Recent advances in antiretroviral treatment and prevention in HIV-infected patients

Abstract

CuÌÌent Opinion in HIV and AIDS 201 1, 6 (suppl l):521 -S30 IntroductionMore than 25 years after the identification of HIV as rhe causative agent of AIDS, the disease continues to spread in some countries [1]. Current antiretrovirals (ARVs) have significantly prolonged the time to both AIDS development and death in those infecced with HIV [2], although ARV success has ultimately been limited by toxicity, drug-drug interactions and other factors that determine patient compliance and, consequently, the emergence of resistance. Thus, there is a continuous need for existing agents to be improved and for the development of new drugs and drug classes that are effective, safe, have a higher genetic barrier to resistance. penetrare viral reservoirs more effectively and have activity against resisrant viruses. Another challenge is to develop strategies that maximize the efficacy of currently available drugs for as long as possible; how to start, when to start, how to change and when to change ARV therapy (ART) are all crucial elements of this strategy. However, it should be noted that access to new drugs and strategies serves no purpose if the chain of new infections is not broken and if the low levels of prevention and education that are currently in place persist. Unfortunately, relative to the advances 1746-630X O 2011 Wolters Kluwer Health I Lìppincott Williams & WilkinsPurpose of review To discuss new antiretroviral agents (ARVs) and alternative ARV treatment strategies that are currently being evaluated, and to provide an overview oÍ the most recent advances in HIV vaccine development. Recent findings There is a continuous need for improvements in ARV therapy (ART) and several new ARVs are currently undergoing clinical investigatìon, including the non-nucleoside reverse transcriptase inhibitor rilpivirine, the integrase inhibitor elvitegravir, the chemokine receptor 5 co-receptor antagonist vicriviroc and the maturation inhibitor bevirimat. Strategies to optimize ART, such as treatment interruption, inductionmaintenance and class-sparing regimens, are also being evaluated and have had varying success to date. However, vaccination still remains the optimal solution, and one second-generation preventative HIV vaccine has produced encouraging results in a recent phase lll tria!. SummaryGlobal prevention and treatment with ARVs that are effective, well tolerated and have high barriers to the development of HIV resistance are the main strategies to fight HIV/ AIDS while we await the develooment of an effective vaccine.

Modeling the allosteric modulation of CCR5 function by Maraviroc

“…[9,10] A third class of CCR5 ligands acting as HIV entry inhibitors comprises structurally diverse non-peptidic, low molecular weight compounds ( Fig. 1): TAK-779, the first inhibitor discovered by Takeda Pharmaceuticals, [11] its derivative TAK-652, [12] Aplaviroc (APL) (AK602 or GW873140) licensed by GlaxoSmithKline and whose development was discontinued because of hepatic toxicity in clinical trials, [13] Schering-Plough's Vicriviroc (SCH-D or SCH-417690) that continues to be evaluated in clinical trials [14] and Pfizer's Maraviroc (MVC) that is used for the treatment of patients who are infected with R5-HIV only. [15] These compounds prevent gp120 from binding to CCR5 but the mechanism involved differs from that of orthosteric ligands.…”

Ethical issues for late‐stage trials of multipurpose prevention technologies for HIV and pregnancy

“…First, if a woman contracts HIV during the trial and is exposed to a hormone/antiretroviral (ARV) combination product (assuming the ARV is also used for HIV treatment), this raises concerns about future resistance to this same ARV if needed for future HIV treatment. The microbicide field has been particularly attentive to the importance of evaluating a variety of ARV‐based drugs for HIV prevention to address concerns over resistance to first‐line treatment regimens [12,13]. The MPT field will also benefit from attention to measures to address drug resistance, as many ARV‐based microbicide products are being paired with hormones or other pregnancy prevention modalities in MPT development [3].…”

Initiation of antiretroviral therapy

“…New drugs have been approved including those that offer new mechanisms of action, improvements in potency and activity against multidrug-resistant virus, and a favorable safety profile. [1] Simplified regimens have been introduced in recent years, including those of the fixed-dose drug combinations, providing a lower pill burden and dosing frequency. [2] This review focuses on key issues relevant to the clinician including when to initiate ART, the choice of the drugs, indications to change the initial regimen as well as the recommendations for special group of children, pregnant and breastfeeding women.…”