neglected communities, a continued strong emphasis on adherence to therapy is essential. Substantial lack of adherence would not only result in treatment failure, but also would contribute to widespread resistance of the virus to therapy. Failure to adhere would thus not only be harmful to individual patients, but would also necessitate even greater investments of human and financial resources to overcome the resulting resistance problems (IOM, 2005).

PEPFAR does not routinely report on adherence as part of its ongoing program monitoring. However, some relevant data have been obtained from independent observational cohort studies in the focus countries, several of which have reported encouraging levels of adherence (Spacek et al., 2005; Calmy et al., 2006; Stringer et al., 2006; Wools-Kaloustian et al., 2006). Continued support for such evaluations will be critical for determining program effectiveness. Relatively short breaks in adherence (2 to 4 weeks) or repeated breaks for shorter intervals can result in viral resistance to two of the three components of recommended first-line ARV regimens. And a single resistance mutation (K103N) to the non-nucleoside component (either nevirapine or efavirenz) renders the virus resistant to the entire class of non-nucleoside reverse transcriptase inhibitor drugs. The consequence of such resistance patterns is that patients require drugs of a different class—protease inhibitors (Hirsch et al., 2003). The protease inhibitors not only cause more frequent undesirable side effects, but are several-fold more expensive than the WHO-recommended first-line drugs. Few protease inhibitors are now available as generics, and the complexity of their production may cause them to remain relatively expensive for the indefinite future.

Stigma Reduction

Clinicians visited by the Committee reported that the excellent clinical response to ART has in many areas led people in the surrounding communities to be more receptive to obtaining HIV testing and, when appropriate, therapy. This same phenomenon has been reported in other settings as well, including South Africa and Haiti (Castro and Farmer, 2005; Nachega et al., 2006). It appears that a benefit of the response to therapy may be a reduction in stigma associated with HIV testing. Recognition that people receiving effective ART rapidly gain weight and strength and do not suffer from recurrent opportunistic infections reportedly has greatly enhanced the perceived value of the PEPFAR program in the focus countries.

Resistance Monitoring

A previous Institute of Medicine report concluded that general screening for resistance to ARVs was not recommended because the prevalence



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