Using viral fitness

Some researchers think that viral fitness can be used to control HIV.

The mutations that make HIV resistant drugs also make HIV less able to reproduce. Resistant HIV is often a weaker strain.

For example, continuing to use 3TC or FTC with the M184V mutation may keep viral load lower because this mutation makes HIV less fit. 3TC or FTC could therefore be used in any treatment-experienced combination. Additional mutations do not appear to develop in this case.

Another strategy for using reduced fitness could be to cycle different combinations. This is a theoretical strategy for someone who has already developed resistance to all available treatments.

The effect of each drug or combination would be to keep changing the type of resistance. Early resistance is usually related to reduced viral fitness for at least the first 4-8 weeks.

Reduced fitness is usually overcome by new mutations, so you want to change before this occurs. Cycles could be weekly or monthly.

This could be a new and important approach for people with no other options. It could also use fewer drugs in each combination.

An Italian study reported this strategy in a group of 34 highly treatment-experienced patients.

Combination therapy was changed based on results from genotype resistance whenever viral load rebounded above 10,000 copies (indicating that a more fit virus had developed). Only 3-4 drugs were included in each combination and this strategy was maintained for over 2 years. In this study each combination lasted an average of 6 months.

This study stressed the importance of aiming for undetectable viral load, but when this is not possible, it showed a new ‘holding’ strategy until new drugs are available.