Background:  Previous prevalence studies of drug resistance failed to capture the effect on future therapy options. Our goal was to estimate the number of patients in the Swiss HIV Cohort Study (SHCS) who have exhausted all standard 2-class regimens due to resistance.

Methods:  ART-exposed individuals were evaluated for calendar-time dependent availability of new standard regimens, defined as 2 of 4 NRTI groups (zidovudine [ATZ]/stavudine [d4T]; lamivudine [3TC]/emtricitabine [FTC]; didanosine [ddI]/abacavir [ABC]; tenofovir [TDF]) and either a protease inhibitor (PI) or a NNRTI. Options were assessed against treatment history and with the Stanford Algorithm if genotypic resistance tests had been performed after initiation of ART. Depending on approach, drugs as part of a virologically failing treatment or with a Stanford genotypic sensitivity score >15 were considered non-active. Virological failure was defined as 2 subsequent HIV RNA >500 copies/mL after >180 days of continuous therapy. For the treatment history approach, cross-resistance was assumed within each NRTI group, within all NNRTI, and, if failure occurred on unboosted PI, within all PI except darunavir (DRV)/tipranavir (TPV). To assess validity, the proportion of individuals with 2 subsequent HIV RNA <50 copies/mL per calendar year was compared by availability of options and approach.

Results: We included7286 patients, of whom 28% had ≥1 genotypic resistance tests and 43% had ever experienced a virological failure. The genotypic approach indicated an increase in the proportion of patients without options from 6% in 1999 to 12% in 2004, and stable levels at 11% since then. Estimates based on treatment history suggested a prevalence of 29% between 1999 and 2001, followed by a drop to a stable plateau at 9%, which coincided with the introduction of TDF. Regardless of approach, lack of active NRTI compounds was the limiting factor in >96% of patients without options, 22% and 8% of whom also had no active NNRTI or PI according to the genotypic approach and treatment history, respectively. Of 5241 persons seen in 2006, 576 had no options left based on genotype. Viral suppression was achieved in 78% (95%CI 77 to 79) with and 58% (54 to 62) without options. Proportions were similar when analysed by treatment history.

Conclusions:  The percentage of individuals without standard therapy options was below previously reported figures of resistance prevalence and remained stable since 2002. Of those, a remarkable number achieved viral suppression, possibly because they still had active NNRTI and PI available. The introduction of new drug classes will further mitigate their situation.