Treatment of HIV infection

Scherer L, Rossi JJ, Weinberg MS (2007) Progress and prospects RNA-based therapies for treatment of HIV infection. Gene Ther 14(14) 1057-1064... 

So far, five different protease inhibitors have been approved by the FDA for the treatment of HIV infection [3, 4]. Clinical trials in which protease inhibitors were evaluated in monotherapy demonstrated the potency of this class of inhibitors (decrease in HIV RNA levels, increase in CD4 cell counts). Treatment regimens were subsequently broadened to include reverse transcriptase inhibitors in combination with protease inhibitors. The result of these clinical trials has led to a list of guidelines with recommendations for the optimal treatment options. Prolonged control of the infection with combination therapy (highly active antiretroviral therapy, HAART ) could be shown. 

Saquinavir was the fust HIV protease inhibitor to obtain FDA approval in 1995 for the treatment of HIV infection... 

Tenofovir in its prodrug form tenofovir, disoproxil fumarate (TDF), is indicated in the treatment of HIV infections (AIDS). It is administered as a single oral dose of 300 mg per day. When combined with emtricitabine and efavirenz, TDF has proven to be more efhcacious than the standard combination therapy of combivir (azidothymidine plus lamivudine) and efavirenz (Gallant et al. 2006) and less prone to cause adverse side effects (Pozniak et al. 2006 De Clercq 2007b). 

The 2, 3 -dideoxynucleoside (ddN) analogues (Fig. 3) encompass a vast group of compounds that have been found active against HIV and HBV, although they have been primarily pursued for the treatment of HIV infections (AIDS). They are targeted at the HIV-associated reverse transcriptase (RT) and therefore also referred to as nucleoside reverse transcriptase inhibitors (NRTIs). They have to be distinguished from the nucleotide reverse transcriptase inhibitors (NtRTIs) such as adefovir (PMEA) and tenofovir (PMPA) (see above) which, like the NRTIs, act as chain... 

Wood A, Armour D (2005) The discovery of the CCR5 receptor antagonist, UK-427,857, a new agent for the treatment of HIV infection and AIDS, Prog Med Chem 43 239-271... 

Effective and complete treatment of HIV infection involves a multidisciplinary approach, which includes pharmacists, clinicians, social workers, and others. Treatment of HIV infection always requires combination prescription antiretroviral therapy, and may include prescription treatment or prophylaxis for opportunistic infections, and prescription or nonprescription treatment for adverse effects. 

Two major panels of experts publish guidelines for the treatment of HIV-infected individuals. Although the recommendations are quite similar, slight differences do exist between the Department of Health and Human Services (DHHS) Guidelines2 and the International AIDS Society-USA (IAS-USA) Panel Recommendations.4 The DHHS Guidelines are updated every 6 months and current and archived versions are available online at www.aidsinfo.nih.gov. The IAS-USA Guidelines were last updated in 2006, and in 2004 prior to that revision. Due to the intense research and constant modifications to therapeutic approaches in the treatment of HIV, the majority of the treatment algorithms and recommendations presented herein follow the most up-to-date information found in the DHHS recommendations. 

Pediatric Patients There are unique considerations in the treatment of HIV-infected children. Specific treatment guidelines exist,23 but a thorough review is outside the scope of this chapter. Most children acquire HIV infection through... 

Panel on Clinical Practices for Treatment of HIV Infection Convened by the Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in HIV-1 Infected Adults and Adolescents. 2006. Available at http //aidsinfo.nih.gov Public Health Service Task Force. Recommendations for use of antiretroviral drugs in pregnant HIV-1 infected women for maternal health and interventions to reduce perinatal HIV-1 transmission in the United States. October 12,2006. (http //aidsinfo.nih.gov) Smith DE, Walker BD, Cooper DA, et al. Is antiretroviral treatment of primary HIV infection clinically justified on the basis of current evidence AIDS 2004 18 709-718. 

There are a few key enzymes for the proliferation of human immunodeficiency virus (HIV). Reverse transcriptase is one of them since HIV is a member of the DNA viruses. Efavirenz (1) is an orally active non-nucleoside reverse transcriptase inhibitor (NNRTI) and was discovered at Merck Research Laboratories [1] for treatment of HIV infections. Efavirenz was originally licensed to DuPont Merck Pharmaceuticals which was later acquired by Bristol-Myers Squibb.11 The typical adult dose is 600 mg once a day and 1 is one of three key ingredients of the once-a-day oral HIV drug, Atripla (Figure 1.1). 

In addition to the three anti-HIV agents [AZT (zidovudine), DDI (dida-nosine) and DDC (zalcitabine)] that have been formally approved by the U.S. Food and Drug Administration for the treatment of HIV infections, several other 2, 3 -dideoxynucleoside (ddN) analogues (Fig. 5), including 3 -fluoro-2, 3 -didcoxy-5-chlorouridine (FddClUrd) and 2, 3 -didehydro-... 

The same principles of antiretroviral therapy apply to both HIV-infected children and adults, although the treatment of HIV-infected children involves unique pharmacologic, virologic, and immunologic considerations. 

Inhibiting viral replication with combination of potent antiretroviral therapy has been the most clinically successful strategy in the treatment of HIV infection. There have been three primary groups of drugs used nucleoside and nonnucleoside reverse transcriptase inhibitors and protease inhibitors (Pis) (Table 40-5). 

Data from Panel on Clinical Practices for the Treatment of HIV Infection. Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents. 2006, http/AMM/vAIDSinfo.NIH.gov Anderson PL, Kakuda TN, Lichtenstein KA. The cellular pharmacology of nucleoside- and nudeotide-andogue reverse-transcriptase inhibitors and its relationship to dinical toxdties. din Infect Dis 2004 38 743-753 and produd information for agents... 

From Panel on Clinical Practices for the Treatment of HIV Infection. Treating Opportunistic Infections among HIV-Infected Adults and Adolescents recommendations from Center for Disease Control and Prevention, the National Institutes of Health and the HIV Medicine Association/lnfedious Diseases Society of America. December 17, 2004, http //mm.AIDSinfo.NIH.gov. 

GlaxoSmithKline recalled in May 2002 three lots of Combivir (Lamivudine/zidovudine, used in treatment of HIV infection) due to the fact that it actually contained a drug known as Ziagen (abacavir sulfate). 

HIV infection Saquinavir mesylate in combination with ritonavir and other antiretroviral agents is indicated for the treatment of HIV infection. The twice-daily administration of saquinavir mesylate in combination with ritonavir is supported by safety data from the MaxCmin 1 study and pharmacokinetic data. The efficacy of saquinavir mesylate with ritonavir or saquinavir soft gelatin capsules (with or without ritonavir coadministration) has not been compared against the efficacy of antiretroviral regimens currently considered standard of care. 

HIV infection Treatment of HIV infection in combination with other antiretroviral agents. 

HIV For the treatment of HIV infection when antiretroviral therapy is warranted. 

HIV treatment In combination with other antiretroviral agents for the treatment of HIV infection. This indication is based on analyses of plasma HIV RNA levels and CD4 cell counts in a controlled study of lopinavir/ritonavir combination of 24 weeks duration and in smaller uncontrolled dose-ranging studies of 72 weeks duration. At present, there are no results from controlled trials evaluating the effect on clinical progression of HIV. 

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