The evolution of drug resistance in HIV occurs by the fixation of specific, 
well-known, drug-resistance mutations, but the underlying population genetic 
processes are not well understood. By analyzing within-patient longitudinal 
sequence data, we make four observations that shed a light on the underlying 
processes and allow us to infer the short-term effective population size of the 
viral population in a patient. Our first observation is that the evolution of 
drug resistance usually occurs by the fixation of one drug-resistance mutation 
at a time, as opposed to several changes simultaneously. Second, we find that 
these fixation events are accompanied by a reduction in genetic diversity in the 
region surrounding the fixed drug-resistance mutation, due to the hitchhiking 
effect. Third, we observe that the fixation of drug-resistance mutations 
involves both hard and soft selective sweeps. In a hard sweep, a resistance 
mutation arises in a single viral particle and drives all linked mutations with 
it when it spreads in the viral population, which dramatically reduces genetic 
diversity. On the other hand, in a soft sweep, a resistance mutation occurs 
multiple times on different genetic backgrounds, and the reduction of diversity 
is weak. Using the frequency of occurrence of hard and soft sweeps we estimate 
the effective population size of HIV to be 1.5 x 10(5) (95% confidence interval 
[0.8 x 10(5),4.8 x 10(5)]). This number is much lower than the actual number of 
infected cells, but much larger than previous population size estimates based on 
synonymous diversity. We propose several explanations for the observed 
discrepancies. Finally, our fourth observation is that genetic diversity at 
non-synonymous sites recovers to its pre-fixation value within 18 months, 
whereas diversity at synonymous sites remains depressed after this time period. 
These results improve our understanding of HIV evolution and have potential 
implications for treatment strategies.