1. Reshma Sougaijam Moderator : Dr. Manish Taywade

2.  Late 1980s in Thailand, there was a dramatic increase in prevalence of infection with (HIV-1)  1995, overall seroprevalence of HIV-1 reached a peak of 3.7% among Royal Thai Army and 12.5% among conscripts from Northern Thailand  Thai Ministry of Public Health responded with an effective HIV- prevention campaign, and number of new HIV-1 infections per year decreased from an estimated 143,000 in 1990 to 14,000 in 2007

3.  The study was designed to evaluate two co primary end points: -prevention of HIV-1 infection and - effect of vaccination on early viral load after infection

4.  Randomized, multicenter, double-blind, placebo-controlled efficacy trial of prime–boost combination of vaccines containing ALVAC-HIV (vCP1521) and AIDSVAX B/E  The trial was conducted in Rayong and Chon Buri provinces.  From September 2003 through December 2005, a total of 16,402 volunteers were enrolled.

5.  Thai men and women who were between the ages of 18 and 30 years and who were not infected with HIV were recruited from the community without regard to HIV risk  Pregnant and breast-feeding women were excluded.  Written informed consent was obtained from all volunteers, who were required to pass a written test of understanding

6.  The ALVAC-HIV vaccine was administered (day 0), 4 weeks, 12 weeks and 24 weeks  Boosting with AIDSVAX B/E occurred at weeks 12 and 24.  All volunteers were followed with the use of HIV testing at day 0, at 24 and 26 weeks, and every 6 months during the 3- year follow-up phase.

7.  Presence of HIV infection was established on the basis of repeated positive results on enzyme immunoassay and Western blotting, with two confirmatory HIV nucleic acid tests  Three measurements of HIV-1 RNA were performed within 6 weeks after sero diagnosis to determine the mean post infection viral load.

8.  Self-administered behavioral questionnaire at baseline and every 6 months thereafter.  High risk if they reported any high-risk behavior  Low risk if they reported that in previous 6 months they had no more than one sex partner and no sexual contact with a commercial sex worker, no symptoms of a sexually transmitted disease  Moderate- risk subjects were considered to be at neither low nor high risk.

9.  The intention-to-treat analysis included all subjects who underwent randomization  The per-protocol analysis included subgroup of subjects in the intention-to-treat analysis who received the entire series of vaccinations within the defined time period, who remained eligible to participate in the study, and who did not have HIV infection at the time of the fourth vaccination  Modified intention-to-treat analysis, excluded the seven volunteers who were found to have HIV infection at baseline.

12. VariableVaccine (N=8187) Placebo (N=8196) All subjects (N=16395) Sex Male Female 5033(61.4%)5031(61.4%)10064(61.4%) 3164(38.6%)3167(38.6%)6331(38.6%) Age group ≤ 20yr2297(28%)2246(27.4%)4543(27.7%) 21-25yr3633(44.3%)3708(45.2%)7341(44.8%) ≥26yr2267(27.7%)2244(27.4%)4511(27.5%) Province Chon Buri4107(50.1%) 8214(50.1%) Rayong4090(49.9%)4091(49.9%)8181(49.9%)

13. VariablesVaccine (N=8187) Placebo (N=8196) All subjects (N=16395) Marital status Single3353(40.9%)3338(40.7%)6691(40.8%) Married4110(50.1%)4169(50.9%)8279(50.5%) Divorced602(7.3%)541(6.6%)1143(7%) Widowed50(0.6%)64(0.8%)114(0.7) Separated81(1%)86(1%)168(1%) No. of sex partner 01864(22.7%)1801(22%)3665(22.4%) 15428(66.2%)5494(67%)10923(66.6%) >1619(7.6%)620(7.6%)1239(7.6%) Did not answer280(3.4%)273(3.3%)553(3.4%) Missing data6(0.1%)9(0.1%)15(0.1%) Risk group Low Medium High 3865(47.2%) 2369(28.9%) 1963(23.9%) 3924(47.9%) 2292(28%) 1982(24.2%) 7789(47.5%) 4661(28.4%) 3945(24.1%)

14. BehavioralVaccine (N=8187) Placebo (N=8196) All subjects (N=16395) Needle sharing68(0.8)65(0.8)133(0.8) No condom use With casual partner497(6.1)439(5.4)936(5.7) With commercial sex worker33(0.4)29(0.4)62(0.4) With same sex partner79(.1)90(1.1)169(1) With HIV-infected partner16(.2)13(0.2)29(0.2) With partner who injects drugs12(0.1)6(0.1)18(0.1) With multiple sex partners128(1.6)130(1.6)258(1.6) Condom use with HIV-infected partner113(1.4)114(1.4)227(1.4) Symptoms of an STD within past 6 months 246(3.0)233(2.8)479(2.9) Drug injection in jail23(0.3)15(0.2)38(0.2) Occupation as CSW42(0.5)44(0.5)86(0.50%) Occupation in entertainment business233(2.8)237(2.9)490(2.9)

18. The observed vaccine efficacy were  Intention-to-treat analysis:26.4% (95% confidence interval [CI], −4.0 to 47.9; P = 0.08)  Per-protocol analysis:26.2% (95% CI, −13.3 to 51.9; P = 0.16)  Modified intention-to treat analysis:31.2% (95% CI, 1.1 to 52.1; P = 0.04 )

19. Variab le Vaccine (N= 8197)Placebo(N=8198)Vaccine efficacy No. evaluat ed No. with infectio n No. of person- years Rate No./per son-yr No. evaluat ed No. with infectio n No. of person- years Rate No./per son-yr %(95%CI ) All subject 796051265070.192798874264780.27931.2(1.7 to 51.8) Sex Male487532162210.197488543161790.26625.8(- 17.3 to 53 Female308519102860.185310331103000.30138.6(-8.6 to 65.3

20. Varia ble Vaccine (N=8197)Placebo (N=8198)Vaccine efficacy No. evalua ted No. with infecti on No. of person -years Rate No./pe rson- yr No. evalua ted No. with infecti on No. of person -years Rate No./pe rson- yr %(95%CI) Age gr ≤20yr22281273850.16321851172160.1527.1(-143 to 52.7 21- 25yr 351720117130.171361040119460.33549(12.8 to 70.2) ≥26yr22151974370.25521932373160.31418.7(-49.3 to 55.7)

21. VariableVaccine (N=8197)Placebo (N=8198)Vaccine efficacy No. evalua ted No. with infecti on No. of person -years Rate No./pe rson- yr No. evalua ted No. with infecti on No. of person -years Rate No./pe rson- yr %(95%CI ) Living with partner Yes401719134660.141408334136120.2543.5(1 to 67.8) No394332130410.242390540128660.31121(-25 to 50) Risk gr Low376717125650.135383729127980.22740.4(-8.5 to 67.2) Medium22971276420.15722222273530.29947.6(-6 to 74) High18962263000.34919292363270.3643.7(-72.7 to 46.3

23.  Modified intention-to-treat analysis showed a significant, reduction in the rate of HIV-1 infection, as compared with placebo.  Vaccination did not affect the viral load in subjects with HIV infection.

24. StudyStudy grType of vaccineResult of study Pitisuttithum P et al, Thialand(1999- 2000) 20–60 years, iv drug user during the past year, being negative for HIV-1 AIDSVAX B/E (VaxGen) (phase3) Vaccine efficacy was estimated at 0.1% and did not prevent HIV-1 infection Flynn NM et al, North America and The Netherlands (1998-1999) 18–62 years, did not use iv drugs, and were either men who have sex with men (MSM) or women at high risk for heterosexual transmission of HIV-1. AIDSVAX B/ B ( VaxGen) (Phase 3) No reduction of infection in vaccine recipients was observed (VE, 6%. No significant differences in viral loads