Transmission of resistant HIV common in clusters of newly infected individuals

Swiss researchers have found that 84% of individuals with newly-diagnosed HIV who were infected with a strain of the virus resistant to antiretroviral drugs were part of transmission clusters composed only of other newly diagnosed individuals. The study, which is published in the online edition of AIDS also found that 9% of recently diagnosed individuals were infected with a drug-resistant strain of HIV, and that 53% of individuals with recent HIV infection could be linked to a transmission cluster.

“Newly diagnosed, untreated individuals are a significant source of resistant strains, thus suggesting an important self-fueling mechanism for transmitted drug resistance”, write the investigators.

HIV transmission chains are poorly defined and documented. Mounting evidence from studies using phylogenetics analysis suggests that individually recently infected with HIV play an important part in the spread of the virus. Transmission clusters have been identified that are composed of recently-infected individuals.

However, the impact of transmission clusters in the frequency of transmitted drug resistant HIV has not been fully evaluated. Swiss investigators analysed viral sequences obtained from all individuals newly diagnosed with HIV in Geneva between 2000 and 2008.

Samples from 637 individuals were included in the investigators’ analysis. Resistance to anti-HIV drugs was present in 54 patients (9%).

Individuals with resistance were more likely to be male (79% vs. 63%, p = 0.02), older (38 vs. 34 years, p = 0.001), have a higher CD4 cell count (452 cells/mm³ vs. 339 cells/mm³, p = 0.02), and a lower viral load (40,000 copies/ml vs. 75,000 copies/ml, p = 0.02).

The overall rate of transmitted resistance increased significantly over the eight year period of the study (p = 0.015). This was entirely due to an increase in transmitted non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance (p = 0.002).

Phylogentic analysis showed that 222 (35%) of the newly diagnosed individuals were part of 105 transmission clusters.

Clusters were more frequent in those recently infected with HIV than those whose HIV infection was of unknown duration (53% vs. 30%, p

Of the 222 newly diagnosed individuals in transmission clusters, 147 (66%) were in clusters composed entirely of newly diagnosed individuals.

Newly diagnosed individuals with drug-resistant virus were significantly more likely to be part of a transmission cluster than individuals with drug-sensitive virus (59% vs. 33%, p

Of the 32 recently diagnosed individuals with transmitted resistance, 27 (84%) were part of transmission clusters composed of recently-infected individuals.

Consistent with these findings, the prevalence of transmitted resistance was higher in individuals who were part of clusters than those who were not (14% vs. 5%, p

“Our findings highlight the role of newly diagnosed individuals, not yet exposed to antiretroviral drugs, in replenishing the pool of individuals infected with drug-resistant HIV”, conclude the investigators.