Women account for nearly one-half of new human immunodeficiency virus type 1 (HIV-1) infections worldwide, including the majority of infections in Africa. Biological and epidemiological studies suggest that hormonal contraceptive use could influence susceptibility to HIV-1, as well as infectivity and disease progression for those who become infected. However, not all studies have shown this relationship, and many questions remain. Safe and effective contraceptive choices are essential for women with and at risk for HIV-1 infection. Thus, understanding the effect, if any, of hormonal contraception on HIV-1 disease among women is a public health priority.
"For example, relative to the follicular and luteal phases of the menstrual cycle, decreases in plasma viral load at ovulation, when estradiol levels are high, have been previously described , although others did not find any effect of the menstrual cycle on HIV-RNA levels in blood . In contrast, analysis of genital secretions throughout the menstrual cycle demonstrated increased HIV-1 shedding during the luteal phase, when progesterone levels are higher, in some reports ,  while others did not find any pattern of genital tract shedding during the menstrual cycle . More recently, significant positive associations were found between the number of days from the luteinizing hormone surge and the number of endocervical HIV-infected cells . "
[Show abstract][Hide abstract] ABSTRACT: The magnitude of the HIV epidemic in women requires urgent efforts to find effective preventive methods. Even though sex hormones have been described to influence HIV infection in epidemiological studies and regulate different immune responses that may affect HIV infection, the direct role that female sex hormones play in altering the susceptibility of target cells to HIV-infection is largely unknown. Here we evaluated the direct effect of 17-β-estradiol (E2) and ethinyl estradiol (EE) in HIV-infection of CD4(+) T-cells and macrophages. Purified CD4(+) T-cells and monocyte-derived macrophages were generated in vitro from peripheral blood and infected with R5 and X4 viruses. Treatment of CD4(+) T-cells and macrophages with E2 prior to viral challenge reduced their susceptibility to HIV infection in a dose-dependent manner. Addition of E2 2 h after viral challenge however did not result in reduced infection. In contrast, EE reduced infection in macrophages to a lesser extent than E2 and had no effect on CD4(+) T-cell infection. Reduction of HIV-infection induced by E2 in CD4(+) T-cells was not due to CCR5 down-regulation, but was an entry-mediated mechanism since infection with VSV-G pseudotyped HIV was not modified by E2. In macrophages, despite the lack of an effect of E2 on CCR5 expression, E2-treatment reduced viral entry 2 h after challenge and increased MIP-1β secretion. These results demonstrate the direct effect of E2 on susceptibility of HIV-target cells to infection and indicate that inhibition of target cell infection involves cell-entry related mechanisms.
PLoS ONE 04/2013; 8(4):e62069. DOI:10.1371/journal.pone.0062069 · 3.23 Impact Factor
"To date, no single product exists that women can use discreetly for simultaneous and effective prevention of STIs and pregnancy . Women would also benefit from more options for chemical contraceptives that are nonhormonal , . In particular, an alternative to nonoxynol-9 (N-9) that is safe and non-toxic, does not alter the vaginal microflora, and does not enhance the risk for HIV-1 infection would have a major impact on women's sexual and reproductive health . "
[Show abstract][Hide abstract] ABSTRACT: Multipurpose prevention technologies (MPTs) that simultaneously prevent sexually transmitted infections (STIs) and unintended pregnancy are a global health priority. Combining chemical and physical barriers offers the greatest potential to design effective MPTs, but integrating both functional modalities into a single device has been challenging. Here we show that drug-eluting fiber meshes designed for topical drug delivery can function as a combination chemical and physical barrier MPT. Using FDA-approved polymers, we fabricated nanofiber meshes with tunable fiber size and controlled degradation kinetics that facilitate simultaneous release of multiple agents against HIV-1, HSV-2, and sperm. We observed that drug-loaded meshes inhibited HIV-1 infection in vitro and physically obstructed sperm penetration. Furthermore, we report on a previously unknown activity of glycerol monolaurate (GML) to potently inhibit sperm motility and viability. The application of drug-eluting nanofibers for HIV-1 prevention and sperm inhibition may serve as an innovative platform technology for drug delivery to the lower female reproductive tract.
PLoS ONE 11/2012; 7(11):e49792. DOI:10.1371/journal.pone.0049792 · 3.23 Impact Factor
"Hel and colleagues  have extensively reviewed the multiple immunoregulatory effects of progesterone. Estrogen treatment is noted to protect macaques against infection; thus providing some biological coherence to the observation in numerous epidemiologic studies, that COCs are associated with a lower risk of HIV acquisition in women, as compared with DMPA, even when controlling for sexual behavior    . Progesterone treatment in some studies increases frequency of Langerhans cells in the vaginal epithelium, an important target cell in HIV early infection events. "
[Show abstract][Hide abstract] ABSTRACT: A recent multi-country study on hormonal contraceptives (HC) and HIV acquisition and transmission among African HIV-serodiscordant couples reported a statistically significant doubling of risk for HIV acquisition among women as well as transmission from women to men for injectable contraceptives. Together with a prior cohort study on African women seeking health services, these data are the strongest yet to appear on the HC-HIV risk. This paper will briefly review the Heffron study strengths and relevant biological and epidemiologic evidence; address the futility of further trials; and propose instead an alternative framework for next steps. The weight of the evidence calls for a discontinuation of progestin-dominant methods. We propose here five types of productive activities: (1) scaling injectable hormones down and out of the contraceptive mix; (2) strengthening and introducing public health strategies with proven potential to reduce HIV spread; (3) providing maximal choice to reduce unplanned pregnancy, starting with quality sexuality education through to safe abortion access; (4) expanding provider training, end-user counseling and access to male and female barriers, with a special renewed focus on female condom; (5) initiating a serious research agenda to determine anti-STI/HIV potential of the contraceptive cervical cap. Trusting women to make informed choices is critical to achieve real progress in dual protection.
AIDS research and treatment 11/2012; 2012:524936. DOI:10.1155/2012/524936
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