Search Results (294)

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

Human Immunodeficiency Virus (HIV) infection remains a major global health issue, with effective antiretroviral therapy (ART) extending life expectancy but also increasing age-related issues like osteopenia and osteoporosis. This cross-sectional study examines bone mineral density (BMD) and related risk factors in Romanian HIV-positive patients, emphasizing regional and therapy influences. The patients varying in HIV infection duration underwent DXA scanning to measure BMD in the lumbar spine, femoral neck, and total femur. A high prevalence of low BMD, especially in the lumbar spine, was identified along with significant associations between reduced BMD and factors such as smoking, alcohol use, vitamin D deficiency and serum phosphorus levels. ART like Protease Inhibitors and Nucleoside Reverse Transcriptase Inhibitors were linked to increased bone loss, emphasizing the multifactorial nature of osteoporosis in HIV-infected individuals and underscore the importance of regular BMD assessments, lifestyle adjustments, and careful management of antiretroviral therapy to minimize fracture risk and enhance overall health and quality of life. Full article

The HIV-1 aspartic protease is an effective target for the treatment of HIV/AIDS. Current therapy utilizes a selection of nine protease inhibitors (PIs) in combination with other classes of antiretroviral drugs. Although PIs were originally developed based on the knowledge of the HIV-1 subtype B protease, the existence of other HIV-1 subtypes and the effects of drug resistance on currently available PIs have become a major challenge in the treatment of HIV/AIDS. Specifically, the HIV-1 subtype C accounts for more than half of the global HIV infections. Considering the importance and relevance of the subtype C virus, in this timely review we discuss the effect of polymorphisms in the HIV-1 subtype C protease on drug resistance, flap flexibility, and hinge region dynamics. We discuss novel paradigms of protease inhibition that attempt to overcome the limitations of currently available inhibitors which fall short considering genetic diversity and resistance mutations. 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

Treatment for HIV infection has become more manageable due to advances in combination antiretroviral therapy (cART). However, HIV still significantly affects the central nervous system (CNS) in infected individuals, even with effective plasma viral suppression, due to persistent viral reservoirs and chronic neuroinflammation. This ongoing inflammation contributes to the development of HIV-associated neurocognitive disorders (HANDs), including dementia and Alzheimer’s disease-like pathology. These complications are particularly prevalent among the aging population with HIV. This review aims to provide a comprehensive overview of HAND, with a focus on the contribution of oxidative stress induced by HIV-mediated reactive oxygen species (ROS) production through viral proteins such as gp120, Tat, Nef, Vpr, and reverse transcriptase. In addition, we discuss current and emerging therapeutic interventions targeting HAND, including antioxidant strategies and poly (ADP-ribose) polymerase (PARP) inhibitors. These are potential adjunctive approaches to mitigate neuroinflammation and oxidative damage in the CNS. Full article

The advent of effective antiretroviral therapy in the mid-1990s, which successfully prevented the progression to AIDS in people living with HIV (PLWH), was associated with the appearance of the so-called HIV-associated lipodystrophy. This condition involved subcutaneous fat atrophy; abdominal fat hypertrophy; and, in some cases, lipomatosis. It was also associated with systemic metabolic disturbances, primarily insulin resistance and dyslipidemia. Following the replacement of certain antiretroviral drugs, particularly the thymidine-analog reverse transcriptase inhibitors stavudine and zidovudine, with less toxic alternatives, the incidences of lipoatrophy and lipomatosis significantly declined. However, lipodystrophy resulting from first-generation antiretroviral therapy does not always resolve after switching to newer agents. Although the widespread use of modern antiretroviral drugs—especially integrase strand transfer inhibitors and non-lipoatrophic reverse transcriptase inhibitors such as tenofovir alafenamide—has reduced the incidences of severe forms of lipodystrophy, these regimens are not entirely free of adipose tissue-related effects. Notably, they are associated with weight gain that resembles common obesity and can have adverse cardiometabolic consequences. Recent evidence also suggests the hypertrophy of specific fat depots, such as epicardial and perivascular adipose tissue, in PLWH on last-generation treatments, potentially contributing to increased cardiovascular risk. This evolving landscape underscores the persistent vulnerability of PLWH to adipose tissue alterations. While these morphological changes may not be as pronounced as those seen in classic HIV-associated lipodystrophy, they can still pose significant health risks. The continued optimization of treatment regimens and the vigilant monitoring of adipose tissue alterations and metabolic status remain essential strategies to improve the health of PLWH. Full article

Acquired immunodeficiency syndrome (AIDS) is a chronic disease condition caused by the human immunodeficiency virus (HIV). The widespread availability of highly active antiretroviral therapies has helped to control HIV. There are ten FDA-approved protease inhibitors (PIs) that are used as part of antiretroviral therapies in HIV treatment. Importantly, all these drugs are designed and developed against the protease (PR) from HIV subtype B. On the other hand, HIV-1 PR subtype C, which is the most dominant strain in countries including South Africa and India, has shown resistance to PIs due to its genetic diversity and varied mutations. The emergence of resistance is concerning because the virus continues to replicate despite treatment; hence, it is necessary to develop drugs specifically against subtype C. This review focuses on the origin, genetic diversity, and mutations associated with HIV-1 PR subtype C. Furthermore, computational studies performed on HIV-1 PR subtype C and mutations associated with its resistance to PIs are highlighted. Moreover, potential research gaps and future directions in the study of HIV-1 PR subtype C are discussed. Full article

Background/Objectives: This study aimed to explore how HTLV-2 infection affects the production of broadly neutralizing antibodies (bNAbs) in persons with HIV-1 (PWH) and to assess the impact of boosted protease inhibitors (PIs). Methods: We evaluated broadly neutralizing antibody (bNAb) activity in 65 PWH, which included 27 who were also co-infected with HTLV-2. All participants were former injection drug users with HCV antibodies and were receiving suppressive antiretroviral therapy (ART). Neutralizing activity was assessed against six recombinant HIV-1 viruses that represent five different subtypes. B cell subsets were also analyzed. Results: HTLV-2 co-infection and the lack of ritonavir-boosted protease inhibitors (r-PIs) were both independently associated with higher neutralization scores (p = 0.017 and p = 0.005, respectively). Among those not on r-PIs, individuals co-infected with HTLV-2 showed significantly higher neutralization scores (p = 0.027) and a broader neutralization breadth (83.4% vs. 48.5%, p = 0.015) compared to those infected only with HIV-1. Additionally, HTLV-2 co-infected individuals had more resting memory B cells (p = 0.001) and fewer activated memory B cells (p = 0.017) than the HIV-1 mono-infected individuals. In our multivariate analysis, only HTLV-2 co-infection remained independently associated with neutralization scores (p = 0.027). Elite neutralizers (with a breadth score of ≥10) had more naive B cells and fewer resting memory B cells compared to those with weaker neutralization in both groups. Conclusions: Co-infection with HTLV-2 enhances bNAb production in PWH on suppressive ART and, in particular, in the absence of r-PI regimens. The prominent neutralizing activity corresponded with B cell subset distributions. The results suggest the complexity regarding the interaction between viral co-infections, antiretroviral regimens, and humoral immune compartments and may inform further H1V-1 pathogenesis inquiries or the appropriate design of a vaccine. Full article

In this study, we investigated the proportion of transmitted drug resistance (TDR) mutations and human immunodeficiency virus (HIV)-1 subtypes among 487 antiretroviral therapy (ART)-naïve individuals in South Korea from 2021 to 2024 to inform more effective treatment strategies. Consistent with previous reports, subtype B was most prevalent among HIV-1 subtypes at 50.7%; however, its proportion decreased annually (p = 0.047). Various subtypes of circulating recombinant forms (CRFs) were analyzed in this study, resulting in high genetic diversity. The subtype distributions of Korean and non-Korean patients differed, with subtype B (53.7%) and CRF01_AE (34.4%) being dominant in the former and latter, respectively. TDR across antiretroviral drug classes was approximately 3.5% in South Korea. Non-nucleoside reverse transcriptase inhibitors elicited the greatest drug resistance, which increased from 2021 to 2023, with a slight decrease in 2024. The integrase strand transfer inhibitor drugs, elvitegravir and raltegravir, most frequently exhibited high resistance scores. We provide a comprehensive overview of the HIV-1 genetic distribution and TDR patterns in South Korea from 2021 to 2024. Within the broader context of HIV-1 epidemiology in Asia and the Pacific, the findings contribute to a comprehensive understanding of the global distribution of HIV-1 resistance and genotypes, enabling the development of effective interventions. Full article

Dolutegravir-based antiretroviral therapy (ART) simplification is increasingly common, although some patients cannot take this drug due to intolerance or drug resistance. Boosted-protease inhibitors (bPI) might be an option in this scenario. Nevertheless, long-term outcomes have not been studied yet. A controlled cohort study comparing 5-year outcomes of ART simplification bPI-based regimens (without integrase strand transfer inhibitor—INSTI) versus ART maintenance was conducted in a Brazilian referral center. Viral suppression rates and mortality after 5 years were the primary outcomes of the study. Eighty individuals were included in each group; 47.5% were women, and the mean age was 56 years. The five-year survival rate was 88.8% in the simplified group and 87.5% in the maintenance arm (log-rank = 0.41). Viral suppression rate was 78.8% and 70.0%, respectively (p = 0.28). Individuals presented less renal function decline (−5 vs. −10 mL/min/1.73 m²; p < 0.05) in the simplified arm. No difference was observed in metabolic parameters. Based on our findings, ART simplification without INSTI has shown efficacy and safety comparable to maintenance of triple therapy even in the long term, and could be an option in these situations, which might be even more important in settings with limited options. 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

A treatment-experienced, highly adherent person living with HIV for over 25 years developed resistance mutations against all four major ART classes, including bictegravir (BIC). This led to viral failure on a quadruple regimen including BIC and doravirine (DOR). Resistance emergence was associated with M184V, thymidine analog mutations (TAMs), NNRTI mutations (108I, 234I, 318F), and INSTI mutations (T97A, G140S, Q148H, G149A), likely driven by suboptimal BIC levels due to divalent cation interactions. During a two-month ART interruption, the resistant virus was rapidly replaced by an ancient wild-type strain. Despite resistance to all four ART classes, a genotype-adapted salvage regimen, including fostemsavir, achieved viral suppression within seven months. Full article

The emergence of HIV strains resistant to the current anti-retroviral drugs has necessitated the search for new anti-retroviral medications. Methanolic and aqueous T. ferdinandiana fruit extracts have potent inhibitory activity against several phases of the HIV-1 replicative cycle. Cell infectivity studies using a non-resistant HIV-1 pseudovirus demonstrated that the methanolic (IC₅₀ 16 µg/mL) and aqueous extracts (IC₅₀ 19 µg/mL) were potent inhibitors of viral infection in a non-replicating HIV-1 assay. Both extracts also inhibited HIV-1 reverse transcriptase (IC₅₀ values of 35 and 33 µg/mL for methanolic and aqueous extracts, respectively) and HIV-1 protease (IC₅₀ values of 19 and 27 µg/mL, respectively) in recombinant enzyme assays. Given their inhibitory activities against multiple phases of HIV-1 replication, T. ferdinandiana fruit extracts may be particularly useful as HIV-1 therapeutics. Furthermore, both extracts displayed good safety profiles and therapeutic indices, indicating their suitability for therapeutic usage. LC-MS metabolomic profiling analysis of the methanolic extract identified several interesting constituents, including a relative abundance of tannins, as well as several flavonoids and stilbenes. All of these compounds have previously been reported to have bioactivities consistent with the anti-HIV-1 activities reported herein. Based on these studies, methanolic and aqueous T. ferdinandiana fruit extracts are promising potential therapies for the prevention, treatment and management of HIV-1. Full article

The scale-up of antiretroviral therapy (ART) has markedly increased pretreatment drug resistance (PDR) among newly diagnosed HIV-infected individuals. This study aims to assess the prevalence and characteristics of PDR, infer the genetic transmission network, and evaluate the effect of PDR on ART in Nanning City, Guangxi. Methods: This study was conducted in the Fourth People’s Hospital of Nanning from 2019 to 2023. PDR was estimated using the Stanford algorithm. Genetic transmission networks were inferred by HIV-TRACE and visualized with Cytoscape. Logistic regression identified PDR-related factors. The Cox proportional hazards model assessed the impact of drug resistance on virological and immunological failure. Among 234 participants, the prevalence of PDR was 8.97%. CRF07_BC (35.9%), CRF-01AE (27.35%), and CRF08_BC (23.9%) were the top three HIV-1 strains. Resistance to non-nucleoside reverse-transcriptase inhibitors, protease inhibitors, nucleoside reverse-transcriptase inhibitors, and integrase strand-transfer inhibitors was 4.27%, 2.56%, 1.28%, and 0.43%, respectively. Overall, 21.37% of the participants exhibited drug resistance mutations (DRMs). Homosexuals were less likely to have PDR compared to heterosexuals ([aOR] 0.09, 95% CI 0.01–0.86). In the genetic network, V179D/E was also the most frequent DRM. Additionally, the incidence of virological failure (19.23%) and immune failure (20.09%) after one year of treatment did not show significant differences in different drug resistance groups. Conclusions: The prevalence of PDR in Nanning City is moderate, driven largely by the V179D and K103N mutations. The cross-transmission networks emphasize the imperative of PDR testing and targeted interventions. Full article

Background: Antiretroviral therapy has transformed HIV infection from a fatal disease to a chronic and manageable condition, but increasing health issues beyond acquired immunodeficiency syndrome, such as metabolic, liver, and cardiovascular diseases, have been observed. Furthermore, the increasing prevalence of HIV strains resistant to older antiretroviral regimens has necessitated a re-evaluation of treatment strategies. Methods: We performed a retrospective, observational study to evaluate the long-term outcomes of an antiretroviral switch from a non-nucleoside reverse transcriptase inhibitor-based to bictegravir-based regimen; this study aimed to assess the impact of this antiretroviral switch on treatment adherence, the safety profile, and virologic outcomes. The secondary objectives were to analyze the changes in lipid, kidney function, liver function, and anthropometric parameters after switching. Results: A total of 25 patients were included in this analysis; virologic suppression was maintained over time, with 100% of patients demonstrating undetectable viral loads at 6, 12, 24, and 36 months. In parallel, a significant increase in CD4+ cell count was observed after switching. No significant differences were observed compared to the previous therapy regarding anthropometric parameters or laboratory parameters. However, a significant reduction in liver steatosis, as assessed by Fibroscan, was observed. Conclusions: bictegravir-based regimens are a valid therapeutic option for people living with HIV, particularly for those with metabolic comorbidities. Full article