HIV and the Vaginal Ecosystem
The vagina, as a potentially healthy structure that can defend against invasion by HIV and other pathogens, received appropriate recognition at the May 1997 National Conference on Women and HIV. Penelope Hitchcock, D.V.M., of the National Institutes of Health gave a state-of-the-art lecture, "The Vaginal Ecosystem: Nature's Gate-Keeper for Reproductive Health of Women." Throughout the conference, researchers offered accolades for the healthy vagina, although many mentioned that such a thing was not easy to find in today's world. The importance of vaginal health was related to risk for acquiring and transmitting HIV and other STDs. Factors related to vaginal health are believed to include: pH (acid/base balance), local immune factors, female hormones, the menstrual cycle, sexual maturity and development, use of contraceptives, douching, sexual practices, and the types of organisms present.
The healthy vagina has a number of natural protective factors against STD/HIV infection and related diseases. At puberty, with the onset of menstruation, the female genital tract undergoes changes due to the influence of the female sex hormone, estrogen. The previously thin and fragile vaginal mucosa grows plump and resilient, and becomes rich in glycogen (a form of glucose). Now, healthy organisms, the lactobacilli, begin to thrive. Lactobacillus uses glycogen as an energy source, breaking it down into glucose and lactic acid. Under the influence of lactic acid, the vagina maintains a low (acidic) pH of approximately 4.0. This acidic condition does two important things: (1) it kills germs, and (2) it causes squamous epithelial cells (mucous membrane) to cover over the exposed, fragile columnar cells of the cervical canal. Lactobacillus also produces hydrogen peroxide, which kills pathogens. Protective immune factors in the vagina include defensins, antibodies, nonspecific cytokines and inflammatory responses.
Factors Increasing Susceptibility to STDs/HIVInflammatory responses (including increased blood vessel permeability, tissue swelling and irritation accompanied by local invasion by lymphocytes and macrophages) also can contribute to increased susceptibility to HIV. Inflammation is triggered by various germs (especially yeast, bacteria and trichomonas) or mechanical trauma (including penetration, douching, tampon use, pelvic examinations and vaginal treatments). When the vagina is inflamed, it is characterized by microabrasions (tiny breaks in the mucosa), presence of white blood cells, red blood cells, infection-causing bacteria and an elevated pH of 5.5-7.0.
Test-tube research showed that there is a synergistic enhancement of HIV replication by both chlamydia and the accompanying presence of inflammatory white blood cells (Landers, 1997). And Sharon Hillier, M.D., reported at the National Conference that data now show an association between bacterial vaginosis (a common vaginal infection) and risk for acquiring HIV infection. Chlamydia infection is also a risk factor for HIV acquisition. Clinicians have logically assumed that STDs that cause genital ulcers (herpes, syphilis, chancroid, granuloma inguinale) in addition to inflammation are associated with further increased risk for acquiring HIV in both males and females.
Hormone levels during menstrual cycling also affect susceptibility to infection. A recent report (Howell, 1997) postulated that there is a waxing and waning of protection against HIV during the menstrual cycle. In the second half of the cycle, the immune system is suppressed so that sperm won't be destroyed, and there is an increased risk of infection. Low estrogen levels directly affect the vaginal mucosa, making it thin and friable. Other factors known to lower estrogen levels include breast-feeding, menopause and malnutrition.
Sexual transmission of HIV is thought to occur by infection of host CD4 lymphocytes, macrophages and dendritic cells, the last of these being especially abundant in the cervical canal, where the columnar epithelium is found. Exposed columnar epithelium cells (referred to as cervical ectopy) are associated with an increased risk of transmission of numerous pathogens, including gonorrhea, chlamydia and HIV. Cervical ectopy is present in adolescents, during pregnancy and after childbirth.
Ectopy also occurs with some hormonal contraceptives. Counter to previously held theories that they offered some protection against STDs, these methods do not protect against gonorrhea and chlamydia and may even contribute to greater susceptibility. Oral contraceptives (OC) contribute to cervical ectopy and the progesterone-based methods (depo-provera, NorplantTM and the mini-pill) can cause irregular bleeding. Both conditions are currently believed to increase transmission of STDs.
In a review of 25 studies regarding risk of HIV acquisition in OC users, Ward Cates, M.D., of the Emory University and University of North Carolina Schools of Public Health, found that there were no case-controlled, prospective studies, and that the range of associations were from slightly protective to clearly harmful. When summing up four studies concerning use of progesterone-based methods at the National Conference on Women and HIV, Cates observed that these methods nearly double a woman's risk for acquiring HIV.
HIV in the Female Genital TractThough HIV can be detected in a majority of genital secretions from HIV-positive women, high HIV levels in genital secretions are often associated with high plasma blood HIV levels and/or genital tract infections or inflammation (Cu-Uvin, 1997; Hart, 1997; Kovacs, 1997). HIV viral load in genital tract secretions is determined by cervicovaginal lavage (CVL), a technique in which saline solution is sprayed into the vaginal vault and then recovered for testing. The cervicovaginal secretions (CVS) can then be tested for HIV by either quantitative culture or PCR testing. The cellular fraction of the sample can be separated from the cell-free fraction for separate quantitative testing. Infectivity is assumed to be possible when either fraction tests positive, but HIV viral shedding is strongly associated with high concentrations of cell-free virus.
Investigation of HIV viral loads in vaginal secretions has been conducted in the natural history studies over the past three years (WIHS, WITS, and HERS), as well as in other cohorts of HIV-positive women. WIHS (Women's Interagency HIV Study) data indicate that 63% of women with HIV have HIV-positive cervicovaginal secretions, with good correlation between the CVS viral load and blood plasma viral load. WIHS found that CVS HIV positivity decreased with increasing CD4 count, but was significantly associated with history of genital tract warts. WIHS data also suggest that HIV-negative women have more acute genital infections, but positive women have more lower genital tract symptoms suggestive of chronic inflammation (discharge, itch, vulvar pain, ulcerations) without a finding of STD on clinical examination.
A substudy within WIHS is examining the role of local immune factors in the lower female genital tract. Twenty-five percent of HIV-positive women had antibody dependent cell-mediated cytotoxicity (ADCC) against HIV gp120. High serum ADCC antibody titers are considered to be associated with better immune function.
In the Emory Vaginal Ecology Study (EVE), cell-free and cell-associated fractions of the CVS were present in about 65% of subjects. There was a good correlation between plasma HIV and CVS HIV. A substudy in EVE measured the effect of antiretroviral therapy on viral load in CVS. For all nine women studied, any new HIV therapy correlated with a decrease in CVS viral load (median decrease of 1.4 logs or 95%), compared to a nonsignificant 33% decrease in CVS viral load in the control group on no treatment.
A similar study of CVS conducted at Harvard Medical School could detect cell-free HIV in 59% of samples. The existence of appreciable free virus was associated with visible blood in the CVS specimen, vaginal candidiasis, and low CD4 counts. Free virus did not correlate with the acidity of the CVS, presence of non-visible red blood cells, use of hormonal contraceptives, other genital tract infections or current use of HIV therapies.
Impact of HIV Infection on Local Vaginal EcologyWomen with HIV have several important concerns regarding vaginal ecology beyond worries about the risk of mucosal transmission of HIV to sexual partners and children. But basic scientific inquiry into how the presence of HIV affects women's lower genital tract remains unanswered. There is clinical and biological evidence that HIV interacts there with other viral infections, notably CMV, HSV (herpes simplex virus) and HPV. HIV's presence in particular may up-regulate local factors that favor growth of HPV.
If vaginal HIV leads to chronic, nonspecific inflammation, are positive women then more vulnerable to additional genital tract infections? Positive women often complain of increased vaginal discharge and irritation. Does chronic inflammation discourage or welcome new pathogens? Are systemic or local immune factors more significant in the increased prevalence of vaginitis, pelvic inflammatory disease and genital warts? Local factors may be responsible for vulvovaginal candidiasis preceding oral/pharyngeal candidiasis in positive women. How does the presence of HIV in cervicovaginal secretions affect vaginal pH and the presence of lactobacillus? In the presence of inflammatory cells, the pH is often increased. Altered pH generally does not favor a healthy vaginal ecology or growth of lactobacilli. Does HIV infection per se, affect female hormonal levels? If so, does this happen due to local factors or systemic factors? Vaginal health can be enhanced by self-inspection, frequent gynecological evaluations, prompt diagnosis and treatment for any genital tract infections, refraining from douching, and using comfort measures for any symptoms (see "Comfort Measure for Vaginal Conditions"). Are there specific interventions that apply to improving the vaginal health of women with HIV? It is critical that research efforts do not ignore these crucial questions in favor of exclusively studying vaginal HIV viral shedding and the mechanics of mucosal HIV transmission.
ReferencesCu-Uvin S. National Conference on Women and HIV. May 1997; abstract 111.1. Farrar DJ et al. National Conference on Women and HIV. May 1997; abstract 111.2.
Hart C. National Conference on Women and HIV. May 1997; abstract 111.4.
Howell AL et al. Journal of Virology. May 1997; 71(5):3498-506.
Kovacs A. National Conference on Women and HIV. May 1997; abstract 111.5.
Landay AL et al. National Conference on Women and HIV. May 1997; abstract 111.6.
Landers DV et al. Fourth Conference on Retroviruses. January 1997; abstract 278.
Palmore M et al. National Conference on Women and HIV. May 1997; abstract 111.3.
This article was provided by Gay Men's Health Crisis. It is a part of the publication GMHC Treatment Issues. Visit GMHC's website to find out more about their activities, publications and services.