human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: CONTEXT Despite enormous improvements achieved through the use of antiretroviral therapies ( ARTs ) , the risk for eventual human immunodeficiency virus ( HIV )  disease progression remains high . Agents that enhance the immunologic mechanism for viral recognition might reduce disease progression . OBJECTIVE To determine whether the addition of HIV-1 Immunogen would confer added clinical efficacy to that achievable by ARTs . DESIGN AND SETTING Multicenter , double-blind , placebo-controlled , r and omized trial beginning March 1996 and ending May 1999 conducted at 77 centers in the United States providing primary care or referral care for persons infected with HIV . PATIENTS Adults infected with HIV who have baseline CD4 cell counts between 300 x 10(6)/L and 549 x 10(6)/L without prior acquired immunodeficiency syndrome-defining conditions receiving stable ART ( or no therapy ) were screened and 2527 were r and omized . INTERVENTIONS Ten units of HIV-1 Immunogen , derived from a Zairian HIV isolate , inactivated and formulated with incomplete Freund adjuvant , was administered intramuscularly every 12 weeks . The placebo was incomplete Freund adjuvant . Changes in ARTs were allowed . MAIN OUTCOME MEASURES HIV progression-free survival ; secondary end points included overall survival , changes in HIV RNA , CD4 cell counts , CD4 percentage , body weight , and immunogenicity . RESULTS The overall event rate was 1.8 per 100 person-years of follow-up . Fifty-three subjects developed clinical progression in each treatment group ( relative risk [ RR ] , 0.97 ; 95 % confidence interval [ CI ] , 0.66 - 1.42 ; P = .89 ) . There were 19 and 23 deaths in the placebo and HIV-1 Immunogen groups , respectively ( RR , 0.81 ; 95 % CI , 0.44 - 1 . 48 ; P = .49 ) . There were no statistically significant differences between the groups with respect to changes in HIV RNA ( P = .59 ) , CD4 percentage ( P = .63 ) , or body weight ( P = .89 ) . Subjects in the HIV-1 Immunogen group had an increase in average CD4 cell count of approximately 10 x 10(6)/L greater than the placebo group ( P = .02 ) . CONCLUSION HIV-1 Immunogen with unrestricted ART failed to demonstrate an increase in HIV progression-free survival . JAMA . 2000;284:2193 - 2202 BACKGROUND We conducted a phase I/II r and omized placebo-controlled trial with the aim of exploring whether priming with a low intradermal dose of a multiclade , multigene HIV-1 DNA vaccine could improve the immunogenicity of the same vaccine given intramuscularly prior to boosting with a heterologous HIV-1 MVA among healthy adults in Dar es Salaam , Tanzania . METHODS Sixty HIV-uninfected volunteers were r and omized to receive DNA plasmid vaccine 1 mg intradermally ( i d ) , n=20 , or 3.8 mg intramuscularly ( i m ) , n=20 , or placebo , n=20 , using a needle-free injection device . DNA plasmids encoding HIV-1 genes gp160 subtype A , B , C ; rev B ; p17/p24 gag A , B and Rtmut B were given at weeks 0 , 4 and 12 . Recombinant MVA ( 10(8)pfu ) expressing HIV-1 Env , Gag , Pol of CRF01_AE or placebo was administered i m at month 9 and 21 . RESULTS The vaccines were well tolerated . Two weeks after the third HIV-DNA injection , 22/38 ( 58 % ) vaccinees had IFN-γ ELISpot responses to Gag . Two weeks after the first HIV-MVA boost all 35 ( 100 % ) vaccinees responded to Gag and 31 ( 89 % ) to Env . Two to four weeks after the second HIV-MVA boost , 28/29 ( 97 % ) vaccinees had IFN-γ ELISpot responses , 27 ( 93 % ) to Gag and 23 ( 79 % ) to Env . The id-primed recipients had significantly higher responses to Env than i m recipients . Intracellular cytokine staining for Gag-specific IFN-γ/IL-2 production showed both CD8(+ ) and CD4(+ ) T cell responses . All vaccinees had HIV-specific lymphoproliferative responses . All vaccinees reacted in diagnostic HIV serological tests and 26/29 ( 90 % ) had antibodies against gp160 after the second HIV-MVA boost . Furthermore , while all of 29 vaccinee sera were negative for neutralizing antibodies against clade B , C and CRF01_AE pseudoviruses in the TZM-bl neutralization assay , in a P BMC assay , the response rate ranged from 31 % to 83 % positives , depending upon the clade B or CRF01_AE virus tested . CONCLUSIONS This vaccine approach is safe and highly immunogenic . Low dose , i d HIV-DNA priming elicited higher and broader cell-mediated immune responses to Env after HIV-MVA boost compared to a higher HIV-DNA priming dose given i m . Three HIV-DNA priming immunizations followed by two HIV-MVA boosts efficiently induced Env-antibody responses Abstract Background Evaluating experiences of volunteers in an HIV vaccine trial will be useful for the conduct of future trials . The purpose of this study among volunteers who participated in a phase I/II HIV vaccine trial in Dar es Salaam , Tanzania was to assess what characterized their experiences during the trial . Methods We conducted four focus group discussion s with 35 out of the 60 individuals ( women and men ) after the five scheduled vaccinations .  An interpretive description approach was applied to data analysis . Results As a result of the trial interventions , both men and women gained confidence in their own abilities to have safer , less risky sexual behaviour . The participants experienced the trial as a way of accessing free [ insured ] medical services . Most of the men said they had gone from self-medication to professional medical consultation . Despite these benefits , the participants faced various challenges during the trial . Such challenges included mistrust of the trial shown by health care providers who were not connected to the trial and discouragement from friends , colleagues and family members who question ed the safety of the trial . However , they managed to cope with these doubts by using both personal and trial related interventions . Conclusion We found that during the phase I/II HIV vaccine trial , participants had both the opportunities and the ability to cope with the doubts from the surrounding community . Follow up visits enhanced the opportunities and individuals ' abilities to cope with the doubts during the trial . Underst and ing this discourse may be useful for the trial implementers when design ing future trials . Trials Registration IS RCT N : IS RCT N90053831 Pan African Clinical Trials Registry ( PACTR ) : Summary : Underst and ing why people join HIV vaccine efficacy trials is critical for trial recruitment and education efforts . We assessed participants ' motivations for joining the VaxGen VAX004 study  , a r and omized , double-blind , placebo-controlled , phase 3 multicenter trial . Of 5417 participants , 94 % were men who have sex with men ( MSM ) and 6 % were women at risk for heterosexual transmission of HIV . Most participants gave altruistic reasons for trial participation : 99 % reported having joined to help find an HIV vaccine , and 98 % reported having joined to help their community . Some gave more personal reasons : 56 % joined to reduce risk behavior  and 46 % joined to get protection from HIV . Additional reasons related to receiving services or compensation included to obtain information about HIV ( 75 % ) , to receive free HIV testing ( 34 % ) , and for financial reimbursement ( 14 % ) . Multivariate logistic regression analysis showed that female participants were significantly more motivated than male participants to join the trial for protection and to receive services or compensation ( all P < 0.05 ) . Participants with 13 or more sex partners in the 6 months before enrollment were more likely than those with fewer sex partners to report having joined the trial for protection but less likely to have joined to reduce risk behavior ( both P < 0.05 ) . Because many participants reported personal protection from HIV as their reason for joining , vaccine trial risk-reduction counseling should continue to emphasize the placebo-controlled trial design and unknown efficacy of the test product , particularly for women and persons with large numbers of sex partners . Because a significant minority of participants reported joining to receive HIV information , HIV testing , and financial reimbursement , a need is indicated for provision of HIV prevention services outside research trials and for monitoring to ensure that participants are not motivated to join trials for financial gain Live attenuated viral vectors that express human immunodeficiency virus ( HIV ) antigens are being developed as potential vaccines to prevent HIV infection . The first phase 2 trial with a canarypox vector ( vCP205 , which expresses gp120 , p55 , and protease ) was conducted in 435 volunteers with and without gp120 boosting  , to exp and the safety data base and to compare the immunogenicity of the vector in volunteers who were at higher risk with that in volunteers at lower risk for HIV infection .  Neutralizing antibodies to the MN strain were stimulated in 94 % of volunteers given vCP205 plus gp120 and in 56 % of volunteers given vCP205 alone . CD8(+ ) cytotoxic T lymphocyte cells developed at some time point in 33 % of volunteers given vCP205 , with or without gp120 . Phase 3 field trials with these or similar vaccines are needed , to determine whether efficacy in preventing HIV infection or in slowing disease progression among vaccinees who become infected is associated with the level and types of immune responses that were induced by the vaccines in this study Behavioral and social issues were investigated in 363 phase I/II preventive HIV-1 vaccine trial volunteers in Thail and . These issues included risk behavior , HIV knowledge , distress , and social consequences of vaccine trial participation . Data were collected at baseline and at 4- , 8- , and 12-month follow-up visits . Volunteers reported relatively low levels of risk behaviors at baseline and at follow-up . Overtly negative reactions from family or friends were reported by 5.9 % . No experiences of discrimination in employment , health care , or insurance were reported . Mean levels of distress were low throughout the trial , and HIV-related knowledge was high , although it was common to consider the possibility of HIV transmission through casual contact . Findings add to the evidence that preventive HIV vaccine trials are feasible in Thail and Objectives : To describe recruitment , screening and baseline characteristics of injection drug users ( IDU ) participating in a phase III HIV vaccine ( AIDSVAX ® B/E ; VaxGen , USA ) trial and to compare enrollment characteristics between trial participants and 1209 IDU from a 1995–1998 vaccine trial preparatory cohort for changes that might impact trial design assumptions . Methods : Enrollment for both studies was conducted at Bangkok narcotic treatment clinics , where a st and ardized question naire was administered on demographics , risk behavior and incarceration history over the previous 6 months . Results : During 1999–2000 , 4943 IDU were screened for enrollment ; successful sources of recruitment included clinic attendees ( 43.4 % ) , an IDU referral program ( 20.4 % ) and preparatory cohort participants ( 14.7 % ) . Of those screened , 1689 ( 34 % ) were HIV seropositive ( HIV subtype B 23.6 % ; subtype E 76.4 % ) . Of the 2545 enrolled , 93.4 % were male . Compared with cohort IDU , trial IDU were younger ( mean age : 28.8 versus 31.3 years ) , better educated ( secondary level or higher : 67.2 % versus 58.7 % ) , and less likely to inject drugs daily ( 39.4 % versus 90.4 % ) ; they were more likely to have been incarcerated ( 78.4 % versus 65.7 % ) , have recently injected stimulants ( 14.8 % versus 5.8 % ) and tranquilizers ( 11.5 % versus 2.3 % ) , and obtained needles/syringes from a source other than a pharmacist ( 7.2 % versus 3.9 % ) ( all P ⩽ 0.003 ) . Conclusions : IDU at high risk for HIV have been successfully enrolled in the AIDSVAX ® B/E efficacy trial . Only minor epidemiologic differences were found at enrollment between trial and preparatory cohort IDU . The latter has proven critical in guiding trial design ; results are expected in late 2003 Objective : To describe recruitment and baseline epidemiologic characteristics of volunteers in the first phase 3 placebo-controlled trial of a recombinant gp120 HIV vaccine ( AIDSVAX B/B ) . Methods : Volunteers were gay/bisexual men or women at risk for sexually transmitted HIV infection . Recruitment strategies , demograph 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: CONTEXT Despite enormous improvements achieved through the use of antiretroviral therapies ( ARTs ) , the risk for eventual human immunodeficiency virus ( HIV )  disease progression remains high . Agents that enhance the immunologic mechanism for viral recognition might reduce disease progression . OBJECTIVE To determine whether the addition of HIV-1 Immunogen would confer added clinical efficacy to that achievable by ARTs . DESIGN AND SETTING Multicenter , double-blind , placebo-controlled , r and omized trial beginning March 1996 and ending May 1999 conducted at 77 centers in the United States providing primary care or referral care for persons infected with HIV . PATIENTS Adults infected with HIV who have baseline CD4 cell counts between 300 x 10(6)/L and 549 x 10(6)/L without prior acquired immunodeficiency syndrome-defining conditions receiving stable ART ( or no therapy ) were screened and 2527 were r and omized . INTERVENTIONS Ten units of HIV-1 Immunogen , derived from a Zairian HIV isolate , inactivated and formulated with incomplete Freund adjuvant , was administered intramuscularly every 12 weeks . The placebo was incomplete Freund adjuvant . Changes in ARTs were allowed . MAIN OUTCOME MEASURES HIV progression-free survival ; secondary end points included overall survival , changes in HIV RNA , CD4 cell counts , CD4 percentage , body weight , and immunogenicity . RESULTS The overall event rate was 1.8 per 100 person-years of follow-up . Fifty-three subjects developed clinical progression in each treatment group ( relative risk [ RR ] , 0.97 ; 95 % confidence interval [ CI ] , 0.66 - 1.42 ; P = .89 ) . There were 19 and 23 deaths in the placebo and HIV-1 Immunogen groups , respectively ( RR , 0.81 ; 95 % CI , 0.44 - 1 . 48 ; P = .49 ) . There were no statistically significant differences between the groups with respect to changes in HIV RNA ( P = .59 ) , CD4 percentage ( P = .63 ) , or body weight ( P = .89 ) . Subjects in the HIV-1 Immunogen group had an increase in average CD4 cell count of approximately 10 x 10(6)/L greater than the placebo group ( P = .02 ) . CONCLUSION HIV-1 Immunogen with unrestricted ART failed to demonstrate an increase in HIV progression-free survival . JAMA . 2000;284:2193 - 2202 BACKGROUND We conducted a phase I/II r and omized placebo-controlled trial with the aim of exploring whether priming with a low intradermal dose of a multiclade , multigene HIV-1 DNA vaccine could improve the immunogenicity of the same vaccine given intramuscularly prior to boosting with a heterologous HIV-1 MVA among healthy adults in Dar es Salaam , Tanzania . METHODS Sixty HIV-uninfected volunteers were r and omized to receive DNA plasmid vaccine 1 mg intradermally ( i d ) , n=20 , or 3.8 mg intramuscularly ( i m ) , n=20 , or placebo , n=20 , using a needle-free injection device . DNA plasmids encoding HIV-1 genes gp160 subtype A , B , C ; rev B ; p17/p24 gag A , B and Rtmut B were given at weeks 0 , 4 and 12 . Recombinant MVA ( 10(8)pfu ) expressing HIV-1 Env , Gag , Pol of CRF01_AE or placebo was administered i m at month 9 and 21 . RESULTS The vaccines were well tolerated . Two weeks after the third HIV-DNA injection , 22/38 ( 58 % ) vaccinees had IFN-γ ELISpot responses to Gag . Two weeks after the first HIV-MVA boost all 35 ( 100 % ) vaccinees responded to Gag and 31 ( 89 % ) to Env . Two to four weeks after the second HIV-MVA boost , 28/29 ( 97 % ) vaccinees had IFN-γ ELISpot responses , 27 ( 93 % ) to Gag and 23 ( 79 % ) to Env . The id-primed recipients had significantly higher responses to Env than i m recipients . Intracellular cytokine staining for Gag-specific IFN-γ/IL-2 production showed both CD8(+ ) and CD4(+ ) T cell responses . All vaccinees had HIV-specific lymphoproliferative responses . All vaccinees reacted in diagnostic HIV serological tests and 26/29 ( 90 % ) had antibodies against gp160 after the second HIV-MVA boost . Furthermore , while all of 29 vaccinee sera were negative for neutralizing antibodies against clade B , C and CRF01_AE pseudoviruses in the TZM-bl neutralization assay , in a P BMC assay , the response rate ranged from 31 % to 83 % positives , depending upon the clade B or CRF01_AE virus tested . CONCLUSIONS This vaccine approach is safe and highly immunogenic . Low dose , i d HIV-DNA priming elicited higher and broader cell-mediated immune responses to Env after HIV-MVA boost compared to a higher HIV-DNA priming dose given i m . Three HIV-DNA priming immunizations followed by two HIV-MVA boosts efficiently induced Env-antibody responses Abstract Background Evaluating experiences of volunteers in an HIV vaccine trial will be useful for the conduct of future trials . The purpose of this study among volunteers who participated in a phase I/II HIV vaccine trial in Dar es Salaam , Tanzania was to assess what characterized their experiences during the trial . Methods We conducted four focus group discussion s with 35 out of the 60 individuals ( women and men ) after the five scheduled vaccinations .  An interpretive description approach was applied to data analysis . Results As a result of the trial interventions , both men and women gained confidence in their own abilities to have safer , less risky sexual behaviour . The participants experienced the trial as a way of accessing free [ insured ] medical services . Most of the men said they had gone from self-medication to professional medical consultation . Despite these benefits , the participants faced various challenges during the trial . Such challenges included mistrust of the trial shown by health care providers who were not connected to the trial and discouragement from friends , colleagues and family members who question ed the safety of the trial . However , they managed to cope with these doubts by using both personal and trial related interventions . Conclusion We found that during the phase I/II HIV vaccine trial , participants had both the opportunities and the ability to cope with the doubts from the surrounding community . Follow up visits enhanced the opportunities and individuals ' abilities to cope with the doubts during the trial . Underst and ing this discourse may be useful for the trial implementers when design ing future trials . Trials Registration IS RCT N : IS RCT N90053831 Pan African Clinical Trials Registry ( PACTR ) : Summary : Underst and ing why people join HIV vaccine efficacy trials is critical for trial recruitment and education efforts . We assessed participants ' motivations for joining the VaxGen VAX004 study  , a r and omized , double-blind , placebo-controlled , phase 3 multicenter trial . Of 5417 participants , 94 % were men who have sex with men ( MSM ) and 6 % were women at risk for heterosexual transmission of HIV . Most participants gave altruistic reasons for trial participation : 99 % reported having joined to help find an HIV vaccine , and 98 % reported having joined to help their community . Some gave more personal reasons : 56 % joined to reduce risk behavior  and 46 % joined to get protection from HIV . Additional reasons related to receiving services or compensation included to obtain information about HIV ( 75 % ) , to receive free HIV testing ( 34 % ) , and for financial reimbursement ( 14 % ) . Multivariate logistic regression analysis showed that female participants were significantly more motivated than male participants to join the trial for protection and to receive services or compensation ( all P < 0.05 ) . Participants with 13 or more sex partners in the 6 months before enrollment were more likely than those with fewer sex partners to report having joined the trial for protection but less likely to have joined to reduce risk behavior ( both P < 0.05 ) . Because many participants reported personal protection from HIV as their reason for joining , vaccine trial risk-reduction counseling should continue to emphasize the placebo-controlled trial design and unknown efficacy of the test product , particularly for women and persons with large numbers of sex partners . Because a significant minority of participants reported joining to receive HIV information , HIV testing , and financial reimbursement , a need is indicated for provision of HIV prevention services outside research trials and for monitoring to ensure that participants are not motivated to join trials for financial gain Live attenuated viral vectors that express human immunodeficiency virus ( HIV ) antigens are being developed as potential vaccines to prevent HIV infection . The first phase 2 trial with a canarypox vector ( vCP205 , which expresses gp120 , p55 , and protease ) was conducted in 435 volunteers with and without gp120 boosting  , to exp and the safety data base and to compare the immunogenicity of the vector in volunteers who were at higher risk with that in volunteers at lower risk for HIV infection .  Neutralizing antibodies to the MN strain were stimulated in 94 % of volunteers given vCP205 plus gp120 and in 56 % of volunteers given vCP205 alone . CD8(+ ) cytotoxic T lymphocyte cells developed at some time point in 33 % of volunteers given vCP205 , with or without gp120 . Phase 3 field trials with these or similar vaccines are needed , to determine whether efficacy in preventing HIV infection or in slowing disease progression among vaccinees who become infected is associated with the level and types of immune responses that were induced by the vaccines in this study Behavioral and social issues were investigated in 363 phase I/II preventive HIV-1 vaccine trial volunteers in Thail and . These issues included risk behavior , HIV knowledge , distress , and social consequences of vaccine trial participation . Data were collected at baseline and at 4- , 8- , and 12-month follow-up visits . Volunteers reported relatively low levels of risk behaviors at baseline and at follow-up . Overtly negative reactions from family or friends were reported by 5.9 % . No experiences of discrimination in employment , health care , or insurance were reported . Mean levels of distress were low throughout the trial , and HIV-related knowledge was high , although it was common to consider the possibility of HIV transmission through casual contact . Findings add to the evidence that preventive HIV vaccine trials are feasible in Thail and Objectives : To describe recruitment , screening and baseline characteristics of injection drug users ( IDU ) participating in a phase III HIV vaccine ( AIDSVAX ® B/E ; VaxGen , USA ) trial and to compare enrollment characteristics between trial participants and 1209 IDU from a 1995–1998 vaccine trial preparatory cohort for changes that might impact trial design assumptions . Methods : Enrollment for both studies was conducted at Bangkok narcotic treatment clinics , where a st and ardized question naire was administered on demographics , risk behavior and incarceration history over the previous 6 months . Results : During 1999–2000 , 4943 IDU were screened for enrollment ; successful sources of recruitment included clinic attendees ( 43.4 % ) , an IDU referral program ( 20.4 % ) and preparatory cohort participants ( 14.7 % ) . Of those screened , 1689 ( 34 % ) were HIV seropositive ( HIV subtype B 23.6 % ; subtype E 76.4 % ) . Of the 2545 enrolled , 93.4 % were male . Compared with cohort IDU , trial IDU were younger ( mean age : 28.8 versus 31.3 years ) , better educated ( secondary level or higher : 67.2 % versus 58.7 % ) , and less likely to inject drugs daily ( 39.4 % versus 90.4 % ) ; they were more likely to have been incarcerated ( 78.4 % versus 65.7 % ) , have recently injected stimulants ( 14.8 % versus 5.8 % ) and tranquilizers ( 11.5 % versus 2.3 % ) , and obtained needles/syringes from a source other than a pharmacist ( 7.2 % versus 3.9 % ) ( all P ⩽ 0.003 ) . Conclusions : IDU at high risk for HIV have been successfully enrolled in the AIDSVAX ® B/E efficacy trial . Only minor epidemiologic differences were found at enrollment between trial and preparatory cohort IDU . The latter has proven critical in guiding trial design ; results are expected in late 2003 Objective : To describe recruitment and baseline epidemiologic characteristics of volunteers in the first phase 3 placebo-controlled trial of a recombinant gp120 HIV vaccine ( AIDSVAX B/B ) . Methods : Volunteers were gay/bisexual men or women at risk for sexually transmitted HIV infection . Recruitment strategies , demograph 
    Output:
    