title: Current and future management of treatment failure in low- and middle-income countries.
abstract: OBJECTIVE
  Access to second-line therapy in low- and middle-income countries has been limited to date. The WHO predicts that between 500 000 and 800 000 HIV-infected people on first-line combination antiretroviral therapy will require switch to second-line therapy by 2010. This paper aims to describe and review access to second-line therapy in low- and middle-income countries at present and examine future possibilities.
  
  
  RESULTS
  The majority of HIV-infected patients failing first-line combination antiretroviral therapy is identified by way of routine monitoring of clinical and immunological status as a surrogate for virological monitoring. Evidence suggests that immunological and clinical monitoring lack both sensitivity and specificity for virological failure. Consequently, at treatment failure, patients have often selected a degree of resistance within the nucleoside/nucleotide reverse transcriptase inhibitor class that questions the efficacy of using nucleoside/nucleotide reverse transcriptase inhibitors in a second-line regimen. There is a paucity of good-quality evidence on which to base guidelines and policy. Optimally, a second-line regimen would be simple, potent, tolerable and lend itself to provision according to the successful 'public health' approach.
  
  
  CONCLUSIONS
  Provision of second-line therapy to HIV-infected individuals failing first-line therapy is a major challenge to the ongoing success of access to HIV care programmes in low- and middle-income countries. The optimal second-line combination antiretroviral therapies are unknown. Research trials to help define best practice are in advanced stages of development and implementation.
authors.affiliation: National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia. mboyd@nchecr.unsw.edu.au
authors.forename: Mark A
authors.initials: MA
authors.lastname: Boyd
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003906:Developing Countries; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D006078:Government Programs; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects*; D006297:Health Services Accessibility; D006801:Humans; D011203:Poverty; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D017211:Treatment Failure
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors