Background: Drug-resistant HIV-1 variants generally display reduced replication capacity compared to drug susceptible viruses. Drug-resistant isolates derived from individuals during primary infection might display different properties since replication capacity is thought to be an important determinant for transmission to a new host.

Methods: Virus was co-cultured from PBMC of 18 newly infected individuals. Co-receptor usage and single cycle infectivity of the isolates were determined using reporter cell lines; and growth kinetics were studied by infection of PBMC. The rates of replication were measured mathematically using p24 values of culture supernatants. Compensatory changes present in gag were assessed by sequencing. The efficiency of Gag processing was determined by Western blotting of concentrated virions.

Results: The replication properties of the 9 drug resistant viruses (3 with mutations in PR and RT, 3 with mutations in PR, 3 with mutations in RT) and 9 viruses without primary drug resistant-associated mutations were assessed. All isolates were CCR5-tropic. Infectivity ranged between 0.6% and 13.7%. The mean infectivity of the drug resistant isolates was higher than the infectivity of the wild type isolates (p < 0.05). The isolates displayed a range of growth rates (g: 0.15–1.01) with a mean g value of 0.61 for drug resistant isolates, and 0.43 for the drug susceptible ones (p > 0.05). Data regarding a pair of epidemiologically-linked PI resistant viruses suggest that the fitness of drug resistant viruses may increase with subsequent transmission (g index virus 0.15; g recipient virus 0.37). Sequence analysis of gag revealed a number of mutations that could be important to restore infectivity. Substitutions were seen in all 5 gag cleavage sites with the highest degree of polymorphisms found in the p2/p7 cleavage site (17/18). Insertions and deletions were observed in p17, p2 or p6 (11/18). The defects in virion-associated gag processing of drug resistant and susceptible variants were minor.

Conclusions: Using a panel of different assays, we found that the characteristics of transmitted viruses were similar irrespective of the presence or absence of drug resistance associated mutations. Thus, it is likely that the event of transmission selects for the viral variant that is best adapted to replicate in a drug-free environment. A better understanding of the mechanisms that allow these special viruses to overcome their replication defects is needed.