He was taking D4T+3TC+RTV+SQV until June. Since then he has been taking AZT+3TC+EFV+AMP+LPV/r. His viral load was 1,555,662 (6.1 log) in June and his CD4 count was 12 (1.9%).
Two months after change of therapy (August), his viral load was 971,000 and his CD4 count was 65 (5%) in August 30th. One month later, his new VL was 354,000. But now his VL is back up to 1,030,000 and his CD4 count is down to 22 (3.6%). What can I do??? What about a new combination? What about tenofovir? There are few options remaining. There are so many RT mutations that I can't offer another option than AZT+3TC or D4T+3TC. He has already received ddI, ddC, AZT, 3TC,d4T, NFV, SAQ, RTV, IDV, AMP, LPV/r and EFV. What about IL-2 to improve his CD4 count?
Dr. Brian Conway responds: The genotype you put forward is a complex one. In the reverse transcriptase gene, we have the fully expressed 151 complex (62/75/77/116/151), conferring multi-NRTI resistance. The K65R mutation is also present, with an impact on susceptibility to d4T, ddI and, to some extent, tenofovir. It is notable that there are no mutations at codons 41, 74, 184 and 215. With respect to NNRTIs, the cardinal K103N mutation is present (conferring broad class cross-resistance), with an additional mutation at codon 100. In the protease gene, the picture is a bit more promising, although the V82A mutation confers fairly broad resistance. The G48V change is fairly specific to saquinavir and there is only one other secondary mutation.
Now, let us consider the patient at hand. In this setting, the regimen should include agents from all three classes, despite the resistance pattern. Given the protease gene mutations, I might have expected the combination of AMP plus LPV/r to have had some efficacy, and it should be maintained. It is possible that the EFV in the regimen could have had negative pharmacokinetic effects on AMP and LPVr blood levels. It is possible that substituting delavirdine (DLV) for EFV may increase the PI levels and enhance their efficacy. Thus, the NNRTI/PI combination could consist of DLV plus AMP plus LPV/r.
Now, on to the NRTIs. Although there is a multi-NRTI resistance pattern, it is one that does not confer resistance to tenofovir (TNV), although the efficacy of this compound could be compromised by the presence of the K65R mutation. On theoretical grounds, 3TC could be maintained in the regimen, especially since it is so well tolerated.
In summary, a possible regimen would consist of 3TC, TDF, DLV, AMP, and LPV/r.
Although IL-2 could be considered here, its efficacy in the setting of advanced immune disease is lessened. In addition, in the setting of a regimen that may not produce virologic suppression, it may stimulate viral replication and lessen the potential efficacy of a regimen that may not work as well as we would want.
I hope this helps, and good luck with this patient.
