses of AS03A-adjuvanted H1N1v vaccine containing 3.75 & mgr;g haemagglutinin ( n = 155 ; group A ) or nonadjuvanted H1N1v vaccine containing 15 & mgr;g haemagglutinin ( n = 151 ; group B ) , were administered 21 days apart . Haemagglutination inhibition and neutralizing antibodies were assessed 6 and 12 months after vaccination . Results : In group A and B , the seroprotection rates were 83.7 and 59.4 % at month 6 , and 70.4 and 49.3 at month 12 , respectively . In a multivariate analysis , persistence of seroprotection 12 months after vaccination was negatively associated with current smoking ( odds ratio = 0.6 , P = 0.03 ) and positively related with the AS03A-adjuvanted H1N1v vaccine ( odds ratio = 2.7 , P = 0.0002 ) . Conclusion : In HIV-1-infected adults , two doses of adjuvanted influenza vaccine induce long-term persistence of immune response up to 1 year after vaccination In this study of influenza vaccination , 37 human immunodeficiency virus (HIV)-1-seropositive patients were r and omized to receive either a vaccine with a conventional subunit or one adjuvanted with MF59 . Blood sample s were collected at the time of vaccination , and then 30 and 180 days later , to evaluate immunogenicity , CD4 + T-lymphocyte count and HIV-1 RNA levels . Seroconversion rates against the three viral strains included in the vaccine ranged between 44 % and 72 % and 53 % and 68 % for the adjuvanted vaccine and the subunit vaccine , respectively . Other criteria of the European Medicines Evaluation Agency were also met . Vaccination was not associated with serious adverse events . Local and systemic effects were mild and of short duration . CD4 + T-lymphocyte counts and viraemia levels were not negatively affected by vaccination . These results confirmed the safety and immunogenicity of these currently available vaccines in HIV-1-seropositive patients , thus supporting the recommendation for influenza immunization in this high-risk category ABSTRACT The objective of this study was to evaluate and compare both the safety and tolerability and the humoral and cell-mediated immune responses for two influenza virus subunit vaccines , one with MF59 adjuvant ( Fluad ) and one without an adjuvant ( Agrippal ) , in healthy and in human immunodeficiency virus type 1 (HIV-1)-infected adult individuals . To achieve this aim , an open , r and omized , comparative clinical trial was performed during the 2005 - 2006 season . A total of 256 subjects were enrolled to receive one dose of vaccine intramuscularly  .  Blood sample s were taken at the time of vaccination and at 1 and 3 months postvaccination . A good humoral antibody response was detected for both vaccines , meeting all the criteria of the Committee for Medical Products for Human Use . After Beyer 's correction for prevaccination status , Fluad exhibited better immunogenicity than Agrippal , as shown from the analysis of the geometric mean titers , with significant differences for some virus strains ; however , no definitive conclusions on the clinical significance of such results can be drawn , because the method used to estimate antibody response is currently nonst and ard for influenza virus vaccines . Significant induction of an antigen-specific CD4 + T-lymphocyte proliferative response was detected at all time points after immunization , for both the vaccines , among HIV-1-seronegative subjects . This was different from what was observed for HIV-1-infected individuals . In this group , significance was not reached at 30 days postvaccination ( T30 ) for those immunized with Agrippal . Also when data were compared between treatment groups , a clear difference in the response at T30 was observed in favor of Fluad ( P = 0.0002 ) . The safety profiles of both vaccines were excellent . For HIV-1-infected individuals , no significant changes either in viremia or in the CD4 + cell count were observed at any time point . The results showed good safety and immunogenicity for both vaccines under study for both uninfected and HIV-1-infected adults , confirming current recommendations for immunization of this high-risk category BACKGROUND Human immunodeficiency virus (HIV)-infected patients have decreased immune response to vaccines . Few data are available about p and emic flu vaccination in this population . METHODS We conducted a multicenter , patient-blinded , r and omized 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 r and omized , 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 In order to evaluate the immunogenicity , safety and tolerability of the 2009 A/H1N1 MF59-adjuvanted influenza vaccine administered sequentially or simultaneously with seasonal virosomal-adjuvanted influenza vaccine to HIV-infected children and adolescents , 36 HIV-infected children and adolescents , and 36 age- and gender-matched healthy controls were r and omised 1:1 to receive the p and emic vaccine upon enrollment and the seasonal vaccine one month later , or to receive the p and emic and seasonal vaccines simultaneously upon enrollment . Seroconversion and seroprotection rates against the p and emic influenza A/H1N1 virus were 100 % two months after vaccine administration in both groups , regardless of the sequence of administration . Geometric mean titres against p and emic and seasonal antigens were significantly higher when the seasonal and p and emic vaccines were administered simultaneously than when the seasonal vaccine was administered alone . Local and systemic reactions were mild and not increased by simultaneous administration . In conclusion , the 2009 p and emic influenza A/H1N1 MF59-adjuvanted vaccine is as immunogenic , safe and well tolerated in HIV-infected children and adolescents as in healthy controls . Its simultaneous administration with virosomal-adjuvanted seasonal antigens seems to increase immune response to both p and emic and seasonal viruses with the same safety profile as that of the p and emic vaccine alone . However , because this finding can not be clearly explained by an immunological viewpoint , further studies are needed to clarify the reasons of its occurrence BACKGROUND This Phase IV study evaluated the safety and immunogenicity of a two-dose , MF59 ® -adjuvanted ( Novartis Vaccines , Marburg , Germany ) , monovalent , A/H1N1 p and emic influenza vaccination schedule in Human Immunodeficiency Virus ( HIV ) positive children and young adults . METHODS A total of 83 children infected with HIV-1 , and 37 non-immunocompromised , age-matched controls were enrolled . All participants received two vaccine doses administered three weeks apart . Antibody responses were assessed by haemagglutination assay at baseline , three weeks after each vaccine dose , and six months after immunization . Vaccines were evaluated according to European influenza vaccine licensure criteria . RESULTS The investigational vaccine was well tolerated . After the first vaccine dose , seroconversion rates were significantly lower in HIV-positive patients ( 60 % ) than controls ( 82 % ) , with GMTs of 419 and 600 , respectively . No significant differences in seroconversion rates were observed between the two study groups in response to the second vaccine dose . Persisting antibody titers were similar for both HIV-positive and non-infected controls , six months after immunization . CONCLUSION One dose of MF59-adjuvanted vaccine was sufficient to provide adequate levels of seroprotection against A/H1N1 influenza disease in HIV-positive children . However , a two-dose vaccination schedule may be optimal for this population
Adjuvanted-influenza vaccination is an efficient method for enhancing the immunogenicity of influenza split-virus vaccines for preventing influenza .
However , the medical community 's underst and ing of its performance in patients infected with HIV remains limited .