In the Journals

Transmission of HIV drug resistance remains stable in Europe

Recent data suggest the European transmission rate of HIV drug resistance between 2008 and 2010 was similar to rates recorded in previous years.

While resistance was detected most often for nucleoside reverse transcriptase inhibitors, the impact of observed mutations on drug susceptibility was greatest for non-nucleoside reverse transcriptase inhibitors, according to L. Marije Hofstra, MD, researcher in the department of infection and immunity of the Luxembourg Institute of Health, and colleagues.

“Surveillance of the transmission of HIV drug resistance (TDR) is essential to inform treatment policymaking and guidance,” Hofstra and colleagues wrote. “Our data underline that the impact of baseline mutation patterns on drug susceptibility should be assessed using clinical algorithms or guidelines.”

Analysis of the SPREAD surveillance program

Using 2008-2010 data from the SPREAD surveillance system, the researchers enrolled adult HIV patients with no exposure to ART from 26 European countries. These patients contributed clinical and virological information along with a blood sample within 6 months of diagnosis. Samples were examined for resistance mutations toward nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) to determine prevalence of TDR. Additional analyses were performed for different risk groups and HIV subtypes, and results were compared with previous patient data from 2002 to 2005 (n = 2,990) and 2006-2007 (n = 2,458).

There was a significantly greater proportion of men who have sex with men during the most recent time period. Nearly half of these patients were from Western Europe, and the majority were infected with subtype B HIV.

The researchers reported an overall TDR prevalence of 8.3% (95% CI, 7.2-9.5) during the 2008-2010 time period. Mutations conferring resistance to NRTIs were observed most frequently (4.5%, 95% CI, 3.6-5.4), although mutations associated with NNRTIs (2.9%; 95% CI, 2.2-3.5) and PIs (2%; 95% CI, 1.4-2.6) also were observed. Although less prevalent than NRTI resistance, baseline mutations predicting reduced susceptibility to NNRTIs were of high concern, the researchers wrote. NRTI-associated mutations were “somewhat more prevalent” among MSM and significantly more prevalent in subtype B (P < .0001), reflecting data from the earlier time periods. NNRTI-associated mutation prevalence was similar between risk groups and investigated subtypes.

When compared with findings from previous years, this most recent data suggested no significant change in TDR prevalence overall or within different drug classes, they wrote.

“However, caution is warranted since relevant polymorphic resistance-related mutations are not included and some mutations that are listed may have only limited clinical impact,” Hofstra and colleagues wrote. “Prevalence figures from epidemiological surveys therefore may not directly translate to susceptibility of HIV to antiretroviral drugs in clinical practice.”

Drug resistance requires patients to switch treatments

In another recent study, the presence of pretreatment HIV drug resistances such as those investigated by Hofstra and colleagues was linked to a nearly fourfold increase in patients switching to second-line ART due to treatment failure.

“The expanding exposure to antiretroviral drugs at a population level will lead to increased transmission of drug-resistant viruses,” Tamara Sonia Boender, MSc, of the Amsterdam Institute for Global Health and Development, Netherlands, and colleagues wrote. “As a consequence, ART programs will be confronted with increasing numbers of patients that already carry drug strains before starting standard first-line ART.”

In a multinational cohort study of adult patients beginning standard first-line ART, Boender and colleagues evaluated the effect of pretreatment drug resistance (PDR) on switching ART regimens after presumed treatment failure, as well as its effect on clinical outcomes including all-cause mortality and new AIDS events. Among their cohort of 2,579 patients enrolled throughout sub-Saharan Africa, 5.5% were reported to have decreased susceptibility to one or more prescribe HIV drugs.

The researchers wrote that this PDR was associated with an increased risk for regimen switching (P = .005). Although adjusted analyses showed no differences in mortality rate and the incidence of new AIDS events, Boender and colleagues advocated for expanded access to second-line treatment and increased use of viral load monitoring to streamline care and limit unnecessary drug use.

“Our findings demonstrate that the presence of PDR diminishes the long-term effectiveness of first-line ART, and is strongly associated with switching to second-line regimens,” they wrote. “In view of rising PDR levels in Africa, these findings underscore the urgent need for increased implementation of [viral load] monitoring and access to affordable second-line regimens to secure durable ART success in sub-Saharan Africa.” – by Dave Muoio

Disclosure: The researchers report no relevant financial disclosures.

Recent data suggest the European transmission rate of HIV drug resistance between 2008 and 2010 was similar to rates recorded in previous years.

While resistance was detected most often for nucleoside reverse transcriptase inhibitors, the impact of observed mutations on drug susceptibility was greatest for non-nucleoside reverse transcriptase inhibitors, according to L. Marije Hofstra, MD, researcher in the department of infection and immunity of the Luxembourg Institute of Health, and colleagues.

“Surveillance of the transmission of HIV drug resistance (TDR) is essential to inform treatment policymaking and guidance,” Hofstra and colleagues wrote. “Our data underline that the impact of baseline mutation patterns on drug susceptibility should be assessed using clinical algorithms or guidelines.”

Analysis of the SPREAD surveillance program

Using 2008-2010 data from the SPREAD surveillance system, the researchers enrolled adult HIV patients with no exposure to ART from 26 European countries. These patients contributed clinical and virological information along with a blood sample within 6 months of diagnosis. Samples were examined for resistance mutations toward nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) to determine prevalence of TDR. Additional analyses were performed for different risk groups and HIV subtypes, and results were compared with previous patient data from 2002 to 2005 (n = 2,990) and 2006-2007 (n = 2,458).

There was a significantly greater proportion of men who have sex with men during the most recent time period. Nearly half of these patients were from Western Europe, and the majority were infected with subtype B HIV.

The researchers reported an overall TDR prevalence of 8.3% (95% CI, 7.2-9.5) during the 2008-2010 time period. Mutations conferring resistance to NRTIs were observed most frequently (4.5%, 95% CI, 3.6-5.4), although mutations associated with NNRTIs (2.9%; 95% CI, 2.2-3.5) and PIs (2%; 95% CI, 1.4-2.6) also were observed. Although less prevalent than NRTI resistance, baseline mutations predicting reduced susceptibility to NNRTIs were of high concern, the researchers wrote. NRTI-associated mutations were “somewhat more prevalent” among MSM and significantly more prevalent in subtype B (P < .0001), reflecting data from the earlier time periods. NNRTI-associated mutation prevalence was similar between risk groups and investigated subtypes.

When compared with findings from previous years, this most recent data suggested no significant change in TDR prevalence overall or within different drug classes, they wrote.

“However, caution is warranted since relevant polymorphic resistance-related mutations are not included and some mutations that are listed may have only limited clinical impact,” Hofstra and colleagues wrote. “Prevalence figures from epidemiological surveys therefore may not directly translate to susceptibility of HIV to antiretroviral drugs in clinical practice.”

Drug resistance requires patients to switch treatments

In another recent study, the presence of pretreatment HIV drug resistances such as those investigated by Hofstra and colleagues was linked to a nearly fourfold increase in patients switching to second-line ART due to treatment failure.

“The expanding exposure to antiretroviral drugs at a population level will lead to increased transmission of drug-resistant viruses,” Tamara Sonia Boender, MSc, of the Amsterdam Institute for Global Health and Development, Netherlands, and colleagues wrote. “As a consequence, ART programs will be confronted with increasing numbers of patients that already carry drug strains before starting standard first-line ART.”

In a multinational cohort study of adult patients beginning standard first-line ART, Boender and colleagues evaluated the effect of pretreatment drug resistance (PDR) on switching ART regimens after presumed treatment failure, as well as its effect on clinical outcomes including all-cause mortality and new AIDS events. Among their cohort of 2,579 patients enrolled throughout sub-Saharan Africa, 5.5% were reported to have decreased susceptibility to one or more prescribe HIV drugs.

The researchers wrote that this PDR was associated with an increased risk for regimen switching (P = .005). Although adjusted analyses showed no differences in mortality rate and the incidence of new AIDS events, Boender and colleagues advocated for expanded access to second-line treatment and increased use of viral load monitoring to streamline care and limit unnecessary drug use.

“Our findings demonstrate that the presence of PDR diminishes the long-term effectiveness of first-line ART, and is strongly associated with switching to second-line regimens,” they wrote. “In view of rising PDR levels in Africa, these findings underscore the urgent need for increased implementation of [viral load] monitoring and access to affordable second-line regimens to secure durable ART success in sub-Saharan Africa.” – by Dave Muoio

Disclosure: The researchers report no relevant financial disclosures.