iconstar paper   HIV Articles  
Back grey arrow rt.gif
 
 
Transmitted HIV Drug Resistance Is High and Longstanding in Metropolitan Washington, DC....22.5% / "at-risk" women
 
 
  Download the PDF here
 
"The overall TDR prevalence was 22.5%.....The proportion with dual-class resistance was 5.4%"....."TDR was most frequently associated with NRTIs (15.5%), followed by NNRTIs (9.6%) and PIs (4.1%)."....."at-risk" women...."28.5% in the DC-WIHS"...."The most frequent NNRTI-associated TDR mutation was K103N/S, which present at 10.1% prevalence in 1997-2006 and then decreased to 8.6% between 2007 and 2013"......across time: "19.7% during 2007-2013.....28.9% during 1994-1996....24.7% during 1997-2006"
 
Clin Inf Dis Aug 24 2016
 
We identified a high prevalence of TDR (22.5%) in metropolitan Washington, DC, between 1994 and 2013.To our knowledge, this is the highest prevalence of TDR mutations reported within the United States or in any region within Europe or Australia, where ART therapy use has been long-standing.The relatively high frequency of non-B subtypes identified in our study likely reflects immigration patterns, especially from African countries, to the metropolitan Washington, DC, area.Our finding of persistently high and longstanding TDR within a generalized epidemic reflects the challenge of access to and retention in care. Recent estimates from Washington, DC, suggest that 62% of HIV-infected individuals are retained within care and only 47% have achieved viral suppression.Delays in treatment initiation, suboptimal treatment adherence, and interruptions in care provide opportunities for selection of drug-resistance mutations and HIV transmission with potential to alter patterns of TDR. We observed a downward trend in the overall prevalence of TDR compared with the early period, but continued high levels of drug resistance are evidence of fragmented care.
 
Overall, 16.2% of individuals had resistance to 1 drug class: 9.8% had resistance to nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs); 5.0% had resistance to nonnucleoside reverse-transcriptase inhibitor (NNRTIs); and 1.4% had resistance to protease inhibitors (PIs). The proportion with dual-class resistance was 5.4%: 3.4% to NRTIs and NNRTIs, 1.6% to NRTIs and PIs, and 0.4% to NNRTIs and PIs. The prevalence of TDR to all 3 classes was 0.9%. TDR varied across time (Figure 1), with prevalence of 28.9% (95% confidence interval [CI], .21-.38) during 1994-1996, 24.7% (95% CI, .16-.35) during 1997-2006, and 19.7% (95% CI, .16-.24) during 2007-2013.
 
Nearly one-half of our study participants were women, and elevated rates of TDR for many years in this group was unexpected. While previous studies demonstrated resistance among MSM, our data suggest women have been affected by transmission of drug resistance for years. It remains uncertain whether this observation is the effect of "bridging," that is, transmission of virus to women by men who had contacts with treated HIV-infected MSM.
 
Current biomedical prevention strategies are broadly recommended for MSM, active IDUs, and women "at risk for HIV acquisition." However, our findings highlight the distinct challenge in identifying "at-risk" women who would benefit from targeted biomedical prevention interventions.Most HIV-infected women acquire HIV through heterosexual transmission, and fewer related to IDU. A high proportion of women in our study did not report high-risk behaviors and were unaware of high-risk behaviors among their partners. While this could be underreporting by self-report, the observation of discordant HIV acquisition risk factors within some transmission clusters supports the concern that HIV acquisition risk is not solely that of the individual but that of the individual's partners, especially in the setting of a generalized epidemic.
 
The proportion of TDR among treatment-naive women and men was similar, 57/235 (24.3%) vs 68/328 (20.7%), respectively (P = .32). The proportions with TDR were also similar among individuals with heterosexual transmission (22.0%), IDU related (20.0%), MSM (21.9%), and unknown risk for HIV acquisition (15.1%).
 
We identified high prevalence of TDR among HIV-infected individuals in metropolitan Washington, DC, regardless of gender.We retrospectively studied individuals enrolled in HIV-related studies at the National Institutes of Health (NIH) or Georgetown University. Among 710 individuals enrolled in 1994-2013, the median age was 38.6 years, 46.2% were female, and 53.3% were African-American. TDR was 22.5% among 566 treatment-naive individuals; 15.8% had nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) resistance, 9.8% had nonnucleoside reverse-transcriptase inhibitor (NNRTI) resistance, and 4.2% had protease inhibitor (PI) resistance. Single class TDR was 10.0%, 5.1%, and 1.6% to NRTIs, NNRTIs, and PIs. Dual TDR to PI and NRTI was seen in 1.6%, NRTI and NNRTI in 3.4%, and triple class TDR in 0.9%. TDR frequency decreased from 1994-2006 (27.1%) to 2007-2013 (19.4%; P = .02). Only 6/79 (7.6%) individuals within transmission clusters had evidence of TDR.
 
Overall, TDR was most frequently associated with NRTIs (15.5%), followed by NNRTIs (9.6%) and PIs (4.1%). NRTI resistance was most common across all 3 periods but declined from 28.9% prevalence during 1994-1996 to 10.3% during 2007-2013. Frequency of TDR associated with NNRTIs peaked at 14.6% in the 1997-2006 period and stabilized at 11.1% during 2007-2013.
 
TDR is more frequent with increasing use of cART. The prevalence of TDR is lower in sub-Saharan Africa than in North America, Europe, and Australia, where cART was introduced earlier and is broadly accessible [11-14]. In the United States, reported estimates of TDR prevalence are 9.1%-13.7% [15, 16] and range from 12% to 18.9% among men who have sex with men (MSM) [17, 18]. These estimates, generated using population-based sequencing irrespective of timing of HIV acquisition, likely underestimate the true prevalence of TDR, as detection declines over time using this approach and often requires specialized methods that capture minority variants of HIV [19-21].
 
The overall TDR prevalence was 22.5%: 113/497 (22.7%) among those with subtype B HIV-1 and 13/69 (18.8%) among those with non-B HIV-1 subtypes (P = .54). Distribution of TDR by race/ethnicity was 11.4% non-Hispanic blacks, 3.4% Hispanic whites, 2.9% non-Hispanic whites, and 1.8% Hispanic blacks. High prevalence of TDR was a consistent finding across the study subgroups: 28.5% in the DC-WIHS, 22.2% in the DC cohort, 25% among ACTG participants, and 19.8% among NIH participants. The proportion of TDR among treatment-naive women and men was similar, 57/235 (24.3%) vs 68/328 (20.7%), respectively (P = .32). The proportions with TDR were also similar among individuals with heterosexual transmission (22.0%), IDU related (20.0%), MSM (21.9%), and unknown risk for HIV acquisition (15.1%).
 
Overall, 16.2% of individuals had resistance to 1 drug class: 9.8% had resistance to nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs); 5.0% had resistance to nonnucleoside reverse-transcriptase inhibitor (NNRTIs); and 1.4% had resistance to protease inhibitors (PIs). The proportion with dual-class resistance was 5.4%: 3.4% to NRTIs and NNRTIs, 1.6% to NRTIs and PIs, and 0.4% to NNRTIs and PIs. The prevalence of TDR to all 3 classes was 0.9%. TDR varied across time (Figure 1), with prevalence of 28.9% (95% confidence interval [CI], .21-.38) during 1994-1996, 24.7% (95% CI, .16-.35) during 1997-2006, and 19.7% (95% CI, .16-.24) during 2007-2013.
 
The pattern of individual TDR mutations varied across the study period, both between and within classes of ART drugs (Figure 2). Among NRTI-associated TDR, the thymidine-associated mutations predominated in the 1994-1996 period and declined over time. The TDR mutation M184V was present at 4.3%, and the prevalence of K65R was <0.5% in the most recent time period from 2007-2013. The most frequent NNRTI-associated TDR mutation was K103N/S, which present at 10.1% prevalence in 1997-2006 and then decreased to 8.6% between 2007 and 2013. Individual PI-associated TDR mutations remained low throughout the study period, all <3% except L90M, which was present at 4.5% prevalence during 1997-2006.
 

 
 
 
 
  iconpaperstack View Older Articles   Back to Top   www.natap.org