Search Results (83)

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

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

Backgrounds and objective: Disorders in the stomatognathic system and otorhinolaryngologic manifestations are frequently observed in individuals living with HIV. Ear, neck, and throat (ENT) signs and symptoms often serve as critical markers of treatment failure, particularly in the advanced stages of HIV infection. This article aims to evaluate and consolidate recent developments in the treatment and management of otorhinolaryngological manifestations in HIV-positive patients. Materials and methods: We carried out a retrospective clinical investigation of patients admitted with HIV/AIDS in the northeastern region of Romania, hospitalized in the “St. Parascheva” Clinical Hospital of Infectious Diseases in Iasi. We followed the viro-immunological status correlated with patients’ otolaryngology and dental symptomatology, aiming to emphasize the comorbidities of HIV/AIDS cases. The study period spanned from 1 January 2020 to 30 November 2024. Results: There were a total of 552 recorded cases of oropharyngeal manifestations in patients with HIV. They were more frequent in men (358 cases, 64.85%) than women (194 cases, 35.15%). The majority of cases were young adults, aged 30 to 39 years, comprising 255 patients (46.19%), and most cases (36.85%) had CD4+ T-lymphocyte values between 200 and 499 cells/μL. The most frequent diagnosis was oral candidiasis, recorded in 335 male and 174 female cases (509, 92.21% total). Other notable conditions included gingivitis/periodontitis, sinusitis/rhinosinusitis, mastoiditis, and dental abscesses, albeit at lower frequencies. Notably, antifungal therapy with fluconazole was the most frequently employed treatment, followed by aminopenicillins and fluoroquinolones. With respect to the antiretroviral treatment, 83.69% of cases were prescribed a single-pill regimen. Conclusions: The key to the management of HIV-positive patients is a multidisciplinary approach, including an ENT specialist and access to antiretroviral therapy. Full article

The integration of artificial intelligence and personalized medicine is transforming HIV management by enhancing diagnostics, treatment optimization, and disease monitoring. Advances in machine learning, deep neural networks, and multi-omics data analysis enable precise prognostication, tailored antiretroviral therapy, and early detection of drug resistance. AI-driven models analyze vast genomic, proteomic, and clinical datasets to refine treatment strategies, predict disease progression, and pre-empt therapy failures. Additionally, AI-powered diagnostic tools, including deep learning imaging and natural language processing, improve screening accuracy, particularly in resource-limited settings. Despite these innovations, challenges such as data privacy, algorithmic bias, and the need for clinical validation remain. Successful integration of AI into HIV care requires robust regulatory frameworks, interdisciplinary collaboration, and equitable technology access. This review explores both the potential and limitations of AI in HIV management, emphasizing the need for ethical implementation and expanded research to maximize its impact. AI-driven approaches hold great promise for a more personalized, efficient, and effective future in HIV treatment and care. 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

Hypercalcemia represents a rare complication of nontuberculous Mycobacterium (NTM) infections, particularly in individuals with human immunodeficiency virus (HIV) positivity. This systematic review examines NTM infections associated with hypercalcemia, including the presentation of a novel and illustrative case of Mycobacterium simiae. A meticulous literature search identified 24 cases relevant to this phenomenon (11 HIV-positive and 13 non-HIV), which were included in the analysis. Key clinical and laboratory findings reveal significant contrasts between HIV-positive and non-HIV patients. In the HIV-positive cohort, hypercalcemia is commonly developed after the initiation of highly active antiretroviral therapy (HAART) or treatment for NTM infections despite severe underlying immunosuppression. Conversely, in the non-HIV group, a spectrum of immunosuppressive conditions, including chronic renal failure and prolonged use of immunosuppressive drugs, was implicated in the pathogenesis of NTM infections with hypercalcemia. Two distinct mechanistic pathways likely underlie this association. In HIV-positive patients, immune restoration following HAART appears to drive granuloma formation and excessive 1,25-dihydroxyvitamin D production. In non-HIV individuals, prolonged immune suppression may facilitate macrophage activation associated with NTM infections, thereby contributing to hypercalcemia. Treatment strategies varied and included bisphosphonates, corticosteroids, and hemodialysis. Notably, bisphosphonates emerged as a safe and effective option in most cases. Antibiotic therapy was deemed unnecessary when hypercalcemia was the sole symptom of NTM infection. This review underscores the importance of recognizing hypercalcemia as a potential complication of NTM infections and tailoring management strategies to the patient’s underlying immunological status. Full article

HIV subtype A6 with the L74I polymorphism, which increases the risk of cabotegravir/rilpivirine treatment failure, causes more and more infections in Poland. In this multicenter, observational, cross-sectional study (2023–2024), we analyzed viral subtypes and drug-resistance mutations to drugs used for long-acting injectable antiretroviral treatment and pre-exposure prophylaxis. Among 357 people with HIV, 247 (69%) were Polish nationals, and 102 (29%) were from former Soviet Union countries. Of the 357 people included, 159 (45%) had subtype B, and 177 (50%) had subtype A6 infections, with 165 (87%) of the latter characterized by the L74I polymorphism. Subtype A6 was more frequent in women (66% vs. 46% in men, p < 0.05) and among people from former Soviet countries (77% vs. 39% in Polish nationals, p < 0.05). About 40% of people had either drug-resistance mutations for cabotegravir/rilpivirine or HIV A6 subtype with the L74I polymorphism; 4.5% had both of these conditions. Compared to subtype B infections, subtype A6 infections were characterized by more frequent major transmitted drug-resistance mutations for non-nucleoside reverse transcriptase inhibitors (8.5% vs. 1.9%, p = 0.007) and rilpivirine (5.1% vs. 0.6%, p = 0.016). Due to the frequent occurrence of the L74I polymorphism and drug-resistance mutations in HIV A6 subtype infection, about 40% of people with HIV in Poland may be at risk of long-acting injectable treatment failure. 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

Real-world data on HIV drug resistance (HIVDR) after transitioning to tenofovir disoproxil fumarate/lamivudine/dolutegravir (TLD) are limited. We assessed HIVDR rates and patterns in clients with virological failure (VF) after switching from an NNRTI-based regimen to TLD. A cross-sectional study was conducted in Gaza, Mozambique (August 2021–February 2022), including adults on first-line ART for ≥12 months who transitioned to TLD and had unsuppressed viral load (VL) ≥ 1000 copies/mL six months post-transition. After three adherence counseling sessions, participants with VF underwent genotyping for drug resistance mutations (DRMs) using the Stanford HIVdb Program. Of 717 participants (median age 39.2 years, 70.7% female), 217 (30.2%) had VF, 193 (88.9%) underwent genotyping, with 183 (94.8%) successfully genotyped. Intermediate–high dolutegravir (DTG) resistance was found in 19.6% (36/183). Unsuppressed VL before DTG transition was independently associated with VF (aOR: 2.14). Resistance patterns included 33.3% (12/36; 95% CI: 14.6–46.3) to all three TLD drugs, 55.6% (20/36; 95% CI: 39.3–71.9) to DTG and 3TC, and 11% (4/36; 95% CI: 0.8–21.3) to DTG only. Major drug resistance mutations to DTG included G118R (9.3%), R263K (6.6%), and Q148H/R/K (4.4%). This study highlights the need to consider virologic status before transitioning PLHIV to TLD and suggests that adherence counseling may not prevent resistance in those with unknown or prior VF. 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

Background/Objectives: Pharmacogenetics (PGx) aims to identify individuals more likely to suffer from adverse reactions or therapeutic failure in drug treatments. However, despite most of the evidence in this area being from European populations, some diseases have also been neglected, such as HIV infection, malaria, and tuberculosis. With this review, we aim to emphasize which pharmacogenetic tests are ready to be implemented in treating neglected diseases that have some evidence and call attention to what is missing for these three diseases. Methods: A critical literature review on the PGx of HIV infection, malaria, and tuberculosis was performed. Results: There are three PGx guidelines for antiretroviral drugs used in HIV infection, one for malaria, and none for tuberculosis. Some evidence is already available, and some genes have already been identified, such as CYP2D6 for primaquine treatment and NAT2 for isoniazid. However, some barriers to the implementation are the lack of evidence due to the few studies on the diseases themselves and the admixture of the most affected populations, which must be considered, given the genetic differentiation of these populations. Conclusions: PGx tests such as abacavir are already implemented in some places, and efavirenz/atazanavir is ready to implement if this medication is used. Other gene–drug associations were found but still do not present a clear recommendation. We call attention to the need to generate more evidence for testing treatments for other neglected diseases, such as malaria and tuberculosis, given their epidemiological importance and for the public health of less favored populations. Full article

Background: With advances in antiretroviral therapy for HIV treatment, newer drug combinations provide improved efficacy, safety, and compliance. This study evaluates switching to a regimen of doravirine (DOR), tenofovir disoproxil fumarate (TDF), and lamivudine (3TC) in a cohort of people living with HIV (PLWH). Methods: this Italian retrospective study included 426 PLWH who switched from rilpivirine (RPV)/TDF/emtricitabine (FTC) to DOR/3TC/TDF. The analysis focused on treatment effectiveness, safety, and metabolic and renal markers. Results: this study reports a treatment failure (defined as virological failure or discontinuation of the regimen) rate of 2.34% (95% confidence interval, 1.28–4.50%), with significant improvement in CD4 counts (+49.93 cells/µL, p < 0.001). Notably, the switch to DOR/3TC/TDF did not result in adverse metabolic effects or significant changes in renal function. Analysis of lipid profiles showed stabilization in the majority of PLWH. Conclusions: this study indicates that switching to a DOR/3TC/TDF from RPV/TDF/FTC is an effective and well-tolerated option for PLWH, with benefits in terms of maintaining viral suppression, CD4 count recovery, and metabolic health, without evidence of renal impairment. These results support the continued use of DOR/3TC/TDF as part of HIV treatment strategies and highlight the need for ongoing research to refine ART regimens for different populations. Full article

Dual therapies (DT) combining integrase strand transfer inhibitors (INSTIs) with second-generation non-nucleoside reverse transcriptase inhibitors (2nd-Gen-NNRTIs) offer new possibilities for HIV treatment to improve adherence. However, drug resistance associated mutations (RAMs) to prior antiretrovirals may jeopardize the efficacy of DT. We herein describe the predicted efficacy of DT combining INSTIs + 2nd-Gen-NNRTI following treatment failure among Cameroonian patients. We genotyped the HIV-1 pol gene using Sanger sequencing and assessed acquired RAMs to NNRTIs and INSTIs in patients failing treatment from March 2019 to December 2023. Drug susceptibility was interpreted using Stanford HIVdb v9.5, and statistical analyses were performed using SPSS v22. Of 130 successfully genotyped participants (median age (IQR): 38 (27–46) years; 59.2% female), 92.3% had RAMs to NNRTIs and 1.5% to INSTIs. Prevailing RAMs were Y181C (32.3%) among NNRTIs and R263K (0.7%) among INSTIs. Among 2nd-Gen-NNRTIs, etravirine, doravirine and rilpivirine had 43.85%, 41.54% and 38.46% genotypic sensitivity, respectively. Among INSTIs, we found 97.69% efficacy for dolutegravir/bictegravir, 96.15% for cabotegravir and 92.31% for elvitegravir/raltegravir. The overall predictive efficacy of DT was lower among participants who failed 1st-Gen-NNRTI (p < 0.001); with etravirine + dolutegravir/bictegravir combination showing the highest score (43.8%). Conclusively, DT combining INSTIs + 2nd-Gen-NNRTIs might be suboptimal in the context of previous ART failure, especially with NNRTI-based treatment in low- and middle-income countries. The general data clearly indicate that without resistance testing, it is nearly impossible to use long-acting dual therapies in previously failing patients. Full article

M184V is a single-base mutation in the YMDD domain of reverse transcriptase (RT). The M184V resistance-associated mutation (RAM) is related to virological unresponsiveness to lamivudine (3TC) and emtricitabine (FTC) and induces high-level resistance to these two antiretroviral agents. M184V is rapidly selected in the setting of non-suppressive antiretroviral therapy (ART) and accumulates in the HIV reservoir. There were continuous efforts to evaluate the impact of the M184V mutation on the treatment outcomes in people living with HIV (PLWH). Since 3TC remains an extensively used part of recommended antiretroviral combinations, M184V is commonly detected in patients with virological failure (VF). ART guidelines do not recommend the use of drugs impacted by RAMs as they have been confirmed to comprise a risk factor for VF. However, there is evidence that 3TC/FTC can remain active even in the presence of M184V. Given the potential benefits of 3TC in ART combinations, the investigation of M184V remains of high interest to clinicians and researchers, especially in certain regions with limited resources, and especially for its unusual effects. This is a review of the literature on the challenges in treating both naïve and experienced individuals carrying the M184V mutation, including virological failure, virological suppression, and resistance to ART. Full article

Background: HIV drug resistance (HIV-DR) may jeopardize the benefit of antiretroviral therapy (ART) in treatment and prevention. This study utilized viral phylogenetics to resolve the influence of transmission networks on sustaining the spread of HIV-DR in Quebec spanning 2002 to 2022. Methods: Time trends in acquired (ADR) and transmitted drug resistance (TDR) were delineated in treatment-experienced (n = 3500) and ART-naïve persons (n = 6011) with subtype B infections. Similarly, non-B-subtype HIV-DR networks were assessed pre- (n = 1577) and post-ART experience (n = 488). Risks of acquisition of resistance-associated mutations (RAMs) were related to clustering using 1, 2–5, vs. 6+ members per cluster as categorical variables. Results: Despite steady declines in treatment failure and ADR since 2007, rates of TDR among newly infected, ART-naive persons remained at 14% spanning the 2007–2011, 2012–2016, and 2017–2022 periods. Notably, half of new infections among men having sex with men and heterosexual groups were linked in large, clustered networks having a median of 35 (14–73 IQR) and 16 (9–26 IQR) members per cluster, respectively. Cluster membership and size were implicated in forward transmission of non-nucleoside reverse transcriptase inhibitor NNRTI RAMs (9%) and thymidine analogue mutations (TAMs) (5%). In contrast, transmission of M184V, K65R, and integrase inhibitors (1–2%) remained rare. Levels of TDR reflected viral replicative fitness. The median baseline viremia in ART-naïve groups having no RAMs, NNRTI RAMs, TAMs, and M184VI were 46.088, 38,447, 20,330, and 6811 copies/mL, respectively (p < 0.0001). Conclusion: Phylogenetics emphasize the need to prioritize ART and pre-exposure prophylaxis strategies to avert the expansion of transmission cascades of HIV-DR. Full article