ABSTRACT
Cytotoxic T lymphocyte (CTL) responses against the HIV Gag protein are associated with lowering viremia; however, immune control is undermined by viral escape mutations. The rapid viral mutation rate is a key factor, but recombination may also contribute. We hypothesized that CTL responses drive the outgrowth of unique intra-patient HIV-recombinants (URFs) and examined gag sequences from a Kenyan sex worker cohort. We determined whether patients with HLA variants associated with effective CTL responses (beneficial HLA variants) were more likely to carry URFs and, if so, examined whether they progressed more rapidly than patients with beneficial HLA-variants who did not carry URFs. Women with beneficial HLA-variants (12/52) were more likely to carry URFs than those without beneficial HLA variants (3/61) (p < 0.0055; odds ratio = 5.7). Beneficial HLA variants were primarily found in slow/standard progressors in the URF group, whereas they predominated in long-term non-progressors/survivors in the remaining cohort (p = 0.0377). The URFs may sometimes spread and become circulating recombinant forms (CRFs) of HIV and local CRF fragments were over-represented in the URF sequences (p < 0.0001). Collectively, our results suggest that CTL-responses associated with beneficial HLA variants likely drive the outgrowth of URFs that might reduce the positive effect of these CTL responses on disease progression.
Subject(s)
Genetic Variation , HIV Infections/virology , HIV-1/genetics , Recombination, Genetic , Sex Workers , Adult , Disease Progression , Female , Genotype , HIV Core Protein p24/genetics , HLA Antigens/genetics , Humans , Leukocytes, Mononuclear/virology , Molecular Typing , Mutation , gag Gene Products, Human Immunodeficiency Virus/geneticsABSTRACT
A campylobacteriosis outbreak investigation provides relevant examples of how two web-based technologies were used in an outbreak setting and potential reasons for their usefulness. A web forum aided in outbreak detection and provided contextual insights for hypothesis generation and questionnaire development. An online questionnaire achieved a high response rate and enabled rapid preliminary data analysis that allowed for a targeted environmental investigation. The usefulness of these tools may in part be attributed to the existence of an internet savvy, close-knit community. Given the right population, public health officials should consider web-based technologies, including web fora and online questionnaires as valuable tools in public health investigations.
