HIV-1 genetic diversity and divergence and its correlation with disease progression among antiretroviral naïve recently infected individuals.

HIV-1 genetic diversity evolution was deeply characterized during the first year of infection among recently-infected patients using deep sequencing technology and correlated with disease progression surrogate markers. RNA and DNA samples from twenty-five individuals (13 female) encoding the protease and reverse transcriptase regions of the pol gene, and the V3 region of the env gene were evaluated at recent infection and during established infection. Infection by a unique HIV-1 strain was inferred in 70.1% of the individuals, with no differences between genders. Infections by multiple strains were associated with higher viral loads and faster CD4+ T cell declines. Either low or high levels of viral loads accompanied low levels of genetic diversity and lower selective pressure. With massive sequence data from 3 distinct genomic HIV-1 regions from plasma and PBMCs over time, we propose a model for HIV-1 genetic diversity, which correlates to basal viral loads of patients.

Insights about minority HIV-1 strains in transmitted drug resistance mutation dynamics and disease progression

Objectives: The presence of minority transmitted drug resistance mutations was assessed using ultra-deep sequencing and correlated with disease progression among recently HIV-1-infected individuals from Brazil. Methods: Samples at baseline during recent infection and 1 year after the establishment of the infection were analysed. Viral RNA and proviral DNA from 25 individuals were subjected to ultra-deep sequencing of the reverse transcriptase and protease regions of HIV-1. Results: Viral strains carrying transmitted drug resistance mutations were detected in 9 out of the 25 patients, for all major antiretroviral classes, ranging from one to five mutations per patient. Ultra-deep sequencing detected strains with frequencies as low as 1.6% and only strains with frequencies.20% were detected by population plasma sequencing (three patients). Transmitted drug resistance strains with frequencies,14.8% did not persist upon established infection. The presence of transmitted drug resistance mutations was negatively correlated with the viral load and with CD4+T cell count decay. Conclusions: Transmitted drug resistance mutations representing small percentages of the viral population do not persist during infection because they are negatively selected in the first year after HIV-1 seroconversion.

Insights about minority HIV-1 strains in transmitted drug resistance mutation dynamics and disease progression

Objectives: The presence of minority transmitted drug resistance mutations was assessed using ultra-deep sequencing and correlated with disease progression among recently HIV-1-infected individuals from Brazil. Methods: Samples at baseline during recent infection and 1 year after the establishment of the infection were analysed. Viral RNA and proviral DNA from 25 individuals were subjected to ultra-deep sequencing of the reverse transcriptase and protease regions of HIV-1. Results: Viral strains carrying transmitted drug resistance mutations were detected in 9 out of the 25 patients, for all major antiretroviral classes, ranging from one to five mutations per patient. Ultra-deep sequencing detected strains with frequencies as low as 1.6% and only strains with frequencies.20% were detected by population plasma sequencing (three patients). Transmitted drug resistance strains with frequencies,14.8% did not persist upon established infection. The presence of transmitted drug resistance mutations was negatively correlated with the viral load and with CD4+T cell count decay. Conclusions: Transmitted drug resistance mutations representing small percentages of the viral population do not persist during infection because they are negatively selected in the first year after HIV-1 seroconversion.