Factors Contributing to the Lack of Human Immunodeficiency Virus Type 1 (HIV‐1) Transmission in HIV‐1–Discordant Partners

Abstract

Correlates of resistance to infection by human immunodeficiency virus type 1 (HIV-1) are important for defining potential therapeutic interventions and for prophylactic vaccination. In this study, 11 couples discordant in their HIV-1 infection status were prospectively evaluated for the presence of protective factors. Behavioral characteristics of all subjects entailed a high risk of transmission. Cytotoxic T lymphocyte (CTL) responses against viruses isolated from the infected partner, and against laboratory virus isolates, were detected in 5 (45%) of 11 HIV-negative partners, including a CCR5Delta32-homozygous and a heterozygous subject. No CTL responses were observed in 6 control unexposed subjects. Marked variation in lymphocyte susceptibility to viral infection was noted. Resistance attributable to major histocompatibility complex discordance or anti-major histocompatibility complex antibodies was not identified. These results suggest that a combination of factors, including cellular immunity, viral characteristics, and coreceptor integrity, may be involved in the persistent nontransmission of HIV.

Low-Level CD4+ T Cell Activation Is Associated with Low Susceptibility to HIV-1 Infection

“…Heterozygosity for the CCR5-⌬32 allele and high expression levels of the CCR5 ligand RANTES have also been associated with resistance to HIV infection (22)(23)(24). HIV-specific CTLs have been identified in many exposed seronegative individuals, suggesting a role for HIV-specific CTL responses in resistance to HIV-1 infection (5,15,(25)(26)(27)(28)(29)(30). However, these responses do not necessarily reflect protective cellular immunity from infection but may merely reflect exposure to the virus since we found similar amounts and specificity of HIV-specific CTLs in seronegative men who later became HIV-1 seropositive (31,32).…”

Favorable and Unfavorable HLA Class I Alleles and Haplotypes in Zambians Predominantly Infected with Clade C Human Immunodeficiency Virus Type 1

“…There is a growing consensus that specific HLA alleles and heterozygosity at HLA class I loci can collectively exert a strong impact on disease progression in human immunodeficiency virus type 1 (HIV-1) infection (6,8,21,22,30,31,35,41,62,63); much of the effect appears to correlate with cytotoxic T-lymphocyte (CTL) responses directly restricted by class I allelic products in both humans (3,16,18,34,56) and chimpanzees (2). HLA markers associated with delayed HIV-1 disease progression may present epitopes found more frequently in various HIV-1 proteins (45), and the two most prominent alleles (B*27 and B*57) have been found experimentally to induce immunodominant CTL responses to conserved HIV-1 epitopes (15,19,20,44).…”

Broad Human Immunodeficiency Virus (HIV)–Specific T Cell Responses to Conserved HIV Proteins in HIV‐Seronegative Women Highly Exposed to a Single HIV‐Infected Partner

“…Only a few of these studies involved male-female serodiscordant couples [18,19]. Most of the data come from studies of commercial sex workers, for whom it is difficult to determine factors that may influence HIV transmission, such as the characteristics of the virus to which these women were exposed, how many times they were exposed, or when they were last exposed.…”