Research ArticleAIDS AND HIV

Intermittent Prophylaxis with Oral Truvada Protects Macaques from Rectal SHIV Infection

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Science Translational Medicine  13 Jan 2010:
Vol. 2, Issue 14, pp. 14ra4
DOI: 10.1126/scitranslmed.3000391

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Rearranging Retroviral Regimens for HIV

Antiretroviral drugs have transformed the lives of HIV-infected people by preventing progression to full-blown AIDS. These drugs also dramatically reduce HIV transmission from mothers to infants during pregnancy and breastfeeding, and work in monkeys suggests that daily doses can also reduce transmission from unprotected sex. But prophylactic treatment with antiretroviral drugs is costly and impractical—even if confined to a high-risk population. García-Lerma et al. now show that in monkeys a more realistic medication schedule may work just as well as daily doses.

To simulate how people are likely to be infected with HIV, the authors exposed macaque monkeys rectally to 14 weekly doses of simian-human immunodeficiency virus (SHIV) engineered to resemble the human virus. Control macaques treated in this way became infected within the first five exposures to SHIV. Researchers then assessed whether oral, human-equivalent doses of antiretroviral agents could prevent infection in monkeys. The best protection—equivalent to that provided by daily antivirals—occurred when the drug Truvada was given 1, 3, or 7 days before virus exposure followed by a second dose 2 hours after exposure. Less effective, but still better than no treatment at all, was a schedule in which the drug was given 2 hours before or after exposure and then again 24 hours later. Drugs given only 24 or 48 hours after exposure did not safeguard against infection.

The results of this study are preliminary, largely because each of the groups had only six macaques, but they are nevertheless promising. If ongoing clinical trials in healthy people show that daily antiretroviral therapy can diminish the chances of acquiring HIV after exposure, a reasonable next step would be to evaluate more practical, less costly drug schedules in humans. For example, a weekly dose followed by a second dose after a possible exposure could prove both effective and tractable. It will also be important to evaluate treatments based solely on exposure, as these would not require ongoing prophylactic drug treatment and would minimize any drug toxicity. If one or more of these therapeutic regimens is successful, antiretroviral drugs may expand the transformation they have already engendered by preventing many more new infections as well as controlling existing ones.

Footnotes

  • Citation: J. G. García-Lerma, M. Cong, J. Mitchell, A. S. Youngpairoj, Q. Zheng, S. Masciotra, A. Martin, Z. Kuklenyik, A. Holder, J. Lipscomb, C.-P. Pau, J. R. Barr, D. L. Hanson, R. Otten, L. Paxton, T. M. Folks, W. Heneine, Intermittent Prophylaxis with Oral Truvada Protects Macaques from Rectal SHIV Infection. Sci. Transl. Med. 2, 14ra4 (2010).

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