Prevalence Of Transmitted Drug Resistance Research Articles

Temporal trends of transmitted HIV drug resistance in a multinational seroconversion cohort.

The rate of transmitted drug resistance (TDR) may increase with wider use of antiretroviral therapy and can contribute to therapeutic failure. We analysed time trends in TDR among HIV seroconverters. Using CASCADE data of individuals with well estimated dates of HIV seroconversion, we examined HIV nucleotide sequences collected prior to antiretroviral therapy use from 1996-2012. All samples were taken within 12 months of testing HIV positive. Using logistic regression, we examined the association between TDR and year of seroconversion, adjusting for confounders. Of 4717 individuals seroconverting between 1996 and 2012, median (IQR) age at seroconversion was 33 (27, 39) years. The majority (3839; 92%) were male, mainly exposed through MSM (3767; 80%), and infected with subtype B (3464; 73%). Overall, 515 (11%) individuals had at least one drug resistance-related mutation; 280 individuals with nucleoside reverse transcriptase, 185 with nonnucleoside reverse transcriptase, and 144 with protease inhibitor mutations. Estimated TDR prevalence was 19.4% (8.2, 36.0) in 1996, significantly decreasing to 8.5% (5.9, 11.9) in 2012 [odds ratio (OR; 95% confidence interval (CI)) = 0.92 (0.90, 0.95) per year increase]. Individuals exposed through sex between men and women were significantly less likely to have been infected with a drug-resistant strain [OR (95% CI) = 0.59 (0.41, 0.87) compared with MSM], and there was marginal evidence that sampling during acute infection was associated with higher odds of resistance [OR (95% CI) = 1.20 (0.97, 1.7), P = 0.093] compared with later sampling. TDR has decreased over calendar time although a significant proportion of new infections still carry resistance-related mutations.

No Difference in Prevalence of Transmitted Drug Resistance between Injection Drug Users and Non-Injection Drug Users: A Cross-Sectional Study among Antiretroviral Treatment-Naïve HIV Patients

Objectives: The epidemiological evidence is inconsistent about whether HIV-positive injection drug users (IDUs) are at higher risk of developing antiretroviral resistance than any other HIV-positive populations. This study aims to investigate and compare transmitted drug resistance (TDR) between IDUs and non-IDUs in Lingshan County, an HIV-hit region in Guangxi, China, where IDU and heterosexual transmission were the two dominant transmission routes and roughly equally contributed to the local HIV transmission. Methods: A cross-sectional study was conducted among newly diagnosed and antiretroviral-treatment (ART)-naïve HIV-1 patients from Lingshan County. The pol gene of HIV-1 from the individuals was sequenced followed by genotyping and TDR analysis. Results: Two dominant transmission routes, heterosexual contact and IDU, accounted for 49.2 and 45.9% of 183 HIV-1 infection cases, respectively. Three genotypes, including CRF08_BC (70.6%), CRF01_AE (24.4%), and CRF07_BC (5.0%), and three unique recombinant forms (1.6%), were identified. There was a significant difference in genotype distribution among the different transmission routes (F = 21.814, p < 0.001). The overall TDR prevalence was 5.5%. There were no significant differences in TDR prevalence among the different transmission routes (F = 1.420, p = 0.439). Conclusions: Injection drug use has little impact on TDR prevalence compared with other routes of transmission.

Prevalence and trends in transmitted and acquired antiretroviral drug resistance, Washington, DC, 1999\u20132014

BackgroundDrug resistance limits options for antiretroviral therapy (ART) and results in poorer health outcomes among HIV-infected persons. We sought to characterize resistance patterns and to identify predictors of resistance in Washington, DC.MethodsWe analyzed resistance in the DC Cohort, a longitudinal study of HIV-infected persons in care in Washington, DC. We measured cumulative drug resistance (CDR) among participants with any genotype between 1999 and 2014 (n = 3411), transmitted drug resistance (TDR) in ART-naïve persons (n = 1503), and acquired drug resistance (ADR) in persons with genotypes before and after ART initiation (n = 309). Using logistic regression, we assessed associations between patient characteristics and transmitted resistance to any antiretroviral.ResultsPrevalence of TDR was 20.5%, of ADR 40.5%, and of CDR 45.1% in the respective analysis groups. From 2004 to 2013, TDR prevalence decreased for nucleoside and nucleotide analogue reverse transcriptase inhibitors (15.0 to 5.5%; p = 0.0003) and increased for integrase strand transfer inhibitors (INSTIs) (0.0–1.4%; p = 0.04). In multivariable analysis, TDR was not associated with age, race/ethnicity, HIV risk group, or years from HIV diagnosis.ConclusionsIn this urban cohort of HIV-infected persons, almost half of participants tested had evidence of CDR; and resistance to INSTIs was increasing. If this trend continues, inclusion of the integrase-encoding region in baseline genotype testing should be strongly considered.

Dynamics and phylogenetic relationships of HIV-1 transmitted drug resistance according to subtype in Italy over the years 2000-14.

Transmitted drug-resistance (TDR) remains a critical aspect for the management of HIV-1-infected individuals. Thus, studying the dynamics of TDR is crucial to optimize HIV care. In total, 4323 HIV-1 protease/reverse-transcriptase sequences from drug-naive individuals diagnosed in north and central Italy between 2000 and 2014 were analysed. TDR was evaluated over time. Maximum-likelihood and Bayesian phylogenetic trees with bootstrap and Bayesian-probability supports defined transmission clusters. Most individuals were males (80.2%) and Italian (72.1%), with a median (IQR) age of 37 (30-45) years. MSM accounted for 42.2% of cases, followed by heterosexuals (36.4%). Non-B subtype infections accounted for 30.8% of the overall population and increased over time (<2005-14: 19.5%-38.5%, P < 0.0001), particularly among Italians (<2005-14: 6.5%-28.8%, P < 0.0001). TDR prevalence was 8.8% and increased over time in non-B subtypes (<2005-14: 2%-7.1%, P = 0.018). Overall, 467 transmission clusters (involving 1207 individuals; 27.9%) were identified. The prevalence of individuals grouping in transmission clusters increased over time in both B (<2005-14: 12.9%-33.5%, P = 0.001) and non-B subtypes (<2005-14: 18.4%-41.9%, P = 0.006). TDR transmission clusters were 13.3% within the overall cluster observed and dramatically increased in recent years (<2005-14: 14.3%-35.5%, P = 0.005). This recent increase was mainly due to non-B subtype-infected individuals, who were also more frequently involved in large transmission clusters than those infected with a B subtype [median number of individuals in transmission clusters: 7 (IQR 6-19) versus 4 (3-4), P = 0.047]. The epidemiology of HIV transmission changed greatly over time; the increasing number of transmission clusters (sometimes with drug resistance) shows that detection and proper treatment of the multi-transmitters is a major target for controlling HIV spread.

Prevalence of HIV-1 transmitted drug resistance in recently infected, treatment-naïve persons in the Southwest of Iran, 2014-2015.

The emergence and transmission of drug resistant HIV mutants is a major concern, especially in resource-limited countries with expanding antiretroviral therapy. Studies have recently reported the prevalence of HIV-1 transmitted drug resistance (TDR) mutations in certain Iranian cities; however, no information is currently available about the level of TDR, as well as the nature of the circulating HIV-1 subtypes, in the Southwestern bordering province of Iran, Khuzestan. Herein, we used a WHO-recommended TDR survey method to classify the prevalence of TDR in indigenous people of Khuzestan province. For this purpose, between March 2014 and February 2015, blood samples were collected from 52 newly diagnosed, antiretroviral treatment-naïve, HIV-1 infected persons aged from 18 to 30 years. TDR mutations were determined by sequencing the protease (PR) and reverse transcriptase (RT) genes and interpreted using the WHO drug resistance mutations surveillance list. HIV-1 subtypes were characterized by sequencing the PR-RT, C2-V5, and p17 regions of the pol, env and gag genes, respectively. Two participants had non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations, specifically K103N in one individual and K101EK/K103KN/G190AG in the other. No nucleoside reverse transcriptase inhibitor (NRTI) or major protease inhibitor (PI) mutations were identified. HIV-1 subtyping revealed that all participants were infected with HIV-1 CRF35_AD. According to the WHO sequential sampling method, the prevalence of HIV-1 TDR in the sampling area (Khuzestan province) was classified as moderate for NNRTIs and low for NRTIs and PIs. This is the first HIV-1 drug resistance threshold survey in the Khuzestan province of Iran and shows a predominance of NNRTI TDR mutations in this area.

Prevalence of HIV-1 transmitted drug resistance in the incarcerated population.

The aim of the study was to determine the prevalence of transmitted drug resistance (TDR)-associated mutations among treatment-naïve, incarcerated individuals with HIV-1 infection in the USA as well as the class TDR and antiretroviral (ARV) mutations present at baseline. Patients over the age of 18 years were included in the study if they had been diagnosed with HIV infection, if their HIV infection was managed through telemedicine and if they were incarcerated in the State of Illinois Department of Corrections between 10 July 2010 and 29 April 2016. Additionally, the patients were required to have a documented genotype and be ARV-naïve. A medical chart review was conducted to assess demographic information, disease burden, and risk factors for acquiring the virus. The inclusion criteria were met for 105 patients. A total of 24 patients (23%) had a clinically significant mutation associated with resistance to any drug class. The prevalence of mutations conferring clinically significant resistance was 19% for nonnucleoside reverse transcriptase inhibitors (NNRTIs), 18% for nucleoside reverse transcriptase inhibitors (NRTIs), and 4% for protease inhibitors (PIs). Five per cent of patients had dual-class TDR to both NRTI and NNRTI drug classes and 2% of patients had mutations to both NNRTI and PI drug classes. There was no significant increase in the prevalence of clinically relevant drug resistance mutations based on demographics, burden of disease, or risk factors for acquiring the virus. A high prevalence of TDR was identified in the ARV-naïve incarcerated population. The results of this study indicate an increased prevalence of TDR in a largely unstudied incarcerated population, demonstrating the need for increased monitoring of resistance in HIV-infected patients world-wide.

HIV-1 Molecular Characterization and Transmitted Drug Resistance Prevalence among Treatment-Naïve Individuals

The distribution of different human immunodeficiency virus type 1 (HIV-1) genotypes and the prevalence of transmitted drug resistance (TDR) mutations vary greatly across different Brazilian regions. This study aimed to describe the HIV-1 molecular diversity and TDR prevalence among treatment-naïve HIV-1 infected individuals in an urban area of Northeastern Brazil.

Transmitted drug resistance in patients with acute/recent HIV infection in Brazil

IntroductionThe widespread use of antiretroviral therapy increased the transmission of antiretroviral resistant HIV strains. Antiretroviral therapy initiation during acute/recent HIV infection limits HIV reservoirs and improves immune response in HIV infected individuals. Transmitted drug resistance may jeopardize the early goals of early antiretroviral treatment among acute/recent HIV infected patients. MethodsPatients with acute/recent HIV infection who underwent resistance test before antiretroviral treatment initiation were included in this analysis. HIV-1 sequences were obtained using an in house protease/reverse transcriptase genotyping assay. Transmitted drug resistance was identified according to the Stanford HIV Database for Transmitted Drug Resistance Mutations, based on WHO 2009 surveillance list, and HIV-1 subtyping according to Rega HIV-1 subtyping tool. Comparison between patients with and without transmitted drug resistance was made using Kruskal–Wallis and Chi-square tests. ResultsForty-three patients were included, 13 with acute HIV infection and 30 with recent HIV infection. The overall transmitted drug resistance prevalence was 16.3% (95% confidence interval [CI]: 8.1–30.0%). The highest prevalence of resistance (11.6%, 95% CI: 8.1–24.5) was against non-nucleoside reverse transcriptase inhibitors, and K103N was the most frequently identified mutation. ConclusionsThe high prevalence of nonnucleoside reverse transcriptase inhibitors resistance indicates that efavirenz-based regimen without prior resistance testing is not ideal for acutely/recently HIV-infected individuals in our setting. In this context, the recent proposal of including integrase inhibitors as a first line regimen in Brazil could be an advantage for the treatment of newly HIV infected individuals. However, it also poses a new challenge, since integrase resistance test is not routinely performed for antiretroviral naive individuals. Further studies on transmitted drug resistance among acutely/recently HIV-infected are needed to inform the predictors of transmitted resistance and the antiretroviral therapy outcomes among these population.

Patterns of Transmitted Drug Resistance and Virological Response to First-line Antiretroviral Treatment Among Human Immunodeficiency Virus-Infected People Who Use Illicit Drugs in a Canadian Setting.

Transmitted drug resistance (TDR) may compromise response to antiretroviral therapy (ART). However, there are limited data on TDR patterns and impacts among people who use illicit drugs (PWUD). Data were drawn from 2 prospective cohorts of PWUD in Vancouver, Canada. We characterized patterns of TDR among human immunodeficiency virus (HIV)-infected PWUD, and assessed its impacts on first-line ART virological outcomes. Between 1996 and 2015, among 573 ART-naive PWUD (18% with recent HIV infection), the overall TDR prevalence was 9.8% (95% confidence interval [CI], 7.3%-12.2%), with an increasing trend over time, from 8.5% in 1996-1999 to 21.1% in 2010-2015 (P = .003), mainly driven by resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs). TDR-associated mutations were more common for NNRTIs (5.4%), followed by nucleoside reverse transcriptase inhibitors (3.0%) and protease inhibitors (1.9%). TDR prevalence was lower among recently infected PWUD (adjusted odds ratio, 0.39 [95% CI, .15-.87]). Participants with TDR had higher risk of virological failure than those without TDR (log-rank P = .037) in the first year of ART. Between 1996 and 2015, TDR prevalence increased significantly among PWUD in Vancouver. Higher risk of virological failure among PWUD with TDR may be explained by some inappropriate ART prescribing, as well as undetected minority resistant variants in participants with chronic HIV infection. Our findings support baseline resistance testing early in the course of HIV infection to guide ART selection among PWUD in our setting.

Low Rates of Transmitted Drug Resistances Among Treatment-Naive HIV-1-infected Students in Beijing, China.

Beijing has seen a rising epidemic of HIV among students. However, little information was known about the molecular epidemiologic data among HIV-infected students. In this study, the diversity and the prevalence of transmitted drug resistance (TDR) in pol sequences derived from 237 HIV-infected students were analyzed. TDR mutations were found in five men who have sex with men (MSM) population among students. The overall prevalence of TDR in students was 2.1%, comprising 1.3% of protease inhibitors and 0.8% of non-nucleoside reverse transcriptase inhibitors. Our finding indicates a low-level prevalence of TDR mutations among students in Beijing.

Drug resistance in antiretroviral-naive children newly diagnosed with HIV-1 in Manaus, Amazonas.

To determine the prevalence of drug resistance mutations (DRM), the prevalence of drug susceptibility [transmitted drug resistance (TDR)] and the prevalence of HIV-1 variants among treatment-naive HIV-infected children in Manaus, Amazonas state, Brazil. Children born to HIV-infected mothers and diagnosed with HIV in an HIV reference service centre and with available pol sequence between 2010 and 2015 prior to antiretroviral initiation were included. TDR was identified using the Calibrated Population Resistance Tool. HIV-1 subtypes were defined by Rega and phylogenetic analyses. One hundred and seventeen HIV-infected children with a median age of 3.7 years were included. Among them, 28.2% had been exposed to some form of prevention of mother-to-child transmission (PMTCT). HIV DRM were present in 21.4% of all children. Among PMTCT-exposed children, 3% had NRTI mutations, 15.2% had NNRTI mutations and 3% had PI mutations. Among PMTCT-unexposed children, 1.2% had NRTI mutations, 21.4% had non-NNRTI mutations and 1.2% had PI mutations. The most common DRM was E138A (8.5%). The prevalence of TDR was 16.2%; 21.1% among PMTCT-exposed children and 14.3% among PMTC-unexposed children. The analysis of HIV-1 subtypes revealed that 80.2% were subtype B, 6.0% were subtype C, 3.4% were subtype F1 and 10.3% were possible unique recombinant forms (BF1, 4.3%; DB, 4.3%; BC, 0.9%; KC, 0.9%). We report a high prevalence of DRM in this population, including in almost a quarter of children with no reported PMTCT. The high prevalence of TDR observed might compromise ART effectiveness. Results show extensive HIV-1 diversity and expansion of subtype C, which highlights the need for surveillance of HIV-1 subtypes in Amazonas state.

Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naïve persons in rural western Kenya.

HIV-1 transmitted drug resistance (TDR) is of increasing public health concern in sub-Saharan Africa with the rollout of antiretroviral (ARV) therapy. Such data are, however, limited in Kenya, where HIV-1 drug resistance testing is not routinely performed. From a population-based household survey conducted between September and November 2012 in rural western Kenya, we retrospectively assessed HIV-1 TDR baseline rates, its determinants, and genetic diversity among drug-naïve persons aged 15–59 years with acute HIV-1 infections (AHI) and recent HIV-1 infections (RHI) as determined by nucleic acid amplification test and both Limiting Antigen and BioRad avidity immunoassays, respectively. HIV-1 pol sequences were scored for drug resistance mutations using Stanford HIVdb and WHO 2009 mutation guidelines. HIV-1 subtyping was computed in MEGA6. Eighty seven (93.5%) of the eligible samples were successfully sequenced. Of these, 8 had at least one TDR mutation, resulting in a TDR prevalence of 9.2% (95% CI 4.7–17.1). No TDR was observed among persons with AHI (n = 7). TDR prevalence was 4.6% (95% CI 1.8–11.2) for nucleoside reverse transcriptase inhibitors (NRTIs), 6.9% (95% CI 3.2–14.2) for non- nucleoside reverse transcriptase inhibitors (NNRTIs), and 1.2% (95% CI 0.2–6.2) for protease inhibitors. Three (3.4% 95% CI 0.8–10.1) persons had dual-class NRTI/NNRTI resistance. Predominant TDR mutations in the reverse transcriptase included K103N/S (4.6%) and M184V (2.3%); only M46I/L (1.1%) occurred in the protease. All the eight persons were predicted to have different grades of resistance to the ARV regimens, ranging from potential low-level to high-level resistance. HIV-1 subtype distribution was heterogeneous: A (57.5%), C (6.9%), D (21.8%), G (2.3%), and circulating recombinant forms (11.5%). Only low CD4 count was associated with TDR (p = 0.0145). Our findings warrant the need for enhanced HIV-1 TDR monitoring in order to inform on population-based therapeutic guidelines and public health interventions.

Decreasing prevalence of transmitted drug resistance among ART-naive HIV-1-infected patients in Iceland, 1996–2012

ABSTRACT Introduction: Resistance to antiretroviral drugs can complicate the management of HIV-1 infection and impair control of its spread. The aim of the current study was to investigate the prevalence and transmission of HIV-1 drug resistance among 106 antiretroviral therapy (ART)-naïve patients diagnosed in Iceland (1996–2012). Methods: HIV-1 polymerase sequences were analysed using the Calibrated Population Resistance tool. Domestic spread of transmitted drug resistance (TDR) was investigated through maximum likelihood and Bayesian approaches. Results: Among ART-naïve patients, the prevalence of TDR to any of the following classes (NRTIs, NNRTIs and PIs) was 8.5% (95% CI: 4.5%- 15.4%): 6.6% to NRTIs, 0.9% to NNRTIs, and 1.9% to PIs. The most frequent NRTI mutation detected was T215C/D (n=7, 5.7%). The only NNRTI mutation detected was K103N (n=1, 0.9%). PI mutations detected were M46I (n=1, 0.9%) and L90M (n=1, 0.9%). Six patients harbouring T215C/D, were linked in a supported phylogenetic cluster. No significant association was found between TDR and demographic or risk groups. Trend analysis showed a decrease in the prevalence of TDR (1996–2012, p=0.003). Conclusions: TDR prevalence in Iceland was at a moderate level and decreased during 1996-2012. Screening for TDR is recommended to limit its local spread and to optimize HIV-1 therapy. A bbreviations: ART: Anti-retroviral therapy; ARV: antiretroviral; ATV/r: atazanavir/ritonavir; AZT: azidothymidine; BEAST: Bayesian evolutionary analysis by sampling trees; CI: confidence interval; CPR: calibrated population resistance; CRF: circulating recombinant form; d4T: stavudine; EFV: efavirenz; FET: Fishers’ exact test; FPV/r: fosamprenavir/ritonavir; HET: heterosexual; IDU: injection drug use; IDV/r: indinavir/ritonavir; LPV/r: lopinavir/ritonavir; MSM: men who have sex with men; M-W: Mann–Whitney U test; NFV: nelfinavir; NNRTIs: non-nucleoside reverse transcriptase inhibitors; NRTIs: nucleoside reverse transcriptase inhibitors; NVP: nevirapine; PIs: protease inhibitors; pol: polymerase gene; SDRM: surveillance drug resistance mutation; SQV/r: saquinavir/ritonavir; TDR: transmitted drug resistance

The prevalence of drug resistance among treatment-naïve HIV-1-infected individuals in China during pre- and post- 2004.

BackgroundThe widespread use of antiretroviral therapies has led to considerable concerns about the prevalence of drug-resistant, as transmission of drug-resistant (TDR) strains poses a challenge for the control of the HIV-1 epidemic.MethodsWe conducted an epidemiological study enrolling treatment-naïve HIV-1-positive subjects at the Peking Union Medical College Hospital since 1991. Drug resistance was determined by submitting the sequences to the Stanford University Network HIV-1 database.ResultsOf 521 participants, 478 samples were amplified and sequenced successfully. HIV Transmitted drug resistance prevalence in China was determined to be 6.7 %. We did not find significant differences in the TDR rate by demographic characteristics. No significant time trend in the prevalence of overall TDR was observed (p > 0.05).ConclusionsWe identified an intermediate prevalence of transmitted drug resistance (TDR), exhibiting a stable time trend. These findings enhance our understanding of HIV-1 drug resistance prevalence and time trend, and provide some guidelines for the comprehensive public health strategy of TDR prevention.

High HIV-1 Diversity and Prevalence of Transmitted Drug Resistance Among Antiretroviral-Naive HIV-Infected Pregnant Women from Rio de Janeiro, Brazil.

Antiretroviral (ARV) resistance mutations in human immunodeficiency virus type 1 (HIV-1) infection may reduce the efficacy of prophylactic therapy to prevent mother-to-child transmission (PMTCT) and future treatment options. This study evaluated the diversity and the prevalence of transmitted drug resistance (TDR) in protease (PR) and reverse transcriptase (RT) regions of HIV-1 pol gene among 87 ARV-naive HIV-1-infected pregnant women from Rio de Janeiro, Brazil, between 2012 and 2015. The viral diversity comprised HIV-1 subtypes B (67.8%), F1 (17.2%), and C (4.6%); the circulating recombinant forms 12_BF (2.3%), 28/29_BF, 39_BF, 02_AG (1.1% each) and unique recombinants forms (4.5%). The overall prevalence of any TDR was 17.2%, of which 5.7% for nucleoside RT inhibitors, 5.7% for non-nucleoside RT inhibitors, and 8% for PR inhibitors. The TDR prevalence found in this population may affect the virological outcome of the standard PMTCT ARV-regimens, reinforcing the importance of continuous monitoring.

Surveillance of HIV Transmitted Drug Resistance in Latin America and the Caribbean: A Systematic Review and Meta-Analysis.

BackgroundHIV transmitted drug resistance (TDR) remains at moderate level in Latin America and the Caribbean (LAC). However, different epidemiologic scenarios could influence national and sub-regional TDR levels and trends.Methods and FindingsWe performed a systematic review of currently available publications on TDR in antiretroviral treatment-naïve adults in LAC. Ninety-eight studies published between January 2000 and June 2015 were included according to critical appraisal criteria and classified by sub-region: Brazil (50), Mesoamerica (17), Southern Cone (16), Andean (8) and Caribbean (7). From these, 81 studies encompassing 11,441 individuals with data on DR mutation frequency were included in a meta-analysis. Overall TDR prevalence in LAC was 7.7% (95% CI: 7.2%-8.2%). An increasing trend was observed for overall TDR when comparing 2000–2005 (6.0%) and 2006–2015 (8.2%) (p<0.0001), which was associated with significant NNRTI TDR increase (p<0.0001). NRTI TDR decreased (4.5% vs. 2.3%, p<0.0001). NNRTI TDR increase was associated mainly with K101E, K103N and G190A. NRTI TDR decrease was associated mainly with M184V, K70R and T215Y. All sub-regions reached moderate overall TDR levels. The rapid increase in TDR to all antiretroviral classes in the Caribbean is notable, as well as the significant increase in NNRTI TDR reaching moderate levels in the Southern Cone. NRTI TDR was dominant in 2000–2005, mainly in the Caribbean, Mesoamerica and Brazil. This dominance was lost in 2006–2015 in all sub-regions, with the Southern Cone and the Caribbean switching to NNRTI dominance. PI TDR remained mostly constant with a significant increase only observed in the Caribbean.ConclusionsGiven the high conceptual and methodological heterogeneity of HIV TDR studies, implementation of surveys with standardized methodology and national representativeness is warranted to generate reliable to inform public health policies. The observed increasing trend in NNRTI TDR supports the need to strengthen TDR surveillance and programme monitoring and evaluation in LAC.

Transmitted HIV Drug Resistance Is High and Longstanding in Metropolitan Washington, DC.

Washington, DC, has 2.5% human immunodeficiency virus (HIV) prevalence, 3.9% among African Americans. Antiretrovirals (ARTs) are the cornerstone for treatment and prevention. Monitoring changes in transmitted drug resistance (TDR) is critical for effective HIV care. HIV genotype data for individuals enrolled in research studies in metropolitan Washington, D.C., were used to identify TDR using the World Health Organization mutation list [Bennett DE, Camacho RJ, Otelea D, et al. Drug resistance mutations for surveillance of transmitted HIV-1 drug-resistance: 2009 update. PloS One 2009; 4:e4724]. HIV phylogenies were reconstructed using maximum likelihood and Bayesian methods. HIV transmission clusters were supported by 1000 bootstrap values >0.70 and posterior probability >0.95 of having a common ancestor. 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. We identified high prevalence of TDR among HIV-infected individuals in metropolitan Washington, DC, regardless of gender. Active surveillance for TDR is needed to guide ART usage and analyses of risk group contributions to HIV transmission and resistance.

Successful Prevention of Transmission of Integrase Resistance in the Swiss HIV Cohort Study.

The prevalence of integrase strand transfer inhibitor (INSTI)-transmitted drug resistance (TDR) may increase with the increasing use of INSTIs. We analyzed the prevalence of INSTI TDR in the Swiss HIV Cohort Study (2008-2014). In 1 of 1316 drug-naive samples (0.1%), a major INSTI TDR mutation was detected. Prevalence was stable, although INSTIs were increasingly used. We showed that this is in contrast to the introduction of previous drug classes, in which more treatment failures with resistant strains occurred and TDR was observed more rapidly. We demonstrated on a population-level that it is possible to avoid TDR to a new drug class for years.

Prevalence of Transmitted HIV Drug Resistance Among Recently Infected Persons in San Diego, CA 1996-2013.

Transmitted drug resistance (TDR) remains an important concern when initiating antiretroviral therapy (ART). Here, we describe the prevalence and phylogenetic relationships of TDR among ART-naive, HIV-infected individuals in San Diego from 1996 to 2013. Data were analyzed from 496 participants of the San Diego Primary Infection Cohort who underwent genotypic resistance testing before initiating therapy. Mutations associated with drug resistance were identified according to the WHO-2009 surveillance list. Network and phylogenetic analyses of the HIV-1 pol sequences were used to evaluate the relationships of TDR within the context of the entire cohort. The overall prevalence of TDR was 13.5% (67/496), with an increasing trend over the study period (P = 0.005). TDR was predominantly toward nonnucleoside reverse transcriptase inhibitors (NNRTIs) [8.5% (42/496)], also increasing over the study period (P = 0.005). By contrast, TDR to protease inhibitors and nucleos(t)ide reverse transcriptase inhibitors were 4.4% (22/496) and 3.8% (19/496), respectively, and did not vary with time. TDR prevalence did not differ by age, gender, race/ethnicity, or risk factors. Using phylogenetic analysis, we identified 52 transmission clusters, including 8 with at least 2 individuals sharing the same mutation, accounting for 23.8% (16/67) of the individuals with TDR. Between 1996 and 2013, the prevalence of TDR significantly increased among recently infected ART-naive individuals in San Diego. Around one-fourth of TDR occurred within clusters of recently infected individuals. These findings highlight the importance of baseline resistance testing to guide selection of ART and for public health monitoring.

Transmission of HIV Drug Resistance and the Predicted Effect on Current First-line Regimens in Europe.

Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD program systematically collects data to gain insight into TDR occurring in Europe since 2001. Demographic, clinical, and virological data from 4140 antiretroviral-naive human immunodeficiency virus (HIV)-infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002 to 2007. Baseline susceptibility to antiretroviral drugs was predicted using the Stanford HIVdb program version 7.0. The overall prevalence of TDR did not change significantly over time and was 8.3% (95% confidence interval, 7.2%-9.5%) in 2008-2010. The most frequent indicators of TDR were nucleoside reverse transcriptase inhibitor (NRTI) mutations (4.5%), followed by nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.9%) and protease inhibitor mutations (2.0%). Baseline mutations were most predictive of reduced susceptibility to initial NNRTI-based regimens: 4.5% and 6.5% of patient isolates were predicted to have resistance to regimens containing efavirenz or rilpivirine, respectively, independent of current NRTI backbones. Although TDR was highest for NRTIs, the impact of baseline drug resistance patterns on susceptibility was largest for NNRTIs. The prevalence of TDR assessed by epidemiological surveys does not clearly indicate to what degree susceptibility to different drug classes is affected.