Women account for approximately one-half of all human immunodeficiency virus (HIV) infections worldwide. Sexual transmission is the dominant mode of HIV transmission to women, and there is a ...concomitant associated epidemic of transmission to infants. The majority of HIV infections in women are in sub-Saharan Africa, with a disproportionate burden in young women <25 years of age. Acquisition and prevention of HIV infection in women is complex and influenced by biological, behavioral, and structural factors. Efforts to reduce the incidence of HIV infection among women in sub-Saharan African could play a substantial role in altering global trajectories of HIV infection. Increasing access to sexual and reproductive health services, addressing gender-based violence and social instability, reducing poverty and the need to engage in sex for survival, and encouraging greater male responsibility are critical short-to-medium-term interventions. Efforts to find a microbicide and HIV vaccine need to be matched with efforts to deepen understanding of acquisition of HIV in the female genital tract to inform development of targeted molecules for prevention of HIV infection.
The Centre for the AIDS Program of Research in South Africa (CAPRISA) 004 trial assessed the effectiveness and safety of a 1% vaginal gel formulation of tenofovir, a nucleotide reverse transcriptase ...inhibitor, for the prevention of HIV acquisition in women. A double-blind, randomized controlled trial was conducted comparing tenofovir gel (n = 445 women) with placebo gel (n = 444 women) in sexually active, HIV-uninfected 18- to 40-year-old women in urban and rural KwaZulu-Natal, South Africa. HIV serostatus, safety, sexual behavior, and gel and condom use were assessed at monthly follow-up visits for 30 months. HIV incidence in the tenofovir gel arm was 5.6 per 100 women-years (person time of study observation) (38 out of 680.6 women-years) compared with 9.1 per 100 women-years (60 out of 660.7 women-years) in the placebo gel arm (incidence rate ratio = 0.61; P = 0.017). In high adherers (gel adherence > 80%), HIV incidence was 54% lower (P = 0.025) in the tenofovir gel arm. In intermediate adherers (gel adherence 50 to 80%) and low adherers (gel adherence < 50%), the HIV incidence reduction was 38 and 28%, respectively. Tenofovir gel reduced HIV acquisition by an estimated 39% overall, and by 54% in women with high gel adherence. No increase in the overall adverse event rates was observed. There were no changes in viral load and no tenofovir resistance in HIV seroconverters. Tenofovir gel could potentially fill an important HIV prevention gap, especially for women unable to successfully negotiate mutual monogamy or condom use.
Two-thirds of people living with human immunodeficiency virus type 1 (HIV-1) infection reside in Sub-Saharan Africa, where there are the highest prevalence and incidence rates of human papillomavirus ...(HPV) infection. Both infections are sexually transmitted and enter the body via the epithelium. This review describes the extent of involvement of the epithelium in each infection in the female genital tract.
A narrative review was conducted on the role of the epithelium in HPV and HIV-1 infections.
An intact epithelial barrier is the predominant form of protection against viral entry and infection, including from HIV-1 and HPV. HPV is an intraepithelial pathogen, and thus, its growth and amplification, which are dependent on squamous cell differentiation, occur in the epithelium. It gains entry to the basal cells of the stratified squamous epithelium via micro-abrasions or other epithelial injuries that expose the basement membrane. HIV-1, conversely, passes through the epithelium to infect subepithelial tissues. Following deposition of the HIV-1-containing inoculum into the lumen, the virus enters the mucosa through breaks in the epithelial barrier within hours of infection. Further, HIV-1 penetrates the epithelium via various mechanisms, including paracellular passage or across epithelial cells through transcytosis. The capture of the virus from the mucosal surface by intraepithelial and/or subepithelial target cells has also been documented.
Epithelial disruption is the major pathogenetic pathway in HIV-1 and HPV infections. Therefore, biochemical compounds that strengthen the epithelial barrier must be prioritized to prevent these infections.
Antiretroviral prophylaxis may be a critical strategy to reduce periconception HIV transmission. Maximizing the benefit of periconception pharmacologic HIV risk-reduction requires an understanding of ...the links between pregnancy and adherence to this prevention strategy.
We assessed study gel adherence among women with pregnancies compared to women without pregnancies enrolled in the CAPRISA 004 phase IIB trial of 1% vaginal tenofovir gel. Pregnancy was assessed with monthly urine tests. Adherence was measured monthly and defined as proportion of sex acts covered by two returned, used applicators based on pre- and post-coital dosing. High adherence was defined as a median adherence score of >80%, that is, more than 80% of sex acts were covered by two applications of study gel. A multivariate generalized estimating equations (GEE) model with a binomial distribution was used to assess covariates associated with high adherence (>80%) over time. Median adherence before and after pregnancy was compared using Wilcoxon signed rank test.
Among 868 women, 53 had at least 1 pregnancy (4.06 per 100 woman years, 95% CI: 3.04, 5.31). Women with pregnancies had lower median adherence compared to women without pregnancies (50% IQR: 45-83 vs. 60% IQR: 50-100, p = 0.02). Women with pregnancies also had a 48% lower odds of high adherence compared to women without pregnancies when adjusting for confounders (aOR 0.52, 95%CI: 0.41-0.66, p<0.0001). Among women with pregnancies, adherence before and after pregnancy was not different (50% IQR: 46-83 vs. 55% IQR: 20-100, p = 0.68).
Women with pregnancies were less likely to have high adherence to study gel compared to women without pregnancies. Understanding these differences may inform findings from HIV prevention trials and future implementation of antiretroviral prophylaxis for at-risk women who choose to conceive. The protocol for the parent trial is registered on ClinicalTrials.gov, NCT00441298, http://www.clinicaltrials.gov/ct2/show/NCT00441298.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Young women in sub-Saharan Africa bear a disproportionate burden of HIV infection compared to men but have limited options to reduce their HIV risk. Microbicides could fill an important HIV ...prevention gap for sexually active women who are unable to successfully negotiate mutual monogamy or condom use.
This paper describes the baseline sample characteristics in the CAPRISA 004 trial which assessed the safety and effectiveness of the vaginal microbicide, 1% tenofovir gel for HIV prevention in South Africa.
This analysis assessed the baseline demographic, clinical and sexual behavior data of women screened and enrolled into the trial. The characteristics were summarized using descriptive summary measures; expressed as means and percent for categorical variables.
HIV prevalence at screening was 25.8% 95% Confidence Interval (CI):23.9-27.7). Of the 889 eligibly enrolled women who contributed follow-up data, rural participants recruited from a family planning (FP) clinic were younger, more likely to be living apart from their regular partner, reported lower coital frequency, had lower condom use (p < 0.001). In contrast, urban participants recruited from a sexually transmitted disease (STD) clinic reported higher numbers of lifetime sexual partners, new partners in the last 30 days and receiving money in exchange for sex (p < 0.001).
The populations selected provide suitable diverse target groups for HIV prevention intervention studies.
ClinicalTrials.gov: NCT 00441298.
Contraception and pregnancy in microbicide trials Sibeko, Sengeziwe, MB ChB, FCOG, MS; Cohen, Gabriel M., BA; Moodley, Jagidesa, MB ChB, FRCOG, MD
Best practice & research. Clinical obstetrics & gynaecology,
08/2012, Letnik:
26, Številka:
4
Journal Article
Recenzirano
Odprti dostop
The distinctive feature of the human immunodeficiency virus (HIV) epidemic in Sub-Saharan Africa is the burden on women, in particular young women of reproductive age. Consequently, most late-phase ...effectiveness microbicide clinical trials are conducted in sub-Saharan Africa where fertility rates are high. Because late-phase clinical trials are conducted over prolonged periods of time, women participating in these trials may fall pregnant during the trial. Their unborn babies may be exposed to a drug whose teratogenic potential is unknown if the investigational drug is not withdrawn. High pregnancy rates in such trials may compromise statistical integrity, as women will be withdrawn from the study drug for the duration of the pregnancy. It is therefore imperative for microbicide trials to implement effective contraceptive and pregnancy management programmes that maintain low pregnancy rates and the safety of unborn babies while not compromising the conduct and statistical integrity of the trial.
Although rates of human immunodeficiency virus (HIV) have declined globally over the past 10 years, United Nations Programme on HIV/AIDS estimates 1.7 million new infections occurred in 2019, with ...cisgender women (cis women) and girls accounting for 48%. Acquired immune deficiency syndrome-related illnesses are the leading global cause of mortality in cis women aged 15 to 49, and in many sub-Saharan Africa countries, young women face substantially higher HIV risk than their male counterparts. Drivers of this increased risk include sexual and reproductive health characteristics unique to cis women. This review discusses the role of sexually transmitted infections, contraception and pregnancy in HIV risk, and biomedical HIV prevention technologies available and in development.
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