Vaginal Microbiocenosis Features in HIV-positive Women of Fertile Age

Aim and Objective of Our Study: The aim and objective of our study is to analyze the research data that has been studying the effect of HIV infection on vaginal microbiocenosis and further, to determine the differences in dysbiotic disorders in seronegative and seropositive women. We have also assessed the effect of vaginal microbiota on pre-exposure prophylaxis of HIV. Materials and Methods: Evaluation of the Russian and other countries results on the microbiota of HIV-positive women studies, published in international databases. Results: The analysis of the research data aimed at studying the effect of HIV infection on the vaginal microbiocenosis indicates that dysbiotic disorders in HIV-infected patients are significantly more frequent. It has been revealed that the atypical clinical picture of changes in the vaginal microbiocenosis prevails. It has been noted that there is a correlation of vaginal microbiocenosis in HIV-positive women and indicators of systemic immunity, CD4 + cell levels. Conclusion: Based on analysis of published in international databases Russian and other countries studies results on the HIV-positive women microbiota, it was found that there is a need for additional studies of the qualitative and quantitative composition of the microbiota of HIVpositive women. It is need to assess the of the vaginalmicrobiotaand other possible connected factors ability to change the concentration of antiretroviral drugs. Review Article Marianian et al.; JPRI, 32(23): 78-84, 2020; Article no.JPRI.60870 79


INTRODUCTION
HIV remains a major problem for public health services. According to the AIDS Center of the Irkutsk region, the number of HIV-positive women who are sexually infected increases every year. In 2018, the incidence rate was 141.7 cases per 100 thousand people in the Irkutsk region, among which 44.8% were women, mostly of reproductive age [1,2,3]. The aim and objective of our study is to analyze the research data that has been studying the effect of HIV infection on vaginal microbiocenosis and further, to determine the differences in dysbiotic disorders in seronegative and seropositive women. We have also assessed the effect of vaginal microbiota on pre-exposure prophylaxis of HIV. The Evaluation of the Russian and other countries results on the microbiota of HIV-positive women studies, published in international databases has been performed.

The Interrelation between Bacterial Vaginosis and the Risk of HIV Transmission
The vaginal microflora includes more than 300 species of micro-organisms that are closely related to the structural components of the vagina. The vaginal epithelium is covered with a multi-layer flat non-corneal epithelium, which changes in response to the action of body hormones. Under the influence of estrogens, epithelial cells are saturated with glycogen, which saturates microorganisms [4].  [14]. Due to the disturbances in the quantitative and qualitative composition of the microbiota, and the antioxidant defenseenzymesactivitydecreases [15]. The hyperperoxidation processwith a decrease in the adaptive capabilities of the antioxidant defensesystem leads to the oxidative stress increasing [16,17].
Most studies related to the black race Africa HIVpositive women vaginal microbiota investigations. To evaluate the data, microscopic methods have mainly been used, which create an incomplete picture of the micro-biota of the vagina.   [24]. The study in Kenya has shown that impaired vaginal microbiocenosis contributes to HIV infection and gonorrhea [25]. Other studies have shown that HIV-positive women with bacterial vaginosis have a higher concentration of the pathogen in the vaginal contents [26]. Taking

Features of Vaginal Microbiocenosis in Highly Active Anti-retroviral Therapy and the Localuse of Drugs
Nowadays the drugs for pre-exposure prophylaxis of HIV has been widely studied [30,31]. Daily oral administration of tenofovirbased drugs is very effective for reducing the incidence of HIV; this type of prevention applies to population groups with a high risk of HIV infection [32,33]. The drugs containing, for example, dapivirin, tenofoviral afenamide, maraviroc, etc., are also at various stages of research and can become promising options for HIV prevention with prolonged action [34,35,36]. However, in 2017 N. R. Klattet al. suggested that the effectiveness of locally applied drugs for preexposure prophylaxis of HIV may decrease their activityif the vaginal microflora is disturbed [37]. This is a serious health problem, given the wide spread of bacterial vaginosis in women in the areas most involved in the epidemic process [38].
The secondary analysis from the CAPRISA-004 cohort has shown that the effect of a 1% tenofovir-based gel in the presence of a vaginal microbiota dominated by Gardnerella vaginalis and other anaerobic bacteria is absent [39].In 2017, a data analysis was published comparing the effectiveness of oral and topical tenofovirbased drugs for pre-exposure prophylaxis of HIV for women with and without bacterial vaginosis. It has been found that the effectiveness of oral drugs for pre-exposure prophylaxis of HIV does not change in the presence of bacterial vaginosis. Gardnerella vaginalis can rapidly metabolize tenofovir, especially when it is only applied locally, and prevent the medicine from entering cells. Vaginal dysbiosis associated with Gardnerella vaginalis disrupts metabolism and reduces the effectiveness of 1% tenofovir gel, but not of oral tenofovir-based drugs for preexposure prophylaxis of HIV. There were no significant differences in the efficiency between oral drugs for pre-exposure prophylaxis of HIV in the period when a woman does not have a microbiota disorder (Nugent score 0-3 points), in the intermediate smear type (4-6 points) and bacterial vaginosis (score 7-10 points) [40]. All this lead to suggestion, that vaginal dysbiotic disorders may not significantly reduce the effectiveness of oral drugs for pre-exposure prophylaxis of HIV. Active metabolites of tenofovir are systemically distributed and are found in higher concentrations in blood plasma when used orally than when used locally [40,41].
Tenofovir metabolism can occur fairly quickly; studies have shown a decrease in the level of tenofovir diphosphate (the active form of tenofovir) in the cervical tissue within two hours and a decrease in its concentration in the cervicovaginal fluid and plasma after one week in the presence of an excess amount of Gardnerella vaginalis [42].
The use of highly active antiretroviral therapy (HAART) has significantly increased the life expectancy of HIV-positive patients. However, one of the important problems for such patients is the addition of opportunistic infections [43]. In 2015, M. Lallar et al. published data on the prevalence of bacterial vaginosis, candidiasis, and trichomoniasis in HIV-seropositive women. The authors have evaluated the interrelation between the use of HAART and CD4 +.The study involved 200 HIV-positive women aged from 18 to 45 years. Bacterial vaginosis was detected in 47.7% of cases, candidiasis in 43.2% and trichomoniasis in 8.8% of cases among them. Reproductive tract infection has been found in 30% of cases in women with the number of CD4+ lymphocytes <200 cells/ml and in 17 % of cases in women with the level of CD4+ >200 cells / ml.Reproductive tract infection was detected in 23% of cases while receiving HAART, and in 18.6% of cases when there was no antiretroviral therapy. At low CD4+ levels in HIV-positive women, the detection of reproductive tract infection is higher, but the use of HAART does not reduce the prevalence of it [44]. The main goal of HAART is to interrupt virus replication in the body and increase the number of CD4 + lymphocytes to restore a normal immune response. In HIV-positive pregnant women, when taking HAART, there was an increase in cases of normocenosis, a decrease in cases of violation of vaginal microbiocenosis associated with Mycoplasma spp. [45,46,47,48].The restoration of local immunity, namely the presence of a stable vaginal microbiocenosis, is possible due to the implementation of the clinical effect of antiretroviral therapy.

CONCLUSION
Most studies reflecting the high prevalence of vaginal microflora disorders in HIV-positive women, compared to seronegative women,have been conducted among the African women.
The data on the study of the microbiota of HIVpositive women of European and Asian race are not available. It is necessary to assess the qualitative and quantitative composition of HIVpositive women in our country.

CONSENT
It is not applicable.

ETHICAL APPROVAL
It is not applicable.