Thymidine analogue-sparing highly active antiretroviral therapy (HAART).
The use of alternative nucleoside reverse transcriptase inhibitors (NRTIs) to the thymidine analogues stavudine (d4T) and zidovudine(ZDV) has been advocated as a means of limiting long-term NRTI-associated toxicity, particularly the development of lipoatrophy or fat wasting. This approach reflects an increasing knowledge of the distinct toxicity profiles of NRTI drugs. However, recent clinical trials have demonstrated that the use of thymidine analogue NRTIs and newer alternative backbone NRTIs, such as tenofovir (TNF) and abacavir (ABC), is associated with comparable short-term efficacy and tolerability. Given the importance of toxicity profile differences in determining clinical management, it is important to recognise that d4T and ZDV cary significantly different risks for long-term NRTI toxicity. Recognising that all NRTIs, including thymidine analogues, have individual toxicity profiles provides a more appropriate basis for selecting optimal antiretroviral therapy. The safety and efficacy of TNF and ABC are also reviewed here, although the available data provide only limited knowledge of the long-term effects of these drugs in terms of toxicity and antiviral durability.
Nolan
David
D
Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital and Murdoch University, Perth, Western Australia. David.Nolan@health.wa.gov.au
Mallal
Simon
S
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D002986:Clinical Trials as Topic; D015224:Dideoxynucleosides / Q000009:adverse effects / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy*; D054303:HIV Reverse Transcriptase / Q000187:drug effects / Q000235:genetics; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced; D006801:Humans; D063065:Organophosphonates / Q000009:adverse effects / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000068698:Tenofovir; D013997:Time Factors; D000099227:Abacavir
D000225:Adenine; D015224:Dideoxynucleosides; D054303:HIV Reverse Transcriptase; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D000099227:Abacavir