Prevalence Of Transmitted Drug Resistance Mutations Research Articles

HIV-1 Diversity and Drug Resistance in Treatment-Naïve Children and Adolescents from Rio de Janeiro, Brazil.

The human immunodeficiency virus type 1 (HIV-1) can be transmitted via parenteral, sexual, or vertical exposure routes. The number of HIV-1 cases detected yearly in children and adolescents in Brazil did not decrease over the last decade, representing ~5% of total cases described in the country. In recent years, the HIV-1 diversity and the prevalence of transmitted drug resistance mutations (TDRM) are moving toward a marked increase. In this study, we retrospectively evaluated the diversity of HIV-1 subtypes and the TDRM prevalence in 135 treatment-naïve HIV-1 vertically infected children and adolescents born in between 1993 and 2012. These children were assessed in either 2001–2007 or 2008–2012 when they were 0 to 17 years old. The individuals assessed in 2001–2007 (n = 38) had median CD4+ T cell counts of 1218 cells/mm3 (IQR: 738–2.084) and median HIV-1 plasma viral load of 4.18 log10 copies/mL (IQR: 3.88–4.08). The individuals (n = 97) evaluated in 2008–2012 showed median CD4+ T cell counts of 898.5 cells/mm3 (IQR: 591.3–1.821) and median HIV-1 plasma viral load of 4.69 log10 copies/mL (IQR: 4.26–5.33). A steady decrease in the median CD4 T+ cell counts was observed with age progression, as expected. The majority HIV-1 pol sequences (87%) were classified as pure HIV-1 subtypes (77% subtype B, 9% subtype F1 and 1.5% subtype C), while 13% of sequences were classified as recombinants (CRF45_cpx, n = 4; CRF28/29_BF1, n = 2; CRF02_AG, n = 1; CRF40_BF1, n = 1, CRF99_BF1, n = 1, URF_BF1, n = 8). The overall prevalence of TDRM was 14% (19/135), conferring resistance to the nucleoside reverse transcriptase inhibitors (NRTI, 13/135–9.6%), non-nucleoside reverse transcriptase inhibitors (NNRTI, 8/135–5.9%), and protease inhibitors (PI, 2/135–1.5%). The main TDRM observed for NNRTI was the K103N (n = 8), while the mutations T215I/Y/D/E (n = 7) and M184V (n = 4) were the main TDRM for NRTI. Only two TDRM were observed for PI in one individual each (M46I and V82A). Most TDRM were found in the HIV-1 subtype B (84%) sequences. This study reveals an HIV-1 epidemic with high diversity and moderate prevalence of TDRM in the pediatric population of Rio de Janeiro, indicating the existence of possible problems in the clinical management of prophylactic therapy to prevent mother-to-child transmission and future treatment options for the affected children.

A2 Phylogenetic investigation of transmitted HIV-1 drug resistance mutations in Denmark, 2009–17

Transmission of HIV-1 resistance mutations among therapy-naïve patients impairs the efficiency of antiretroviral therapy (ART). Therefore, genotypic resistance testing of patients is recommended at baseline, as this both allows for the selection of the correct ART regimen and for surveillance of transmitted drug resistance mutations (TDRM) among therapy naive HIV-1 patients. In Denmark, the occurrence of TDRM in newly diagnosed and therapy naïve HIV-1 patients is monitored through the SERO project. Here, we investigated if the prevalence of TDRM differed between patients within and outside of phylogenetically identified transmission clusters. Samples from 1,227 newly diagnosed HIV-1 patients were sent along with epidemiological information to the Virological Surveillance and Research group at Statens Serum Institut. HIV-1 RNA extraction, RT-PCR and Sanger sequencing of the pol gene was performed using an in-house assay. The sequences were analyzed using BioNumerics v. 6.6 and manually checked for the presence of mixed mutations and analyzed for mutations using the HIVDB 8.4 algorithm implemented at the Stanford database. Sequence alignments were performed in Mafft, and phylogenetic analysis was performed using Mega 6.0 using the Maximum likelihood general time reversible model with 100 bootstrap replicates. Clusters were identified with ClusterPicker at default settings (cluster support = 90%, genetic distance 4.5%). Active clusters contained newly diagnosed patients from the 2015 to 2017 period. HIV-1 sequences from 588 patients belonged to one of 154 clusters, and sequences from 639 patients did not belong to a cluster. Patients in clusters were significantly more likely to be men who have sex with men and subtype B and significantly less likely to be late presenters (Fisher’s test P < 0.05). The TDRM prevalence was significantly higher for patients outside of clusters than within clusters, 16.6 per cent versus 12.1 per cent, respectively (Fisher’s test P < 0.05); however, no significant differences were found in the TDRM prevalence between the 75 active and 79 inactive clusters, nor between small (<3 patients) and large (≥3 patients) clusters. E138A, V179D, and K103N were the three most prevalent TDRMs for both patient groups, whereas M41L differed between them. In Denmark, the TDRM prevalence is lower within clusters than outside, indicating that TDRM cases are either imported and/or belong to yet unidentified clusters.

Caution is needed in interpreting HIV transmission chains by ultradeep sequencing.

Molecular epidemiology is applied to various aspects of HIV transmission analyses. With ultradeep sequencing (UDS), in-depth characterization of transmission episodes involving minority variants is permitted. We explored HIV-1 epidemiological linkage and evaluated characteristics of transmission dynamics and transmitted drug resistance (TDR) detection through the added value of UDS. HIV pol gene fragments were sequenced by UDS and Sanger sequencing on samples of 70 HIV-1-infected, treatment-naive recently diagnosed MSM. Pairwise genetic distances and maximum likelihood phylogenies were computed. Transmission events were identified as clades with branch support at least 70% and intraclade genetic difference less than 4.5%. TDR mutations were recognized from the TDR consensus list. Transmission directionality, directness and inoculum size were inferred from tree topologies. Both datasets concurred in the identification of seven transmission pairs and one cluster of three patients. With UDS, direction of transmission was inferred in four out of eight chains. Evidence for multiple founder viruses was found in two out of eight chains. No transmission of minority-resistant variants was evidenced. TDR mutations prevalence in protease and reverse transcriptase fragments was 4.3% with Sanger sequencing and 18.6% with UDS. Although Sanger sequencing and UDS identified the same transmission chains, UDS provided additional information on founder viruses, direction of transmission and levels of TDR. Nevertheless, topology of clusters was not always consistent across gene fragments, calling for a cautious interpretation of the data. Moreover, unobserved intermediary links cannot be excluded. Phylogenetic analysis use as a forensic technique for HIV transmission investigations is risky.

Moderate prevalence of HIV-1 transmitted drug resistance mutations in southern Brazil

BackgroundDespite the advances in therapy, the occurrence of drug-resistant human immunodeficiency virus type 1 (HIV-1) is a major obstacle to successful treatment. This study aimed to characterize the genetic diversity and to determine the prevalence of transmitted drug resistance mutations (TDRM) between individuals recently or chronically diagnosed with HIV-1 from Paraná, Brazil.MethodsA total of 260 HIV-1 positive antiretroviral therapy-naïve patients were recruited to participate on the study, of which 39 were recently diagnosed. HIV-1 genotyping was performed using sequencing reaction followed by phylogenetic analyses to determine the HIV-1 subtype. TDRM were defined using the Calibrated Population Resistance Tool program.ResultsThe HIV-1 subtypes frequency found in the studied population were 54.0% of subtype B, 26.7% subtype C, 6.7% subtype F1 and 12.7% recombinant forms. The overall prevalence of TDRM was 6.7%, including 13.3% for recently diagnosed subjects and 5.9% for the chronic group.ConclusionsThe prevalence of resistance mutations found in this study is considered moderate, thus to perform genotyping tests before the initiation of antiretroviral therapy may be important to define the first line therapy and contribute for the improvement of regional prevention strategies for epidemic control.

Sexual intermingling of Arab and Jewish MSM in Israel: results of a molecular epidemiology study.

MSM comprise ∼30% of new HIV infections in Israel, a country with mixed Jewish and Arab populations. We molecularly characterized HIV-1 in the Arab and Jewish MSM (AMSM, JMSM) populations to reveal possible interethnical connections. Cross-sectional study. All Israeli-born, HIV-1-infected MSM diagnosed between 2005 and 2016 (n = 1143) were cross-matched with the National Civil Registry to identify religion (Jews/Muslims/Christians). Transmitted drug-resistance mutations (TDRM) and HIV-1 subtypes were determined on the first partial protease and reverse transcriptase sequences from treatment-naive patients and phylogenetic trees were constructed. Among MSM, 6.4% (73/1143) were Arabs and 93.6% (1070/1143) were Jews. Interestingly, a higher proportion of Arabs was identified among non-MSM (19%, 46/247 versus 6.4%, 73/1143, P < 0.01). Subtype analysis of 62 HIV-1 AMSM and 440 randomly selected HIV-1 JMSM sequences revealed 80.6, 8.1, 4.8 and 6.5% of AMSM and 82.3, 9.5, 4.1 and 4.1% of JMSM had B, A, C and non-A/B/C, respectively. Overall, 13.1% (66/502) had TDRM; reverse transcriptase-K103N/S, M184 V, T215S and protease-L90M were the most common. TDRM prevalence was not significantly higher in JMSM compared to AMSM (P = 0.1) and no temporal changes were observed in their frequency. Phylogenetic analysis demonstrated AMSM and JMSM clusters including L90M, K103N/S or T215S TDRM. Intermingling of AMSM and JMSM HIV-1 in clusters of HIV-1 sequences suggest interethnical sexual contacts among these MSM. Interventions aiming to prevent HIV-transmission in MSM should similarly address both populations groups. The high TDRM frequency requires continuation of resistance testing.

Prevalence and persistence of transmitted drug resistance mutations in the German HIV-1 Seroconverter Study Cohort.

The prevalence of transmitted drug resistance (TDR) in antiretroviral therapy (ART)-naïve individuals remains stable in most developed countries despite a decrease in the prevalence of acquired drug resistance. This suggests that persistence and further transmission of HIV-1 that encodes transmitted drug resistance mutations (TDRMs) is occurring in ART-naïve individuals. In this study, we analysed the prevalence and persistence of TDRMs in the protease and reverse transcriptase-sequences of ART-naïve patients within the German HIV-1 Seroconverter Study Cohort who were infected between 1996 and 2017. The prevalence of TDRMs and baseline susceptibility to antiretroviral drugs were assessed using the Stanford HIVdb list and algorithm. Mean survival times of TDRMs were calculated by Kaplan-Meier analysis. The overall prevalence of TDR was 17.2% (95% CI 15.7–18.6, N = 466/2715). Transmitted NNRTI resistance was observed most frequently with 7.8% (95% CI 6.8–8.8), followed by NRTI resistance (5.0%, 95% CI 4.2–5.9) and PI resistance (2.8%, 95% CI 2.2–3.4). Total TDR (OR = 0.89, p = 0.034) and transmitted NRTI resistance (OR = 0.65, p = 0.000) decreased between 1996 and 2017 but has remained stable during the last decade. Viral susceptibility to NNRTIs (6.5%-6.9% for individual drugs) was mainly reduced, while <3% of the recommended NRTIs and PIs were affected. The longest mean survival times were calculated for the NNRTI mutations K103N (5.3 years, 95% CI 4.2–5.6) and E138A/G/K (8.0 years, 95% CI 5.8–10.2 / 7.9 years, 95% CI 5.4–10.3 / 6.7 years, 95% CI 6.7–6.7) and for the NRTI mutation M41L (6.4 years, 95% CI 6.0–6.7).The long persistence of single TDRMs indicates that onward transmission from ART-naïve individuals is the main cause for TDR in Germany. Transmitted NNRTI resistance was the most frequent TDR, showing simultaneously the highest impact on baseline ART susceptibility and on TDRMs with prolonged persistence. These results give cause for concern regarding the use of NNRTI in first-line regimens.

High prevalence of HIV-1 transmitted drug-resistance mutations from proviral DNA massively parallel sequencing data of therapy-naïve chronically infected Brazilian blood donors.

BackgroundAn improved understanding of the prevalence of low-abundance transmitted drug-resistance mutations (TDRM) in therapy-naïve HIV-1–infected patients may help determine which patients are the best candidates for therapy. In this study, we aimed to obtain a comprehensive picture of the evolving HIV-1 TDRM across the massive parallel sequences (MPS) of the viral entire proviral genome in a well-characterized Brazilian blood donor naïve to antiretroviral drugs.Materials and methodsThe MPS data from 128 samples used in the analysis were sourced from Brazilian blood donors and were previously classified by less-sensitive (LS) or “detuned” enzyme immunoassay as non-recent or longstanding HIV-1 infections. The Stanford HIV Resistance Database (HIVDBv 6.2) and IAS-USA mutation lists were used to interpret the pattern of drug resistance. The minority variants with TDRM were identified using a threshold of ≥ 1.0% and ≤ 20% of the reads sequenced. The rate of TDRM in the MPS data of the proviral genome were compared with the corresponding published consensus sequences of their plasma viruses.ResultsNo TDRM were detected in the integrase or envelope regions. The overall prevalence of TDRM in the protease (PR) and reverse transcriptase (RT) regions of the HIV-1 pol gene was 44.5% (57/128), including any mutations to the nucleoside analogue reverse transcriptase inhibitors (NRTI) and non-nucleoside analogue reverse transcriptase inhibitors (NNRTI). Of the 57 subjects, 43 (75.4%) harbored a minority variant containing at least one clinically relevant TDRM. Among the 43 subjects, 33 (76.7%) had detectable minority resistant variants to NRTIs, 6 (13.9%) to NNRTIs, and 16 (37.2%) to PR inhibitors. The comparison of viral sequences in both sources, plasma and cells, would have detected 48 DNA provirus disclosed TDRM by MPS previously missed by plasma bulk analysis.ConclusionOur findings revealed a high prevalence of TDRM found in this group, as the use of MPS drastically increased the detection of these mutations. Sequencing proviral DNA provided additional information about TDRM, which may impact treatment decisions. The overall results emphasize the importance of continuous monitoring.

Recent trends and patterns in HIV-1 transmitted drug resistance in the United Kingdom.

ObjectivesTransmission of drug‐resistant HIV‐1 has decreased in the UK since the early 2000s. This analysis reports recent trends and characteristics of transmitted drug resistance (TDR) in the UK from 2010 to 2013.MethodsResistance tests conducted in antiretroviral treatment (ART)‐naïve individuals between 2010 and 2013 were analysed for the presence of transmitted drug resistance mutations (TDRMs), defined as any mutations from a modified 2009 World Health Organization surveillance list, or a modified 2013 International Antiviral Society‐USA list for integrase tests. Logistic regression was used to examine associations between demographics and the prevalence of TDRMs.Results TDRMs were observed in 1223 (7.5%) of 16 425 individuals; prevalence declined from 8.1% in 2010 to 6.6% in 2013 (P = 0.02). The prevalence of TDRMs was higher among men who have sex with men (MSM) compared with heterosexual men and women (8.7% versus 6.4%, respectively) with a trend for decreasing TDRMs among MSM (P = 0.008) driven by a reduction in nucleoside reverse transcriptase inhibitor (NRTI)‐related mutations. The most frequently detected TDRMs were K103N (2.2%), T215 revertants (1.6%), M41L (0.9%) and L90M (0.7%). Predicted phenotypic resistance to first‐line ART was highest to the nonnucleoside reverse transcriptase inhibitors (NNRTIs) rilpivirine and efavirenz (6.2% and 3.4%, respectively) but minimal to NRTIs, including tenofovir, and protease inhibitors (PIs). No major integrase TDRMs were detected among 101 individuals tested while ART‐naïve.ConclusionsWe observed a decrease in TDRMs in recent years. However, this was confined to the MSM population and rates remained stable in those with heterosexually acquired HIV infection. Resistance to currently recommended first‐line ART, including integrase inhibitors, remained reassuringly low.

HIV-1 Pol Gene Polymorphism and Antiretroviral Resistance Mutations in Treatment-Naive Adult Patients in French Guiana Between 2006 and 2012.

Little information is available on the molecular epidemiologic profile of HIV-1 in French Guiana, the French department with the highest HIV/AIDS incidence. To follow the evolution of HIV-1 diversity, we carried out a molecular analysis of HIV-1 isolates from 305 treatment-naive patients between 2006 and 2012. Protease and reverse-transcriptase sequences were obtained for subtype characterization, polymorphism analysis, and identification of drug resistance mutations. Of 305 HIV-1 strains, 95.1% were subtype B viruses. The overall prevalence of transmitted drug-resistance mutations (TDRMs) was 4.6% (14/305), ranging from 1.9% to 7.1% depending on the year. This study shows a low level of HIV-1 genetic diversity and a moderate prevalence of TDRMs with no evidence of an increasing trend over the study period. Nevertheless, the strong genetic polymorphism observed on both genes may be of concern for long-term treatment of people living with HIV-1 and thus deserves continuous monitoring.

HIV-1 Transmitted Drug Resistance Mutations in Newly Diagnosed Antiretroviral-Naive Patients in Turkey.

HIV-1 replication is rapid and highly error-prone. Transmission of a drug-resistant HIV-1 strain is possible and occurs within the HIV-1-infected population. In this study, we aimed to determine the prevalence of transmitted drug resistance mutations (TDRMs) in 1,306 newly diagnosed untreated HIV-1-infected patients from 21 cities across six regions of Turkey between 2010 and 2015. TDRMs were identified according to the criteria provided by the World Health Organization's 2009 list of surveillance drug resistance mutations. The HIV-1 TDRM prevalence was 10.1% (133/1,306) in Turkey. Primary drug resistance mutations (K65R, M184V) and thymidine analogue-associated mutations (TAMs) were evaluated together as nucleos(t)ide reverse transcriptase inhibitor (NRTI) mutations. NRTI TDRMs were found in 8.1% (107/1,306) of patients. However, TAMs were divided into three categories and M41L, L210W, and T215Y mutations were found for TAM1 in 97 (7.4%) patients, D67N, K70R, K219E/Q/N/R, T215F, and T215C/D/S mutations were detected for TAM2 in 52 (3.9%) patients, and M41L + K219N and M41L + T215C/D/S mutations were detected for the TAM1 + TAM2 profile in 22 (1.7%) patients, respectively. Nonnucleoside reverse transcriptase inhibitor-associated TDRMs were detected in 3.3% (44/1,306) of patients (L100I, K101E/P, K103N/S, V179F, Y188H/L/M, Y181I/C, and G190A/E/S) and TDRMs to protease inhibitors were detected in 2.3% (30/1,306) of patients (M46L, I50V, I54V, Q58E, L76V, V82A/C/L/T, N83D, I84V, and L90M). In conclusion, long-term and large-scale monitoring of regional levels of HIV-1 TDRMs informs treatment guidelines and provides feedback on the success of HIV-1 prevention and treatment efforts.

Transmitted Drug Resistance Among Recently Diagnosed Adults and Children in São Paulo, Brazil

Transmitted drug resistance mutations (TDRM) have been a constant threat to treatment efficacy. We evaluated TDRM in plasma RNA of 217 antiretroviral therapy-naive patients from sites in the São Paulo metropolitan area, collected from 2012 to 2014. The partial HIV-1 polymerase region was sequenced using Big Dye terminators at an ABI 3130 Genetic Analyzer. TDRM was defined according to the Stanford database calibrated population resistance (CPR v.6.0), but other drug resistance mutations (DRM) considered at the IAS list (IAS, 2014) and at the Stanford HIV Database Genotyping Resistance Interpretation (GRI-HIVdb) were also described. Out of 78% (170/217) of patients with information on the time of diagnosis, most (83%, 141/170) had been recently diagnosed, with the first positive HIV serology at a median of 58 days (IQR 18-184). Subtype B predominated (70%), followed by subtype F (10%), BF (7.5%), C (7.5%), and BC (5%). TDRMs were observed in 9.2% (20/217, CI 95% 5.9% to 13.6%), mostly (5.2%) to nonnucleoside reverse transcriptase inhibitor (NNRTI) antiretroviral class. Among children and adolescents, only a single patient showed TDRMs. Additional non-CPR mutations were observed: 11.5% (25/217) according to IAS or 4.6% (10/217) according to GRI-HIVdb. Overall, 23.5% (51/217) of the cases had one or more DRM identified. TDRM prevalence differed significantly among some sites. These trends deserve continuous and systematic surveillance, especially with the new policies of treatment as prevention being implemented in the country.

Transmitted antiretroviral drug resistance mutations in newly diagnosed HIV-1 positive patients in Turkey.

IntroductionThe objective of this study was to determine the transmitted drug resistance mutations (TDRMs) in newly diagnosed HIV-1 positive patients in Turkey.Materials and MethodsThe study was carried out between 2009 and 2014 and antiretroviral naïve 774 HIV-1 infected patients from 19 Infectious Diseases and Clinical Microbiology Departments in Turkey were included; gender: 664 (86%) male, median age: 37 (range; 1–77), median CD4+T-cell: 360 (range; 1–1320) count/mm3, median HIV-RNA load: 2.10+E6 (range; 4.2+E2–7.41+E8) IU/mL. HIV-1 drug resistance mutations were detected by population based sequencing of the reverse transcriptase (codon 41–238) and protease (codon 1–99) domains of pol gene of HIV-1, and analyzed according to the criteria by the World Health Organization 2009 list of surveillance drug resistance mutations [1].ResultsThe patients had TDRMs to NRTIs (K65R, M184V), NNRTIs (K101E, K103N/S, G190A/E/S, Y181I/C, Y188H/L) and PIs (M46L, I54V, L76V, V82L/T, N83D, I84V, L90M). The prevalence of overall TDRMs was 6.7% (52/774). Resistance mutations were found to be 0.7% (6/774), 4.1% (32/774) and 2.1% (17/774) to NRTIs, NNRTIs and PIs drug groups, respectively. Three patients had NRTIs+NNRTs resistance mutations (M184V+K103N) as multi-class drug resistance. However, thymidine analogue resistance mutations (TAMs) determined two distinct genotypic profiles in the HIV-1 reverse transcriptase: TAM1: M41L, L210W and T215Y, and TAM2: D67N, K70R, K219E/Q, and T215F. The prevalence of TAM1 and TAM2 were 7.7% (60/774) and 4.3% (34/774), respectively.ConclusionsThe TDRMs prevalence of antiretroviral naïve HIV-1 infected patients may be suggested current situation of Turkey. These long-term and large-scale results show that the resistance testing must be an integral part of the management of HIV infection in Turkey.

Patterns of transmitted HIV drug resistance in Europe vary by risk group.

BackgroundIn Europe, a continuous programme (SPREAD) has been in place for ten years to study transmission of drug resistant HIV. We analysed time trends of transmitted drug resistance mutations (TDRM) in relation to the risk behaviour reported.MethodsHIV-1 patients newly diagnosed in 27 countries from 2002 through 2007 were included. Inclusion was representative for risk group and geographical distribution in the participating countries in Europe. Trends over time were calculated by logistic regression.ResultsFrom the 4317 patients included, the majority was men-having-sex-with-men -MSM (2084, 48%), followed by heterosexuals (1501, 35%) and injection drug users (IDU) (355, 8%). MSM were more often from Western Europe origin, infected with subtype B virus, and recently infected (<1 year) (p<0.001). The prevalence of TDRM was highest in MSM (prevalence of 11.1%), followed by heterosexuals (6.6%) and IDU (5.1%, p<0.001). TDRM was predominantly ascribed to nucleoside reverse transcriptase inhibitors (NRTI) with a prevalence of 6.6% in MSM, 3.3% in heterosexuals and 2.0% in IDU (p = 0.001). A significant increase in resistance to non- nucleoside reverse transcriptase inhibitors (NNRTIs) and a decrease in resistance to protease inhibitors was observed in MSM (p = 0.008 and p = 0.006, respectively), but not in heterosexual patients (p = 0.68 and p = 0.14, respectively).ConclusionsMSM showed to have significantly higher TDRM prevalence compared to heterosexuals and IDU. The increasing NNRTI resistance in MSM is likely to negatively influence the therapy response of first-line therapy, as most include NNRTI drugs.

Decreasing trends of drug resistance and increase of non-B subtypes amongst subjects recently diagnosed as HIV-infected over the period 2004-2012 in the Veneto Region, Italy.

The present study was designed to prospectively monitor transmitted drug resistance mutations (TDRMs) in the Veneto Region, Italy. Genotypic resistance testing was conducted on the plasma of 1882 patients consecutively enrolled at the time of diagnosis of human immunodeficiency virus (HIV) infection from 2004 to 2012. TDRMs were defined according to the Stanford HIV database algorithm. In total, 214 (16.1%) B subtype-infected and 58 (10.5%) non-B subtype-infected individuals were identified as having a primary or recent HIV-1 infection. In subtype B-infected subjects in 2004-2006, the prevalence of TDRMs was 20.0% in chronic infections and 25.5% in recent infections; in 2007-2009 the rates were 11.5% and 5.3%, respectively; and in 2010-2012 they were 11.3% and 15.2%, respectively. In non-B subtype-infected subjects in 2004-2006, the prevalence of TDRMs was 18.0% in chronic infections and 16.5% in recent infections; in 2007-2009 the rates were 5.7% and 0%, respectively; and in 2010-2012 they were 6.2% and 8.7%, respectively. Protease inhibitor resistance and combined resistance to two or three classes of drugs declined during the three study periods. The observed decrease in TDRMs and a simplification of the resistance patterns may reflect a change over time in the characteristics of the infecting subjects who are often unaware of their infection and transmit a wild-type strain.

Substantial Multiclass Transmitted Drug Resistance and Drug-Relevant Polymorphisms Among Treatment-Naïve Behaviorally HIV-Infected Youth

Substantial Multiclass Transmitted Drug Resistance and Drug-Relevant Polymorphisms Among Treatment-Naïve Behaviorally HIV-Infected Youth