[PubMed] [Google Scholar] 44. estimated 33 million infected adults worldwide, an estimated 2.7 million new infections per year, and 2 million deaths from the disease annually.1 Despite these dismal statistics, treatment of HIV infection has improved dramatically over the past 15 years due to the development of simple and effective combination antiretroviral therapy (cART). Incidence rates of AIDS-defining conditions and HIV-related mortality have decreased considerably with advances in cART.2,3 Over time, medications for the treatment of HIV have become simpler, less toxic, and more potent. There are now several effective cART regimens with a burden of one to three pills dosed once SRI-011381 hydrochloride daily, which requires minimal clinical monitoring. These advancements have allowed cART to be rolled out extensively to primary care clinics in both resource-rich and -poor settings throughout the world. As of 2008, the International AIDS Society (IAS) and the British HIV Association (BHIVA) recommend two nucleoside reverse transcriptase inhibitors (NRTIs) plus either efavirenz (a non-nucleoside reverse transcriptase inhibitor [NNRTI]) or a protease inhibitor (PI) boosted with a low dose of ritonavir for initial cART of HIV-infected adults.4,5 Preferred NRTI components of cART are fixed-dose combinations (FDC) of tenofovir and emtricitabine or abacavir and lamivudine. More recently, the 2009 2009 guidelines from the US Department of Health and Human Services (DHHS)6 have recommended tenofovir and emtricitabine SRI-011381 hydrochloride or lamivudine as SRI-011381 hydrochloride the preferred NRTIs in an initial cART regimen. For several reasons that will be discussed further in this review, abacavir is now considered an alternative to tenofovir by the DHHS. A 2009 update to World Health Organization (WHO) guidelines does not include abacavir in first-line cART.7 Finally, revisions to IAS and BHIVA guidelines in the near future are also expected to downgrade abacavir to an alternate agent. An important development in the advancement of HIV treatment was the FDC of abacavir/lamivudine (Epzicom and Kivexa; GlaxoSmithKline, Brentford, Middlesex, UK) which is usually FDA-approved for the treatment of HIV as a part of cART. It has been widely used throughout the US, Europe, and in some resource-limited settings due to its ease of dosing, favorable toxicity profile, and virologic potency. Despite extensive past use, recent controversial findings regarding abacavir/ lamivudine-FDC and one of its components, abacavir, may limit future use of this compound. In particular, patients on abacavir can develop a rare, but potentially life-threatening hypersensitivity reaction.8,9 Also, in several large, observational studies, abacavir has been associated with myocardial infarction (MI).10C13 Finally, in a recent randomized trial, abacavir/ lamivudine-FDC was found to be inferior to tenofovir/emtricitabine (Truvada; Gilead Sciences, Foster City, CA, USA) with regard to virologic suppression in patients with higher HIV viral load levels.14 We reviewed the treatment Bmp2 of HIV with abacavir/ lamivudine-FDC and these recent controversial findings that will likely limit its future use. MECHANISM OF ACTION AND PHARMACOLOGY Abacavir/lamivudine-FDC has exhibited bioequivalence to the individual components of abacavir 600 mg and lamivudine 300 mg given once daily.8,15 This makes the combination product a preferable formulation due to ease of administration and lower pill burden, without jeopardizing any therapeutic effect. Pharmacologic properties of the combination tablet can be interpreted from the individual components as discussed below. Abacavir Abacavir is usually a synthetic carbocyclic nucleoside analog, which requires intracellular phosphorylation to its active anabolite, carbovir triphosphate (CBV-TP), similar to other NRTIs. CBV-TP inhibits transcription of HIV viral RNA to DNA by competing with an endogenous nucleotid*transcriptase enzyme. The nucleoside substitution of CBV-TP lacks the 3hydroxyl group required for DNA polymerization, resulting in chain termination. Abacavir is usually a potent antiviral agent which can inhibit both HIV-1 and HIV-2, while demonstrating only poor inhibition of human cellular DNA polymerases , , and .8 Abacavir tablets are 83% bioavailable after oral administration and rapidly reach peak plasma concentrations between 0.63 to 2.5 hours.16,17 Abacavir is modestly affected by.