Abstract
IntroductionAntiretroviral therapy (ART) in resource-limited settings has expanded in the last decade, reaching >8 million individuals and reducing AIDS mortality and morbidity. Continued success of ART programs will require understanding the emergence of HIV drug resistance patterns among individuals in whom treatment has failed and managing ART from both an individual and public health perspective. We review data on the emergence of HIV drug resistance among individuals in whom first-line therapy has failed and clinical and resistance outcomes of those receiving second-line therapy in resource-limited settings.ResultsResistance surveys among patients initiating first-line nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based therapy suggest that 76%-90% of living patients achieve HIV RNA suppression by 12 months after ART initiation. Among patients with detectable HIV RNA at 12 months, HIV drug resistance, primarily due to M184V and NNRTI mutations, has been identified in 60%-72%, although the antiretroviral activity of proposed second-line regimens has been preserved. Complex mutation patterns, including thymidine-analog mutations, K65R, and multinucleoside mutations, are prevalent among cases of treatment failure identified by clinical or immunologic methods. Approximately 22% of patients receiving second-line therapy do not achieve HIV RNA suppression by 6 months, with poor adherence, rather than HIV drug resistance, driving most failures. Major protease inhibitor resistance at the time of second-line failure ranges from 0% to 50%, but studies are limited.ConclusionsResistance of HIV to first-line therapy is predictable at 12 months when evaluated by means of HIV RNA monitoring and, when detected, largely preserves second-line therapy options. Optimizing adherence, performing resistance surveillance, and improving treatment monitoring are critical for long-term prevention of drug resistance.
| Original language | English (US) |
|---|---|
| Journal | Journal of Infectious Diseases |
| Volume | 207 |
| Issue number | SUPPL.2 |
| DOIs | |
| State | Published - Jun 15 2013 |
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Keywords
- antiretroviral drug resistance
- resource-limited settings
- second-line therapy
ASJC Scopus subject areas
- Infectious Diseases
- Immunology and Allergy
Cite this
Emergence of HIV drug resistance during first- and second-line antiretroviral therapy in resource-limited settings. / Hosseinipour, Mina C.; Gupta, Ravindra K.; Van Zyl, Gert; Eron, Joseph J.; Nachega, Jean B.
In: Journal of Infectious Diseases, Vol. 207, No. SUPPL.2, 15.06.2013.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Emergence of HIV drug resistance during first- and second-line antiretroviral therapy in resource-limited settings
AU - Hosseinipour, Mina C.
AU - Gupta, Ravindra K.
AU - Van Zyl, Gert
AU - Eron, Joseph J.
AU - Nachega, Jean B.
PY - 2013/6/15
Y1 - 2013/6/15
N2 - IntroductionAntiretroviral therapy (ART) in resource-limited settings has expanded in the last decade, reaching >8 million individuals and reducing AIDS mortality and morbidity. Continued success of ART programs will require understanding the emergence of HIV drug resistance patterns among individuals in whom treatment has failed and managing ART from both an individual and public health perspective. We review data on the emergence of HIV drug resistance among individuals in whom first-line therapy has failed and clinical and resistance outcomes of those receiving second-line therapy in resource-limited settings.ResultsResistance surveys among patients initiating first-line nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based therapy suggest that 76%-90% of living patients achieve HIV RNA suppression by 12 months after ART initiation. Among patients with detectable HIV RNA at 12 months, HIV drug resistance, primarily due to M184V and NNRTI mutations, has been identified in 60%-72%, although the antiretroviral activity of proposed second-line regimens has been preserved. Complex mutation patterns, including thymidine-analog mutations, K65R, and multinucleoside mutations, are prevalent among cases of treatment failure identified by clinical or immunologic methods. Approximately 22% of patients receiving second-line therapy do not achieve HIV RNA suppression by 6 months, with poor adherence, rather than HIV drug resistance, driving most failures. Major protease inhibitor resistance at the time of second-line failure ranges from 0% to 50%, but studies are limited.ConclusionsResistance of HIV to first-line therapy is predictable at 12 months when evaluated by means of HIV RNA monitoring and, when detected, largely preserves second-line therapy options. Optimizing adherence, performing resistance surveillance, and improving treatment monitoring are critical for long-term prevention of drug resistance.
AB - IntroductionAntiretroviral therapy (ART) in resource-limited settings has expanded in the last decade, reaching >8 million individuals and reducing AIDS mortality and morbidity. Continued success of ART programs will require understanding the emergence of HIV drug resistance patterns among individuals in whom treatment has failed and managing ART from both an individual and public health perspective. We review data on the emergence of HIV drug resistance among individuals in whom first-line therapy has failed and clinical and resistance outcomes of those receiving second-line therapy in resource-limited settings.ResultsResistance surveys among patients initiating first-line nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based therapy suggest that 76%-90% of living patients achieve HIV RNA suppression by 12 months after ART initiation. Among patients with detectable HIV RNA at 12 months, HIV drug resistance, primarily due to M184V and NNRTI mutations, has been identified in 60%-72%, although the antiretroviral activity of proposed second-line regimens has been preserved. Complex mutation patterns, including thymidine-analog mutations, K65R, and multinucleoside mutations, are prevalent among cases of treatment failure identified by clinical or immunologic methods. Approximately 22% of patients receiving second-line therapy do not achieve HIV RNA suppression by 6 months, with poor adherence, rather than HIV drug resistance, driving most failures. Major protease inhibitor resistance at the time of second-line failure ranges from 0% to 50%, but studies are limited.ConclusionsResistance of HIV to first-line therapy is predictable at 12 months when evaluated by means of HIV RNA monitoring and, when detected, largely preserves second-line therapy options. Optimizing adherence, performing resistance surveillance, and improving treatment monitoring are critical for long-term prevention of drug resistance.
KW - antiretroviral drug resistance
KW - resource-limited settings
KW - second-line therapy
UR - http://www.scopus.com/inward/record.url?scp=84878333879&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84878333879&partnerID=8YFLogxK
U2 - 10.1093/infdis/jit107
DO - 10.1093/infdis/jit107
M3 - Article
C2 - 23687289
AN - SCOPUS:84878333879
VL - 207
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - SUPPL.2
ER -