Postexposure Prophylaxis for HIV Infection
University of California at Los Angeles Center for Clinical AIDS Research and Education and the David Geffen School of Medicine at UCLA, Los Angeles, CA 90035, USA. New England Journal of Medicine
(Impact Factor: 55.87).
10/2009; 361(18):1768-75. DOI: 10.1056/NEJMcp0904189
A 24-year-old man presents to an outpatient clinic, reporting that 36 hours previously he had receptive anal intercourse without the use of a condom with an anonymous male partner who was known to have had sex with other men. The patient is known to the clinical practice and has had several negative tests for human immunodeficiency virus (HIV) infection, most recently 6 months previously. How should he be evaluated and treated?
Available from: PubMed Central
- "Conceivably, treatment with these medicines may effectively prevent HIV replication and AIDS development if a natural infection occurs with a dose of HIV. Our data are consistent with a previous report that prophylactic treatment with a single substance post exposure reduces the probability of an infection
. Our results suggest that the animal model infected with RT-SHIV can be used to evaluate new NRTIs for the treatment and prevention of AIDS. "
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ABSTRACT: The precise efficacy of nucleoside analogue reverse-transcriptase inhibitors (NRTIs) in preventing and inhibiting virus replication remains unknown in RT-SHIV infected Chinese-origin rhesus macaques (Ch RM).
Ch RM were inoculated intravenously with 200 TCID50 RT-SHIV and treated by gavage with NRTIs (20 mg AZT and 10 mg 3TC twice per day) for four consecutive weeks beginning at one hour, on day 217 or 297 post inoculation, respectively. Treatment with AZT/3TC inhibited transiently RT-SHIV replication during chronic infection, but did not significantly affect peripheral blood CD4+ T cells in macaques. Treatment with AZT/3TC at 1 hour post infection prevented RT-SHIV infection in two out of four animals during the 120-day observation period.
Therefore, the Ch RM model with RT-SHIV infection can be used to evaluate the efficacy of new NRTIs.
AIDS Research and Therapy 03/2014; 11(1):12. DOI:10.1186/1742-6405-11-12 · 1.46 Impact Factor
Available from: Bernhard Konrad
- "Second, phylogenetic analysis of the viral strains dominant in chronically infected individuals points to a strong evolutionary bottleneck during early infection, with many infections arising from a single founder strain . Finally, it appears that there is a narrow window of opportunity for postexposure drug treatment (or potentially, an immune response) to help prevent infection  . "
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ABSTRACT: The events that occur following HIV exposure, preceding any detectable infection, are difficult to study experimentally. However, there is considerable evidence that these events can be influenced by the action of antiretroviral drugs, taken either as pre- or postexposure prophylaxis (PrEP and PEP, respectively). We present simple theoretical models of HIV dynamics immediately following exposure, and apply these models to understanding how drug prophylaxis can act to reduce the risk of infection. Because HIV infection following exposure is a relatively rare event, we work with stochastic models which we base on continuous-time branching processes, allowing us to compute the risk of infection under different scenarios. We obtain analytical solutions for viral extinction probabilities, allowing us to avoid extensive computer simulations. We predict in the case of PrEP that reverse transcriptase inhibitors should be somewhat more effective than protease inhibitors and also that single drugs should be nearly as effective as a combination approach. We then model viral dynamics under PEP and find that fast initiation of therapy is essential for risk reduction. However, we predict that a two-week PEP regimen would be nearly as effective as the current recommendation of four weeks of therapy. Our work provides a coherent platform for studying the early dynamics of HIV and indicates possible directions for experimental and theoretical work.
SIAM Journal on Applied Mathematics 04/2013; 73(2):904-928. DOI:10.2307/23479955 · 1.43 Impact Factor
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ABSTRACT: There is a range of settings in which antiretroviral therapy can decrease the incidence of HIV. Recently, it was revealed that the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC) plan to study a test and treat strategy to reduce the spread of HIV. A test and treat strategy presents numerous implementation, operational, structural, and policy issues that will require research to be effectively addressed. The timing of the interest in a test and treat strategy and this first foray into exploring its potential implementation come at a critical juncture in the history of HIV/AIDS in the United States, where recent data from the CDC indicate that the prevalence and incidence of HIV are considerably higher than had previously been thought, and the Obama administration is currently developing a National HIV/AIDS Strategy (NHAS) whose three primary goals are reducing HIV incidence, increasing access to care, and reducing HIV-related health disparities. Indeed, the test and treat strategy is possibly unique in its direct relevance to all three main goals of the NHAS. A strategic approach to research will define portfolios and allocate resources based on their ability to move toward accomplishing the three NHAS goals. A National HIV/AIDS Strategy that both informs and is informed by a strong research agenda is a long-awaited and much anticipated development in the battle against HIV/AIDS in the United States.
AIDS research and human retroviruses 01/2010; 26(1):1-4. DOI:10.1089/aid.2009.0267 · 2.33 Impact Factor
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