Deenan Pillay from University College London (UCL) reported on some good news from Brighton. In a collaborative effort between the MRC, UCL and Brighton Healthcare, the study provided an elegant confirmation of what we suspect but as yet had not been confirmed – that over time, the burden of drug-resistant infectious viral burden is falling in the infected population.
The premise for the study was to correlate viral load burden in potential transmitters and to determine how much resistance mutations in fact contribute to virus levels and its subsequent impact on infectivity. Total infectious viral load is the result of patients either un-treated or virologically failing on non-suppressive regimens. What is less well understood however, is how resistance mutations contribute to viral load and whether this precipitates infectivity with drug-resistant mutations.
The study was located in a fairly homogenous, well-defined and closely monitored group of MSM, all served by the same health care centre in Brighton since 1998. 1,482 patients both treated and naïve had a median of 9 viral loads and a total 495 resistance tests. The burden of resistance was calculated by mutations in the reverse transcriptase at positions 41, 103, 184 and 215 and in protease at position 90. The results from 2000 to 2003 demonstrate that 35% of this group had a VL >1,000 copies/ml. Nearly 7% had virus containing one or more key mutations. But this proportion fell by 20% during the period of study.
The predominant mutations in chronically infected or treated patients were in order of frequency: T215 (any) > M41L > K103N > M184V > L90M. Twenty-four individuals were also detected during this time with acute infection, most frequently harbouring: K103N > T215 (any) > M41L > L90M. But M184V was not detected. This correlates with previous reporting of M184V as a mutation that is not easily transmitted and unlikely to be detected in naïve patients. More interestingly, the impact of M184V on viral burden was found to be less than half of that observed with mutation T215.
The study confirms that the viral burden of infectious drug-resistant virus has indeed fallen over the past few years. With potent therapies and more patients on treatment, this trend can be expected to continue. The overall message is that patients are being treated more effectively and are therefore less infectious. This is due both to reduced viral loads and the overall reduction of drug-resistant infectious viral burden that can serve to facilitate resistance transmission.
D Pillay et al. What is the drug-resistance mutational infectious burden in an HIV-1 prevalent cohort and the relationship to incidence of transmitted resistance? Fifteenth HIV Drug Resistance Workshop, Sitges, Spain, abstract 101, 2006.