HIV Drug Resistance Research Articles

Epidemiological characteristics of HIV transmission in southeastern China from 2015 to 2020 based on HIV molecular network.

HIV/AIDS remains a global public health problem, and understanding the structure of social networks of people living with HIV/AIDS is of great importance to unravel HIV transmission, propose precision control and reduce new infections. This study aimed to investigate the epidemiological characteristics of HIV transmission in Fujian province, southeastern China from 2015 to 2020 based on HIV molecular network. Newly diagnosed, treatment-naive HIV/AIDS patients were randomly sampled from Fujian province in 2015 and 2020. Plasma was sampled for in-house genotyping resistance test, and HIV molecular network was created using the HIV-TRACE tool. Factors affecting the inclusion of variables in the HIV molecular network were identified using univariate and multivariate logistic regression analyses. A total of 1,714 eligible cases were finally recruited, including 806 cases in 2015 and 908 cases in 2020. The dominant HIV subtypes were CRF01_AE (41.7%) and CRF07_BC (38.3%) in 2015 and CRF07_BC (53. 3%) and CRF01_AE (29.1%) in 2020, and the prevalence of HIV drug resistance was 4.2% in 2015 and 5.3% in 2020. Sequences of CRF07_BC formed the largest HIV-1 transmission cluster at a genetic distance threshold of both 1.5 and 0.5%. Univariate and multivariate logistic regression analyses showed that ages of under 20 years and over 60 years, CRF07_BC subtype, Han ethnicity, sampling in 2015, absence of HIV drug resistance, married with spouse, sampling from three cities of Jinjiang, Nanping and Quanzhou resulted in higher proportions of sequences included in the HIV transmission molecular network at a genetic distance threshold of 1.5% (p < 0.05). Our findings unravel the HIV molecular transmission network of newly diagnosed HIV/AIDS patients in Fujian province, southeastern China, which facilitates the understanding of HIV transmission patterns in the province.

Development and validation of an ultra-high performance liquid chromatography-tandem mass spectrometry method for quantifying lenacapavir plasma concentrations: Application to therapeutic monitoring

Although current antiretroviral therapy (ART) effectively suppresses HIV in the blood, regimens may fail due to suboptimal treatment history and non-adherence to ART. In these scenarios, accumulation of viral resistance mutations to ART drug classes may occur. For these treatment-experienced people living with HIV (PLWH), activity against resistant viral strains is required; lack of therapeutic efficacy will result in continued viral replication and progression to acquired immunodeficiency syndrome. New treatment options have emerged. Lenacapavir is a first-in-class long-acting HIV-1 capsid inhibitor approved for the treatment of HIV in treatment-experienced patients. Lenacapavir is approved with an initiation regimen of oral and subcutaneous injection dosing followed by subcutaneous self-injection every 6 months. With infrequent dosing, therapeutic drug monitoring may be necessary to ensure adequate concentrations are consistently achieved in the plasma to assure treatment adherence and prevent further HIV resistance formation. To this end, we developed and validated a highly selective ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to quantify lenacapavir concentrations in human plasma. A simple protein precipitation with acetonitrile followed by supernatant dilution was performed. Lenacapavir and its stable labeled internal standard were separated at 1.90 min using a multi-step UPLC gradient. The assay for lenacapavir quantification was extensively validated according to the United States Food and Drug Administration Bioanalytical Guidelines over a clinically relevant range of 0.1 to 500 ng/mL with excellent linearity (R2 ≥ 0.9960). This analytical method achieves acceptable performance of trueness (89.7–104.1 %), repeatability, and precision (CV < 15 %). We applied this method to quantify a clinical sample and to determine the percent protein-unbound. This method can be utilized for the therapeutic monitoring of lenacapavir in human plasma for monitoring HIV treatment efficacy.

HIV-1 Subtype Diversity and Factors Affecting Drug Resistance among Patients with Virologic Failure in Antiretroviral Therapy in Hainan Province, China, 2014–2020

ObjectiveThis study aimed to determine the HIV-1 subtype distribution and HIV drug resistance (HIVDR) in patients with ART failure from 2014 to 2020 in Hainan, China. MethodsA 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan. We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences. Drug resistance mutations (DRMs) were analyzed using the Stanford University HIV Drug Resistance Database. ResultsA total of 307 HIV-infected patients with ART failure were included, and 241 available pol sequences were obtained. Among 241 patients, CRF01_AE accounted for 68.88%, followed by CRF07_BC (17.00%) and eight other subtypes (14.12%). The overall prevalence of HIVDR was 61.41%, and the HIVDR against non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) were 59.75%, 45.64%, and 2.49%, respectively. Unemployed patients, hypoimmunity or opportunistic infections in individuals, and samples from 2017 to 2020 increased the odd ratios of HIVDR. Also, HIVDR was less likely to affect female patients. The common DRMs to NNRTIs were K103N (21.99%) and Y181C (20.33%), and M184V (28.21%) and K65R (19.09%) were the main DRMs against NRTIs. ConclusionThe present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.

HIV-1 drug resistance and genetic transmission network among newly diagnosed people living with HIV/AIDS in Ningbo, China between 2018 and 2021

BackgroundAs the HIV epidemic continues to grow, transmitted drug resistance(TDR) and determining relationship of HIV transmission are major barriers to reduce the risk of HIV transmissions.This study aimed to examine the molecular epidemiology and TDR and evaluated the transmission pattern among newly diagnosed people living with HIV/AIDS(PLWHA) in Ningbo city, which could contribute to the development of targeted precision interventions.MethodsConsecutive cross-sectional surveys were conducted in Ningbo City between January 2018 and December 2021. The HIV-1 pol gene region was amplified and sequenced for drug resistance and genetic transmission network analysis. TDR was determined using the Stanford University HIV Drug Resistance Database. Genetic transmission network was visualized using Cytoscape with the genetic distance threshold of 0.013.ResultsA total of 1006 sequences were sequenced successfully, of which 61 (6.1%) showed evidence of TDR. The most common mutations were K103N (2.3%), E138A/G/Q (1.7%) and V179D/E (1.2%). 12 HIV-1 genotypes were identified, with CRF07_BC being the major genotype (43.3%, 332/767), followed by CRF01_AE (33.7%, 339/1006). 444 (44.1%) pol sequences formed 856 links within 120 transmission clusters in the network. An increasing trend in clustering rate between 2018 and 2021(χ2 = 9.546, P = 0.023) was observed. The odds of older age (≥ 60 years:OR = 2.038, 95%CI = 1.072 ~ 3.872, compared to < 25 years), HIV-1 genotypes (CRF07_BC: OR = 2.147, 95%CI = 1.582 ~ 2.914; CRF55_01B:OR = 2.217, 95%CI = 1.201 ~ 4.091, compared to CRF01_AE) were significantly related to clustering. Compared with CRF01_AE, CRF07_BC were prone to form larger clusters. The largest cluster with CRF07_BC was increased from 15 cases in 2018 to 83 cases in 2021.ConclusionsThis study revealed distribution of HIV-1 genotypes, and genetic transmission network were diverse and complex in Ningbo city. The prevalence of TDR was moderate, and NVP and EFV were high-level NNRTI resistance. Individuals aged ≥ 60 years old were more easily detected in the networks and CRF07_BC were prone to form rapid growth and larger clusters. These date suggested that surveillance and comprehensive intervention should be designed for key rapid growth clusters to reduce the potential risk factors of HIV-1 transmission.

HIV Drug Resistance Patterns and Characteristics Associated with Clinically Significant Drug Resistance among Children with Virologic Failure on Antiretroviral Treatment in Kenya: Findings from the Opt4Kids Randomized Controlled Trial.

Increasing HIV drug resistance (DR) among children with HIV (CHIV) on antiretroviral treatment (ART) is concerning. CHIV ages 1-14 years enrolled from March 2019 to December 2020 from five facilities in Kisumu County, Kenya, were included. Children were randomized 1:1 to control (standard-of-care) or intervention (point-of-care viral load (POC VL) testing every three months with targeted genotypic drug resistance testing (DRT) for virologic failure (VF) (≥1000 copies/mL)). A multidisciplinary committee reviewed CHIV with DRT results and offered treatment recommendations. We describe DR mutations and present logistic regression models to identify factors associated with clinically significant DR. We enrolled 704 children in the study; the median age was 9 years (interquartile range (IQR) 7, 12), 344 (49%) were female, and the median time on ART was 5 years (IQR 3, 8). During the study period, 106 (15%) children had DRT results (84 intervention and 22 control). DRT detected mutations associated with DR in all participants tested, with 93 (88%) having major mutations, including 51 (54%) with dual-class resistance. A history of VF in the prior 2 years (adjusted odds ratio (aOR) 11.1; 95% confidence interval (CI) 6.3, 20.0) and less than 2 years on ART at enrollment (aOR 2.2; 95% CI 1.1, 4.4) were associated with increased odds of major DR. DR is highly prevalent among CHIV on ART with VF in Kenya. Factors associated with drug resistance may be used to determine which children should be prioritized for DRT.

HIV-1 drug resistance in people on dolutegravir-based antiretroviral therapy: a collaborative cohort analysis

The widespread use of the integrase strand transfer inhibitor (INSTI) dolutegravir in first-line and second-line antiretroviral therapy (ART) might facilitate emerging resistance. The DTG RESIST study combined data from HIV cohorts to examine patterns of drug resistance mutations (DRMs) and identify risk factors for dolutegravir resistance. We included cohorts with INSTI resistance data from two collaborations (ART Cohort Collaboration, International epidemiology Databases to Evaluate AIDS in Southern Africa), and the UK Collaborative HIV Cohort. Eight cohorts from Canada, France, Germany, Italy, the Netherlands, Switzerland, South Africa, and the UK contributed data on individuals who were viraemic on dolutegravir-based ART and underwent genotypic resistance testing. Individuals with unknown dolutegravir initiation date were excluded. Resistance levels were categorised using the Stanford algorithm. We identified risk factors for resistance using mixed-effects ordinal logistic regression models. We included 599 people with genotypic resistance testing on dolutegravir-based ART between May 22, 2013, and Dec 20, 2021. Most had HIV-1 subtype B (n=351, 59%), a third had been exposed to first-generation INSTIs (n=193, 32%), 70 (12%) were on dolutegravir dual therapy, and 18 (3%) were on dolutegravir monotherapy. INSTI DRMs were detected in 86 (14%) individuals; 20 (3%) had more than one mutation. Most (n=563, 94%) were susceptible to dolutegravir, seven (1%) had potential low, six (1%) low, 17 (3%) intermediate, and six (1%) high-level dolutegravir resistance. The risk of dolutegravir resistance was higher on dolutegravir monotherapy (adjusted odds ratio [aOR] 34·1, 95% CI 9·93-117) and dolutegravir plus lamivudine dual therapy (aOR 9·21, 2·20-38·6) compared with combination ART, and in the presence of potential low or low (aOR 5·23, 1·32-20·7) or intermediate or high-level (aOR 13·4, 4·55-39·7) nucleoside reverse transcriptase inhibitor (NRTI) resistance. Among people with viraemia on dolutegravir-based ART, INSTI DRMs and dolutegravir resistance were rare. NRTI resistance substantially increased the risk of dolutegravir resistance, which is of concern, notably in resource-limited settings. Monitoring is important to prevent resistance at the individual and population level and ensure the long-term sustainability of ART. US National Institutes of Health, Swiss National Science Foundation.

Transmitted drug resistance and subtype patterns of viruses from reported new HIV diagnoses in Germany, 2017–2020

BackgroundThe transmission of resistant HIV variants jeopardizes the effective use of antiretrovirals for therapy and prophylaxis. Molecular surveillance of new HIV diagnoses with a focus on prevalence and type of resistance associated mutations and the subtype of circulating viruses is mandatory.MethodFrom 2017 to 2020, 11,527 new HIV diagnoses were reported in Germany to the Robert Koch Institute (RKI). Protease (PR) and reverse-transcriptase (RT) sequences were obtained from 4559 (39.6%) cases, and PR, RT and integrase (IN) sequences were obtained from 3097 (26.9%) cases. The sequences were analyzed with data from the national HIV reports.ResultsAmong all cases in the analysis, the proportion of primary resistance was 4.3% for nucleoside reverse-transcriptase inhibitors (NRTIs), 9.2% for non-NRTI (NNRTIs), 3.3% for protease inhibitors (PIs) and 1.4% for integrase inhibitors (INIs). Dual-class resistance was highest for NRTIs/NNRTIs with 1.2%. There was no trend in the proportion of viruses resistant to drug classes. Most individual key mutations associated with relevant resistance had a prevalence below 1% including K65R (0.1%) and M184V (0.6%). A notable exception was K103NS, with a prevalence of 2.9% and a significant increase (pTrend=0.024) during 2017–2020. In this period, diagnoses of infections with HIV-1 subtype B were the most common at 58.7%, but its prevalence was declining (pTrend=0.049) while the frequency of minority subtypes (each < 1%) increased (pTrend=0.007). Subtype B was highest (75.6%) in men who have sex with men (MSM) and lowest in reported heterosexual transmissions (HETs, 22.6%).ConclusionThe percentage of primary resistance was high but at a stable level. A genotypic determination of resistance is therefore still required before the start of therapy. The subtype diversity of circulating HIV-1 is increasing.

Global burden of disease due to rifampicin-resistant tuberculosis: a mathematical modeling analysis

In 2020, almost half a million individuals developed rifampicin-resistant tuberculosis (RR-TB). We estimated the global burden of RR-TB over the lifetime of affected individuals. We synthesized data on incidence, case detection, and treatment outcomes in 192 countries (99.99% of global tuberculosis). Using a mathematical model, we projected disability-adjusted life years (DALYs) over the lifetime for individuals developing tuberculosis in 2020 stratified by country, age, sex, HIV, and rifampicin resistance. Here we show that incident RR-TB in 2020 was responsible for an estimated 6.9 (95% uncertainty interval: 5.5, 8.5) million DALYs, 44% (31, 54) of which accrued among TB survivors. We estimated an average of 17 (14, 21) DALYs per person developing RR-TB, 34% (12, 56) greater than for rifampicin-susceptible tuberculosis. RR-TB burden per 100,000 was highest in former Soviet Union countries and southern African countries. While RR-TB causes substantial short-term morbidity and mortality, nearly half of the overall disease burden of RR-TB accrues among tuberculosis survivors. The substantial long-term health impacts among those surviving RR-TB disease suggest the need for improved post-treatment care and further justify increased health expenditures to prevent RR-TB transmission.

Rate of response to initial antiretroviral therapy according to level of pre-existing HIV-1 drug resistance detected by next-generation sequencing in the strategic timing of antiretroviral treatment (START) study.

The main objective of this analysis was to evaluate the impact of pre-existing drug resistance by next-generation sequencing (NGS) on the risk of treatment failure (TF) of first-line regimens in participants enrolled in the START study. Stored plasma from participants with entry HIV RNA >1000 copies/mL were analysed using NGS (llumina MiSeq). Pre-existing drug resistance was defined using the mutations considered by the Stanford HIV Drug Resistance Database (HIVDB v8.6) to calculate the genotypic susceptibility score (GSS, estimating the number of active drugs) for the first-line regimen at the detection threshold windows of >20%, >5%, and >2% of the viral population. Survival analysis was conducted to evaluate the association between the GSS and risk of TF (viral load >200 copies/mL plus treatment change). Baseline NGS data were available for 1380 antiretroviral therapy (ART)-naïve participants enrolled over 2009-2013. First-line ART included a non-nucleoside reverse transcriptase inhibitor (NNRTI) in 976 (71%), a boosted protease inhibitor in 297 (22%), or an integrase strand transfer inhibitor in 107 (8%). The proportions of participants with GSS <3 were 7% for >20%, 10% for >5%, and 17% for the >2% thresholds, respectively. The adjusted hazard ratio of TF associated with a GSS of 0-2.75 versus 3 in the subset of participants with mutations detected at the >2% threshold was 1.66 (95% confidence interval 1.01-2.74; p = 0.05) and 2.32 (95% confidence interval 1.32-4.09; p = 0.003) after restricting the analysis to participants who started an NNRTI-based regimen. Up to 17% of participants initiated ART with a GSS <3 on the basis of NGS data. Minority variants were predictive of TF, especially for participants starting NNRTI-based regimens.

Impact of pretreatment low-abundance HIV-1 drug resistance on virological failure after 1 year of antiretroviral therapy in China.

To assess the impact of pretreatment low-abundance HIV drug-resistant variants (LA-DRVs) on virological outcomes among ART-naive HIV-1-infected Chinese people who initiated ART. A nested case-control study was conducted among HIV-1-infected individuals who had pretreatment drug resistance (PDR) genotypic results. Cases were defined as individuals with virological failure (HIV-1 RNA viral load ≥1000 copies/mL) after 1 year of ART, and controls were individuals from the same cohort whose viral load was less than 1000 copies/mL. Next-generation sequencing was used to identify low-abundance PDR mutations at detection thresholds of 10%, 2% and 1%. The mutant load was calculated by multiplying the abundance of HIV-1 drug-resistant variants by the pretreatment viral load. The impact of pretreatment low-abundance mutations on virological failure was estimated in logistic regression models. Participants (43 cases and 100 controls) were included in this study for the analysis. The proportion of participants with PDR was higher in cases than in controls at different detection thresholds (44.2% versus 22.0%, P = 0.007 at 10% threshold; 58.1% versus 31.0%, P = 0.002 at 2% threshold; 90.7% versus 69.0%, P = 0.006 at 1% threshold). Compared with participants without PDR, participants with ≥10% detectable PDR mutations were associated with an increased risk of virological failure (adjusted OR 8.0, 95% CI 2.4-26.3, P = 0.001). Besides this, individuals with pretreatment LA-DRVs (2%-9% abundance range) had 5-fold higher odds of virological failure (adjusted OR 5.0, 95% CI 1.3-19.6, P = 0.021). Furthermore, LA-DRVs at 2%-9% abundance resistant to NRTIs and mutants with abundance of ≥10% resistant to NNRTIs had a 4-fold and 8-fold risk of experiencing virological failure, respectively. It was also found that a mutant load of more than 1000 copies/mL was predictive of virological failure (adjusted OR 7.2, 95% CI 2.5-21.1, P = 0.0003). Low-abundance PDR mutations ranging from 2% to 9% of abundance can increase the risk of virological failure. Further studies are warranted to define a clinically relevant threshold of LA-DRVs and the role of NRTI LA-DRVs.

HIV Drug Resistance Mutations and Subtype Profiles among Pregnant Women of Ho Chi Minh City, South Vietnam.

According to the latest data released by UNAIDS, the global number of people living with HIV (PLHIV) in 2021 was 38.4 million, with 1.5 million new HIV infections. In different countries, a significant proportion of these cases occur in the adult fertile population aged 15-49 years. According to UNAIDS, Vietnam had a national HIV prevalence of 0.3% of the total population at the end of 2019, with approximately 230,000 PLHIV. The most effective way to prevent mother-to-child transmission of HIV is ART to reduce maternal viral load. HIV-infected pregnant women should undergo monthly monitoring, especially before the expected date of delivery. The aim of our work was to analyze subtypic structure and drug-resistant variants of HIV in pregnant women in Ho Chi Minh City. The study material was blood plasma samples from HIV-infected pregnant women: 31 women showed virological failure of ART, and 30 women had not previously received therapy. HIV-1 genotyping and mutation detection were performed based on analysis of the nucleotide sequences of the pol gene region. More than 98% of sequences genotyped as HIV-1 sub-subtype CRF01_AE. When assessing the occurrence of drug resistance mutations, genetic resistance to any drug was detected in 74.41% (95% CI: 62.71-85.54%) of patients. These included resistance mutations to protease inhibitors in 60.66% (95% CI: 47.31-72.93%) of patients, to NRTIs in 8.20% (95% CI: 2.72-18.10%), and to NNRTIs in 44.26% (95% CI: 31.55-57.52%). Mutations associated with NRTI (2) and NNRTI (8) resistance as well as PI mutations (12), including minor ones, were identified. The high prevalence of drug resistance mutations found in this study among pregnant women, both in therapeutically naive individuals and in patients with virological failure of ART, indicates that currently used regimens in Vietnam are insufficient to prevent vertical HIV infection.

HIV drug resistance in the era of contemporary antiretroviral therapy: A clinical perspective.

Contemporary antiretroviral therapy (ART) regimens have high barriers to the development of drug resistance. However, resistance to earlier antiretrovirals and uncommon cases of resistance to contemporary ART illustrate the continued need for good clinical management of HIV drug resistance. Here, we describe HIV drug-resistance mechanisms, the interaction of HIV drug-resistant mutations and the patterns of drug resistance to contemporary ART. We then provide guidance on the management of HIV drug resistance, including how to limit the development of resistance and manage virologic failure that is complicated by resistance. To complement this, links to resources and treatment guidelines are provided that can assist with the interpretation of HIV drug resistance test results and optimal ART selection in the clinic.

Resistance To Antiretroviral Therapy In People With HIV

Human Immunodeficiency Virus (HIV) is a virus that damages the immune system, and has RNA genetic material which is converted by the reverse transcriptase enzyme into DNA. This research aims to determine the existence of resistance by identifying mutations related to drug resistance in HIV-1, especially in the genes encoding the PR and RT enzymes which are the targets of ARVs. This research uses the observational method. Research data analysis was carried out in the form of descriptive data analysis of the output of each formula based on the results of HIV measurements. This study contains a series of reviews that focus on the topic and incidence and possibility of HIV drug resistance (ART) in PLHIV/PLWHA. The main and important thing in detecting the possibility of resistance to ARV therapy is by examining the genotype and phenotype. Standardization between laboratories for drug resistance studies through the use of various methods, especially to identify mixed bases that cause estimated resistance mutations. Additionally, sequencing of protease, RT, and/or integrase is used to identify the clinical significance of DRM. There are two genetic mechanisms of NRTI resistance, namely: (1) discriminative mutations that activate RT to differentiate between the dideoxy-NRTI chain terminator and the cell's own dNTP; and (2) unblocking mutations that facilitate phosphorylytic excision of NRTI-triphosphate from viral DNA. Blocking mutations are also referred to as thymidine analogue mutations (TAMs). ARV resistance can be detected by examining the virus genotype which aims to determine the occurrence of mutations in one of the virus codons compared to ARV-sensitive wild type HIV-1 and by in vitro phenotyping, where this method takes quite a long time and is usually focused on finding a regimen new drug

Dolutegravir resistance in sub-Saharan Africa: should resource-limited settings be concerned for future treatment?

In sub-Saharan Africa (SSA) the burden of non-nucleoside reverse transcriptase inhibitor (NNRTI) HIV drug resistance (HIVDR) has been high over the years. Therefore, in 2018 the World Health Organization (WHO) recommended a regimen based on a integrase strand transfer inhibitor (INSTI), dolutegravir, as the default first-line antiretroviral therapy (ART) in countries in SSA. The scale-up of DTG-based regimens in SSA has gained significant momentum since 2018 and has continued to expand across multiple countries in recent years. However, whether or not the DTG robustness experienced in the developed world will also be achieved in SSA settings is still an important question. Evidence generated from in vitro and in vivo studies suggests that the emergence of DTG HIVDR is HIV-1 subtype dependent. These findings demonstrate that the extensive HIV-1 diversity in SSA can influence DTG effectiveness and the emergence of drug resistance. In addition, the programmatic approach to the transition to DTG adopted by many countries in the SSA region potentially exposes individuals to DTG functional monotherapy, which is associated with the emergence of DTG resistance. In this mini review, we describe the current trends of the effectiveness of DTG as reflected by viral suppression and DTG resistance. Furthermore, we explore how HIV-1 diversity and the programmatic approach in SSA could shape DTG effectiveness and DTG HIVDR in the region.

Recommendations on data sharing in HIV drug resistance research.

• Human immunodeficiency virus (HIV) drug resistance has implications for antiretroviral treatment strategies and for containing the HIV pandemic because the development of HIV drug resistance leads to the requirement for antiretroviral drugs that may be less effective, less well-tolerated, and more expensive than those used in first-line regimens. • HIV drug resistance studies are designed to determine which HIV mutations are selected by antiretroviral drugs and, in turn, how these mutations affect antiretroviral drug susceptibility and response to future antiretroviral treatment regimens. • Such studies collectively form a vital knowledge base essential for monitoring global HIV drug resistance trends, interpreting HIV genotypic tests, and updating HIV treatment guidelines. • Although HIV drug resistance data are collected in many studies, such data are often not publicly shared, prompting the need to recommend best practices to encourage and standardize HIV drug resistance data sharing. • In contrast to other viruses, sharing HIV sequences from phylogenetic studies of transmission dynamics requires additional precautions as HIV transmission is criminalized in many countries and regions. • Our recommendations are designed to ensure that the data that contribute to HIV drug resistance knowledge will be available without undue hardship to those publishing HIV drug resistance studies and without risk to people living with HIV.

Tenofovir diphosphate in dried blood spots and HIV-1 resistance in South Africa

BackgroundSuboptimal antiretroviral (ART) adherence can lead to virologic failure with consequent HIV-1 resistance. Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is a powerful biomarker of cumulative adherence, predictive of future viremia. It has been associated with resistance in Persons With HIV (PWH) in South Africa and the US. We explored the relationship of TFV-DP concentrations with antiretroviral drug resistance at the time of treatment failure in SA.MethodsAdult PWH from health clinics in Cape Town, South Africa on efavirenz-based first-line ART containing tenofovir disoproxil fumarate (TDF) with an undetectable (< 50 copies/mL) HIV-1 viral load (VL) were prospectively enrolled in an observational cohort for 12 months. Monthly study visits included blood collection for HIV-1 VL and DBS for TFV-DP. The first confirmed viral breakthrough (VB) > 400 copies/mL triggered HIV-1 genotyping at the subsequent visit. An electronic adherence (EA) device monitored ART adherence in real-time, estimated as a percent for the 30-days prior to VB. Wilcoxon rank sum test was used to compare median [IQR] TFV-DP by genotype outcome.ResultsOf 250 individuals, (n = 195, 78% women), 21 experienced VB, with a median of 5 [4;7] months on study, and a median EA of 33.3 [13.3;53.3]%. Demographic characteristics between those with and without VB were similar. Median VL at VB was 4.0 [3.2;4.5] log copies/mL. TFV-DP concentrations trended down towards the VB visit. Median TFV-DP concentrations were significantly higher in those HIV-1 genotype did not amplify due to being virally suppressed at the subsequent visit (n = 10; 380 [227–661] fmol/punch, p = 0.035; EA 45 [24.9; 59.2]%); than in those who were successfully genotyped with evidence of drug resistance (n = 5, 241 [150–247] fmol/punch, EA 20 [6.7;36.7]%) and in individuals who did not have resistance (n = 3, 39.9 [16.6; 93.9] fmol/punch; EA 33.3 [16–38]%). Three genotype collections were not done. Only non-nucleoside reverse transcriptase inhibitor-associated mutations were identified on resistance testing. (K103N, E138K, Y118H).ConclusionTFV-DP in DBS showed a step-wise inverse relationship with VB and drug resistance, with evidence of low cumulative ART adherence in PWH who developed antiretroviral resistance. Monitoring TFV-DP concentrations could be a valuable tool for predicting future VB and future resistance.

Prevalence of viral load suppression and acquired drug resistance among people living with HIV in Nepal: a nationally representative surveillance study

This is the first nationally representative study to estimate the prevalence of viral load (VL) suppression and acquired HIV drug resistance (ADR) among people living with HIV (PLHIV) in Nepal. A cross-sectional study recruited 1418 PLHIV from 20 ART centres in Nepal, using a two-stage cluster design. Participants were eligible if they were HIV-positive individuals on ART for 9-15 months or at least 48 months. Plasma specimens were collected and tested for the quantification of HIV-1 RNA. Specimens with a VL ≥1000 copies/mL were further processed for sequencing of PR and RT genes of HIV-1. The sequences were then analysed to detect mutations causing HIV drug resistance. The prevalence of ADR was 3.7% (95% confidence interval [CI]: 1.8-7.6) and 3.0% (95% CI: 1.8-5.2) among PLHIV who received ART for 9-15 months and 48 months or more, respectively. The prevalence of VL suppression was 95.3% (95% CI: 91.7-97.4) among those on ART for 9-15 months, and 96.5% (95% CI: 94.7-97.7) among those on ART for at least 48 months. The prevalence of any detectable acquired resistance to antiretroviral drugs was 80.7% (95% CI: 58.6-92.5) among those on ART for 9-15 months with VL ≥1000 copies/mL and 81.6% (95% CI: 55.4-94.0) among those on ART for at least 48 months with VL ≥1000 copies/mL. This study suggests that improved accessibility to VL monitoring and timely assessment of drug resistance in routine HIV programs are crucial in Nepal to ensure access to HIV treatment for all in need.

Emergent HIV drug resistance in non-inferiority trials

Emergent HIV drug resistance in non-inferiority trials

Preliminary report of transmitted drug resistance to integrase strand chain transfer inhibitors in treatment-naïve HIV infected patients

Transmitted Resistance exists in a newly diagnosed person who has not yet started their treatment. Our objective was to obtain a profile of HIV-1 resistance to integrase inhibitors in newly diagnosed treatment-naïve patients. Fifty people newly diagnosed with HIV-1 infection who had never received antiretroviral treatment were recruited. The complete integrase gene was amplified by nested RTPCR and the sequences obtained were analyzed with the ReCall and HIVdb v9.0. The overall prevalence transmitted due to mutations with some impact on integrase strand transfer inhibitors (INSTI) activity during the study period was 8%. The major E138K mutation was detected in only 1 patient and the secondary G163R mutation was detected in the other 3. The transmitted resistance for the first generation INSTI was 8% and for the second generation it was 0%. In Chile the resistance transmitted to INSTI is low and it is in according values detect in other part of the world.

Low Prevalence of Pre-Treatment and Acquired Drug Resistance to Dolutegravir among Treatment Naïve Individuals Initiating on Tenofovir, Lamivudine and Dolutegravir in Zimbabwe.

Dolutegravir (DTG) use in combination with tenofovir and lamivudine (TLD) is scaling up in Africa. However, HIV drug resistance (HIVDR) data to DTG remain scarce in Zimbabwe. We assessed the prevalence and genetic mechanisms of DTG resistance in people living with HIV initiating on TLD. A prospective cohort study was conducted between October 2021 and April 2023 among antiretroviral therapy (ART) naïve adults (≥18 years) attending care at an HIV clinic in Zimbabwe. Pre-treatment drug resistance (PDR) was assessed prior to TLD initiation and viral load (VL) outcome and acquired drug resistance (ADR) to TLD were described after 24 weeks follow-up. In total, 172 participants were enrolled in the study. The median (IQR) age and log10 VL were 39 (29-48) years and 5.41 (4.80-5.74) copies/mL, respectively. At baseline, no PDR to DTG was found. However, as previously reported, PDR to non-nucleotide reverse transcriptase inhibitor (NNRTI) was high (15%) whilst PDR to NRTI was low (4%). After a median duration of 27 (25-30) weeks on TLD, virological suppression (VL < 1000 copies/mL) was 98% and among the 2 participants with VL ≥ 1000 copies/mL, no ADR was found. HIVDR to DTG is rare among ART naïve individuals. DTG is more likely to address the problems of HIVDR in Africa.