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Category: Scientific publications

Postexposure prophylaxis, preexposure prophylaxis or universal test and treat: the strategic use of antiretroviral drugs to prevent HIV acquisition and transmission

Weber, Jonathan; Tatoud, Roger; Fidler, Sarah

AIDS 24 (S4): S27–S39, 2010.

This review considers the use of antiretroviral drugs specifically to prevent HIV transmission. Antiretroviral therapy (ART) can be implemented for the protection of uninfected individuals both before (preexposure prophylaxis) and after (postexposure prophylaxis) exposure to HIV infection. Preexposure prophylaxis may be used coitally dependently when individuals are intermittently exposed or by continuous daily dosing for those constantly exposed; postexposure prophylaxis is used in 28-day courses. Alternatively, ART can be used strategically to reduce the viral load and consequent infectiousness of an HIV-infected individual, thereby limiting the risk of onward viral transmission. A policy of universal HIV testing to enhance the identification of all HIV-positive individuals followed by immediate treatment of all HIV-positive individuals, irrespective of their CD4 cell counts (universal test and treat), has been postulated as a potential tool capable of reducing HIV incidence at a population level. This concept represents a paradigm shift in the use of ART, targeting infectious individuals for prevention rather than protecting uninfected exposed populations. This strategy could have the advantage of preventing transmission and reducing HIV incidence at a population level, as well as delivering universal access to therapy for all people living with HIV and AIDS, potentially eliminating mother-to-child HIV transmission and limiting concomitant diseases such as tuberculosis. This review critically examines the scientific basis of ART for HIV prevention, summarizing the risks and opportunities of the potential expansion of ART for prevention. Specifically, we consider the evidences for and against targeting HIV-uninfected individuals compared with enhanced HIV testing and treatment of HIV-infected individuals in terms of impact on viral transmission.?

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Scientific Publications

  • Fearnside JF, Dumas ME, Rothwell AR, Wilder SP, Cloarec O, Toye A, Blancher C, Holmes E, Tatoud R, Barton RH, Scott J, Nicholson JK, Gauguier D. Phylometabonomic patterns of adaptation to high fat diet feeding in inbred mice. PLoS ONE 3, e1668 (2008).
  • Toye AA, Dumas ME, Blancher C, Rothwell AR, Fearnside JF, Wilder SP, Bihoreau MT, Cloarec O, Azzouzi I, Young S, Barton RH, Holmes E, McCarthy MI, Tatoud R, Nicholson JK, Scott J, Gauguier D.  Subtle metabolic and liver gene transcriptional changes underlie diet-induced fatty liver susceptibility in insulin-resistant mice. Diabetologia 50, 1867-79 (2007).
  • Daly-Burns B, Alam TN, Mackay A. Clark J, Shepherd CJ, Rizzo S, Tatoud R. O’Hare MJ, Masters JR, Hudson DL. A conditionally immortalized cell line model for the study of human prostatic epithelial cell differentiation. Differentiation 75:35–48, (2007).
  • Dumas ME, Barton RH, Toye A, Cloarec O, Blancher C, Rothwell A, Fearnside A, Tatoud R, Blanc V, Lindon JC, Mitchell SC, Holmes E, McCarthy MI, Scott J, Gauguier J, Nicholson JK. Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice. P.N.A.S. 103:12511–12516, (2006).
  • Arya M, Patel HR, McGurk C, Tatoud R, Klocker H, Masters J, Williamson M. The importance of the CXCL12-CXCR4 chemokine ligand-receptor interaction in prostate cancer metastasis. J Exp Ther Oncol. 4, 291-303 (2004).
  • Stephen RL, Gustafsson MC, Jarvis M, Tatoud R, Marshall BR, Knight D, Ehrenborg E, Harris AL, Wolf CR, Palmer CN. Activation of peroxisome proliferator-activated receptor delta stimulates the proliferation of human breast and prostate cancer cell lines. Cancer Res. 64, 3162-70 (2004)
  • Adamson DJA, Frew D, Tatoud R, Wolf CR & Palmer CNA. Diclofenac antagonizes peroxisome proliferator-activated receptor-? signalling. Mol Pharmacol. 61, 7-12 (2002).
  • Maillard M, Cadot B, Ball RY, Sethia K, Perbal B, Edwards D & Tatoud R. Differential expression of novH proto-oncogene in human prostate cell lines and tissues. Mol Pathol. 54, 275-280 (2001).
  • Tatoud R. Insulin-like growth factor (IGF) network in prostate pathologies. Pr Cancer Pr Dis 2,66-69 (1999).
  • Sangrajrang S, Denoulet P, Millot G, Tatoud R, Podgorniak MP, Tew KD, Calvo F, & Fellous A. Estramustine resistance correlates with tau over-expression in human prostatic carcinoma cells. Int J Cancer 77,626-631 (1998).
  • Sangrajrang S, Denoulet P, Laing NM, Tatoud R, Millot G, Calvo F, Tew KD & Fellous A. Association of estramustine resistance in human prostatic carcinoma cells with modified patterns of tubulin expression. Biochem Pharmacol 55, 325-331 (1998).
  • Le Moyec L, Millot G, Tatoud R, Calvo F & Eugene M. Lipid signals detected by NMR proton spectroscopy of whole cells are not correlated to lipid droplets evidenced by the Nile red staining. Cell Molec Biol 43, 703-709, (1997).
  • deCremoux P, Ravery V, Podgorniak MP, Chevillard S, Toublanc M, Thiounn N, Tatoud R, Delmas V, Calvo F & Boccon-Gibod L. Value of the preoperative detection of prostate-specific-antigen-positive circulating cells by nested RT-PCR in patients submitted to radical prostatectomy. Eur Urol 32, 69-74 (1997).
  • Prévost G, Benamouzig R, Veber N, Fajac A, Tatoud R, Degeorges A. & Eden P. The somatostatin receptor subtype 2 is expressed in normal and tumoral human tissues. Cancer Detection & Prevention 21, 62-70 (1997)
  • Lebbe C, Pellet C, Tatoud R, Agbalika F, Dosquet P, Desgrez JP, Morel P & Calvo F. Absence of human herpesvirus 8 sequences in prostate specimens. AIDS 11, 270 (1997).
  • Lebbé C, Tatoud R, Morel P, Calvo F, Euvrard S, Kanitakis J, Faure M, & Claudy A. Human herpesvirus 8 sequences are not detected in epithelial tumors from patients receiving transplant. Arch Dermatol 133, 111 (1997).
  • Degeorges A, Tatoud R, Fauvel-Lafève F, Podgorniak MP, Millot G, de Cremoux P. & Calvo F. Stromal cells from human benign prostate hyperplasia produce a growth inhibitory factor for LNCaP prostate cancer cells. Int. J. Cancer 68, 207-214 (1996).
  • Le Moyec L, Tatoud R, Degeorges A, Calabresse C, Bauza G, Eugène M. & Calvo F. Multidrug resistance and cellular lipids detected by proton nuclear magnetic resonance spectroscopy in K562 leukemia cell line. Cancer Res 56, 3461-3467 (1996).
  • Tatoud R, Degeorges A, Prévost G, Hoepffner JL, Gauvillé C, Millot G, Thomas F. & Calvo F. Somatostatin receptors in prostate tissues and derived cell cultures, and the in vitro growth inhibitory effect of BIM-23014 analog. Mol Cell Endocrinol 113, 195-204, (1995).
  • Tatoud R, Desgranchamps F, Degeorges A, & Thomas, F. Les facteurs de croissances peptidiques de la prostate. Pathol Biol 41, 731-740, (1993).
  • Le Moyec L, Tatoud R, Eugène M, Gauvillé C, Primot I, Charlemagne D, & Calvo F. Cell and lipid membrane lipid analysis by proton magnetic resonance spectroscopy in five breast cancer cell lines. Br J Cancer 66, 623-628, (1992).
  • Desgranchamps F, Tatoud R, Cussenot O, Teillac P, & Leduc A. Facteurs de croissance prostatiques et hypertrophie bénigne de la prostate. Etat des connaissances actuelles et perspectives. Progres Urol 2, 1031-1044 (1992).
  • Le Moyec L, Eugène M, Gauvillé C, Tatoud R, Ouvrard BN, & Calvo F. Profils lipidiques de lignées de cancer du sein: spectrométrie par résonance magnétique nucléaire du proton. C R Acad Sci Paris, 312(III), 25-30, (1991).