RESUMEN
The uptake of and adherence to HIV prevention products in South Africa has not achieved widespread success. This study aimed to develop a holistic understanding of the psychographics of adolescent girls and young women in South Africa, a primary audience for HIV prevention products, in order to inform market segmentation and marketing strategies. Extensive ethnographic analyses were complemented with a survey (n = 1,500) centered on personal care product journeys. Clustering and qualitative methods yielded six segments with measurable differences, and revealed common themes surrounding empowerment and self-determination, patriarchy, and misinformation risk. The findings enable targeted approaches for HIV prevention product campaigns.
Asunto(s)
Infecciones por VIH , Adolescente , Femenino , Infecciones por VIH/prevención & control , Humanos , Mercadotecnía , SudáfricaRESUMEN
The efficacy of HIV pre-exposure prophylaxis (PrEP) relies on adherence and may also depend on the route of HIV acquisition. Clinical studies of systemic tenofovir disoproxil fumarate (TDF) PrEP revealed reduced efficacy in women compared to men with similar degrees of adherence. To select the most effective PrEP strategies, preclinical studies are critically needed to establish correlations between drug concentrations (pharmacokinetics [PK]) and protective efficacy (pharmacodynamics [PD]). We utilized an in vivo preclinical model to perform a PK-PD analysis of systemic TDF PrEP for vaginal HIV acquisition. TDF PrEP prevented vaginal HIV acquisition in a dose-dependent manner. PK-PD modeling of tenofovir (TFV) in plasma, female reproductive tract tissue, cervicovaginal lavage fluid and its intracellular metabolite (TFV diphosphate) revealed that TDF PrEP efficacy was best described by plasma TFV levels. When administered at 50 mg/kg, TDF achieved plasma TFV concentrations (370 ng/ml) that closely mimicked those observed in humans and demonstrated the same risk reduction (70%) previously attained in women with high adherence. This PK-PD model mimics the human condition and can be applied to other PrEP approaches and routes of HIV acquisition, accelerating clinical implementation of the most efficacious PrEP strategies.
Asunto(s)
Antirretrovirales/uso terapéutico , Infecciones por VIH/prevención & control , Profilaxis Pre-Exposición , Tenofovir/uso terapéutico , Animales , Antirretrovirales/sangre , Antirretrovirales/farmacocinética , Relación Dosis-Respuesta a Droga , Emtricitabina/sangre , Emtricitabina/farmacocinética , Emtricitabina/uso terapéutico , Femenino , Infecciones por VIH/transmisión , Infecciones por VIH/virología , VIH-1/genética , VIH-1/aislamiento & purificación , VIH-1/patogenicidad , Semivida , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Transgénicos , Modelos de Riesgos Proporcionales , ARN Viral/sangre , Tenofovir/sangre , Tenofovir/farmacocinéticaRESUMEN
Adolescent boys and girls are disproportionately affected in the current HIV epidemic. Numerous sociobehavioral studies have addressed the indirect drivers surrounding this vulnerability-for example, socioeconomic, geographical locale, and all forms of violence. However, the direct factors that may influence infection, such as the anatomical and physiological maturation of the anogenital tracts of adolescents or the trauma and wound-healing processes of injured mucosal tissue, are understudied and represent a gap within the HIV prevention field. This article reviews the epidemiology of HIV infection and violence in adolescents and the available basic science knowledge attending this research area. More importantly, this review highlights the most critical gaps that need to be addressed to design preventive interventions that are safe and effective for this population, which is key to ending the HIV pandemic.
Asunto(s)
Factores de Edad , Susceptibilidad a Enfermedades , Infecciones por VIH/inmunología , Membrana Mucosa/lesiones , Cicatrización de Heridas , Adolescente , Femenino , Infecciones por VIH/epidemiología , Humanos , Masculino , Delitos Sexuales , Adulto JovenRESUMEN
Treatment as prevention is expected to have a major role in reducing HIV incidence, but other prevention interventions will also be required to bring the epidemic under control, particularly among key populations. One or more forms of pre-exposure prophylaxis (PrEP) will likely play a critical role. Oral PrEP with emtricitabine-tenofovir (Truvada®) is currently available in the US and some other countries, but uptake has been slow. We review the concerns that have contributed to this slow uptake and discuss current and future research in this critical area of HIV prevention research.
Asunto(s)
Antirretrovirales/administración & dosificación , Desoxicitidina/análogos & derivados , Infecciones por VIH/prevención & control , Compuestos Organofosforados/administración & dosificación , Profilaxis Pre-Exposición/tendencias , Administración Oral , Desoxicitidina/administración & dosificación , Combinación de Medicamentos , Combinación Emtricitabina y Fumarato de Tenofovir Disoproxil , Femenino , Humanos , Masculino , Profilaxis Pre-Exposición/economíaAsunto(s)
Hormonas Esteroides Gonadales/biosíntesis , Infecciones por VIH/prevención & control , Membrana Mucosa/metabolismo , Ovario/metabolismo , Testículo/metabolismo , Femenino , Fertilidad , VIH-1/patogenicidad , Humanos , Masculino , Membrana Mucosa/virología , Ovario/virología , Testículo/virologíaRESUMEN
Thirty years after its beginning, the HIV/AIDS epidemic is still raging around the world. According to UNAIDS, in 2011 alone 1.7M deaths were attributable to AIDS, and 2.5M people were newly infected by the virus. Despite the success in treating HIV-infected people with potent antiretroviral drugs, preventing HIV infection is the key to ending the epidemic. Recently, the efficacy of topical and systemic antiviral chemoprophylaxis (i.e., preexposure prophylaxis or "PrEP"), using the same drugs used for HIV treatment, has been demonstrated in a number of clinical trials. However, results from other trials have been inconsistent, especially those evaluating PrEP in women. These inconsistencies may result from our incomplete understanding of pharmacokinetics (PK)/pharmacodynamics (PD) at the mucosal sites of sexual transmission: the male and female gastrointestinal and reproductive tracts. The drug concentrations used in these trials were derived from those used for treatment; however, we still do not know the relationship between the therapeutic and the preventive dose. This article presents the first comprehensive review of the available data in the HIV pharmacology field from animal models to human studies, and outlines gaps, challenges, and future directions. Addressing these pharmacological gaps and challenges will be critical in selecting and advancing future PrEP candidates and strategies with the greatest impact on the HIV epidemic.
Asunto(s)
Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/farmacocinética , Quimioprevención/métodos , Transmisión de Enfermedad Infecciosa/prevención & control , Infecciones por VIH/prevención & control , Animales , Tracto Gastrointestinal/química , Genitales/química , Humanos , Membrana Mucosa/químicaRESUMEN
The links between sexual violence, genitoanal injury, and HIV are understudied but potentially significant for understanding the epidemic's disproportionate impacts on young women and girls, particularly in sub-Saharan Africa, other hyperendemic areas, and conflict-affected regions. A Scientific Research Planning Meeting was convened by the Social Science Research Council at the Greentree Foundation in New York, March 19-20, 2012, bringing together an interdisciplinary group of researchers, clinicians, and policy makers to identify knowledge needs and gaps in three key areas: (1) the role of genitoanal injury on HIV transmission, acquisition, and pathogenesis; (2) the influence of sex and age-related anatomic characteristics on HIV transmission, acquisition, and pathogenesis; and (3) the role of heterosexual anal intercourse in HIV transmission. This article reflects the consensus that emerged from the Greentree Meeting regarding priority scientific research questions in these three areas, associated data collection and measurement challenges and opportunities, and implications for policy and practice.
Asunto(s)
Canal Anal/lesiones , Infecciones por VIH/prevención & control , Prevención Primaria/organización & administración , Delitos Sexuales/prevención & control , Vagina/lesiones , Adolescente , África del Sur del Sahara , Canal Anal/virología , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/transmisión , Conocimientos, Actitudes y Práctica en Salud , Política de Salud , Prioridades en Salud , Humanos , Masculino , Guías de Práctica Clínica como Asunto , Delitos Sexuales/estadística & datos numéricos , Vagina/virología , Adulto JovenRESUMEN
Abstract Six randomized clinical trials have been implemented to examine the efficacy of tenofovir disoproxil fumarate (TDF) and/or TDF/emtricitabine (TDF/FTC) as preexposure prophylaxis for HIV-1 infection (PrEP). Although largely complementary, the six trials have many similar features. As the earliest results become available, an urgent question may arise regarding whether changes should be made in the conduct of the other trials. To consider this in advance, a Consultation on the Implications of HIV Pre-Exposure Prophylaxis (PrEP) Trials Results sponsored by the Division of AIDS (DAIDS) of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), and the Bill and Melinda Gates Foundation (BMGF) was held on January 29, 2010, at the Natcher Conference Center, NIH, Bethesda, MD. Participants included basic scientists, clinical researchers (including investigators performing the current PrEP trials), and representatives from the U.S. Food and Drug Administration (FDA) and the agencies sponsoring the trials: the U.S. Centers for Disease Control and Prevention (CDC), the U.S. Agency for International Development (USAID), the BMGF, and the U.S. NIH. We report here a summary of the presentations and highlights of salient discussion topics from this workshop.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Quimioprevención/métodos , Infecciones por VIH/prevención & control , VIH-1/efectos de los fármacos , Adenina/análogos & derivados , Adenina/uso terapéutico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Quimioterapia Combinada , Emtricitabina , Femenino , Humanos , Masculino , Organofosfonatos/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Tenofovir , Resultado del Tratamiento , Estados UnidosRESUMEN
Abstract A workshop entitled Beyond 2010: Gaps, Challenges, and Priorities for the Future of Preclinical HIV Pre-Exposure Prophylaxis (PrEP) was sponsored by the Division of AIDS (DAIDS) of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), on October 20-21, 2009, in Bethesda, Maryland. The objective of the workshop was to identify the main gaps in current knowledge, challenges, and priorities for the establishment of a PrEP preclinical pipeline and to also provide guidance for future directions of the field and DAIDS activities in this area. This 2-day workshop, through various presentations and breakout group discussions, specifically addressed four main topics that will be critical in identifying and advancing the next generation of PrEP candidates for clinical testing. The topics were (1) drug discovery, (2) pharmacokinetics (PK) and pharmacodynamics (PD), (3) animal models, and (4) delivery systems for prolonged activity. We report here a summary of the presentations and highlights of salient discussion topics from this workshop.
RESUMEN
There is an urgent need to expand the range of interventions to prevent HIV transmission and acquisition, especially those that can be controlled by women. Microbicides, defined as antimicrobial products that can be applied topically for the prevention of HIV and other sexually transmitted infections, may offer one of the most promising preventive interventions, because they could be inexpensive, readily available, and widely acceptable. The first microbial product to be clinically evaluated contained Nonoxynol-9 (nonylpenoxypolyethoxyethanol [N-9]), a nonionic surfactant, as the active agent. This article presents a review of the in vitro, ex vivo, and animal model data on the safety of N-9 and a critical analysis of their predictive power based on the results of multiple safety and efficacy trials.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Fármacos Anti-VIH/química , Nonoxinol/química , Animales , Fármacos Anti-VIH/uso terapéutico , Ensayos Clínicos como Asunto , Modelos Animales de Enfermedad , Humanos , Ratones , Nonoxinol/uso terapéutico , Reproducibilidad de los Resultados , Tensoactivos/química , Tensoactivos/uso terapéuticoRESUMEN
The most effective means of preventing human immunodeficiency virus (HIV) infection is preventing exposure. The provision of antiretroviral drugs to prevent HIV infection after unanticipated sexual or injection-drug--use exposure might be beneficial. The U.S. Department of Health and Human Services (DHHS) Working Group on Nonoccupational Postexposure Prophylaxis (nPEP) made the following recommendations for the United States. For persons seeking care < or =72 hours after nonoccupational exposure to blood, genital secretions, or other potentially infectious body fluids of a person known to be HIV infected, when that exposure represents a substantial risk for transmission, a 28-day course of highly active antiretroviral therapy (HAART) is recommended. Antiretroviral medications should be initiated as soon as possible after exposure. For persons seeking care < or =72 hours after nonoccupational exposure to blood, genital secretions, or other potentially infectious body fluids of a person of unknown HIV status, when such exposure would represent a substantial risk for transmission if the source were HIV infected, no recommendations are made for the use of nPEP. Clinicians should evaluate risks and benefits of nPEP on a case-by-case basis. For persons with exposure histories that represent no substantial risk for HIV transmission or who seek care >72 hours after exposure, DHHS does not recommend the use of nPEP. Clinicians might consider prescribing nPEP for exposures conferring a serious risk for transmission, even if the person seeks care >72 hours after exposure if, in their judgment, the diminished potential benefit of nPEP outweighs the risks for transmission and adverse events. For all exposures, other health risks resulting from the exposure should be considered and prophylaxis administered when indicated. Risk-reduction counseling and indicated intervention services should be provided to reduce the risk for recurrent exposures.
Asunto(s)
Terapia Antirretroviral Altamente Activa/normas , Infecciones por VIH/prevención & control , Terapia Antirretroviral Altamente Activa/economía , Análisis Costo-Beneficio , Exposición a Riesgos Ambientales , Infecciones por VIH/economía , Infecciones por VIH/transmisión , Humanos , Riesgo , Factores de Tiempo , Estados UnidosAsunto(s)
Fármacos Anti-VIH/farmacología , Células Presentadoras de Antígenos/inmunología , Infecciones por VIH/inmunología , VIH/inmunología , Fármacos Anti-VIH/uso terapéutico , Células Presentadoras de Antígenos/virología , VIH/metabolismo , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , HumanosRESUMEN
We undertook a critical epidemiological review of the available evidence concerning whether women have lower levels of human immunodeficiency virus (HIV) RNA than do men at similar stages of HIV infection. The 13 studies included in this analysis reported viral load measurements in HIV-infected men and women at a single point in time (cross-sectional studies) or over time (longitudinal studies). Seven of the 9 cross-sectional studies demonstrated that women had 0.13-0.35 log(10) ( approximately 2-fold) lower levels of HIV RNA than do men, despite controlling for CD4(+) cell count. Four longitudinal studies revealed that women had 0.33-0.78 log(10) (2- to 6-fold) lower levels of HIV RNA than do men, even when controlling for time since seroconversion. Adjustment for possible confounders of the relationship between sex and viral load, including age, race, mode of virus transmission, and antiretroviral therapy use, did not change this outcome. This finding is significant, because viral loads are frequently used to guide the initiation and modification of antiretroviral therapy.