Objective To estimate the lost investment of domestically educated doctors migrating from sub-Saharan African countries to Australia, Canada, the United Kingdom, and the United States.
BackgroundRecent studies have suggested that failing nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens may have greater potential to induce the development of resistance mutations, which may limit options for second-line therapy.
MethodsAntiretroviral therapy (ART)-naïve individuals aged 18 years who initiated triple combination ART between January 2000 and June 2006 in British Columbia, Canada were enrolled in the study. We compared genotypic sensitivity scores (GSSs) derived from the development of resistance mutations between participants who initiated ART with ritonavir-boosted protease inhibitors (PIs) with those who initiated ART with NNRTIs, and determined the effects of these mutations on remaining active drugs.
ResultsA total of 1666 participants initiated ART, 818 (49.1%) with NNRTI-based regimens and 848 (50.9%) with boosted PI-based regimens. Among participants who developed resistance mutations, those who initiated NNRTI-based regimens had a lower median GSS than those on boosted PI-based regimens (9.8 vs. 11.0, respectively; Po0.001). Participants on boosted PI-based regimens [adjusted odds ratio (AOR) 3.68; 95% confidence interval (CI) 2.25, 6.01], those with 95% adherence to highly active antiretroviral therapy (HAART) (AOR 1.84; 95% CI 1.16, 2.92) and those with baseline CD4 count 4200 cells/mL (AOR 3.44; 95% CI 1.73, 6.84) were more likely to have the maximum number of drug options.
ConclusionThe use of NNRTI-based first-line ART regimens may limit the options for second-line treatment when the number of available drugs is limited. , before they are diagnosed with treatment failure and switched to a second-line therapy. Most patients who fail NNRTI-based therapy can be expected to have NNRTI cross-resistance and many will have some degree of NRTI resistance by the time they are switched to a second-line regimen [2,7]. It is hoped that these mutations will not affect the probability of treatment success on second-line regimens as they are based on a PI coupled with two novel NRTIs to which the patient has not been previously exposed [1]. A number of studies have provided data consistent with this expectation [8][9][10]. However, the development of thymidine analogue mutations (TAMs) or other major NRTI mutations has the potential to render these second-line regimens ineffective because of the widespread cross-resistance with other NRTIs [11]. Recent studies have suggested that failing NNRTI-based regimens have a greater susceptibility to the development of NRTI resistance mutations than do boosted PI-based regimens [12,13]. In industrialized countries, the increased frequency of these mutations is likely to be of little clinical consequence as regimens can be tailored to the individual resistance mutation profiles. However, whether these mutations would reduce effectiveness of the commonly available second-line regimens in RLSs is unknown. The aim of this study was to examine how the development of specific drug resistance mutations among individuals on highly active antiretro...
Results of this study suggest that the newer tablet formulation of ritonavir is better tolerated and has fewer gastrointestinal side effects than the older capsule formulation.
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