Biological cofactors of HIV transmission in women

• Main Author: Sturm-Ramirez, Katharine Marie
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01.01.2001
• Subjects: Disease transmission; HIV; Human immunodeficiency virus; Immunology; Microbiology; Public health; Women
• ISBN: 0493216774; 9780493216775

Epidemiological studies have shown that ulcerative sexually transmitted infections (STIs) enhance sexual transmission of HIV. The impact of non-ulcerative genital infections is not as clear. In this thesis, we proposed to investigate the biological impact of non-ulcerative, inflammatory genital infections and the potential mechanism by which they can enhance HIV transmission in women. First, using a sensitive PCR-based detection assay we determined the prevalence (28.5%) and diversity of Chlamydia trachomatis in a cohort of female sex workers in Senegal, West Africa. Six C. trachomatis genotypes were identified based on phylogenetic analysis of the omp1 gene. Genotype E predominated (47.6%) and was associated with asymptomatic cervical infection. Inflammatory symptoms associated with infection, rather than the detection of an STI-causing pathogen, may be a more relevant cofactor for HIV transmission. Various inflammatory STIs are associated with an increase in proinflammatory cytokines in vitro or in animal models. Proinflammatory cytokines TNF-α and IL-1β enhance HIV replication in vitro. Therefore, it seemed particularly relevant to study these cytokines in the genital tract of women, where HIV transmission occurs. In the second study, we determined that IL-1β and TNF-α could be routinely quantified in cervical secretions of HIV-negative women. Additionally, bacterial vaginosis (BV) was associated with high levels of cervical IL-1β and TNF-α. This may in part explain why BV enhances susceptibility to HIV infection in women. In the final study we investigated the association between increased levels of pro-inflammatory cytokines—due to STIs or BV—and viral shedding in the genital tract of HIV-1 infected women. The impact of STI or BV treatment on genital cytokines and viral shedding was also assessed. Cervical proviral DNA levels were associated with BV, trichomoniasis and concentrations of IL-1β and TNF-α in cervical secretions. STI or BV treatment had no effect on cervical proviral DNA levels and led to moderately decreased cytokine levels. This small study allowed us to tailor novel ultra-sensitive quantitative methods for work with genital secretions of women. Future studies will be required to appropriately quantify the impact of STI or BV treatment on HIV-1 shedding in the female genital tract.