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Review
. 2010 Nov;88(5):598-609.
doi: 10.1038/clpt.2010.189. Epub 2010 Sep 29.

Pharmacologic opportunities for HIV prevention

M R Nicol  1 , A D M Kashuba
Affiliations
Review

Pharmacologic opportunities for HIV prevention

M R Nicol et al. Clin Pharmacol Ther. 2010 Nov.

Erratum in

  • Clin Pharmacol Ther. 2011 Aug;90(2):343

Abstract

Innovations in antiretroviral (ARV) treatment strategies have resulted in treated HIV-infected patients having life expectancies similar to those of uninfected individuals. Yet the number of individuals capable of HIV transmission is increasing-for every person in whom ARV treatment is initiated, four others are becoming newly infected with HIV. The limited progress with microbicides and vaccines for HIV prevention reinforce the need for a concentrated exploration of the utility of ARVs. Preliminary animal studies with topical and systemic ARVs show promising results. However, current clinical trials were designed without a comprehensive understanding of ARV pharmacokinetic-pharmacodynamic relationships in HIV prevention. This review focuses on current strategies for the prevention of HIV infection and on the ways in which the tools of pharmacology can be a valuable resource for determining pharmacodynamic targets, providing interspecies scaling of exposures, identifying the optimal drugs/drug combinations, doses, and dosing regimens, and designing efficient clinical trials.

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Figures

Figure 1
Figure 1
Opportunities for prevention. PEP, postexposure prophylaxis; PrEP, pre-exposure prophylaxis.
Figure 2
Figure 2
Timeline of mucosal infection. ARV, antiretroviral.
Figure 3
Figure 3
Relationship of total genital tract exposure to blood plasma protein binding. 3TC, lamivudine; ABC, abacavir; APV, amprenavir; ATV, atazanavir; AZT, zidovudine; D4T, stavudine; DDI, didanosine; DLV, delavirdine; EFV, efavirenz; FTC, emtricitabine; IDV, indinavir; LPV, lopinavir; MVC, maraviroc; NVP, nevirapine; RTV, ritonavir; SQV, saquinavir; TNF, tenofovir.
Figure 4
Figure 4
What should be measured for accurate pharmacokinetic–pharmacodynamic evaluations? *Only nucleoside/tide analog reverse-transcriptase inhibitors require phosphorylation for activation. ARV-P-P-P = tri-phosphorylated metabolite; fub = fraction of drug that is unbound from protein.
See this image and copyright information in PMC

References

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