Contraceptive Methods and Risk of HIV Acquisition or Female-to-Male Transmission

Haddad, Lisa; Polis, Chelsea B.; Sheth, Anandi N.; Brown, Jennifer L.; Kourtis, Athena P.; King, Caroline C.; Chakraborty, Rana; Ofotokun, Igho

doi:10.1007/s11904-014-0236-6

Cited by 24 publications

(25 citation statements)

References 132 publications

(148 reference statements)

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“…Some studies indicate no link between contraceptive use and risk of HIV-1 (Heffron et al 2013, whereas others reported significant risk with contraceptive use (Heffron et al 2012, Haddad et al 2014. Recently, by examining individual participant data instead of an aggregate of different studies, an increase in risk was found to be associated with the use of P 4 -containing contraceptives (Morrison et al 2015).…”

Section: Discussionmentioning

confidence: 99%

Progesterone augments cell susceptibility to HIV-1 and HIV-1/HSV-2 co-infections

Ragupathy

Wang

Tan

et al. 2016

Journal of Molecular Endocrinology

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In human immunodeficiency virus type 1 (HIV-1)-infected women, oral or injectable progesterone containing contraceptive pills may enhance HIV-1 acquisition in vivo, and the mechanism by which this occurs is not fully understood. In developing countries, Herpes simplex virus type-2 (HSV-2) co-infection has been shown to be a risk for increase of HIV-1 acquisition and, if co-infected women use progesterone pills, infections may increase several fold. In this study, we used an in vitro cell culture system to study the effects of progesterone on HIV-1 replication and to explore the molecular mechanism of progesterone effects on infected cells. In our in vitro model, CEMss cells (lymphoblastoid cell line) were infected with either HIV-1 alone or co-infected with HSV-2. HIV-1 viral load was measured with and without sex hormone treatment. Progesterone-treated cells showed an increase in HIV-1 viral load (1411.2 pg/mL) compared with cells without progesterone treatment (993.1 pg/mL). Increased cell death was noted with HSV-2 co-infection and in progesterone-treated cells. Similar observations were noted in peripheral blood mononuclear cells (PBMC) cells derived from three female donors. Progesterone-treated cells also showed reduced antiviral efficacy. Inflammatory cytokines and associations with biomarkers of disease progression were explored. Progesterone upregulated inflammatory cytokines and chemokines conversely and downregulated anti-apoptotic Bcl-2 expression. Nuclear protein analysis by electrophoretic mobility shift assay showed the association of progesterone with progesterone response element (PRE), which may lead to downregulation of Bcl-2. These data indicate that progesterone treatment enhances HIV-1 replication in infected cells and co-infection with HSV-2 may further fuel this process.

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Section: Discussionmentioning

confidence: 99%

Progesterone augments cell susceptibility to HIV-1 and HIV-1/HSV-2 co-infections

Ragupathy

Wang

Tan

et al. 2016

Journal of Molecular Endocrinology

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“…The use of injectable hormonal contraceptives in women increased from 4.5% in 1995 to 23% in 2006 to 2010 (28). A number of studies have suggested an increased risk of acquisition of HIV in association with DMPA (29)(30)(31). It is of interest that one of the highest reported rates of HSV-1 genital herpes was detected in participants of the Herpevac trial study, all of which were required to use a highly effective method of birth control that included hormonal contraceptives.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of the Herpes Simplex Virus 2 (HSV-2) Glycoprotein D/AS04 Vaccine against Genital HSV-2 and HSV-1 Infection and Disease in the Cotton Rat Sigmodon hispidus Model

Boukhvalova

McKay

Mbaye

et al. 2015

J Virol

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Subunit vaccines based on the herpes simplex virus 2 (HSV-2) glycoprotein D (gD-2) have been the major focus of HSV-2 vaccine development for the past 2 decades. Based on the promising data generated in the guinea pig model, a formulation containing truncated gD-2, aluminum salt, and MPL (gD/AS04) advanced to clinical trials. The results of these trials, however, were unexpected, as the vaccine protected against HSV-1 infection but not against HSV-2. To address this discrepancy, we developed a Depot medroxyprogesterone acetate (DMPA)-treated cotton rat Sigmodon hispidus model of HSV-2 and HSV-1 genital infection. The severity of HSV-1 genital herpes was less than that of HSV-2 genital herpes in cotton rats, and yet the model allowed for comparative evaluation of gD/AS04 immunogenicity and efficacy. Cotton rats were intramuscularly vaccinated using a prime boost strategy with gD/AS04 (Simplirix vaccine) or control vaccine formulation (hepatitis B vaccine FENDrix) and subsequently challenged intravaginally with HSV-2 or HSV-1. The gD/AS04 vaccine was immunogenic in cotton rats and induced serum IgG directed against gD-2 and serum HSV-2 neutralizing antibodies but failed to efficiently protect against HSV-2 disease or to decrease the HSV-2 viral load. However, gD/AS04 significantly reduced vaginal titers of HSV-1 and better protected animals against HSV-1 compared to HSV-2 genital disease. The latter finding is generally consistent with the clinical outcome of the Herpevac trial of Simplirix. Passive transfer of serum from gD/AS04-immunized cotton rats conferred stronger protection against HSV-1 genital disease. These findings suggest the need for alternative vaccine strategies and the identification of new correlates of protection. IMPORTANCEIn spite of the high health burden of genital herpes, there is still no effective intervention against the disease. The significant gap in knowledge on genital herpes pathogenesis has been further highlighted by the recent failure of GSK HSV-2 vaccine Simplirix (gD/AS04) to protect humans against HSV-2 and the surprising finding that the vaccine protected against HSV-1 genital herpes instead. In this study, we report that gD/AS04 has higher efficacy against HSV-1 compared to HSV-2 genital herpes in the novel DMPA-synchronized cotton rat model of HSV-1 and HSV-2 infection. The findings help explain the results of the Simplirix trial.T he disease burden associated with herpes simplex virus 2 (HSV-2) infection, an important cause of genital herpes worldwide, is high and presents an additional threat due to its association with an increased risk of HIV acquisition and transmission (1-3). Globally, HSV-2 is a major health threat, with 16% of the U.S. population infected by age 30 and 50 to 90% of the population in sub-Saharan Africa infected (3-5). Recent reports emphasize the importance of HSV-1 as an important etiologic agent of genital herpes particularly in the United States and other developed countries (6-8). Seroprevalence of HSV-1 among 14-to 49-year-olds in the Uni...

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“…13,14 Recently, much attention has been given to the impact of hormonal contraception on HIV disease progression and HIV transmission and acquisition, though evidence of the impact on transmission and acquisition remains inconclusive. [15][16][17][18][19] There have been many calls for integrated family planning and HIV programming efforts; however, evidence of effective integration models have lagged behind and are only slowly emerging. 20,21 The legal status of abortion in many countries and pervasive stigma have also resulted in less information on the relationship between HIV and abortion, including the safety of abortion in the context of HIV and access to post-abortion care.…”

Section: Resultsmentioning

confidence: 99%

Fertility-related research needs among women at the margins

Schwartz¹,

Baral

2015

Reproductive Health Matters

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Fertility-related research encompasses fertility intentions, preconception care, research amongst pregnant women, and post-partum outcomes of mothers and children. However, some women remain underrepresented within this domain of study. Women frequently missing within fertility-related research include those who are already the most vulnerable to health disparities, including female sex workers, lesbian, gay, bisexual, and transgender women, women living with HIV, and women who use drugs. Yet characterization of the needs of these women is important, given their unique fertility-related concerns, including risks and barriers to care emanating from social stigmas and discrimination. This synthesis provides an overview of fertility-related evidence, highlighting where there are clear research gaps among marginalized women and the potential implications of these data shortfalls. Overall, research among marginalized women to date has addressed pregnancy prevention and in some cases fertility intentions, but the majority of studies have focused on postconception pregnancy safety and the well-being of the child. However, among female sex workers specifically, data on pregnancy safety and the well-being of the child are largely unavailable. Within each marginalized group, preconception care and effectiveness of conception methods are consistently understudied. Ultimately, the absence of epidemiologic, clinical and programmatic evidence limits the availability and quality of reproductive health services for all women and prevents social action to address these gaps.

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Contraceptive Methods and Risk of HIV Acquisition or Female-to-Male Transmission

Cited by 24 publications

References 132 publications

Progesterone augments cell susceptibility to HIV-1 and HIV-1/HSV-2 co-infections

Progesterone augments cell susceptibility to HIV-1 and HIV-1/HSV-2 co-infections

Efficacy of the Herpes Simplex Virus 2 (HSV-2) Glycoprotein D/AS04 Vaccine against Genital HSV-2 and HSV-1 Infection and Disease in the Cotton Rat Sigmodon hispidus Model

Fertility-related research needs among women at the margins

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