|
Resistance profile of patients failing first line ART in Malawi when using clinical and immunologic monitoring
Presented by Mina Hosseinipour, Malawi.
M. Hosseinipour1, J.J. van Oosterhout2, R. Weigel3, J. Nelson4, S. Fiscus4, J. Eron4, J. Kumwenda2
1UNC Project, Lilongwe, Malawi, 2Malawi College of Medicine, Blantyre, Malawi, 3Lighthouse Clinic, Lilongwe, Malawi, 4University of North Carolina, Chapel Hill, United States
Background: Over 130,000 Malawians have ever started ART, where first line therapy is d4T/3TC/NVP. Those who fail d4T/3TC/NVP are started on ZDV/3TC/Tenofovir/Lopinavir/ritonavir. Failure is based on clinical or immunological grounds as viral load is rarely available. We evaluated the resistance mutations among patients failing first line ART in Lilongwe and Blantyre.
Methods: Patients meeting the definition of ART failure according to Malawi national guidelines (New Stage 4 condition, CD4 decline>50%, CD4<pre-treatment) from December 2005 to July 2007 were evaluated. Among those with HIVRNA >1000 copies/ml prior to starting second line treatment, genotyping was performed.
Results: 101 confirmed ART failure patients were identified. Mean (sd) CD4 count, HIVRNA, and duration on ART were: 121cells/ml (131), 135984 copies/ml (201278), and 38 months (20.4), respectively. Four samples did not amplify and 5 samples had no mutations identified. Seven samples had M184V plus NNRTI mutations only. NNRTI mutations 181C, 103N, 106M, 188L, 190 occurred with similar frequency. The most common mutation pattern was M184V plus NNRTI mutations with one or more TAM (most common = 215F/Y) which occurred in 55% of patients. Surprisingly, 19% of patients acquired NNRTI mutations (with or without 184V) plus either the K70E or K65R mutations. 16% of the patients had pan-nucleoside resistance which corresponded to K65R or K70E and additional multi-nucleoside resistance mutations, most commonly the 151 complex and/or rarely 69 insertions.
Conclusions: Upon first line ART failure diagnosis which relied on clinical and CD4 monitoring, extensive resistance was present to NRTI/NNRTI agents, including 16% of patients who acquired pan-NRTI resistant virus and an additional 55% who likely had reduced susceptibility to multiple but not all NRTI. These findings have profound implications for the optimal time to switch treatment and the choice of second line therapy for developing countries.
|