BACKGROUND: Drug resistance testing before initiation of, or during, antiretroviral therapy (ART) is not routinely performed in resource-limited settings. High levels of viral resistance circulating within the population will have impact on treatment programs by increasing the chances of transmission of resistant strains and treatment failure. Here, we investigate Drug Resistance Mutations (DRMs) from blood samples obtained at regular intervals from patients on ART (Baseline-22 months) in Karonga District, Malawi. One hundred and forty nine reverse transcriptase (RT) consensus sequences were obtained via nested PCR and automated sequencing from blood samples collected at three-month intervals from 75 HIV-1 subtype C infected individuals in the ART programme. RESULTS: Fifteen individuals showed DRMs, and in ten individuals DRMs were seen from baseline samples (reported to be ART naïve). Three individuals in whom no DRMs were observed at baseline showed the emergence of DRMs during ART exposure. Four individuals who did show DRMs at baseline showed additional DRMs at subsequent time points, while two individuals showed evidence of DRMs at baseline and either no DRMs, or different DRMs, at later timepoints. Three individuals had immune failure but none appeared to be failing clinically. CONCLUSION: Despite the presence of DRMs to drugs included in the current regimen in some individuals, and immune failure in three, no signs of clinical failure were seen during this study. This cohort will continue to be monitored as part of the Karonga Prevention Study so that the long-term impact of these mutations can be assessed. Documenting proviral population is also important in monitoring the emergence of drug resistance as selective pressure provided by ART compromises the current plasma population, archived viruses can re-emerge.
BACKGROUND: Drug resistance testing before initiation of, or during, antiretroviral therapy (ART) is not routinely performed in resource-limited settings. High levels of viral resistance circulating within the population will have impact on treatment programs by increasing the chances of transmission of resistant strains and treatment failure. Here, we investigate Drug Resistance Mutations (DRMs) from blood samples obtained at regular intervals from patients on ART (Baseline-22 months) in Karonga District, Malawi. One hundred and forty nine reverse transcriptase (RT) consensus sequences were obtained via nested PCR and automated sequencing from blood samples collected at three-month intervals from 75 HIV-1 subtype C infected individuals in the ART programme. RESULTS: Fifteen individuals showed DRMs, and in ten individuals DRMs were seen from baseline samples (reported to be ART naïve). Three individuals in whom no DRMs were observed at baseline showed the emergence of DRMs during ART exposure. Four individuals who did show DRMs at baseline showed additional DRMs at subsequent time points, while two individuals showed evidence of DRMs at baseline and either no DRMs, or different DRMs, at later timepoints. Three individuals had immune failure but none appeared to be failing clinically. CONCLUSION: Despite the presence of DRMs to drugs included in the current regimen in some individuals, and immune failure in three, no signs of clinical failure were seen during this study. This cohort will continue to be monitored as part of the Karonga Prevention Study so that the long-term impact of these mutations can be assessed. Documenting proviral population is also important in monitoring the emergence of drug resistance as selective pressure provided by ART compromises the current plasma population, archived viruses can re-emerge.
Authors: Rami Kantor; Lynn S Zijenah; Robert W Shafer; Solomon Mutetwa; Elizabeth Johnston; Robert Lloyd; Andrea von Lieven; Dennis Israelski; David A Katzenstein Journal: AIDS Res Hum Retroviruses Date: 2002-12-10 Impact factor: 2.205
Authors: Beda Joos; Marek Fischer; Herbert Kuster; Satish K Pillai; Joseph K Wong; Jürg Böni; Bernard Hirschel; Rainer Weber; Alexandra Trkola; Huldrych F Günthard Journal: Proc Natl Acad Sci U S A Date: 2008-10-20 Impact factor: 11.205
Authors: Grace P McCormack; Judith R Glynn; Amelia C Crampin; Felix Sibande; Dominic Mulawa; Lyn Bliss; Philip Broadbent; Katia Abarca; Jorg M Pönnighaus; Paul E M Fine; Jonathan P Clewley Journal: J Virol Date: 2002-12 Impact factor: 5.103
Authors: Diane E Bennett; Ricardo J Camacho; Dan Otelea; Daniel R Kuritzkes; Hervé Fleury; Mark Kiuchi; Walid Heneine; Rami Kantor; Michael R Jordan; Jonathan M Schapiro; Anne-Mieke Vandamme; Paul Sandstrom; Charles A B Boucher; David van de Vijver; Soo-Yon Rhee; Tommy F Liu; Deenan Pillay; Robert W Shafer Journal: PLoS One Date: 2009-03-06 Impact factor: 3.240
Authors: Vijay Bansode; Grace P McCormack; Amelia C Crampin; Bagrey Ngwira; Ram K Shrestha; Neil French; Judith R Glynn; Simon A Travers Journal: BMC Infect Dis Date: 2013-01-30 Impact factor: 3.090