Transmitted HIV Drug Resistance Research Articles

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.

Short Communication: Population-Based Surveillance of HIV-1 Drug Resistance in Cameroonian Adults Initiating Antiretroviral Therapy According to the World Health Organization Guidelines.

With ongoing earlier enrollment on and rapid scale-up of antiretroviral therapy (ART) in Cameroon, there are increasing risks of transmitted HIV drug resistance (HIVDR) at population levels. We, therefore, evaluated the threshold of HIVDR in a population initiating ART, to inform on the effectiveness of first-line regimens, considering HIV-1 diversity, plasma viral load (PVL), and CD4-based disease progression. A total of 53 adults [median (interquartile range, IQR) CD4: 162 cell/mm(3) (48-284); median (IQR) PVL: 5.34 log10 RNA (4.17-6.42) copies/ml] initiating ART in 2014 at the Yaoundé Central Hospital were enrolled for HIV-1 protease-reverse transcriptase sequencing. Drug resistance mutations (DRMs) were interpreted using the 2009 World Health Organization (WHO) list versus the Stanford HIVdb algorithm version 7.0. Level of DRMs was low (3.77%) versus moderate (7.55%), respectively, following the WHO list (T69D, K103N) versus Stanford HIVdb (T69D, A98G, K103N, K238T), respectively. Prevailing clade was CRF02_AG (71.70%). Based on Stanford HIVdb, a slightly higher proportion of patients with DRMs were found among ones infected with CRF02_AG than in those non-CRF02_AG infected (7.89% vs. 6.67%, p = 1.000), with lower PVL (7.69% <5.5 vs. 0% ≥5.5 log10 RNA copies/ml, p = .488) and with higher CD4 counts (9.52% CD4 ≥200 vs. 3.33% CD4 <200 cells/mm(3), p = .749). Thresholds of DRMs suggest that standard first-line regimens currently used in Cameroon may remain effective at population levels, despite scale-up of ART in the country, pending adherence, and closed virological monitoring. With an intent-to-diagnose approach, the discrepant levels of DRMs support using Stanford HIVdb to evaluate initial ART, while revising the WHO list for surveillance.

Transmitted HIV-1 Drug resistance and the Role of Herpes Simplex Virus -2 Coinfection among Fishermen along the Shores of Lake Victoria, Kisumu, Kenya

Introduction: Herpes simplex virus type 2 (HSV-2) infection has been associated with a 3-fold risk of HIV-1 acquisition. The prevalence of HIV-1 and HSV-2 in the fishing communities along the shores of Lake Victoria in Kisumu have been reported to be high. This may contribute to the growing HIV epidemic in Kenya including the spread of transmitted drug resistance (TDR). We report data on the association of HSV2/HIV-1 co-infection and TDR in this antiretroviral (ARV)-naïve population. Methods: Blood samples were obtained from 249 consenting fishermen from 5 beaches and a detailed sociodemographic questionnaire was administered. Blood samples were analyzed for HIV-1/HSV2 co-infection. The HSV-2 serology was performed using Kalon HSV type 2 enzyme-linked immunosorbent assay (ELISA). The HIV-1 counselling and serology were carried out according to local standards of practice in Kenya, using two parallel rapid assays (Alere Determine HIV-1/2 and Trinity Biotech Uni- Gold), with a third ELISA-Vironostika HIV Uni-Form II Ag/Ab for resolving discrepancies. All HIV positive samples were tested for TDR using an in house HIV-1 pol-RT genotyping protocol. Results: Of the 249 recruited fishermen (mean age 35.1 years), 134 (53.8%) were positive for HSV-2, 59 (23.7%) were HIV positive while 48 (19.3%) were HIV/HSV-2 coinfected. Twenty-three of 59 (38.9%) HIV positive men had TDR, with the majority (19/23, 82.6%) in HIV/HSV-2 coinfected fishermen. Among the 48 HIV/HSV-2 co-infected fishermen, 9 had nucleoside reverse-transcriptase inhibitor (NRTI) resistance mutations with NRTI- associated mutations [NAMS], M184V (77.8%) and K65R (11.1%) being the highest. Nineteen (19) fishermen had Non-NRTI (NNRTIs) mutations including; four (21.1%) each of K103N, Y181C and G190A. Three (15.7%) V179T, two V901V and single A98G and Y188L mutations. Among the 11 fishermen who had HIV-1 mono-infection, four (36.4%) had drug resistant mutations. One fisherman had NRTI resistance mutation M184V. In addition, three men (3/4) had NNRTI resistance; K103N, G190A and Y181C mutations each. In the regression model, HIV/HSV-2 co-infection was independently associated with TDR [OR 4.1 (95% CI 1.4 to 11.9)]. Conclusion: The level of TDR to NNRTIs in these ARV-naive fishermen was significantly high especially among those coinfected with HSV-2. HSV-2 infection may increase the risk of TDR in this population.

HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing.

The increasing prevalence of acquired and transmitted HIV-1 drug resistance is an obstacle to successful antiretroviral therapy (ART) in the low- and middle-income countries (LMICs) hardest hit by the HIV-1 pandemic. Genotypic drug resistance testing could facilitate the choice of initial ART in areas with rising transmitted drug resistance (TDR) and enable care-providers to determine which individuals with virological failure (VF) on a first- or second-line ART regimen require a change in treatment. An inexpensive near point-of-care (POC) genotypic resistance test would be useful in settings where the resources, capacity, and infrastructure to perform standard genotypic drug resistance testing are limited. Such a test would be particularly useful in conjunction with the POC HIV-1 viral load tests that are currently being introduced in LMICs. A POC genotypic resistance test is likely to involve the use of allele-specific point mutation assays for detecting drug-resistance mutations (DRMs). This study proposes that two major nucleoside reverse transcriptase inhibitor (NRTI)-associated DRMs (M184V and K65R) and four major NNRTI-associated DRMs (K103N, Y181C, G190A, and V106M) would be the most useful for POC genotypic resistance testing in LMIC settings. One or more of these six DRMs was present in 61.2% of analyzed virus sequences from ART-naïve individuals with intermediate or high-level TDR and 98.8% of analyzed virus sequences from individuals on a first-line NRTI/NNRTI-containing regimen with intermediate or high-level acquired drug resistance. The detection of one or more of these DRMs in an ART-naïve individual or in a individual with VF on a first-line NRTI/NNRTI-containing regimen may be considered an indication for a protease inhibitor (PI)-containing regimen or closer virological monitoring based on cost-effectiveness or country policy.

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.

Transmission of Drug-Resistant HIV by ART-Naive Individuals

What proportion of transmitted HIV drug resistance originates from antiretroviral therapy (ART)-naive sources? To find out, investigators studied

Frequency of transmitted drug resistance mutations among treatment-naïve HIV-1-infected individuals at a tertiary care centre in South India.

Morbidity and mortality among HIV-1-infected individuals has been dramatically reduced by the implementation of combinational antiretroviral therapy (ART). However, the efficiency of these therapies is compromised due to HIV-1 transmitted drug resistance mutations (TDRMs). We collected a total of 127 samples from ART-naïve HIV-infected individuals and sequenced the pol gene and analysed for drug resistance mutations using the Calibrated Population Resistance (CPR) tool in the Stanford database. All the 127 clinical samples (100%) were identified as HIV-1 subtype C. Based on the CPR tool, three strains (2.4%) had TDRMs, and these were K101E, Y181C and G190A. Our findings correlated well with the WHO surveys conducted in Asia, including India, which consistently reported<5% TDRM among the specific populations assessed. In countries like India, regular monitoring of TDRMs will provide better information for clinical practice improvement and policy making.

HIV-1 Genetic Diversity and Transmitted Drug Resistance Among Recently Infected Individuals at Men Who Have Sex with Men Sentinel Surveillance Points in Hebei Province, China.

For this study, 50 HIV-1 plasma samples of recently infected men who have sex with men (MSM) were amplified and sequenced. Multiple subtypes were identified by phylogenetic analyses of HIV-1 gag, env, and pol gene regions, including CRF01_AE (56.0%), CRF07_BC (30.0%), subtype B (12.0%), and unique recombinant forms (URFs, 6.0%). CRF01_AE was the most frequent genotype in the epidemic. Three recombination patterns of URFs were identified: 01BC, 01B, and 01C. The rate of HIV-1 transmitted drug resistance (TDR) mutation (M46L) was 2.08% (1/48). URFs and TDR first identified in this study suggest that HIV-1 prevalence is more and more complicated, and HIV-1 drug-resistant strains have begun to spread among at risk populations in Hebei. Our findings can provide vital information for an efficient surveillance system and strategic HIV prevention and control measures in China by revealing the evolutionary status and HIV-1 TDR of HIV-1 strains among recently infected MSM in Hebei Province.

Trends in Transmission of Drug Resistance and Prevalence of Non-B Subtypes in Patients with Acute or Recent HIV-1 Infection in Barcelona in the Last 16 Years (1997-2012).

ObjectivesTo evaluate the prevalence of transmitted drug resistance (TDR) and non-B subtypes in patients with acute/recent HIV-1 infection in Barcelona during the period 1997-2012.MethodsPatients from the “Hospital Clínic Primary HIV-1 Infection Cohort” with a genotyping test performed within 180 days of infection were included. The 2009 WHO List of Mutations for Surveillance of Transmitted HIV-1 Drug Resistance was used for estimating the prevalence of TDR and phylogenetic analysis for subtype determination.Results189 patients with acute/recent HIV-1 infection were analyzed in 4 time periods (1997-2000, n=28; 2001-4, n=42; 2005-8, n=55 and 2009-12, n=64). The proportion of patients with acute/recent HIV-1 infection with respect to the total of newly HIV-diagnosed patients in our center increased over the time and was 2.18%, 3.82%, 4.15% and 4.55% for the 4 periods, respectively (p=0.005). The global prevalence of TDR was 9%, or 17.9%, 9.5%, 3.6% and 9.4% by study period (p=0.2). The increase in the last period was driven by protease-inhibitor and nucleoside-reverse-transcriptase-inhibitor resistance mutations while non-nucleoside-reverse-transcriptase inhibitor TDR and TDR of more than one family decreased. The overall prevalence of non-B subtypes was 11.1%, or 0%, 4.8%, 9.1% and 20.3 by study period (p=0.01). B/F recombinants, B/G recombinants and subtype F emerged in the last period. We also noticed an increase in the number of immigrant patients (p=0.052). The proportion of men-who-have-sex-with-men (MSM) among patients with acute/recent HIV-1 infection increased over the time (p=0.04).ConclusionsThe overall prevalence of TDR in patients with acute/recent HIV-1 infection in Barcelona was 9%, and it has stayed relatively stable in recent years. Non-B subtypes and immigrants proportions progressively increased.

Analysis on HIV-1 genetics and threshold of drug resistance in Dehong prefecture of Yunnan province in 2013

To study the HIV-1 genotypes and transmitted drug resistance (TDR) in Dehong prefecture of Yunnan province in 2013. Referring to the guidelines for HIV drug resistance threshold survey (HIVDR-TS), 54 plasma samples of recently reported HIV-infected individuals, aged between 16 and 25 years, were collected in Dehong prefecture from January to August 2013. Genotyping of partial pol gene was performed by using reverse transcriptional PCR. HIV-1 genotype. Prevalent levels of HIV-1 drug resistance transmission were analyzed. Forty-eight plasma samples were successfully sequenced and analyzed. Among them, 45.8% were Chinese and the rest 54.2% were all Burmese. Based on pol sequences, identified HIV genotypes included subtype C (41.7%), URF (31.3%), CRF01_AE (12.5%), CRF07_BC (10.4%), CRF08_BC (2.1%) and subtype B (2.1%), C subtype appeared dominated in Chinese while URF was dominated in Burmese. One drug resistant mutation to non-nucleoside reverse transcriptase inhibitors (NNRTIs) was detected in one sequence from Burmese. Based on the statistical method of HIVDR-TS, the prevalence of transmitted HIV-1 drug resistance was adjusted as < 5%. Diverse HIV-1 genotypes were found in this study, and the current HIV-1 drug resistant strains transmission was catalogued as at low prevalence level, in Dehong. To prevent the increase of the prevalence of transmitted HIV-1 drug resistance, standard treatment and scientific management for people living with HIV/AIDS should be strictly followed. Meanwhile, relevant surveillance, including drug resistance surveillance should also be performed among cross-border migrant population.

Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations.

Our objectives were to carry out an epidemiological surveillance study on transmitted drug resistance (TDR) among individuals newly diagnosed of HIV-1 infection during a nine year period in Spain and to assess the role of transmission clusters (TC) in the propagation of resistant strains. An overall of 1614 newly diagnosed individuals were included in the study from January 2004 through December 2012. Individuals come from two different Spanish regions: Galicia and the Basque Country. Resistance mutations to reverse transcriptase inhibitors (RTI) and protease inhibitors (PI) were analyzed according to mutations included in the surveillance drug-resistance mutations list updated in 2009. TC were defined as those comprising viruses from five or more individuals whose sequences clustered in maximum likelihood phylogenetic trees with a bootstrap value ≥90%. The overall prevalence of TDR to any drug was 9.9%: 4.9% to nucleoside RTIs (NRTIs), 3.6% to non-nucleoside RTIs (NNRTIs), and 2.7% to PIs. A significant decrease of TDR to NRTIs over time was observed [from 10% in 2004 to 2% in 2012 (p=0.01)]. Sixty eight (42.2%) of 161 sequences with TDR were included in 25 TC composed of 5 or more individuals. Of them, 9 clusters harbored TDR associated with high level resistance to antiretroviral drugs. T215D revertant mutation was transmitted in a large cluster comprising 25 individuals. The impact of epidemiological networks on TDR frequency may explain its persistence in newly diagnosed individuals. The knowledge of the populations involved in TC would facilitate the design of prevention programs and public health interventions.

Genetic diversity of HIV-1 and transmitted drug resistance among newly diagnosed individuals with HIV infection in Hangzhou, China.

HIV transmitted drug resistance (TDR) can compromise antiretroviral therapy (ART) in resource-limited countries like China where ART has been scaled up and thus leads to an important public health concern. The aim of the study was to elucidate the HIV-1 genetic characteristics and TDR in Hangzhou, China. Two-hundred eleven ART-naive, newly diagnosed individuals were enrolled during January and August 2013. Specimens were classified as recent or chronic infections using the BED capture enzyme immunoassay (BED-CEIA). The pol fragment covering the entire protease and the first 300 codons of the reverse transcriptase gene was amplified by RT-PCR and nested PCR. Genotypic drug resistance (DR) and phylogenetic analysis were performed on the 200 obtained sequences. Multiple genotypes were identified, including CRF01_AE (62.0%), CRF07_BC (31.0%), subtype B (2.0%), CRF08_BC (1.5%), CRF55_01B (1.0%), CRF18_cpx (0.5%), and unique recombinant forms (URFs, 2.0%). All the four URFs were found in men who have sex with men, consisting of a recombination of CRF01_AE with subtype B or CRF07_BC. The prevalence of primary DR in newly diagnosed individuals in Hangzhou was low (4.0%). The proportion of DR mutation to protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) was 1.5%, 1.5%, and 1.0%, respectively. BED-CEIA revealed that 21.8% (45/211) of the specimens were associated with recent infections. The prevalence of TDR in recent infections was moderate (6.5%). High HIV diversity and relatively high prevalence of TDR in new infections has been found in Hangzhou, indicating an increasing challenge for future HIV prevention and treatment.

Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis.

BackgroundRegional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We sought to understand the molecular epidemiology of TDR and to identify the HIV-1 drug-resistance mutations responsible for TDR in different regions and virus subtypes.Methods and FindingsWe reviewed all GenBank submissions of HIV-1 reverse transcriptase sequences with or without protease and identified 287 studies published between March 1, 2000, and December 31, 2013, with more than 25 recently or chronically infected ARV-naïve individuals. These studies comprised 50,870 individuals from 111 countries. Each set of study sequences was analyzed for phylogenetic clustering and the presence of 93 surveillance drug-resistance mutations (SDRMs). The median overall TDR prevalence in sub-Saharan Africa (SSA), south/southeast Asia (SSEA), upper-income Asian countries, Latin America/Caribbean, Europe, and North America was 2.8%, 2.9%, 5.6%, 7.6%, 9.4%, and 11.5%, respectively. In SSA, there was a yearly 1.09-fold (95% CI: 1.05–1.14) increase in odds of TDR since national ARV scale-up attributable to an increase in non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. The odds of NNRTI-associated TDR also increased in Latin America/Caribbean (odds ratio [OR] = 1.16; 95% CI: 1.06–1.25), North America (OR = 1.19; 95% CI: 1.12–1.26), Europe (OR = 1.07; 95% CI: 1.01–1.13), and upper-income Asian countries (OR = 1.33; 95% CI: 1.12–1.55). In SSEA, there was no significant change in the odds of TDR since national ARV scale-up (OR = 0.97; 95% CI: 0.92–1.02). An analysis limited to sequences with mixtures at less than 0.5% of their nucleotide positions—a proxy for recent infection—yielded trends comparable to those obtained using the complete dataset. Four NNRTI SDRMs—K101E, K103N, Y181C, and G190A—accounted for >80% of NNRTI-associated TDR in all regions and subtypes. Sixteen nucleoside reverse transcriptase inhibitor (NRTI) SDRMs accounted for >69% of NRTI-associated TDR in all regions and subtypes. In SSA and SSEA, 89% of NNRTI SDRMs were associated with high-level resistance to nevirapine or efavirenz, whereas only 27% of NRTI SDRMs were associated with high-level resistance to zidovudine, lamivudine, tenofovir, or abacavir. Of 763 viruses with TDR in SSA and SSEA, 725 (95%) were genetically dissimilar; 38 (5%) formed 19 sequence pairs. Inherent limitations of this study are that some cohorts may not represent the broader regional population and that studies were heterogeneous with respect to duration of infection prior to sampling.ConclusionsMost TDR strains in SSA and SSEA arose independently, suggesting that ARV regimens with a high genetic barrier to resistance combined with improved patient adherence may mitigate TDR increases by reducing the generation of new ARV-resistant strains. A small number of NNRTI-resistance mutations were responsible for most cases of high-level resistance, suggesting that inexpensive point-mutation assays to detect these mutations may be useful for pre-therapy screening in regions with high levels of TDR. In the context of a public health approach to ARV therapy, a reliable point-of-care genotypic resistance test could identify which patients should receive standard first-line therapy and which should receive a protease-inhibitor-containing regimen.

Chemokine co-receptor usage in HIV-1-infected treatment-naïve voluntary counselling and testing clients in Southern Taiwan

ObjectiveThe goal of this present study was to determine the proportion of CCR5-tropic and CXCR4-tropic viruses and impact of tropism test on clinical presentation, CD4 cell counts, viral load and...

Prevalence of Transmitted HIV-1 Drug Resistance among Young Adults Attending HIV Counselling and Testing Clinics in Kigali, Rwanda

Scaling-up antiretroviral therapy (ART) in resource-limited settings has raised concerns of emerging HIV drug resistance (DR) and its transmission to newly infected individuals. To assess the prevalence of transmitted drug resistance (TDR) in recently HIV-infected individuals, a WHO TDR threshold survey was conducted among young adults in Kigali, Rwanda. Between May and July 2011, HIV subtype and genotyping were performed on dried blood spots (DBS) prepared from blood specimens collected from newly HIV-diagnosed and ART-naive individuals aged 15 to 21 years in eight HIV voluntary counselling and testing (VCT) sites in Kigali. In total, 57 of the 68 DBS collected from eligible participants were successfully amplified. The median age of participants was 20 years and 86% were female. Most participants (96%) were infected with subtype A1 virus. Two participants (4%) had the K103N non-nucleoside reverse transcriptase inhibitor (NNRTI) mutation and one (2%) had the M46L protease inhibitor (PI) mutation. The TDR prevalence was 3.5% (95% CI 0.4, 12.1) for NNRTI and 1.8% (95% CI 0.0, 9.4) for PI. The prevalence of HIV TDR in VCT attendees in Kigali was characterized as low (<5%) for all drug classes according to the WHO HIV DR threshold survey methodology. Despite a decade of widespread ART in Rwanda, TDR prevalence remains low, and so the current first-line ART regimens should continue to be effective. However, as scale-up of ART continues, frequent HIV DR surveillance is needed to monitor the effectiveness of available ART regimens at the population level.

Increase of RT-related transmitted drug resistance in non-CRF01_AE among HIV type 1-infected men who have sex with men in the 7 cities of China.

To elucidate new features in the prevalence of HIV-1 transmitted drug resistance (TDR) in men who have sex with men (MSM) in China. A total of 441 HIV-1-positive subjects were recruited from high-risk MSM populations in 7 cities across China between 2012 and 2013. Nucleotide sequences of 1.1-kb pol-RT regions were amplified and sequenced from 367 of the 441 samples. Phylogenetic and genetic drug-resistant analyses were performed. The overall distribution of HIV-1 genotypes was as the following: CRF01_AE, 52.3%; CRF07_BC, 33.2%; 01/B recombinants, 6.0%; subtype B (United States-European), 3.8%; subtype B', 3.8%; and CRF08_BC, 0.8%. About 91.3% of the sequences clustered together. An overall 4.6% TDR rate was found. Reverse transcriptase (RT)-related TDR reached 2.7%. TDR of 2.2% was detected in protease region. Most of RT-related TDRs were detected in non-CRF01_AE subtypes (90.0%, 9/10), including T215A/S, K101E, K103N, V106M, and E138G. Most of the strains with TDRs (88.2%, 15/17) were presented in the clusters. TDR strains against non-nucleoside reverse transcriptase inhibitors in non-CRF01_AE subtypes also formed some subclusters (70.0%, 7/10). One CRF07_BC subject with K103N in Kunming had a very close genetic distance with one that received highly active antiretroviral therapy locally (bootstrap = 99%). Two CRF55_01B subjects carrying K103N in Changsha and Nanjing also had a very close genetic distance (bootstrap = 100%). RT-related TDR of non-CRF01_AE became the main TDR among MSM in China. There is an increasing trend and a potential transmission risk for the RT-related TDR among MSM throughout China. Some TDRs could have already been transmitted among different cities. Intervention efforts should be strengthened among MSM to prevent further transmission of HIV and the proliferation of the strains with TDR.

Global HIV-1 transmitted drug resistance in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.

HIV-1 transmitted drug resistance (TDR) in treatment-naïve individuals is a well-described phenomenon. Baseline genotypic resistance testing is considered standard of care in most developed areas of the world. The aim of this analysis was to characterize HIV-1 TDR and the use of resistance testing in START trial participants. In the Strategic Timing of AntiRetroviral Treatment (START) trial, baseline genotypic resistance testing results were collected at study entry and analysed centrally to determine the prevalence of TDR in the study population. Resistance was based on a modified 2009 World Health Organization definition to reflect newer resistance mutations. Baseline resistance testing was available in 1946 study participants. Higher rates of testing occurred in Europe (86.7%), the USA (81.3%) and Australia (89.9%) as compared with Asia (22.2%), South America (1.8%) and Africa (0.1%). The overall prevalence of TDR was 10.1%, more commonly to nonnucleoside reverse transcriptase inhibitors (4.5%) and nucleoside reverse transcriptase inhibitors (4%) compared with protease inhibitors (2.8%). The most frequent TDR mutations observed were M41L, D67N/G/E, T215F/Y/I/S/C/D/E/V/N, 219Q/E/N/R, K103N/S, and G190A/S/E in reverse transcriptase, and M46I/L and L90M in protease. By country, the prevalence of TDR was highest in Australia (17.5%), France (16.7%), the USA (12.6%) and Spain (12.6%). No participant characteristics were identified as predictors of the presence of TDR. START participants enrolled in resource-rich areas of the world were more likely to have baseline resistance testing. In Europe, the USA and Australia, TDR prevalence rates varied by country.

HIV-1 transmitted drug resistance mutations among antiretroviral therapy-Naïve individuals in Surabaya, Indonesia.

BackgroundThe emergence of transmitted drug resistance (TDR) compromises the effect of antiretroviral therapy (ART), resulting in treatment failure of human immunodeficiency virus (HIV) disease. Although more than a decade has passed since ART was introduced into Indonesia, information on TDR is limited. Here, a genotypic study of TDR among ART-naïve individuals was conducted in Surabaya, Indonesia.MethodHIV-1 seropositive participants were recruited from the communities of commercial sex workers and intravenous drug users as well as from the university teaching hospital in Surabaya. Protease (PR) and reverse transcriptase (RT) genes were sequenced in order to conduct HIV-1 subtyping and phylogenetic analysis and to detect TDR. TDR was defined as the presence of at least one surveillance drug resistance mutation on the WHO list or major drug resistance mutations in the International AIDS Society-USA panel.ResultFifty two and 47 of the PR and RT genes, respectively, were successfully sequenced in the 58 samples. HIV-1 subtyping revealed that 86.3% (50/58) of the sequenced samples were classified as CRF01_AE, 8.6% as subtype B, 3.4% as B/CRF01_AE, and 1.7% as A/G/CRF01_AE. TDR of PR inhibitors was not detected in this study. In contrast, TDR of RT inhibitors was detected in 4.3% (2/47) of samples. In addition, minor drug resistance mutations were detected in 98.1% (51/52) and 12.8% (6/47) of PR and RT genes, respectively.ConclusionThis study clarified the predominance of the CRF01_AE strain in Surabaya, Indonesia. The prevalence of TDR was below 5%, indicating that the currently available first-line regimen is still effective in Surabaya. However, the prevalence might be underestimated since we detected only major population of HIV-1 in individuals. Therefore, continuous surveillance is required in order to detect the emergence of TDR in the early phase.Electronic supplementary materialThe online version of this article (doi:10.1186/s12981-015-0046-y) contains supplementary material, which is available to authorized users.

Low prevalence of the transmitted HIV-1 drug resistance among newly diagnosed HIV-1 individuals in Jiangsu Province, China during 2009-2011.

BackgroundPrevalence of The transmitted HIV drug resistance (THDR) has been reported in many countries. In China, the low level THDR was found in only a few provinces. To know the transmitted HIV drug resistance in east of China, we investigated THDR during 2009–2011 in Jiangsu province of China.MethodsBetween January and August of 2009, 2010, and 2011, we consecutively collected 50, 54, 53 blood specimens respectively from qualified individuals at surveillance sentinel sites in Jiangsu province according to protocol of HIV Drug Resistance Threshold Survey (HIVDR-TS) recommended by WHO. The region of pol gene including protease and partial retro-transcriptase was amplified, sequenced and edited. Then the sequences were submitted to HIV drug resistance database to analysis transmitted HIV drug resistance mutations using Calibrated Population Resistance tool. The reference sequences of different HIV-1 subtypes were downloaded from HIV database and Genebank. The phylogenetic trees were inferred using the neighbor-joining method.ResultsOur results show that THDR has been at low level from 2009 to 2011, only K101E and V179D mutation was detected which did not belong to the major HIV-1 drug resistance mutations. Phylogenetic analysis showed that CRF01_AE is the predominant subtype, and followed by CRF07_BC and B subtype. Subtype B consists of the two distinct clusters.ConclusionsThe low level of THDR suggests that anti-retroviral treatment was implemented more effectively and THDR surveillance should be conducted two years later in Jiangsu province of China. CRF01_AE has become the predominant subtype and dual infection of HIV may be common in Jiangsu province.

HIV-1 transmitted drug resistance and genetic diversity among patients from Piauí State, Northeast Brazil.

HIV-1 transmitted-drug-resistance and genetic diversity are dynamic and may differ in distinct locations/risk groups. In Brazil, increased AIDS incidence and related mortality have been detected in the Northeast region, differently from the epicenter in the Southeast. This cross-sectional study describes transmitted-dru- resistance and HIV-1 subtypes in protease/PR and reverse transcriptase/RT regions among antiretroviral naïve patients from Piauí State, Northeast Brazil. Among 96 patients recruited 89 (92.7%) had HIV-1 PR/RT regions sequenced: 44 females and 45 males, 22 self-declared as men who have sex with men. Transmitted-drug-resistance was investigated by CPR tool (Stanford HIV-1 Drug Resistance/SDRM). HIV-1 subtypes were assigned by REGA and phylogenetic inference. Overall, transmitted-drug-resistance rate was 11.2% (10/89; CI 95%: 5.8-19.1%); 22.7% among men who have sex with men (5/22; CI 95%: 8.8-43.4%), 10% in heterosexual men (2/20; CI 95%: 1.7-29.3%) and 6.8% in women (3/44; CI 95%: 1.8-17.4%). Singleton mutations to protease-inhibitor/PI, nucleoside-reverse-transcriptase-inhibitor/NRTI or non-nucleoside-reverse-transcriptase-inhibitor/NNRTI predominated (8/10): PI mutations (M46L, V82F, L90M); NRTI mutations (M41L, D67N) and NNRTI mutations (K103N/S). Dual class resistance mutations to NRTI and NNRTI were observed: T215L (NRTI), Y188L (NNRTI) and T215N (NRTI), F227L (NNRTI). Subtype B prevailed (86.6%; 77/89), followed by subtype F1 (1.1%, 1/89) and subtype C (1.1%, 1/89). B/F1 and B/C intersubtype recombinants represented 11.2% (10/89). In Piauí State extensive testing of incidence and transmitted-drug-resistance in all populations with risk behaviors may help control AIDS epidemic locally.