Search Results (106)

Objective: To characterize the profiles of resistance mutations to HIV reverse transcriptase inhibitors in Gabon. Design: Cross-sectional study conducted over 37 months, from October 2019 to October 2022, at the IST/HIV/AIDS Reference Laboratory, a reference center for the biological monitoring of people living with the human immunodeficiency virus (PWHIV) in Gabon. Methods: Plasma from 666 PWHIV receiving antiretroviral treatment was collected, followed by RNA extraction, amplification, and reverse transcriptase gene sequencing. Statistical analyses were performed using Stata^® 14.0 software (USA). Results: Six hundred and sixty-six (666) PWHIV plasma collected from 252 male and 414 female patients were analyzed and 1654 mutations were detected in 388 patients, including 849 (51.3%) associated with nucleoside reverse transcriptase inhibitors (NRTIs) and 805 (48.7%) with non-nucleoside reverse transcriptase inhibitors (NNRTIs). Three of the most prescribed treatment regimens were associated to the appearance of both NRTIs and NNRTIs resistance mutations: TDF + 3TC + EFV (24.02%; 160/666); TDF + FTC + EFV) (17.2%; 114/666) and AZT + 3TC + EFV (14.6%; 97/666). Additionally, stage 3 of CD4 T-lymphocyte deficiency, the higher viral load, and treatment duration are risk factors influencing the appearance of virus mutations. Also, treatment containing TDF-3TC + DTG is more protective against mutations. Conclusions: Drug resistance mutations are common in Gabon and compromise the efficacy of ART. Further study must search for other causes of therapeutic failure in Gabon in PWHIV. Full article

Pregnancy introduces significant physiological changes that alter the pharmacokinetics (PK) of antiretroviral therapy (ART), impacting its safety and efficacy in HIV-positive women. Optimizing ART during pregnancy is critical to maintaining maternal virological suppression and preventing mother-to-child transmission (MTCT) of HIV. This review evaluates the impact of pregnancy-induced PK changes on ART and proposes strategies for tailored regimens to improve outcomes. A comprehensive review of published literature was conducted, focusing on PK adaptations during pregnancy and their implications for different ART classes, including protease inhibitors (PIs), integrase strand transfer inhibitors (INSTIs), and nucleoside reverse transcriptase inhibitors (NRTIs). Key studies were analyzed to assess drug exposure, efficacy, and safety. Pregnancy significantly alters the PK of antiretrovirals, with increased hepatic metabolism, renal clearance, and changes in plasma protein binding leading to reduced drug exposure. For example, drugs like lopinavir and atazanavir require dose adjustments, while dolutegravir maintains efficacy despite reduced plasma levels. Integrase inhibitors demonstrate favorable virological suppression, although cobicistat-boosted regimens show subtherapeutic levels. Tailored approaches, such as therapeutic drug monitoring (TDM), optimize ART efficacy while minimizing toxicity. Pregnancy-specific PK changes necessitate evidence-based ART adjustments to ensure virological suppression and reduce MTCT risk. Incorporating TDM, leveraging pharmacogenomic insights, and prioritizing maternal and neonatal safety are critical for personalized ART management. Further research into long-acting formulations and global guideline harmonization is needed to address disparities in care and improve outcomes for HIV-positive pregnant women. Full article

Background: Argentina has reported moderate to high levels of transmitted drug resistance in people living with HIV/AIDS (PLWHA), mostly to non-nucleoside reverse transcriptase inhibitors (NNRTIs). Doravirine (DOR) has a unique resistance profile and retains potent antiviral activity in the presence of the most prevalent NNRTI-associated resistant viruses. Scarce data exist regarding the frequency of DOR resistance-associated mutations (RAMs) in Latin America. We describe the prevalence of DOR RAMs in samples from adults PLWHA in Buenos Aires, Argentina, in the context of a survey of transmitted drug resistance (TDR). Material and Methods: A cross-sectional study was undertaken utilizing samples collected between 2017 and 2021 at two reference HIV clinics. Samples were analyzed for RAMs using the World Health Organization (WHO) mutation list. Mutations to DOR were assessed with the Stanford and Agence Nationale de Recherches sur le SIDA (ANRS) algorithms. Rilpivirine (RPV) RAMs were assessed using the Stanford algorithm. Susceptibility to NNRTIs was evaluated using the HIVdb Program with Stanford and ANRS criteria. Results: Samples from 1667 PLWHA were analyzed: 81.2% were male, with 52.6% identifying as men who have sex with men. According to the WHO list, the overall TDR was 12.1% (n = 203). The prevalence of RAMs was 10.1% (170/1667) for NNRTIs, 4% (67/1667) for nucleoside reverse-transcriptase inhibitors (NRTIs), and 1.7% (30/1667) for protease inhibitors (PIs). The most frequent NNRTI mutations were K103N (5.6%), G190A (0.89%), and K103S (0.77%). The prevalence of DOR RAMs was <2%, with the most common being Y188L (0.53%). Rilpivirine RAM prevalence was 6%. Susceptibility to DOR, RPV, efavirenz, and nevirapine as given by the Stanford algorithm was 97.4%, 92%, 91.4%, and 90.4%, respectively. The ANRS criteria yielded susceptibility rates of 98.3%, 93.3%, 92.3%, and 90.8%, respectively. Regarding NRTIs, thymidine analog mutations (including T215 revertants) were the most frequent RAMs. Among PIs, the most prevalent RAMs were M46L (0.47%) and V82A (0.35%). Conclusions: Our study shows the persistence of moderate to high levels of resistance to first-generation NNRTIs. Despite this, prevalence was low for DOR. Surveillance of TDR remains critical for recommendations of ART initiation. Full article

Background: Vietnam has made significant strides in reducing the prevalence of HIV infection and achievements in its antiretroviral treatment program. However, the COVID-19 pandemic and financial challenges in the healthcare system have posed significant obstacles to maintaining effective HIV treatment and monitoring, particularly among vulnerable populations. This study aims to evaluate the situation of HIV drug resistance among patients who have experienced treatment failure in the Mekong Delta region and to compare data from 2019 to 2022. Methods: The study material was blood plasma samples from HIV-infected individuals with ART failure: 316 collected in 2019 and 326 collected in 2022. HIV-1 genotyping and mutation detection were performed based on an analysis of the nucleotide sequences of the Pol gene region. A total of 116 HIV-infected individuals with virological failure in 2019 and 2022 were assessed for HIV drug resistance. Results: The study revealed a high proportion of participants with viral loads exceeding 1000 copies/mL, significantly increasing from 12.0% in 2019 to 23.9% in 2022 (OR = 2.3; p = 0.0001). HIV drug resistance mutations were detected in 84.21% of cases in 2019 and 92.59% in 2022. The prevalence of concurrent resistance to NRTIs and NNRTIs was 37.5% and 30.13% in 2019 and 2022, respectively. There was a statistically significant decrease in NNRTI resistance (OR = 0.32, χ² = 5.43, p < 0.05). In contrast, multi-drug resistance to protease inhibitors rose from 18.52% to 45.21% (φ* = 0.00403, p < 0.05). Triple-class resistance was identified only in 2022 (17.81%). The most common mutations included M184I/V, D67N, K103N, Y181C, and V82A/S/T, with D67N rising significantly from 3.13% to 21.92%. The predominant subtype was CRF01_AE. Conclusion: A high prevalence of viral non-suppression and HIV drug resistance was observed among patients in the Mekong Delta region, particularly after the onset of the COVID-19 pandemic. Our study highlights the ongoing challenges that the HIV/AIDS treatment program in Vietnam must address in the post-pandemic period to sustain its success and achieve the goals of the country’s HIV prevention strategies. Full article

Nucleoside reverse transcriptase inhibitors (NRTIs) and platinum-based chemotherapeutics are widely utilized in cancer treatment. Evidence suggests that drug plasma concentrations are closely linked to both therapeutic efficacy and the risk of adverse effects. Consequently, developing therapeutic drug monitoring (TDM) methods is essential. Here, an effective procedure utilizing QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) techniques for preparing samples and UPLC-MS/MS for simultaneously measuring eight NRTIs and platinum-based drugs in human plasma is described. Chromatographic separation was conducted with an Agilent Eclipse Plus C18 column (4.6 × 100 mm, 3.5 μm) with acetonitrile with 0.1% formic acid as Phase A and 0.1% formic acid in water as Phase B, achieving complete separation within 10 min. The target analytes—lamivudine, telbivudine, emtricitabine, entecavir, tenofovir, nedaplatin, oxaliplatin, and adefovir dipivoxil—exhibited strong linearity within the 10–1000 ng/mL and 1–100 ng/mL ranges, showing correlations (r²) ≥ 0.9962. The method demonstrated excellent accuracy (−6.72% to 7.82%) and selectivity (84.53%–110.49%), as well as satisfactory recovery and stability. Overall, this analytical approach can be used to detect the combination of eight NRTIs and platinum-based drugs in human plasma. This method enables plasma drug-level monitoring in real time, with applications for individualized treatment approaches. Full article

By 2022, Bulgaria’s National Reference Laboratory had confirmed 4024 HIV cases. We analyzed 132 pol gene sequences to characterize the molecular epidemiology of HIV-1 subtypes A1, A6, and A7 (2001–2022). A1 accounted for 50.0% (66/132) of cases, increasing after 2014, with peaks in 2019 and 2022. A6 comprised 48.5% (64/132), dominating from 2005 to 2014 before stabilizing. A7 was rare (1.5%, 2/132), detected in 2003 and 2011. Transmission patterns varied: A1 was linked to men who have sex with men (MSM) (62.1%), while A6 was primarily heterosexual (HET) (82.8%) with a balanced gender distribution (56.3% male, 43.8% female). Resistance mutations were identified in 29.6% of cases, with A6 showing higher rates of nucleoside reverse transcriptase inhibitor (NRTI) (20.3%) and non-nucleoside reverse transcriptase inhibitor (NNRTI) (7.8%) resistance than A1. Phylogenetic analysis revealed that 13 Bulgarian sequences (9.8%) were involved in transmission clusters, including 10 (7.6%) from sub-subtype A1 and 3 (2.3%) from sub-subtype A6, highlighting distinct genetic diversity and transmission patterns. Despite significant migration from Ukraine in 2022, A6 prevalence remained unchanged, suggesting localized transmission dynamics. These findings highlight a shifting HIV-1 sub-subtype distribution in Bulgaria and emphasize the need for targeted prevention, diagnosis, and treatment strategies tailored to the evolving molecular landscape. Full article

HIV-1 genotyping and drug resistance tests are routinely performed in virology laboratories in some countries, aiding clinical management. In Istanbul, between January 2021 and March 2024, plasma samples from 1029 HIV-1-infected patients were analyzed using the NGS method, and mutation and drug resistance results were retrospectively evaluated alongside demographic data. Subtype B (54.4%) was most frequent in Turkish patients, while Subtype A1 (43.5%) was predominant among foreign nationals. The most common CRFs were CRF02_AG (3.8%) and CRF56_cpx (1.6%). According to the change in detection rates during the study period, Subtype B decreased, and Subtype A increased. The most frequent mutations detected were A62V (38.7%) and M184V (22.4%) for NRTIs; E138A (55.5%) and E138G (11.5%) for NNRTIs; M46I (33.3%) and M46L (25%) for PIs; and E92Q and G for INIs (total rate: 35.2%). Darunavir/ritonavir had the highest sensitivity rate, while resistance rates for NNRTIs and INIs increased over time. We anticipate that this study, in which we evaluate the routine use of an FDA-approved NGS kit alongside integrated bioinformatics data analysis and automated reporting software for the first time in Türkiye, will contribute to both national and international molecular epidemiological data and public health strategies by providing reliable results that align with international standarts. Full article

Acute HIV-1 infection (AHI) is a transient period where the virus causes evident damage to the immune system, including an extensive apoptosis of CD4+ T cells associated with a high level of activation and a major cytokine storm to fight the invading virus. HIV infection establishes persistence by integrating the viral genome into host cell DNA in both replicating and non-replicating forms, effectively hiding from immune surveillance within infected lymphocytes as cellular reservoirs. The measurement of total HIV-1 DNA in peripheral blood mononuclear cells (PBMCs) is a reliable reflection of this reservoir. Initiating treatments during AHI with nucleoside reverse transcriptase inhibitors (NRTIs) and/or integrase strand transfer inhibitors (INSTIs) is essential to alter the dynamics of the global reservoir expansion, and to reduce the establishment of long-lived cellular and tissue reservoirs, while preserving and enhancing specific and non-specific immune responses. Furthermore, some of the patients treated at the AHI stage may become post-treatment controllers and should be informative regarding the mechanism of viral control, so patients treated during AHI are undoubtedly the best candidates to test innovative remission strategies toward a functional cure that could play a pivotal role in long-term HIV control. AHI is characterized by high levels of viral replication, with a significant increase in the risk of HIV transmission. Detecting AHI and initiating early treatment following diagnosis provides a window of opportunity to control the epidemic, particularly in high-risk populations. Full article

HIV drug resistance (HIVDR) presents a significant challenge to antiretroviral therapy (ART) success, particularly in resource-limited settings like Ethiopia. This cross-sectional study investigated viral suppression rates and resistance patterns among patients on second-line ART across 28 Ethiopian health facilities. Blood samples collected from 586 participants were analyzed to measure CD4 count and viral load and assess HIVDR in patients experiencing virological failure (VF) (viral load ≥ 1000 copies/mL). Demographic and clinical data were analyzed using logistic regression to identify factors associated with VF. Results showed that 13.82% of participants experienced VF, with 67.57% of genotyped samples exhibiting at least one drug resistance mutation. Resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs) was detected in 48.64%, 64.86%, and 18.92% of cases, respectively. Dual-class resistance was identified in 48.64% of patients, while triple-class resistance was detected in 18.92%. VF was more likely among students and those with CD4 counts below 200 cells/mm³, but less likely in patients on second-line treatment for 12 months or more. Our findings highlight a substantial HIVDR burden among patients on second-line ART with VF, emphasizing the need for comprehensive HIV care, including adherence support, regular viral load monitoring, and HIVDR testing. Full article

Islatravir (ISL) is a novel antiretroviral that inhibits HIV-1 reverse transcriptase translocation. The M184V mutation, known to reduce ISL’s viral susceptibility in vitro, could arise from prolonged exposure to nucleoside reverse transcriptase inhibitors (NRTI) (3TC). This study evaluated the predictive efficacy of ISL and identified potentially active antiretrovirals in combination among treatment-experienced patients in Cameroon, where NRTIs (3TC) have been the backbone of ART for decades now. Although ISL is a long-acting antiretroviral, it will provide other therapeutic options in combination with other reverse transcriptase inhibitors that remain effective. We analyzed 1170 HIV-1 sequences from patients failing first-, second-, and third-line ART using the CIRCB Antiviral Resistance Evaluation (CIRCB-CARE) database. Drug resistance mutations (DRMs) were interpreted using Stanford HIVdb.v9, and covariation patterns between M184V and major NRTI/NNRTI DRMs were assessed. The study population, with a median age of 40 years, showed a high prevalence of resistance to NRTIs (77.4%) and NNRTIs (49.2%). The most frequent NRTI DRMs were M184V/I (83.3%), M41L (25.0%), and T215FY (36.8%), while common NNRTI DRMs included K103NS (53.3%), Y181CIV (27.7%), and G190ASE (22.2%). In first-line ART failure, M184V significantly covaried with K70R, L74I, and M41L for NRTIs and K103N and G190A for NNRTIs. In second-line failure, the covariation with M184V extended to T215Y, M41L, and D67N for NRTIs and G190A, K103N, and K103S for NNRTIs. No significant covariation with M184V was observed in third-line treatment failures. Based on these covariations and on the effect of these mutations on available anti-HIV drugs, TDF (partial efficacy) and Doravirine (fully active) were identified as potentially suitable candidates in combination with ISL among patients failing the first, second, and third lines, and could serve as a valuable therapeutic option in LMICs facing similar treatment challenges. Full article

The high genetic variability of HIV-1 and the emergence of transmitted drug resistance (TDR) can impact treatment efficacy. In this study, we investigated the prevalent HIV-1 genotypes and drug-resistance-associated mutations in drug-naïve HIV-1 individuals in Cabo Verde. The study, conducted between 2018 and 2019, included drug-naïve HIV-1 individuals from the São Vicente, Boa Vista, Fogo, and Santiago islands. The HIV-1 pol gene was sequenced using Sanger sequencing. TDR was identified using the Stanford Calibrated Population Resistance tool, and resistance levels to different drugs were interpreted with the Stanford HIV database. The genetic diversity of HIV-1 was determined through phylogenetic analysis, and epidemiological and behavioural data were collected via questionnaires. Of the 73 participants, the majority were male (52.1%). The CRF02_AG recombinant form predominated (41.1%), followed by subtype G (37.0%). The overall prevalence of TDR was 9.6%. Nucleoside Reverse Transcriptase Inhibitor (NRTI) mutations occurred in 2.7% of individuals, while Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) mutations occurred in 9.6%. The most prevalent mutations were K103N (5.5%) and M184V (2.7%). No protease- or integrase-associated mutations were found. The high levels of resistance to NNRTIs found demonstrate the need for surveillance of resistance mutations to ensure the efficacy and durability of the current therapeutic regimen, which includes Dolutegravir. Full article

Nucleoside reverse transcriptase inhibitors (NRTIs) are the backbone of highly active antiretroviral therapy (HAART)—the current standard of care for treating human immunodeficiency virus (HIV) infection. Despite their efficacy, NRTIs cause numerous treatment-limiting adverse effects, including a distinct peripheral neuropathy, called antiretroviral toxic neuropathy (ATN). ATN primarily affects the extremities with shock-like tingling pain, a pins-and-needles prickling sensation, and numbness. Despite its negative impact on patient quality of life, ATN remains poorly understood, which limits treatment options and potential interventions for people living with HIV (PLWH). Elucidating the underlying pathophysiology of NRTI-induced ATN will facilitate the development of effective treatment strategies and improved patient outcomes. In this article, we will comprehensively review ATN in the setting of NRTI treatment for HIV infection. Full article

Islatravir (ISL) is the first-in-class nucleoside reverse transcriptase translocation inhibitor (NRTtI) with novel modes of action. Data on ISL resistance are currently limited, particularly to HIV-1 non-B subtypes. This study aimed to assess prevalent nucleos(t)ide reverse transcriptase inhibitor (NRTI)-resistant mutations in HIV-1 subtype C for their phenotypic resistance to ISL. Prevalent single and combinations of NRTI-resistant mutations were selected from a routine HIV-1 genotypic drug resistance testing database and introduced into HIV-1 subtype C-like pseudoviruses, which were then tested for ISL susceptibility. Single NRTI-resistant mutations were susceptible or showed only a low level of resistance to ISL. This included thymidine analogue mutations (TAMs, i.e., M41L, D67N, K70R, T215FY, and K219EQ) and non-TAMs (i.e., A62V, K65R, K70ET, L74IV, A114S, Y115F, and M184V). Combinations of M184V with one or more additional NRTI-resistant mutations generally displayed reduced ISL susceptibilities. This was more prominent for combinations that included M184V+TAMs, and particularly M184V+TAM-2 mutations. Combinations that included M184V+K65R did not impact significantly on ISL susceptibility. Our study suggests that ISL would be effective in treating people living with HIV (PLWH) failing tenofovir disoproxil fumarate (TDF)/lamivudine (3TC) or TDF/emtricitabine (FTC)-containing regimens, but would be less effective in PLH failing zidovudine (AZT) with 3TC or FTC-containing regimens. Full article

This systematic review assessed the prevalence of transmitted and acquired HIV drug resistance (HIVDR) and the associated risk factors in Mozambique. A search of the PubMed, Cochrane, B-On, and Scopus databases up to December 2023 was conducted and included 11 studies with 1118 HIV-1 pol sequences. Drug resistance mutations (DRMs) to NNRTIs were found in 13% of the drug-naive individuals and 31% of those on ART, while NRTI resistance occurred in 5% and 10%, respectively. Dual-class resistance (NNRTI + NRTI) was detected in 2% of the drug-naive and 8% of ART-experienced individuals. DRMs to protease inhibitors (PIs) were found in 2% of the drug-naive and 5% of ART-experienced individuals. The rate of DRMs was significantly higher in Beira than in Maputo, as well as in pediatric patients than in adults and pregnant women. Subtype C predominated (94%) and was associated with lower viral loads and DRM rates as compared to the other subtypes. The high prevalence of DRMs, particularly to NNRTIs and NRTIs, highlights the need for ongoing surveillance and targeted interventions. These findings are critical for optimizing ART regimens and informing public health strategies in Mozambique, with particular attention to regions such as Beira and vulnerable populations such as pediatric patients. Full article

Next-generation sequencing (NGS) for HIV drug resistance (DR) testing has an increasing number of applications for the detection of low-abundance drug-resistant variants (LA-DRVs) in regard to its features as a quasi-species. However, there is less information on its detection performance in DR detection with NGS. To determine the feasibility of using NGS technology in LA-DRV detection for HIV-1 pretreatment drug resistance, 80 HIV-infected individuals who had never undergone antiretroviral therapy were subjected to both NGS and Sanger sequencing (SS) in HIV-1 drug resistance testing. The results reported in this study show that NGS exhibits higher sensitivity for drug resistance identification than SS at a 5% detection threshold. NGS showed a better consistency compared with that of SS for both protease inhibitors (PIs) and integrase inhibitors (INSTIs), with a figure amounting to more than 90%, but worse consistency in nucleotide reverse transcriptase inhibitors (NRTIs), with a consistency ranging from only 61.25% to 87.50%. The consistency of non-nucleotide reverse transcriptase inhibitors (NNRTIs) between NGS and SS was around 85%. NGS showed the highest sensitivity of 87.0% at a 5% threshold. The application of NGS technology in HIV-1 genotype resistance detection in different populations infected with HIV requires further documentation and validation. Full article