Transmitted Drug Resistance in Persons with Acute/Early HIV-1 in San Francisco, 2002-2009

Abstract

BackgroundTransmitted HIV-1 drug resistance (TDR) is an ongoing public health problem, representing 10–20% of new HIV infections in many geographic areas. TDR usually arises from two main sources: individuals on antiretroviral therapy (ART) who are failing to achieve virologic suppression, and individuals who acquired TDR and transmit it while still ART-naïve. TDR rates can be impacted when novel antiretroviral medications are introduced that allow for greater virologic suppression of source patients. Although several new HIV medications were introduced starting in late 2007, including raltegravir, maraviroc, and etravirine, it is not known whether the prevalence of TDR was subsequently affected in 2008–2009.Methodology/Principal FindingsWe performed population sequence genotyping on individuals who were diagnosed with acute or early HIV (<6 months duration) and who enrolled in the Options Project, a prospective cohort, between 2002 and 2009. We used logistic regression to compare the odds of acquiring drug-resistant HIV before versus after the arrival of new ART (2005–2007 vs. 2008–2009). From 2003–2007, TDR rose from 7% to 24%. Prevalence of TDR was then 15% in 2008 and in 2009. While the odds of acquiring TDR were lower in 2008–2009 compared to 2005–2007, this was not statistically significant (odds ratio 0.65, 95% CI 0.31–1.38; p = 0.27).ConclusionsOur study suggests that transmitted drug resistance rose from 2003–2007, but this upward trend did not continue in 2008 and 2009. Nevertheless, the TDR prevalence in 2008–2009 remained substantial, emphasizing that improved management strategies for drug-resistant HIV are needed if TDR is to be further reduced. Continued surveillance for TDR will be important in understanding the full impact of new antiretroviral medications.

Prevalence of Transmitted HIV-1 Drug Resistance (TDR) Associated Mutations and Predicted Drug Sensitivity in Newly Diagnosed HIV-1 Patient Cohort in a Western New York, 2005-2011

“…As PIs use in the US was much more popular than NNRTIs, TDR related to the NRTIs and NNRTIs are more common as compared to TDR related to PIs, which is consistent with other studies [4,10,11].…”

“…There are two important sources of TDR: (1) persons who develop drug resistance mutations while on ART and subsequently transmit HIV and (2) persons who acquire TDR mutations during initial infection and maintain the mutations in the absence of ART until they transmit HIV [4]. If TDR trends are driven primarily by persons with drug-resistant HIV who are viremic despite taking ART, changes in ART can help achieve better suppression of drug resistance and rapidly decrease TDR rates.…”

“…Since late 2007, several newer HIV medications, including Raltegravir, Maraviroc, Darunavir and Etravirine, were introduced, allowing for greater virologic suppression in patients on those treatment regimens. But studies have shown, that although the upward trend of the TDR rate from 2003-2007 has ceased due to the introduction of the new drugs, the TDR prevalence in 2008-2009 remained substantial, and was not significantly different than in prior years [4,5].…”

Mutations in HIV-1gagandpolCompensate for the Loss of Viral Fitness Caused by a Highly Mutated Protease

“…In the past, the transmission of drug-resistant viruses, which can sometimes persist even without the selective pressure of HAART, was becoming increasingly frequent (9,20). Nowadays, several studies show a decline in the transmission of drug-resistant variants in the western world to approximately 10% (2,14), whereas other studies still report stable transmission rates for certain resistance-associated mutations (RAMs) (5,45). The key to an effective treatment regimen relies on both the genetic barrier to resistance to a specific drug and on the ability of antiviral drugs to decrease viral load.…”

Issues in resistance, adherence, and comparative efficacy of the single-tablet regimen combination of tenofovir, emtricitabine, and efavirenz in the management of HIV-1 infection

“…Recent large populationbased studies in the United States, Africa, and Europe have found TDR rates in the range of 6%-16%, with higher levels of resistance in certain urban populations, particularly those who engage in high-risk sex and intravenous drug users (Table 2). [101][102][103][104][105][106][107][108][109][110] In a study of 1277 newly infected patients with HIV-1 in South Carolina, 184 (14%) had TDR. 54 (4%) had an NRTI mutation, 37 (3%) had a PI mutation, and 126 (10%) had an NNRTI mutation.…”