|
A 5 year old child has been on d4T and 3TC for three years (June 1998 - June 2001). Her viral load was 1,171,084 copies/mL and CD4 percentage was 24% at commencement of therapy. She has been growing well and has not been hospitalized since therapy. She had LIP before initiation of therapy. Since starting ARVs she has not been ill besides the odd URTI and some bronchospasm which resolves with inhaled bronchodilators and inhaled steroids. Her latest viral load, however, is 9, 667 copies/mL and it has been in this range since the initiation of therapy. She never had undetectable virus. Her CD4 percentage increased from 24% to 45%, her latest is 31%.
Her mom wants her to go onto triple therapy to achieve undetectable virus levels. We did a genotypic resistance profile on her at our local lab in South Africa which showed the following mutations: M184V, K70R, D76N, K219Q, signifying ABC resistance, 3TC resistance and low-level AZT resistance.
The question is: should we change her regimen from dual therapy to triple therapy? If so what regimen should we choose?
Dr. David Katzenstein responds:
From a clinical point of view, it sounds like you are definitely ahead with this child who is doing well on dual nucleoside therapy with d4T and 3TC, which is a forgiving and relatively well tolerated regimen. The child has had a stable 2 log decrease in virus (from more than a million to less than 10,000 copies/mL) with a reasonable CD4 percentage that should protect her from OIs. I would advise the mother that the relatively low-level viremia and the robust growth, development and CD4 count argue most strongly in favor of maintaining the current regimen. Balanced against this is the concern that her virus will develop increasing resistance. A suppressive regimen at this point could, if successful, prevent continued evolution of resistance with the possibility of increased virus replication with continued exposure. The danger is that use of an NNRTI (and I believe a new class of drug is warranted) could also lead to resistance against this class if there is not strict adherence and careful attention paid to the response.
Based on the mutations I would (1) continue the 3TC based on the premise that it is well tolerated and the M184V is increasing fidelity (impairing the rapidity of mutation), (2) stop the d4T and (3) add NNRTI + AZT + ddI . Would use either nevirapine or efavirenz, although there is more experience with NVP in children. Would recheck virus load after 4 weeks and at 1 month intervals. Follow closely for anemia, intolerance (nausea/headache), and regular clinical examination for evidence of distal symmetric neuropathy. This regimen could be "deintensified" (stop whichever of the nucleosides appears to be least well tolerated) after 6 months. This approach preserves PIs as a future option and tenofovir (soon to be licensed here) will provide a new nucleoside option.
Parenthetically, I would ask if the complete nucleotide sequence is available from the provider of the "genotype". The interpretation seems reasonable based on the RT mutations you named. However, it may be useful to know the algorithm used to interpret the RT sequence, whether there were mixtures or additional mutations at other sites, etc. If it is possible we would like to examine the sequence of the RT using the expertise of Drs. Robert Shafer and Rami Kantor at Stanford, who have compiled a database of non-subtype B resistance where this child's sequence and treatment history would be a valuable addition. If the complete sequence is available, we would also apply our current assessment of resistance and see if there is evidence for or against AZT and ddI in particular.
Return to Ask the Experts Home Page
|
