Clinical and Resistance Consequences of Misquantification of Plasma and Cerebrospinal Fluid Human Immunodeficiency Virus Type 1 (HIV-1) RNA in Samples from an HIV-1 Subtype G-Infected Patient

Department of Virology, Saint-Louis Hospital, 1 avenue Claude Vellefaux, 75010 Paris, France.
Journal of clinical microbiology (Impact Factor: 3.99). 09/2009; 47(11):3763-4. DOI: 10.1128/JCM.00206-09
Source: PubMed


Human immunodeficiency virus (HIV) load is the main marker used to monitor antiviral treatment efficacy and resistance. We
report a case of underquantification of HIV type 1 (HIV-1) RNA in plasma and cerebrospinal fluid from an HIV-1 subtype G-infected
woman, leading to delayed diagnosis of HIV encephalitis and to the emergence of drug resistance.

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Available from: Thomas Mourez, Jun 16, 2014
    • "As this subtype represents only 11% of all circulating strains worldwide [1], and as it has been largely shown that the wide diversity of HIV-1 could lead to major quantification discrepancies [2] [3] [4] [5], it is relevant to evaluate each new version of a quantification assay. Indeed, pVL under-quantification has major clinical repercussions and delays the detection of drug resistance, as we have shown in our previous research [6]. Moreover, these discrepancies are even more pronounced with the highly divergent non-M (N, O, and P) groups of HIV-1 [7] [8]. "
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    ABSTRACT: In the last 25 years, HIV-1, the retrovirus responsible for the acquired immunodeficiency syndrome (AIDS), has gone from being an "inherently untreatable" infectious agent to one eminently susceptible to a range of approved therapies. During a five-year period, starting in the mid-1980s, my group at the National Cancer Institute played a role in the discovery and development of the first generation of antiretroviral agents, starting in 1985 with Retrovir (zidovudine, AZT) in a collaboration with scientists at the Burroughs-Wellcome Company (now GlaxoSmithKline). We focused on AZT and related congeners in the dideoxynucleoside family of nucleoside reverse transcriptase inhibitors (NRTIs), taking them from the laboratory to the clinic in response to the pandemic of AIDS, then a terrifying and lethal disease. These drugs proved, above all else, that HIV-1 infection is treatable, and such proof provided momentum for new therapies from many sources, directed at a range of viral targets, at a pace that has rarely if ever been matched in modern drug development. Antiretroviral therapy has brought about a substantial decrease in the death rate due to HIV-1 infection, changing it from a rapidly lethal disease into a chronic manageable condition, compatible with very long survival. This has special implications within the classic boundaries of public health around the world, but at the same time in certain regions may also affect a cycle of economic and civil instability in which HIV-1/AIDS is both cause and consequence. Many challenges remain, including (1) the life-long duration of therapy; (2) the ultimate role of pre-exposure prophylaxis (PrEP); (3) the cardiometabolic side-effects or other toxicities of long-term therapy; (4) the emergence of drug-resistance and viral genetic diversity (non-B subtypes); (5) the specter of new cross-species transmissions from established retroviral reservoirs in apes and Old World monkeys; and (6) the continued pace of new HIV-1 infections in many parts of the world. All of these factors make refining current therapies and developing new therapeutic paradigms essential priorities, topics covered in articles within this special issue of Antiviral Research. Fortunately, there are exciting new insights into the biology of HIV-1, its interaction with cellular resistance factors, and novel points of attack for future therapies. Moreover, it is a short journey from basic research to public health benefit around the world. The current science will lead to new therapeutic strategies with far-reaching implications in the HIV-1/AIDS pandemic. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, Vol. 85, issue 1, 2010.
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