Chirasak Khamboonruang

Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand

BACKGROUND The development of a safe and effective vaccine against the human immunodeficiency virus type 1 (HIV-1) is critical to pandemic control. METHODS In a community-based, randomized, multicenter, double-blind, placebo-controlled efficacy trial, we evaluated four priming injections of a recombinant canarypox vector vaccine (ALVAC-HIV [vCP1521]) plus two booster injections of a recombinant glycoprotein 120 subunit vaccine (AIDSVAX B/E). The vaccine and placebo injections were administered to 16,402 healthy men and women between the ages of 18 and 30 years in Rayong and Chon Buri provinces in Thailand. The volunteers, primarily at heterosexual risk for HIV infection, were monitored for the coprimary end points: HIV-1 infection and early HIV-1 viremia, at the end of the 6-month vaccination series and every 6 months thereafter for 3 years. RESULTS In the intention-to-treat analysis involving 16,402 subjects, there was a trend toward the prevention of HIV-1 infection among the vaccine recipients, with a vaccine efficacy of 26.4% (95% confidence interval [CI], -4.0 to 47.9; P=0.08). In the per-protocol analysis involving 12,542 subjects, the vaccine efficacy was 26.2% (95% CI, -13.3 to 51.9; P=0.16). In the modified intention-to-treat analysis involving 16,395 subjects (with the exclusion of 7 subjects who were found to have had HIV-1 infection at baseline), the vaccine efficacy was 31.2% (95% CI, 1.1 to 52.1; P=0.04). Vaccination did not affect the degree of viremia or the CD4+ T-cell count in subjects in whom HIV-1 infection was subsequently diagnosed. CONCLUSIONS This ALVAC-HIV and AIDSVAX B/E vaccine regimen may reduce the risk of HIV infection in a community-based population with largely heterosexual risk. Vaccination did not affect the viral load or CD4+ count in subjects with HIV infection. Although the results show only a modest benefit, they offer insight for future research. (ClinicalTrials.gov number, NCT00223080.)

Changes in Sexual Behavior and a Decline in HIV Infection among Young Men in Thailand

BACKGROUND In Thailand the epidemic of human immunodeficiency virus (HIV) infection is of recent origin. Because of the high seroprevalence of HIV among sex workers, the Ministry of Public Health began a program in 1990 and 1991 to promote the use of condoms during commercial sex. We evaluated the effect of this and other programs to prevent HIV infection in Thailand. METHODS Using direct interviews, we studied five cohorts of 21-year-old men from northern Thailand who were conscripted into the army by a lottery in 1991, 1993, and 1995. In all, 4311 men were tested for HIV antibodies by enzyme-linked immunosorbent assay, with confirmation by Western blot assay. RESULTS In the 1991 and 1993 cohorts, the prevalence of HIV infection was 10.4 to 12.5 percent. In 1995, it fell to 6.7 percent (P < 0.001). The seroprevalence was only 0.7 percent among men who did not have sexual relations with a sex worker before 1992. Over the study period, the proportion of men who reported having sexual relations with a sex worker fell from 81.4 percent to 63.8 percent (P < 0.001). From 1991 to 1995, the mens reported use of condoms during the most recent sexual contacts with sex workers increased from 61.0 percent to 92.5 percent (P < 0.001); and in 1995, 15.2 percent of men had a history of a sexually transmitted disease, as compared with 42.2 percent in 1991 (P < 0.001). CONCLUSIONS Public health programs in Thailand have led to substantial changes in sexual behavior among young men, especially an increased use of condoms, and the rate of new HIV infections has declined.

Epidemiologic and biologic characterization of a cohort of human immunodeficiency virus type 1 highly exposed, persistently seronegative female sex workers in northern Thailand

Characterization of persons highly exposed to human immunodeficiency virus (HIV)-1 who remain uninfected may help define protective immunity. Seventeen HIV-1-seronegative Thai female sex workers (CSWs) with epidemiologic evidence of exposure to HIV-1 were studied for humoral immune responses and phenotypic and genotypic analyses of HLA class I and CCR5 allelic profiles. Infected CSWs and low-risk HIV-1-seronegative Thai women were controls. Highly exposed, persistently seronegative (HEPS) CSWs did not differ from HIV-infected CSWs in HIV risks, condom use, or sexually transmitted diseases. Significant differences were seen in humoral immune responses: gp160-specific IgA responses were detected in cervicovaginal lavage fluids in 6 of 13 HEPS CSWs but 0 of 21 seronegative subjects. All women had wild-type CCR5. HEPS CSWs were more likely to have the HLA-B18 phenotype and genotype than were matched controls (corrected P=.018). Epidemiologic exposure to HIV-1 without apparent infection, an unusual distribution of HLA class I alleles, and HIV-1 gp160-specific IgA responses suggest a biologic basis for this phenomenon.

Decreasing incidence of HIV and sexually transmitted diseases in young Thai men: Evidence for success of the HIV/AIDS control and prevention program

Objective:To determine whether HIV and sexually transmitted disease (STD) incidence rates among young men in northern Thailand have declined since the establishment of the ‘100% Condom Program’, and to prospectively document changes in the association between behavioral risk factors and incident HIV and STD infections. Setting:Thirteen military bases in northern Thailand. Methods:Serial prospective cohorts of 19–23-year-old male conscripts (n = 4086) inducted into military service from six northern Thai provinces between 1991 and 1993 were followed at 6-month intervals for incident HIV and STD through May 1995. HIV incidence was determined by serology, and incident STD were reported by conscripts as diagnosed by health-care providers. Results:HIV incidence declined from a rate of 2.48 per 100 person-years during 1991–1993 to 0.55 per 100 person-years during 1993–1995. STD incidence showed an even greater decline, with a 10-fold decrease from 1991–1993 to 1993–1995. Behavioral risk factors for incident STD infections included a history of prior STD and sex with girlfriends and sex workers. Inconsistent condom use remained a strong predictor of incident STD among brothel visitors. Other previously-reported risk factors in 1991–1993 such as illicit drug use, frequency and cost of brothel visits, and low socioeconomic status were not associated with incident STD or HIV in 1993–1995. Conclusions:Although several studies have recently reported decreased prevalence of HIV and STD infections in Thailand, these data demonstrate that a dramatic decrease in the incidence rates of STD, including HIV infection, has occurred among young men in military service in northern Thailand. The Thai AIDS prevention and control program might be implemented by other countries experiencing major epidemics of heterosexually transmitted HIV infections. Similar prevention programs targeted at other populations in Thailand and elsewhere in Asia are needed to decrease the spread of the HIV epidemic.

Risk behaviour and time as covariates for efficacy of the HIV vaccine regimen ALVAC-HIV (vCP1521) and AIDSVAX B/E: a post-hoc analysis of the Thai phase 3 efficacy trial RV 144.

Background The Thai phase III HIV vaccine trials modest efficacy (VE 31.2% 95% CI 1.1, 51.2) represents the first demonstration that a vaccine can protect against HIV acquisition. Baseline variables of age, gender, marital status, and risk did not modify vaccine efficacy (VE). Here we explore behavioral risk and efficacy at 6 monthly intervals following vaccination.

A phase 1/2 comparative vaccine trial of the safety and immunogenicity of a CRF01_AE (subtype E) candidate vaccine: ALVAC-HIV (vCP1521) prime with oligomeric gp160 (92TH023/LAI-DID) or bivalent gp120 (CM235/SF2) boost.

Background:The development of an effective HIV-1 vaccine is critical to control the pandemic. A prime-boost HIV-1 vaccine trial assessing safety and immunogenicity was conducted in Thailand as part of an evaluation of candidate regimens for a phase 3 efficacy trial. Methods:ALVAC-HIV (vCP1521), expressing circulating recombinant form 01_AE (CRF01_AE) gp120/subtype B LAI and subtype B Gag/Protease boosted with recombinant envelope oligomeric CRF01_AE gp160 (ogp160) or bivalent CRF01_AE/subtype B gp120 CM235/SF2, was evaluated in a phase 1/II trial of 130 HIV-negative Thai adults. Results:One hundred forty volunteers were enrolled, and 130 completed all safety and immunogenicity visits. Reactogenicity was common but generally mild, and there was no significant difference in the adverse event rate between vaccine and placebo recipients (P = 0.26). There were 7 serious adverse events during the follow-up period, none of which were vaccine related. Cumulative HIV-specific, CD8-mediated, cytotoxic T-lymphocyte responses were observed in 11 (25%) of 44 subjects who received ALVAC boosted by bivalent gp120 and in 5 (11%) of 45 subjects who received ALVAC boosted by ogp160, but these differences were not statistically significant compared with those in placebo recipients (P = 0.62 and P = 0.37, respectively). HIV-specific lymphoproliferative responses were detected in 84% of subunit-boosted vaccine recipients and in 10% of placebo recipients. Neutralizing antibody responses to CRF01_AE and subtype B laboratory strains were seen in 95% of ogp160-boosted and 100% of gp120 B/E-boosted vaccinees, respectively. Conclusions:These 2 different prime-boost regimens seem to be safe and displayed cell-mediated immune responses consistent with those in other trials of canarypox vectors.

Same-sex behavior, sexually transmitted diseases and HIV risks among young northern Thai men.

Objectives: To assess the risks for HIV infection and sexually transmitted diseases (STD) among young northern Thai men who have sex with men (MSM), and to examine the possible role of male same‐sex behavior in the northern Thai HIV/AIDS epidemic. Methods: Two cohorts of northern Thai military conscripts and one cohort of recently discharged conscripts, a total of 2047 men, were studied. Data were collected by interview on behavioral risk factors, and sera were examined for syphilis and HIV‐1 antibodies. Univariate and multiple logistic regression analyses were used to determine risk factors associated with HIV and STD, and to assess the frequency and patterns of same‐sex behaviors among these men. Results: Of 2047 men, 134 (6.5%) reported one or more male lifetime sex partners. Of these MSM, 130 (97.0%) also had female partners, and four (3.0%) had exclusively male partners. Compared with men who reported only female sex partners, MSM had a higher number of lifetime sex partners, a higher mean number of female sex partners, more female and male commercial sex worker (CSW) partners, and were more likely to be married. MSM were significantly more likely than exclusively heterosexual men to report having had any STD [odds ratio (OR), 2.72], gonorrhea (OR, 2.05), syphilis (OR, 3.17), non‐gonococcal urethritis (OR, 4.54) and penile discharges (OR, 6.24). They were at borderline increased risk for HIV infection [OR, 1.51; 95% confidence interval (Cl), 0.95‐2.41]. Men with more than one lifetime male sex partner compared with those with only one partner were significantly more likely to be HIV‐infected (OR, 2.81; 95% Cl, 1.09‐7.19). Conclusions: Northern Thai MSM are a high‐risk population for STD, including HIV. Reported same‐sex behavior in this population appears to vary considerably with data collection techniques. HIV and STD prevention strategies aimed at changing unsafe sexual practices may need to be targeted to the general population of young Thai men.

Ovitrap surveys of dengue vector mosquitoes in Chiang Mai, northern Thailand: seasonal shifts in relative abundance of Aedes albopictus and Ae. aegypti

ABSTRACT. Aedes aegypti (L.) and Aedes albopictus (Skuse) were surveyed using ovitraps in residential areas in Chiang Mai, northern Thailand. Egg populations (both species inclusive) remained low in the dry season, but increased/decreased exponentially during the first/latter half of the rainy season, respectively. This seasonal pattern was similar to the seasonal distribution of dengue haemorrhagic fever cases in the area. During the dry season (November–March) Ae. aegypti was dominant in urban and indoor ovitraps. With onset of the rainy season in April, relative abundance of Ae. albopictus increased in rural and outdoor ovitraps. Ae. albopictus displaced Ae. aegypti in the latter half of the rainy season in the rural area. Possible mechanisms to account for this seasonal decline of Ae. aegypti and reciprocal fluctuations in relative abundance of Ae. albopictus are discussed in relation to food availability for larvae in container habitats.

A phase I/II trial of HIV SF2 gp120/MF59 vaccine in seronegative Thais.

Abstract Fifty-two human immunodeficiency virus type 1, seronegative Thai adults from the community were enrolled in a double-blind, placebo controlled, phase I/II trial of HIV SF2 gp120/MF59 vaccine to determine the safety and immunogenicity of this recombinant, B clade, HIV envelope protein vaccine. Twenty-six subjects were enrolled at each of two sites in Thailand, Bangkok and Chiang Mai. Twelve subjects received placebo and 40 subjects received vaccine (50 μg). Subjects were immunized according to one of two schedules, 0, 1 and 4 or 0, 1 and 6 months. The frequency of adverse reactions was not different between placebo and vaccine subjects, nor between immunization schedules. Of vaccinees, all developed high-titer binding antibody to the immunogen (rgp120), 39 developed neutralizing antibody (NA) responses against homologous virus (HIV-1SF2), and 22 developed NA against heterologous virus (HIV-1MN). No subject demonstrated intercurrent HIV infection, however screening EIA reactivity occurred in 27% of recipients. Thus, this candidate HIV vaccine was found to be safe and immunogenic in Thai adults, laying the foundation for development of a subtype E construct in this population.

Safety and Immunogenicity of Combinations of Recombinant Subtype E and B Human Immunodeficiency Virus Type 1 Envelope Glycoprotein 120 Vaccines in Healthy Thai Adults

Safety and immunogenicity of 2 recombinant human immunodeficiency virus (HIV) type 1 envelope glycoprotein (gp) 120 vaccines derived from SF2 (subtype B) and CM235 (CRF01_AE, Thai E) were evaluated in 370 Thai adults at low risk of HIV infection. Various doses of CM235 (25, 50, or 100 microg) and SF2 (0, 25, or 50 microg) gp120 were used. Eighty volunteers received placebo. There were no serious adverse events related to vaccination. Binding antibody developed in all vaccine recipients. There was no dose response to CM235 gp120, but a dose response to gp120 SF2 was present. Neutralizing antibodies to subtype E HIV-1 NPO3 and subtype B HIV-1 SF2 developed in 84% and 82% of vaccine recipients, respectively. Lymphoproliferative responses were detected in >95% of vaccine recipients. There was no evidence of antigenic interference in HIV-specific humoral or cellular responses. The gp120 Thai E and SF2 vaccines were safe and immunogenic in combination and could be advanced into phase 3 testing.