Integrated systems approach defines the antiviral pathways conferring protection by the RV144 HIV vaccine.

The RV144 vaccine trial showed reduced risk of HIV-1 acquisition by 31.2%, although mechanisms that led to protection remain poorly understood. Here we identify transcriptional correlates for reduced HIV-1 acquisition after vaccination. We assess the transcriptomic profile of blood collected from 223 participants and 40 placebo recipients. Pathway-level analysis of HIV-1 negative vaccinees reveals that type I interferons that activate the IRF7 antiviral program and type II interferon-stimulated genes implicated in antigen-presentation are both associated with a reduced risk of HIV-1 acquisition. In contrast, genes upstream and downstream of NF-κB, mTORC1 and host genes required for viral infection are associated with an increased risk of HIV-1 acquisition among vaccinees and placebo recipients, defining a vaccine independent association with HIV-1 acquisition. Our transcriptomic analysis of RV144 trial samples identifies IRF7 as a mediator of protection and the activation of mTORC1 as a correlate of the risk of HIV-1 acquisition.

HLA class II diversity in HIV-1 uninfected individuals from the placebo arm of the RV144 Thai vaccine efficacy trial.

The RV144 HIV vaccine trial in Thailand elicited antibody responses to the envelope of HIV-1, which correlated significantly with the risk of HIV-1 acquisition. Human leukocyte antigen (HLA) class II molecules are essential in antigen presentation to CD4 T cells for activation of B cells to produce antibodies. We genotyped the classical HLA-DRB1, DQB1, and DPB1 genes in 450 individuals from the placebo arm of the RV144 study to determine the background allele and haplotype frequencies of these genes in this cohort. High-resolution 4 and 6-digit class II HLA typing data was generated using sequencing-based methods. The observed diversity for the HLA loci was 33 HLA-DRB1, 15 HLA-DQB1, and 26 HLA-DPB1 alleles. Common alleles with frequencies greater than 10% were DRB1*07:01, DRB1*09:01, DRB1*12:02, DRB1*15:02, DQB1*02:01/02, DQB1*03:01, DQB1*03:03, DQB1*05:01, DQB1*05:02, DPB1*04:01:01, DPB1*05:01:01, and DPB1*13:01:01. We identified 28 rare alleles with frequencies of less than 1% in the Thai individuals. Ambiguity for HLA-DPB1*28:01 in exon 2 was resolved to DPB1*296:01 by next-generation sequencing of all exons. Multi-locus haplotypes including HLA class I and II loci were reported in this study. This is the first comprehensive report of allele and haplotype frequencies of all three HLA class II genes from a Thai population. A high-resolution genotyping method such as next-generation sequencing avoids missing rare alleles and resolves ambiguous calls. The HLA class II genotyping data generated in this study will be beneficial not only for future disease association/vaccine efficacy studies related to the RV144 study, but also for similar studies in other diseases in the Thai population, as well as population genetics and transplantation studies.

Sex-ratio patterns of AIDS patients in Thailand.

The summary report of AIDS cases in Thailand, as of 31 July 1996, was reviewed for the information on male-to female sex-ratio. The ratios were recalculated for different risk-factors and for different age-groups annually and cumulatively. The male-to-female ratios calculated for annual case reports are lower than the cumulative number. This finding demonstrates the earlier detection of change in risk behaviour among the general population by the sex-ratio from annual case reports, compared to the ratio from the cumulative number of cases. Among different age-groups, the older age shows the highest male-to-female ratio. The ratio among sexually active age-group (15-49 years of age) is declining during the most recent year. These changes confirm the present pattern of AIDS epidemic in Thailand, the fourth wave among females, followed by the last wave-pediatric AIDS.

PIP: The summary report of AIDS cases in Thailand as of July 31, 1996, was reviewed for information on the male-to-female sex ratio. The ratios were recalculated for different risk factors and different age groups both annually and cumulatively to find that the male-to-female ratios calculated for annual case reports are lower than the ratio calculated based upon the cumulative number of AIDS cases in the country. While AIDS was almost exclusively among men at the onset and during the early years of the epidemic, women are increasingly becoming infected with HIV at rates comparable to that among men. Among different age groups, the highest male-to-female ratio is among older individuals, while the ratio among people aged 15-49 years declined during the most recent year. Thailand is now facing the final waves of the HIV/AIDS epidemic, among females and increasingly among infants and very young children.

HIV-1 subtypes and male-to-female transmission in Thailand.

We examined the risk factors for heterosexual transmission of HIV in a case-control study of couples in Thailand. 90 HIV-positive men and their regular sex partners were enrolled at the immune clinic, Chulalongkorn Hospital, where 92% of male index cases had HIV-1 serotype A (subtype E). Most index cases had acquired HIV through sexual intercourse. 95 couples were enrolled at 15 detoxification clinics, where 79% of them had HIV-1 serotype B (subtype B). Most men had acquired HIV through injecting drug use (IDU).

PIP: A case control study was conducted during February 1992-April 1993 in Bangkok, Thailand, among 62 couples of which both partners were HIV seropositive (concordant couples [cases]) and 46 couples of which the man was HIV seropositive and the woman was HIV seronegative. The subjects were patients in the Immune Clinic in Chulalongkorn Hospital and in 15 drug detoxification (IDU) clinics. Couples in the immune clinic were more likely to be HIV seroconcordant than those in the IDU clinics (69% vs. 48%; 67% vs. 27%, after excluding females who were intravenous [IV] drug users; p 0.01). HIV-1 serotype B (subtype B) was more common among men in the IDU clinics while HIV-1 serotype A (subtype E) (79%) was more common among men in the immune clinic (92%). Seroconcordance was much more common when HIV-1 was of serotype A than when it was of serotype B (70% vs. 52%; odds ratio [OR] = 2.1; p 0.05). Further, when the researchers did not include couples of which the woman was an IV drug user, the difference in concordance was even greater (70% vs. 26%, OR = 6.8; p 0.01). These differences in concordance suggest that HIV-1 serotype A may be more efficiently transmitted than HIV-1 serotype B. The multivariate logistic regression analysis showed that independent risk factors of HIV seroconcordance were HIV-1 serotype A of male partners (adjusted OR = 3.1) and history of IV drug use in female partners (AOR = 4.8). HIV-1 subtype E may be linked to a higher risk of heterosexual transmission than subtype B. If so, the predominance of HIV-1 subtype E in Thailand could explain the rapid spread of HIV infection in Thailand.