Clinical management of treatment-experienced, HIV/AIDS patients in the combination antiretroviral therapy era.

Abstract

Despite the success of combination antiretroviral therapy (ART) in improving clinical outcomes, treatment failure remains a significant challenge, particularly for highly treatment-experienced patients. This review evaluates current issues in the management of HIV-infected, treatment-experienced patients. It may provide guidance in selecting active, tolerable drug combinations that promote a reasonable quality of life, full adherence and a durable treatment response. Current treatment guidelines and clinical trial data were reviewed to identify reasons for treatment failure and to summarize therapy options for treatment-experienced and highly treatment-experienced patients. Current treatment options include nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and inhibitors of viral fusion, entry and integration. The use of NRTIs may be limited by resistance and short- and long-term toxicities. Resistance has restricted the NNRTI class with cross-resistance preventing their sequential use. Etravirine, a next-generation NNRTI, however, demonstrates effective virological suppression in patients with baseline NNRTI resistance. Boosted PIs are key components of ART for treatment-experienced patients. The newer boosted PIs tipranavir and darunavir have demonstrated impressive activity in patients with resistance to NRTIs, NNRTIs and PIs, as well as in less treatment-experienced patients for darunavir. The fusion inhibitor enfuvirtide has demonstrated efficacy in heavily treatment-experienced patients, although injection-site reactions can be problematical. The recently approved integrase inhibitor raltegravir has also shown impressive potency and tolerability in highly treatment-experienced patients. Finally, the entry inhibitor maraviroc has also been approved recently, although its use is somewhat limited by the need for HIV tropism testing. The availability of potent next-generation PIs, NNRTIs, integrase and entry-inhibitors may offer improved therapy for treatment-experienced patients, including those with multiresistant virus. These new drugs may reduce HIV immunological and clinical progression and in doing so may also reduce treatment costs.

• Authors: Mark A Boyd, Andrew M Hill
• Journal: PharmacoEconomics (Pharmacoeconomics) Vol. 28 Suppl 1 Pg. 17-34 ( 2010) ISSN: 1179-2027 [Electronic] New Zealand
• PMID: 21182341 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Anti-HIV Agents

Topics

• Anti-HIV Agents (therapeutic use)
• Antiretroviral Therapy, Highly Active
• Drug Resistance, Viral
• HIV Infections (drug therapy, virology)
• HIV-1 (drug effects)
• Humans
• Treatment Failure