Drug Resistance Mutation Profiles Research Articles

CRF08_BC subtype is more prone to ART failure and new-generation NNRTI-resistance under long-term first-line ART

ObjectiveTo investigate the characteristics of drug resistance mutations (DRMs) and their contextual influence on drug susceptibility in CRF07_BC and CRF_08BC subtypes. MethodsPatients with virological failure were genotyped using phylogenetic analysis. DRMs and susceptibility to antiretroviral drugs were analysed using the Stanford University HIV Drug Resistance Database. ResultsSix HIV subtypes were identified among 1296 successfully amplified sequences, with the CRF07_BC subtype prevailing at a rate of 91.7%, followed by CRF08_BC. Overall, the CRF07_BC and CRF08_BC subtypes were similar in the distribution and frequency of DRMs, the most common DRMs were K103N and M184V. However, among patients with antiretroviral therapy duration of ≥3 y who developed resistance, CRF08_BC exhibited a higher mutation frequency at sites 184, 138, 221, and 188 (Chi-square test, P < 0.05), and compared with CRF07_BC, patients with CRF08_BC had higher prevalence of abacavir, emtricitabine, lamivudine, doravirine, etravirine, and rilpivirine resistance. Moreover, there was an increased prevalence of cross-resistance between efavirenz/nevirapine and new-generation NNRTIs in patients with CRF08_BC; doravirine (r = 1.0), rilpivirine (r = 0.93), and etravirine (r = 0.86) resistance highly correlated with efavirenz/nevirapine. ConclusionsThe present study provides valuable insights into the profile of DRMs and resistance patterns in patients with CRF07_BC and CRF08_BC experiencing treatment failure in Butuo. These findings have the potential to contribute to future strategies for HIV control and treatment.

The profile of HIV-1 drug resistance in Shanghai, China: a retrospective study from 2017 to 2021.

HIV-1 drug resistance is a huge challenge in the era of ART. To investigate the prevalence and characteristics of acquired HIV-1 drug resistance (ADR) in Shanghai, China. An epidemiological study was performed among people living with human immunodeficiency virus (PLWH) receiving ART in Shanghai from January 2017 to December 2021. A total of 8669 PLWH were tested for drug resistance by genotypic resistance testing. Drug resistance mutations (DRMs) were identified using the Stanford University HIV Drug Resistance Database program. Ten HIV-1 subtypes/circulating recombinant forms (CRFs) were identified, mainly including CRF01_AE (46.8%), CRF07_BC (35.7%), B (6.4%), CRF55_01B (2.8%) and CRF08_BC (2.4%). The prevalence of ADR was 48% (389/811). Three NRTI-associated mutations (M184V/I/L, S68G/N/R and K65R/N) and four NNRTI-associated mutations (V179D/E/T/L, K103N/R/S/T, V106M/I/A and G190A/S/T/C/D/E/Q) were the most common DRMs. These DRMs caused high-level resistance to lamivudine, emtricitabine, efavirenz and nevirapine. The DRM profiles appeared to be significantly different among different subtypes. We revealed HIV-1 subtype characteristics and the DRM profile in Shanghai, which provide crucial guidance for clinical treatment and management of PLWH.

Risk assessment of first-line treatment failure in untreated HIV patients in Northwestern Federal District of the Russian Federation

The HIV infection epidemic in Russia continues to evolve, and HIV infection cases have been registered in all territorial entities of the Russian Federation. 2021 Treatment coverage was 82.2% and 56.4% individuals under dispensary observation and living with diagnosed HIV infection. 79.9% receiving ART subjects were shown to achieve undetectable viral load. Highly active antiretroviral therapy (HAART) currently represents a combination of three (less frequently four) antiretroviral drugs targeting pathways involved in various stages of HIV replication in vivo. Treatment failure is a problem facing doctors and patients using HAART. The most common cause of therapeutic failure is the development of HIV drug resistance. The emergence of resistance is associated with processes involving mutation occurring in the viral genome influenced by evolutionary factors. Therefore, it is important clinically and programmatically to learn more about the rate of first-line treatment failure, the rate of switching to a second-line ART regimen, and to identify patients at risk to develop strategies for preventing development of further failure cases. The study was aimed at analyzing ineffectiveness of first-line ART therapy in patients in Northwestern Federal District of the Russian Federation. Materials and methods. Sequencing reactions were performed using the AmpliSens HIV Resist-Seq. Assembly of consensus sequences from fragments obtained during sequencing was carried out using Unipro UGENE software. Isolate genotyping was performed using the MEGA-X software with the Neighbor-joining algorithm. Results. The HIV pol genes in 239 patients with first-line ART failure and 100 nave patients were sequenced; all sequences genotyped as HIV-1 subsubtype A6. According to analysis, 82% of patients had at least one significant mutation associated with drug resistance for the corresponding viral subtype. In total, we encountered 87 different drug resistance mutations. Conclusion. We have shown increased proportion of patients with first-line ART failure among all patients with treatment failure. The main cause for such changes is probably related to the prevalence of primary drug resistance, estimated here at 8%. Specific differences were found between drug resistance mutation profiles in patients without suppressed viral load and patients with virological breakthrough. The overall results of the study indicate a need to diagnose and characterize HIV drug resistance prior to initiation of therapy in order to avoid ineffective first-line antiretroviral treatment.

Archiving of mutations in HIV-1 cellular reservoirs among vertically infected adolescents is contingent with clinical stages and plasma viral load: Evidence from the EDCTP-READY study.

Globally, HIV-related adolescent deaths have increased about 50%, especially for those who are vertically infected. This could be driven by archived drug resistance mutations (DRMs) as children grow up, which might jeopardize antiretroviral therapy (ART). Our objective was to compare HIV-1genotypic variation between plasma RNA and proviral DNA of vertically infected adolescents (aged 10-19years) failing ART. A comparative study was conducted in 2019 among 296 adolescents with perinatal HIV infection (ALPHI) failing ART in health facilities of the Centre Region of Cameroon. The WHO clinical stage, CD4 count and plasma viral load (PVL) were measured. For those failing ART (PVL ≥1000 copies/mL), RNA (plasma) and proviral DNA (buffy coat) were sequenced in the pol gene at Chantal BIYA International Reference Centre (CIRCB), Yaoundé, Cameroon. HIV-1subtypes and DRMs were interpreted using Stanford HIVdb v.8.8 and MEGA-X. Of the 30% (89/296) failing ART, 81had both RNA and DNA sequences generated and three were excluded for APOBEC mutations: the mean age was 16±3years; female-to-male ratio was 3:5; median PVL was 46856 copies/mL [interquartile range (IQR): 19898-271410]; median CD4 count was 264 cells/μL (IQR: 131-574); and 42% were at WHO clinical stage 3/4. Subtype concordance between RNA and DNA viral strains was 100%, with CRF02_AG being predominant (65%) and two potential new recombinants found (A1/G/K; F1/G). Adolescents with DRMs were significantly higher in plasma than in proviral DNA (92% vs. 86%, p<0.0001). Prevalent DRMs by drug class (RNA vs. DNA respectively) were at position M184 (74% vs. 67%) for nucleoside reverse transcriptase inhibitors (NRTIs), K103 (63% vs. 59%) for non-NRTIs, and V82, L76 and M46 (2% vs. 2%) for protease inhibitors. A total of 35% (27/78) of adolescents had concordant DRM profiles in RNA and DNA, while 27% (21/78) had DRMs only in proviral DNA. The presence of archived DRMs was associated with advanced clinical stage 3/4 (OR = 0.14, p=0.0003) and PVL <5Log (Copies/mL) (OR: 4.88, p=0.006). Although plasma RNA remains more sensitive for detecting HIV-1 DRMs, about a quarter of ALPHI experiencing ART failure in an African setting might have archived DRMs in viral reservoirs, indicating clinically occult resistance. Thus, to ensure effective ART success, proviral DNA profiling (alongside RNA genotyping) would provide additional DRMs for adolescents with advanced clinical stages and/or moderate PVL.

The genotype distribution, infection stage and drug resistance mutation profile of human immunodeficiency virus-1 among the infected blood donors from five Chinese blood centers, 2014–2017

Human immunodeficiency virus-1 (HIV-1) exhibits high diversity and complexity in China, challenging the disease surveillance and antiretroviral therapy. Between July 1, 2014 and January 30, 2017, we investigated the profiles of HIV-1 infection stages, genotype distribution and drug resistance mutations (DRMs) using plasma samples from HIV Western blot (WB) confirmed blood donors from five Chinese blood centers (Chongqing, Guangxi, Luoyang, Mianyang, and Urumqi). HIV pol regions consisted of whole protease and partial reverse transcriptase were genotyped and analyzed for DRMs. Lag-Avidity testing was performed to identify the infection stages. Of the 356 HIV-1 WB positive samples tested by Lag-avidity assay, 19.1% (68/356) were recent infections. Genotyping on 356 amplified sequences presented the subtype distributions as following: CRF07_BC (65.7%), CRF08_BC (7.3%), CRF01_AE (19.1%), B (4.2%), CRF55_01B (3.1%), CRF59_01B (0.3%) and CRF68_01B (0.3%). No significant difference in genotype distribution was observed between recent and long-term infections. 48 DRMs were identified from 43 samples, indicating a drug resistance prevalence of 12.1% (43/356), which include seven protease inhibitors (PIs) accessory DRMs (Q58E, L23I and I84M), two PIs major DRMs (M46I, M46L), seven nucleoside RT inhibitors DRMs (D67N, K70Q, K219R and M184L), and 32 non-nucleoside RT inhibitors DRMs (K103N, V179E, K238N, V179D, E138G, G190E, A98G, Y188D and E138A). In addition, we had also identified CRFs from the 01B subtype including CRF55_01B (3.1%), CRF59_01B (0.3%) and CRF68_01B (0.3%). As an important part of the continuous monitoring of HIV-1 circulating strains among blood donors, our findings were expected to contribute to the comprehensive AIDS control and development of proper diagnostics for HIV-1 in China.

Prevalence of drug resistance mutations in HIV-infected individuals with low-level viraemia under combination antiretroviral therapy: an observational study in a tertiary hospital in Northern Taiwan, 2017-19.

Effective ART is crucial for combating the HIV pandemic. Clinically, plasma viral load monitoring to achieve virological suppression is the guide for an optimal ART. The presence of low-level viraemia (LLV) below the definition level of virological failure is a risk factor for ART failure. However, there is no treatment consensus over LLV yet, mainly due to the limitation of standard HIV-RNA genotyping and the resultant insufficient understanding of LLV characteristics. To better profile drug resistance mutations (DRMs) and the associated factors in cases experiencing LLV. A prospective observational study was conducted from 2017 to 2019. HIV-DNA was used as an alternative to HIV-RNA for HIV genotyping coupled with deep sequencing for ART-naive and ART-failure cases, as well as those with LLV. Eighty-one ART-naive, 18 ART-failure and 16 LLV cases received HIV genotyping in the study. Three-quarters (12/16) of cases experiencing LLV harboured DRMs. Cases with LLV had higher prevalence of DRMs to NNRTIs than the ART-naive group (69% versus 20%, P < 0.001), but lower DRM prevalence to NRTIs than the ART-failure group (25% versus 61%, P < 0.001). Approximately half of the LLV cases had issues of suboptimal ART compliance/ART interruption, and 68.8% (11/16) did not display drug resistance to their ART at the time of LLV. HIV DRM profiles in LLV cases were significantly different to those in ART-naive and ART-failure cases. Approaches to consolidate ART compliance and early exploration of potential ART resistance may be needed for cases experiencing LLV episodes.

HIV-1 pol gene diversity and molecular dating of subtype C from Sri Lanka.

BackgroundThe first case of HIV infection in Sri Lanka was reported in 1987 and at the end of 2018 there were 3500 people living with HIV. There have been commendable efforts made towards the detection, treatment, and prevention of HIV in the country. Even though the genetic diversity of HIV has been shown to affect the parameters ranging from detection to vaccine development, there is no data available with respect to the molecular epidemiology of HIV-1 in Sri Lanka.MethodsIn this report we have performed the ancillary analysis of pol gene region sequences (n = 85) obtained primarily for the purpose of HIV-1 drug resistance genotyping. Briefly, dried blood spot specimens (DBS) collected from HIV-1 infected individuals between December 2015 and August 2018 were subjected to pol gene amplification and sequencing. These pol gene sequences were used to interpret the drug resistance mutation profiles. Further, sequences were subjected to HIV-1 subtyping using REGA 3.0, COMET, jPHMM and, RIP online subtyping tools. Moreover, Bayesian phylogenetic analysis was employed to estimate the evolutionary history of HIV-1 subtype C in Sri Lanka.ResultsOur analysis revealed that the majority (51.8%) of pol gene sequences were subtype C. Other than subtype C, there were sequences categorized as subtypes A1, B, D and G. In addition to pure subtypes there were sequences which were observed to be circulating recombinant forms (CRFs) and a few of the recombinants were identified as potential unique recombinants (URFs). We also observed the presence of drug resistance mutations in 56 (65.9%) out of 85 sequences. Estimates of the Bayesian evolutionary analysis suggested that the HIV-1 subtype C was introduced to Sri Lanka during the early 1970s (1972.8).ConclusionThe findings presented here indicate the presence of multiple HIV-1 subtypes and the prevalence of drug resistance mutations in Sri Lanka. The majority of the sequences were subtype C, having their most recent common ancestor traced back to the early 1970s. Continuous molecular surveillance of HIV-1 molecular epidemiology will be crucial to keep track of drug resistance, genetic diversity, and evolutionary history of HIV-1 in Sri Lanka.

Nosocomial transmission of extensively drug resistant Acinetobacter baumannii strains in a tertiary level hospital.

Acinetobacter baumannii is an opportunistic infectious agent that affects primarily immunocompromised individuals. A. baumannii is highly prevalent in hospital settings being commonly associated with nosocomial transmission and drug resistance. Here, we report the identification and genetic characterization of A. baumannii strains among patients in a tertiary level hospital in Mexico. Whole genome sequencing analysis was performed to establish their genetic relationship and drug resistance mutations profile. Ten genetically different, extensively drug resistant strains were identified circulating among seven wards. The genetic profiles showed resistance primarily against aminoglycosides and beta-lactam antibiotics. Importantly, no mutants conferring resistance to colistin were observed. The results highlight the importance of implementing robust classification schemes for advanced genetic characterization of A. baumannii clinical isolates and simultaneous detection of drug resistance markers for adequate patient’s management in clinical settings.

HIV-1 Drug Resistance in ART-Naïve Individuals in Myanmar.

BackgroundEstimating the prevalence and characterizing the transmission of HIV-1 drug resistance in treatment-naïve individuals are very important in the prevention and control of HIV/AIDS. As one of the areas most affected by HIV/AIDS, few data are currently available for HIV-1 drug resistance in antiretroviral therapy (ART)-naïve individuals in Myanmar, which borders Yunnan, China.MethodsHIV-1 pol sequences from ART-naïve HIV-1-infected individuals during 2008 and 2014 in Myanmar were retrieved from our previous studies. HIV-1 transmitted drug resistance (TDR) and susceptibility to antiretroviral drugs were predicted using the Stanford HIVdb program. HIV-1 transmission cluster (TC) was determined by Cluster Picker.ResultsA total of 169 partial pol sequences from ART-naïve HIV-1 positive Burmese were analyzed. The prevalence of TDR was 20.1%. CRF01_AE and BC recombinants appeared to have a higher prevalence of TDR than other subtypes. The V179D/T was found to be very common in the China–Myanmar border region and was involved in half of the transmission clusters formed by HIV-1 drug-resistance strains in this region. Comparison showed that drug-resistance mutation profile in Myanmar was very similar to that in Dehong prefecture of Yunnan. By further phylogenetic analysis with all available sequences from the China–Myanmar border region, four HIV-1 drug-resistance-related TCs were identified. Three of them were formed by Burmese long-distance truck drivers and the Burmese staying in Yunnan, and another was formed by Burmese injection drug users staying in Myanmar and Yunnan. These results suggest a potential transmission link of HIV-1 drug resistance between Myanmar and Yunnan.ConclusionGiven the high prevalence of TDR in Myanmar, and the potential risk of cross-border transmission of HIV-1 drug-resistant strains between Myanmar and Yunnan, China, ongoing monitoring of HIV-1 drug resistance in ART-naïve individuals will provide a guideline for clinical antiretroviral treatment and benefit the prevention and control of HIV/AIDS in this border region.

Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China

BackgroundThe impacts of genetic polymorphisms on drug resistance mutations (DRMs) among various HIV-1 subtypes have long been debated. In this study, we aimed to analyze the natural polymorphisms and acquired DRM profile in HIV-1 CRF01_AE-infected patients in a large first-line antiretroviral therapy (ART) cohort in northeastern China.MethodsThe natural polymorphisms of CRF01_AE were analyzed in 2034 patients from a long-term ART cohort in northeastern China. The polymorphisms in 105 treatment failure (TF) patients were compared with those in 1148 treatment success (TS) patients. The acquired DRM profile of 42 patients who experienced TF with tenofovir/lamivudine/efavirenz (TDF/3TC/EFV) treatment was analyzed by comparing the mutations at TF time point to those at baseline. The Stanford HIVdb algorithm was used to interpret the DRMs. Binomial distribution, McNemar test, Wilcoxon test and CorMut package were used to analyze the mutation rates and co-variation. Deep sequencing was used to analyze the evolutionary dynamics of co-variation.ResultsBefore ART, there were significantly more natural polymorphisms of 31 sites on reverse transcriptase (RT) in CRF01_AE than subtype B HIV-1 (|Z value| ≥ 3), including five known drug resistance-associated sites (238, 118, 179, 103, and 40). However, only the polymorphism at site 75 was associated with TF (|Z value| ≥ 3). The mutation rate at 14 sites increased significantly at TF time point compared to baseline, with the most common DRMs comprising G190S/C, K65R, K101E/N/Q, M184 V/I, and V179D/I/A/T/E, ranging from 66.7 to 45.2%. Moreover, two unknown mutations (V75 L and L228R) increased by 19.0 and 11.9% respectively, and they were under positive selection (Ka/Ks > 1, log odds ratio [LOD] > 2) and were associated with several other DRMs (cKa/Ks > 1, LOD > 2). Deep sequencing of longitudinal plasma samples showed that L228R occurred simultaneously or followed the appearance of Y181C.ConclusionThe high levels of natural polymorphisms in CRF01_AE had little impact on treatment outcomes. The findings regarding potential new CRF01_AE-specific minor DRMs indicate the need for more studies on the drug resistance phenotype of CRF01_AE.

Antiretroviral resistance in HIV-1 patients at a tertiary medical institute in Saudi Arabia: a retrospective study and analysis

BackgroundSince the early 90’s antiretroviral drugs have been available at King Faisal Specialist Hospital and Research Centre (KFSH&RC), a referral hospital in Riyadh, Saudi Arabia, for the treatment of both adults and children infected with HIV-1. However, up to date, there are no genetic profiling data for the resistance-causing mutations in HIV-1 virus in patients on antiretroviral drugs therapy. This paper presents an initial report and a profiling survey of drug resistance-associated mutations of 103 HIV-1 patients seen at KFSH&RC.MethodsThis is a retrospective study on Patients treated at KFSH&RC since 2003 up to 2016. The analysis was done on the drug resistance mutations profiles of 103 patients who were undergoing highly active antiretroviral therapy protocols.ResultsOur analysis shows that the drug resistance mutations reported in our treatment cohort of HIV-infected adults patients is similar what is internationally reported to some extent. Additionally, we have identified novel drug resistance causing mutations. Furthermore, different profile of drug resistance causing mutations was also observed.ConclusionPatients showed both similar and new drug resistant causing mutations, early identification of these mutations is crucial to guide and avoid failure future therapy.

Prevalence of drug-resistant mutation among drug-treated HIV/AIDS inpatient in Airlangga University teaching hospital, Surabaya, Indonesia

Increased use of antiretroviral therapy did not completely reduce the incidence of HIV/AIDShospitalization. Various factors can be involved. The aim of this study is to examine HIV-1 drug resistance mutations profile in drug-treated HIV/AIDS patients who underwent hospitalization. HIV/AIDS patients who are admitted to hospital who had received ART are included in the study and then examined for the presence of drug resistance-associated mutations. A total of 17 samples were included in the study, but only 11 samples that could be sequence analyzed. On the mutation examination of drug resistance in reverse transcriptase gene, it werefound a major mutation in K103N (9%) and G190A (9%). Most minor mutations were found in A98S (18.1%), followed by M41L, M184V, L210W, T215Y, V108l, Y181C and H221Y at 9% each. Whereas, on examination of drug resistance mutations in protease genes, there is a major mutation in I84V of 9%. Most minor mutations on M36I (45.4%), followed by L10I (36.3%), H69K (36.3%), I93L (27.2%), G16E, L89M, K20R 18.1%, L64V and V771I 9% respectively.A large number of mutated samples pose a challenge in long-term antiretroviral treatment, so a breakthrough policy is needed to minimize the impact.

Moderate Levels of Pretreatment HIV Drug Resistance — Zimbabwe, April–July 2015

BackgroundThe World Health Organization (WHO) HIV Drug Resistance (HIVDR) report 2012 demonstrated that the levels of HIVDR to first-line antiretroviral therapy (ART) are increasing. This finding threatens to reverse a decade of gains in HIV/AIDS epidemic control. The WHO Global Action Plan for HIVDR emphasizes strengthening surveillance of drug resistance through the implementation of national cross-sectional surveys. We conducted such survey to determine the prevalence of HIVDR among ART-naive patients in Zimbabwe and to describe the profile of the surveillance drug resistance mutations (SDRM) encountered in the country.MethodsA prospective, nationally representative, cross-sectional survey was conducted in 35 clinical sites selected using two stage probability proportional to size sampling. Patients were enrolled during April–July 2015. Specimens were sent for genotyping to CDC Atlanta. SDRM were interpreted using Stanford HIV Drug Resistance Database classification.ResultsA total of 361 subjects were surveyed. Most participants were female (60.3%) and the median age was 35.8 years. Thirty-four out of 361subjects presented with ≥1 SDRM (9.4%, 95% confidence interval: 6.8–12.8%) prior to initiation antiretroviral therapy (ART). Non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations were the most commonly detected mutation (n = 30). Only two patients presented with a nucleoside reverse transcriptase inhibitor mutation and one patient presented with a protease inhibitor mutation. In two patients, ≥3 SDRMs were detected, which may suggest they were not truly ART-naïve.ConclusionThis study provides national estimates of HIVDR in a high burden country with broad access to ART and provides valuable inisight on the state of HIVDR in such setting. Zimbabwe has reached moderate levels of HIVDR in ART-naive patients, as specified by the WHO classification. These levels may impact the ability to achieve viral suppression in a significant number of patients initiating standard ART regimens in Zimbabwe, where NNRTI-based regimens are used as the first line. The use of drugs with high resistance barrier, such as dolutegravir, may improve the care of patients in the developing world, where individualized pretreatment genotype is not feasible.Disclosures All authors: No reported disclosures.

Drug resistance mutation profiles of the drug-naïve and first-line regimen-treated HIV-1-infected population of Suzhou, China.

Little is known about the prevalence of drug-resistant mutations in HIV-1-positive individuals in Suzhou, China. To elucidate the transmitted drug resistance (TDR) and acquired drug resistance mutation (ADR) profiles, we collected blood specimens from 127 drug-naïve and 117 first-line drug-treated HIV-1-infected individuals sampled from 2014 to 2016 in Suzhou. We successfully amplified pol fragments from 100 drug-naïve and 20 drug-treated samples. We then determined the drug-resistant mutations to protease (PR) and reverse-transcriptase (RT) inhibitors according to the Stanford drug resistance database. Overall, 11 and 13 individuals had transmitted (drug-naïve group) and acquired (treated group) resistance mutations, respectively. Six transmitted drug-resistant mutations were found, including two mutations (L33F and L76V) in the protease region and four (K70N/E and V179D/E) in the RT region. Only L76V was a major mutation, and K70N/E and V179D/E are known to cause low-level resistance to RT inhibitors. All 13 treated participants who had major drug resistance mutations demonstrated intermediate to high resistance to efavirenz and nevirapine, and six had a treatment duration of less than three months. No major mutations to RT inhibitors were found, implying that the epidemic of transmitted resistance mutations was not significant in this area. Our results suggest that more frequent virus load and drug resistance mutation tests should be conducted for individuals receiving antiretroviral treatment, especially for newly treated patients. Our research provides insights into the occurrence of HIV-1 drug resistance in Suzhou and will help to optimize the treatment strategy for this population.

Genetic Analyses of HIV-1 Strains Transmitted from Mother to Child in Northern Vietnam.

We previously reported mother-to-child transmission of HIV-1 in nine (6.7%) of 135 children on nevirapine prophylaxis in Vietnam. In the current study, we investigated the appearance and profile of antiretroviral drug (ARV) resistance mutations, the predicted coreceptor usage, and the genetic diversity of HIV-1 strains isolated from the eight pairs of HIV-1-infected mothers and their children, who were followed up to 12 months after birth. Portions of the pol and env C2V3 regions of the HIV-1 strains were analyzed genetically. HIV-1 CRF01_AE RNA was detected in four (50%) children at delivery. Y181C, a nevirapine resistance mutation, appeared in two (25%) children 1 and 3 months after birth, respectively. No ARV resistance mutation was detected in the mothers, though three mothers were on ARV prophylaxis. Five mothers and their children harbored CCR5-tropic (R5) viruses. Two mothers harbored both R5 and CXCR4-tropic (X4) viruses, but their children harbored only R5 viruses even though the X4 viruses were dominant in the mothers. In the remaining one mother, HIV-1 RNA was not amplified and her child harbored both R5 and X4 viruses at birth, but only X4 virus 12 months after delivery. The infants' viruses were more homogeneous than their mothers' viruses (mean distance: 0.5% vs. 1.1%, respectively). This is the first molecular epidemiological study of vertical HIV-1 infections in Vietnam. These findings may provide useful knowledge for the prevention of mother-to-child transmission of HIV-1 and the antiretroviral treatment of children in Vietnam.

HIV-1 subtype B/B' and baseline drug resistance mutation are associated with virologic failure: a multicenter cohort study in China.

Distribution of HIV-1 subtypes, transmitted drug resistance (TDR)/drug resistance mutation (DRM), and their impact on response to combination antiretroviral therapy remain poorly understood in China. We analyzed data from our multicenter cohort study with 444 antiretroviral-naive participants recruited between 2008 and 2010. HIV-1 subtype and tropism were determined by V3 sequencing, and TDR/DRM was determined by Pol sequencing. Virologic and immunologic responses were monitored over 96 weeks of follow-up. The initial combination antiretroviral therapy regimen for all patients was nevirapine + lamivudine + zidovudine or stavudine. Analysis 1 included patients who finished 96 weeks of follow-up (n = 379), and analysis 2 included all 444 patients. Subtype B/B' was associated with higher prevalence of TDR/DRM to nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors. Median time to HIV-1 suppression was 18 weeks in all 3 subtype groups. In Cox proportional models for viral suppression, neither viral tropism nor HIV-1 subtypes had any impact on viral suppression; however, subtypes CRF01_AE and C/CRF07_BC/CRF08_BC were associated with lower risk of virologic failure compared with subtype B/B', with adjusted hazard ratio of 0.11 (P = 0.032) and 0.06 (P = 0.036), respectively in analysis 1, 0.42 (P = 0.047) and 0.22 (P = 0.008), respectively in analysis 2. This association was attenuated by adding DRM profiles to multivariate regression models. Neither subtype nor HIV-1 tropism affected immunologic response. HIV-1 subtype tended to be associated with virologic but not immunologic response; this effect could be ascribed to baseline DRM.

Evolution and transmission patterns of extensively drug-resistant tuberculosis in China.

The emergence and transmission of extensively drug-resistant tuberculosis (XDR-TB) pose an increasing threat to global TB control. This study aimed to identify the patterns of evolution and transmission dynamics of XDR-TB in populations in a region of China where TB is highly endemic. We analyzed a total of 95 XDR-TB isolates collected from 2003 to 2009 in Chongqing, China. Eight drug resistance genes covering 7 drugs that define XDR-TB were amplified by PCR followed by DNA sequencing. Variable-number tandem repeat 16-locus (VNTR-16) genotyping and genotypic drug resistance profiles were used to determine the evolution or transmission patterns of XDR-TB strains. Our results indicated that the Beijing genotype was predominant (85/95 [89.5%]) in XDR-TB strains, and as many as 40.0% (38/95) of the isolates were distributed into 6 clusters based on VNTR-16 genotyping and drug resistance mutation profiles. All isolates of each cluster harbored as many as six identical resistance mutations in the drug resistance genes rpoB, katG, inhA promoter, embB, rpsL, and gidB. Among the nine cases with continuous isolates from multidrug-resistant (MDR) to XDR-TB, 4 cases represented acquired drug resistance, 4 cases were caused by transmission, and 1 case was due to exogenous superinfection. The XDR-TB epidemic in China is mainly caused by a high degree of clonal transmission, but evolution from MDR to XDR and even superinfection with a new XDR strain can also occur.

Drug resistance mutations and genetic diversity in adults treated for HIV type 1 infection in Mauritania

The aim of this cross-sectional study was to evaluate the drug resistance mutationprofile observed in patients receiving antiretroviral therapy with virological failure and to document the HIV-1 genetic diversity in Mauritania. Eighty-six subjects were included and 65 samples were amplified successfully and sequenced. HIV-1 genotyping was performed using the Agence Nationale de Recherche sur le SIDA AC11 resistance procedure. The median treatment duration was 32 months (range: 6-88) and the median viral load, 5 log10 copies/ml (range: 3.13-7). Fifty-nine patients (90.8%) were on first line regimens including 32.0% (19/59) on triomune fixed-dose and six on second-line therapy with NonNucleoside Reverse Transcriptase plus a protease inhibitor. Forty-seven patients (72.3%) had at least one drug resistance mutation including 73.0% (43/59) on first-line therapy. For the second-line, one out of six patients presented resistance mutations and only one presented PI DRM. Overall, the most common DRMs detected were M184V/I (n = 32; 49.2%), K103N (n = 28; 43%), and Y181C (n = 13; 20%). Thymidine Analog Mutations (TAMs) were found in 26.0% (n = 17) of strains and the most common was T215Y (n = 11, 16.9%). Phylogenetic analysis revealed 17 HIV-1 variants with the predominance of CRF02_AG (n = 42; 64.6%). A high rate of DRM was found in this study and shows the potential need for a structured virological surveillance including viral load quantification and genotyping. Further studies may also be needed in regards to the great variability of HIV-1 strains in Mauritania.

HIV-1 drug resistance prevalence, drug susceptibility and variant characterization in the Jacobi Medical Center paediatric cohort, Bronx, NY, USA

With the advent of combined antiretroviral therapy (cART), perinatally HIV-infected children are surviving into adolescence and beyond. However, drug resistance mutations (DRMs) compromise viral control, affecting the long-term effectiveness of ART. The aims of this study were to detect and identify DRMs in a HIV-1 infected paediatric cohort. Paired plasma and dried blood spots (DBSs) specimens were obtained from HIV-1 perinatally infected patients attending the Jacobi Medical Center, New York, USA. Clinical, virological and immunological data for these patients were analysed. HIV-1 pol sequences were generated from samples to identify DRMs according to the International AIDS Society (IAS) 2011 list. Forty-seven perinatally infected patients were selected, with a median age of 17.7 years, of whom 97.4% were carrying subtype B. They had a mean viral load of 3143 HIV-1 RNA copies/mL and a mean CD4 count of 486 cells/μL at the time of sampling. Nineteen patients (40.4%) had achieved undetectable viraemia (< 50 copies/mL) and 40.5% had a CD4 count of > 500 cells/μL. Most of the patients (97.9%) had received cART, including protease inhibitor (PI)-based regimens in 59.6% of cases. The DRM prevalence was 54.1, 27.6 and 27.0% for nucleoside reverse transcriptase inhibitors (NRTIs), PIs and nonnucleoside reverse transcriptase inhibitors (NNRTIs), respectively. Almost two-thirds (64.9%) of the patients harboured DRMs to at least one drug class and 5.4% were triple resistant. The mean nucleotide similarity between plasma and DBS sequences was 97.9%. Identical DRM profiles were present in 60% of plasma-DBS paired sequences. A total of 30 DRMs were detected in plasma and 26 in DBSs, with 23 present in both. Although more perinatally HIV-1-infected children are reaching adulthood as a result of advances in cART, our study cohort presented a high prevalence of resistant viruses, especially viruses resistant to NRTIs. DBS specimens can be used for DRM detection.

Encouraging high‐quality research publications from the developing world

Encouraging high‐quality research publications from the developing world