Prevalence of Transmitted Antiretroviral Drug-Resistant HIV-1
Prevalence of Transmitted Antiretroviral Drug-Resistant HIV-1
Summary: Transmitted resistance to antiretroviral drugs in acute and early HIV-1 infection has been well documented, although overall trends vary depending on geography and cohort characteristics. To describe the changing pattern of transmitted drug-resistant HIV-1 in a well-defined cohort in New York City, a total of 361 patients with acute or recent HIV-1 infection were prospectively studied over a decade (1995-2004) with respect to HIV-1 genotypes and longitudinal T-cell subsets and HIV-1 RNA levels. The prevalence of overall transmitted resistance changed from 13.2% to 24.1% (P = 0.11) during the periods 1995 to 1998 and 2003 to 2004. Nonnucleoside reverse transcriptase inhibitor resistance prevalence increased significantly from 2.6% to 13.4% (P = 0.007) during the same periods, whereas prevalence of multidrug-resistant virus shifted from 2.6% to 9.8% (P = 0.07) but did not achieve statistical significance. A comparable immunologic and virologic response of appropriately treated individuals was observed regardless of viral drug susceptibility status, suggesting that initial combination therapy guided by baseline resistance testing in the case of acute and early infection may result in a favorable treatment response even in the case of a drug-resistant virus. These data have important implications for selection of empiric first-line regimens for treatment of acutely infected antiretroviral-naive individuals and reinforce the need for baseline resistance testing in acute and early HIV-1 infection.
The occurrence of transmitted HIV-1 drug resistance is an evolutionary process that proceeds on temporal, environmental, and genomic scales. Rapid viral turnover and viral genetic variability continue to shape emerging trends in HIV-1 drug resistance. Recent epidemiological reports on transmitted drug resistance show conflicting trends, with some studies demonstrating a decline in prevalence and others revealing an increase in the transmission of drug-resistant HIV-1. Transmission of multidrug-resistant (MDR) HIV-1 (defined as viral variants with resistance to 2 or more classes of antiretroviral drugs) is also a major concern in primary HIV-1 infection. Some reports do not indicate increasing transmission of MDR HIV-1, suggesting that MDR variants may have impaired fitness and may be less efficiently transmitted. However, there is growing recognition that initial fitness impairment that results from emergence of certain resistance mutations can be improved by the accumulation of secondary mutations, occasionally restoring viral fitness to levels that may surpass that of the parental wild-type virus. Thus, temporal trends and clinical fitness of MDR HIV-1 continue to remain as topics of active debate. In this report, we summarize the changing epidemiology of transmitted HIV-1 drug resistance within this well-defined cohort in New York City during the past decade, with emphasis on the years 2003 and 2004.
Summary: Transmitted resistance to antiretroviral drugs in acute and early HIV-1 infection has been well documented, although overall trends vary depending on geography and cohort characteristics. To describe the changing pattern of transmitted drug-resistant HIV-1 in a well-defined cohort in New York City, a total of 361 patients with acute or recent HIV-1 infection were prospectively studied over a decade (1995-2004) with respect to HIV-1 genotypes and longitudinal T-cell subsets and HIV-1 RNA levels. The prevalence of overall transmitted resistance changed from 13.2% to 24.1% (P = 0.11) during the periods 1995 to 1998 and 2003 to 2004. Nonnucleoside reverse transcriptase inhibitor resistance prevalence increased significantly from 2.6% to 13.4% (P = 0.007) during the same periods, whereas prevalence of multidrug-resistant virus shifted from 2.6% to 9.8% (P = 0.07) but did not achieve statistical significance. A comparable immunologic and virologic response of appropriately treated individuals was observed regardless of viral drug susceptibility status, suggesting that initial combination therapy guided by baseline resistance testing in the case of acute and early infection may result in a favorable treatment response even in the case of a drug-resistant virus. These data have important implications for selection of empiric first-line regimens for treatment of acutely infected antiretroviral-naive individuals and reinforce the need for baseline resistance testing in acute and early HIV-1 infection.
The occurrence of transmitted HIV-1 drug resistance is an evolutionary process that proceeds on temporal, environmental, and genomic scales. Rapid viral turnover and viral genetic variability continue to shape emerging trends in HIV-1 drug resistance. Recent epidemiological reports on transmitted drug resistance show conflicting trends, with some studies demonstrating a decline in prevalence and others revealing an increase in the transmission of drug-resistant HIV-1. Transmission of multidrug-resistant (MDR) HIV-1 (defined as viral variants with resistance to 2 or more classes of antiretroviral drugs) is also a major concern in primary HIV-1 infection. Some reports do not indicate increasing transmission of MDR HIV-1, suggesting that MDR variants may have impaired fitness and may be less efficiently transmitted. However, there is growing recognition that initial fitness impairment that results from emergence of certain resistance mutations can be improved by the accumulation of secondary mutations, occasionally restoring viral fitness to levels that may surpass that of the parental wild-type virus. Thus, temporal trends and clinical fitness of MDR HIV-1 continue to remain as topics of active debate. In this report, we summarize the changing epidemiology of transmitted HIV-1 drug resistance within this well-defined cohort in New York City during the past decade, with emphasis on the years 2003 and 2004.