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Life (Basel, Switzerland) Jun 2024Chronic liver disease is one of the main causes of morbidity and mortality in people living with HIV (PLWH). The increasing life expectancy of PLWH, effective treatment... (Review)
Review
Chronic liver disease is one of the main causes of morbidity and mortality in people living with HIV (PLWH). The increasing life expectancy of PLWH, effective treatment for viral hepatitis, and Western dietary patterns as well as the adverse effects of antiretroviral therapy (ART) have rendered metabolic dysfunction-associated steatotic liver disease (MASLD) the most common chronic liver disease in PLWH. The risk factors for MASLD in PLWH include traditional MASLD risk factors and additional virus-specific factors, including the adverse effects of ART. The management of patients suffering from HIV and MASLD is often challenging. Apart from the conventional management of MASLD, there are also certain limitations concerning the use of ART in this patient population. In general, the appropriate combination of antiretroviral drugs should be chosen to achieve the triad of effective viral suppression, avoidance of mitochondrial dysfunction, and deterrence of worsening the patient's metabolic profile. In the current review, we discuss the epidemiology of MASLD in PLWH, the risk factors, and the disease pathogenesis, as well as the limitations in the use of ART in this patient population, while practical recommendations on how to overcome these limitations are also given.
PubMed: 38929725
DOI: 10.3390/life14060742 -
Medicina (Kaunas, Lithuania) May 2024: Antiretroviral therapy (ART) has revolutionized the management of HIV infection, transforming it from a once-debilitating disease to a chronic, manageable condition....
: Antiretroviral therapy (ART) has revolutionized the management of HIV infection, transforming it from a once-debilitating disease to a chronic, manageable condition. However, challenges such as treatment resistance, medication side effects, and long-term tolerability persist, prompting the exploration of novel therapeutic approaches. We aimed to highlight the characteristics and related comorbidities of HIV/AIDS cases in which the antiretroviral therapy was modified. : A cross-sectional clinical investigation was conducted on adults diagnosed with HIV/AIDS who were hospitalized at the "St. Parascheva" Clinical Hospital of Infectious Diseases in Iasi in the Northeastern region of Romania. The timeframe under investigation was 1 January 2023 to 30 June 2023. : In the Northeastern part of Romania, from a total of 1692 patients in the active records, there were a total of 148 recorded cases of antiretroviral therapy switch in HIV-infected patients. The main reason for the ART switch was the simplification of the ART regimen (82 cases, 55.40%), viro-immunological failure (16 cases, 10.66%), other disturbances correlated to the ART regimen, dyslipidemia (34 cases 22.97%), depression (3 cases, 2.02%), suicide attempt (1 case, 0.67%), new situations, including the appearance of pregnancy (3 cases 2.02%), and tuberculosis (9 cases, 6.08%). ART before the switch was represented by protease inhibitors that accounted for 84 cases (56.75%) of the ART switch. Following the therapy switch, integrase inhibitor-based ART single-tablet regimens accounted for 43.91% (65 cases) of all changeovers, with non-nucleoside reverse transcriptase inhibitor regimens coming in second, in 63 cases, 42.66%. : ART switch as an experimental therapy offers a promising approach to optimizing HIV treatment outcomes. By focusing on viral suppression and immune reconstitution, addressing treatment challenges, and exploring novel ARV agents, ART switch strategies aim to improve the overall health and well-being of individuals living with HIV.
Topics: Humans; Romania; Female; Adult; Male; HIV Infections; Cross-Sectional Studies; Middle Aged; Anti-Retroviral Agents; Anti-HIV Agents
PubMed: 38929471
DOI: 10.3390/medicina60060854 -
Journal of the International AIDS... Jun 2024Outside of pregnancy, evidence shows that persons with HIV initiating or switching to dolutegravir (DTG)-based antiretroviral therapy (ART) experience greater weight...
INTRODUCTION
Outside of pregnancy, evidence shows that persons with HIV initiating or switching to dolutegravir (DTG)-based antiretroviral therapy (ART) experience greater weight gain compared to those on other ART classes. However, there are few data on the impact of DTG-based ART on gestational weight gain (GWG) in sub-Saharan Africa where HIV is most common. According to the National Academy of Medicine (NAM), GWG below and above NAM guidelines is associated with adverse birth outcomes. Therefore, the objective of this study was to describe GWG by HIV status and ART regimen, and examine the associations with adverse birth outcomes.
METHODS
We enrolled pregnant women with HIV (WHIV) and without HIV (≥18 years) in a peri-urban primary healthcare facility in Cape Town, South Africa between 2019 and 2022. GWG was study-measured at 24-28 (baseline) and 33-38 weeks gestation and converted to GWG rate (kg/week) in accordance with NAM guidelines. GWG z-scores were generated using the INTEGROWTH-21 and US standards to account for differing lengths of gestation. Birth outcome data were obtained from medical records. Associations of GWG z-score with adverse birth outcomes were assessed using multivariable linear or log-binomial regression.
RESULTS
Among 292 participants (48% WHIV), median age was 29 years (IQR, 25-33), median pre-pregnancy body mass index (BMI) was 31 kg/m (IQR, 26-36) and 20% were primiparous at baseline. The median weekly rate of GWG was 0.30 kg/week (IQR, 0.12-0.50), 35% had GWG below NAM standards (59% WHIV) and 48% had GWG above NAM standards (36% WHIV). WHIV gained weight more slowly (0.25 vs. 0.37 kg/week, p<0.01) than women without HIV. Weekly rate of GWG did not differ by ART regimen (DTG-based ART 0.25 vs. efavirenz-based ART 0.27 kg/week, p = 0.80). In multivariable analyses, GWG z-score was positively associated with continuous birth weight (mean difference = 68.53 95% CI 8.96, 128.10) and categorical high birth weight of >4000 g (RR = 2.18 95% CI 1.18, 4.01).
CONCLUSIONS
Despite slower GWG among WHIV, nearly half of all women gained weight faster than recommended by the NAM. GWG was positively associated with infant birth weight. Interventions to support healthy GWG in sub-Saharan Africa are urgently needed.
Topics: Humans; Female; Pregnancy; HIV Infections; Adult; South Africa; Prospective Studies; Gestational Weight Gain; Pregnancy Complications, Infectious; Young Adult; Pregnancy Outcome; Infant, Newborn; Pyridones; Oxazines; Anti-HIV Agents; Heterocyclic Compounds, 3-Ring; Piperazines
PubMed: 38926935
DOI: 10.1002/jia2.26313 -
European Journal of Medical Research Jun 2024The COVID-19 pandemic affected the self-management and care of people living with HIV, requiring adaptations in the way health services are provided. However, it is... (Review)
Review
Repercussions of the COVID-19 pandemic on the HIV care continuum and related factors in economically disadvantaged nations: an integrated analysis using mixed-methods systematic review.
BACKGROUND
The COVID-19 pandemic affected the self-management and care of people living with HIV, requiring adaptations in the way health services are provided. However, it is unclear how these changes impacted HIV care in low-income countries.
METHODS
A systematic review including the current evidence related to changes in HIV care continuum during COVID-19 was conducted through a systematic search in the online databases including CINAHL, OVID-Medline, CAB Direct, and OVID-Embase. A two-step screening process was carried out to include eligible papers and reports according to inclusion criteria.
RESULTS
From the searches we identified 21 total studies published between 2021 and 2024, the studies revealed mostly negative impacts on all stages of the HIV care continuum in low-income countries. There were impacts related to the blocking measures due to COVID-19, fear of contracting the disease, difficulties in providing resources such as income, food and transports, reductions in the provision of care from prevention to viral suppression.
CONCLUSION
Overall, researchers identified several negative impacts of COVID-19 restrictions on HIV care continuum during pandemic; however, some observations indicated indirect positive impacts on some aspects of HIV care. Decline in HIV care practices during pandemic compared to before pandemic were observed including using preventative methods, counseling and testing, receiving HIV healthcare services, HIV medical appointments, antiretroviral adherence, engagement with treatment, and poor viral suppression. However, in some evidence improvement in ART adherence and PrEP use were observed.
Topics: Humans; COVID-19; HIV Infections; Continuity of Patient Care; Developing Countries; Pandemics; SARS-CoV-2
PubMed: 38926792
DOI: 10.1186/s40001-024-01917-1 -
BMC Infectious Diseases Jun 2024Late human immunodeficiency virus (HIV) diagnosis is the most prominent cause of HIV/AIDS-related mortality and also increases the risk of transmission and spread of the...
BACKGROUND
Late human immunodeficiency virus (HIV) diagnosis is the most prominent cause of HIV/AIDS-related mortality and also increases the risk of transmission and spread of the disease in society. Adolescents are the most vulnerable population's age group for HIV infection in several settings, but expanding access to early HIV testing remains a challenge. Consequently, a significant proportion of adolescents are still dying of HIV-related causes, and the current study aimed at assessing the effect of late presentation on HIV-related mortality among adolescents living with HIV.
METHODS
An institutional-based retrospective cohort study was conducted from August 21-November 21, 2022, at selected public hospitals in the North Showa Zone of Oromiya, Ethiopia. All adolescents living with HIV who had received no ART and presented for ART follow-up at public hospitals from September 1, 2012, to August 31, 2021, were included in the study. Data entry was done by Epi-data version 3.1.1 software and exported to Stata version 16 for further analysis. Both bi-variable and multivariable analyses were performed using the Cox proportional hazard model to compare the HIV-related mortality of early and late-presented adolescents using an adjusted hazard ratio at a 95% confidence interval (CI).
RESULTS
A total of 341 medical records of adolescents were included in the study, contributing an overall incidence rate of 3.15 (95% CI: 2.21-4.26) deaths per 100 person-years of observation throughout the total follow-up period of 1173.98 person-years. Adolescents with late presentation for HIV care had three times the higher hazard of mortality (adjusted hazard ratio (aHR) = 3.00; 95% CI: 1.22-7.37) as compared to those with early presentation for HIV/AIDS care. Adolescents within the age range of 15-19 years old (aHR = 3.56; 95% CI: 1.44-8.77), rural residence (aHR = 2.81; 95% CI: 1.39-5.68), poor adherence to ART (aHR = 3.17; 95% CI: 1.49-6.76), and being anemic (aHR = 3.09; 95% CI: 1.52-6.29) were other independent predictors of HIV-related mortality.
CONCLUSION
The study found a substantial link between HIV late presentation to care and mortality among adolescents. Residence, age, antiretroviral therapy (ART) medication adherence, and anemia status were also found to be other independent predictors of HIV-related mortality. To achieve the ultimate aim of lowering mortality among adolescents living with HIV, rigorous emphasis must be placed on early presentation for HIV/AIDS care. In addition, counseling on adherence and prompt diagnosis and treatment of anemia are highly recommended to reduce mortality.
Topics: Humans; Ethiopia; Adolescent; Retrospective Studies; Male; HIV Infections; Female; Hospitals, Public; Young Adult; Delayed Diagnosis; Proportional Hazards Models
PubMed: 38926656
DOI: 10.1186/s12879-024-09550-3 -
The Lancet. HIV Jul 2024Approximately 200 000 South Africans acquired HIV in 2021 despite the availability of universal HIV test and treat and pre-exposure prophylaxis (PrEP). The aim of this... (Randomized Controlled Trial)
Randomized Controlled Trial
Effectiveness of integrating HIV prevention within sexual reproductive health services with or without peer support among adolescents and young adults in rural KwaZulu-Natal, South Africa (Isisekelo Sempilo): 2 × 2 factorial, open-label, randomised controlled trial.
BACKGROUND
Approximately 200 000 South Africans acquired HIV in 2021 despite the availability of universal HIV test and treat and pre-exposure prophylaxis (PrEP). The aim of this study was to test the effectiveness of sexual and reproductive health services or peer support, or both, on the uptake of serostatus neutral HIV services or reduction of sexually transmissible HIV.
METHODS
We did an open-label, 2 × 2 randomised factorial trial among young people in a mostly rural area of KwaZulu-Natal, South Africa. Inclusion criteria included being aged 16-29 years, living in the mapped geographical areas that were accessible to the area-based peer navigators, being willing and able to provide informed consent, and being willing to provide a dried blood spot for anonymous HIV testing and HIV viral load measurement at 12 months. Participants were randomly allocated by computer-generated algorithm to one of four groups: those in the standard-of-care group were referred to youth-friendly services for differentiated HIV prevention (condoms, universal HIV test and treat with antiretroviral therapy, and PrEP if eligible); those in the sexual and reproductive health services group received baseline self-collected specimens for sexually transmitted infection (STI) testing and referral to integrated sexual and reproductive health and HIV prevention services; those in the peer support group were referred to peer navigators for health promotion, condom provision, and facilitation of attendance for differentiated HIV prevention services; and those in the final group received a combination of sexual and reproductive health services and peer support. Coprimary outcomes were linkage to clinical services within 60 days of enrolment, proportion of participants who had sexually transmissible HIV at 12 months after enrolment, and proportion of sampled individuals who consented to participation and gave a dried blood spot for HIV testing at 12 months. Logistic regression was used for analyses, and adjusted for age, sex, and rural or peri-urban area of residence. This study is registered with ClinicalTrials.gov (NCT04532307) and is closed.
FINDINGS
Between March 2, 2020, and July 7, 2022, 1743 (75·7%) of 2301 eligible individuals were enrolled and followed up. 12-month dried blood spots were collected from 1168 participants (67·0%). The median age of the participants was 21 years (IQR 18-25), 51·4% were female, and 51·1% had secondary level education. Baseline characteristics and 12-month outcome ascertainment were similar between groups. 755 (43·3%) linked to services by 60 days. 430 (49·8%) of 863 who were in the sexual reproductive health services group were linked to care compared with 325 (36·9%) of 880 who were not in the sexual and reproductive health services group (adjusted odds ratio [aOR] 1·68; 95% CI 1·39-2·04); peer support had no effect: 385 (43·5%) of 858 compared with 370 (43·1%) of 885 (1·02, 0·84-1·23). At 12 months, 227 (19%) tested ELISA-positive for HIV, of whom 41 (18%) had viral loads of 400 copies per mL; overall prevalence of transmissible HIV was 3·5%. 22 (3·7%) of 578 participants in the sexual and reproductive health services group had transmissible HIV compared with 19 (3·3%) of 590 not in the sexual and reproductive health services group (aOR 1·12; 95% CI 0·60-2·11). The findings were also non-significant for peer support: 21 (3·3%) of 565 compared with 20 (3·3%) of 603 (aOR 1·03; 95% CI 0·55-1·94). There were no serious adverse events or deaths during the study.
INTERPRETATION
This study provides evidence that STI testing and sexual and reproductive health services create demand for serostatus neutral HIV prevention in adolescents and young adults in Africa. STI testing and integration of HIV and sexual health has the potential to reach those at risk and tackle unmet sexual health needs.
FUNDING
US National Institute of Health, Bill & Melinda Gates Foundation, and 3ie.
Topics: Humans; Adolescent; HIV Infections; South Africa; Female; Young Adult; Male; Rural Population; Adult; Peer Group; Reproductive Health Services; HIV Testing; Pre-Exposure Prophylaxis; Viral Load
PubMed: 38925731
DOI: 10.1016/S2352-3018(24)00119-X -
Ageing Research Reviews Jun 2024The present perspective article proposes an etiopathological model for multiple sclerosis pathogenesis and progression associated with the activation of human endogenous... (Review)
Review
The present perspective article proposes an etiopathological model for multiple sclerosis pathogenesis and progression associated with the activation of human endogenous retroviruses. We reviewed preclinical, clinical, epidemiological, and evolutionary evidence indicating how the complex, multi-level interplay of genetic traits and environmental factors contributes to multiple sclerosis. We propose that endogenous retroviruses transactivation acts as a critical node in disease development. We also discuss the rationale for combined anti-retroviral therapy in multiple sclerosis as a disease-modifying therapeutic strategy. Finally, we propose that the immuno-pathogenic process triggered by endogenous retrovirus activation can be extended to aging and aging-related neurodegeneration. In this regard, endogenous retroviruses can be envisioned to act as epigenetic noise, favoring the proliferation of disorganized cellular subpopulations and accelerating system-specific "aging". Since inflammation and aging are two sides of the same coin (plastic dis-adaptation to external stimuli with system-specific degree of freedom), the two conditions may be epiphenomenal products of increased epigenomic entropy. Inflammation accelerates organ-specific aging, disrupting communication throughout critical systems of the body and producing symptoms. Overlapping neurological symptoms and syndromes may emerge from the activity of shared molecular networks that respond to endogenous retroviruses' reactivation.
PubMed: 38925481
DOI: 10.1016/j.arr.2024.102392 -
Antiviral Research Jun 2024Combinational antiretroviral therapy (cART) suppresses human immunodeficiency virus type 1 (HIV-1) viral replication and pathogenesis in acquired immunodeficiency...
Combinational antiretroviral therapy (cART) suppresses human immunodeficiency virus type 1 (HIV-1) viral replication and pathogenesis in acquired immunodeficiency syndrome (AIDS) patients. However, HIV-1 remains in the latent stage of infection by suppressing viral transcription, which hinders an HIV-1 cure. One approach for an HIV-1 cure is the "shock and kill" strategy. The strategy focuses on reactivating latent HIV-1, inducing the viral cytopathic effect and facilitating the immune clearance for the elimination of latent HIV-1 reservoirs. Here, we reported that the H3K4 trimethylation (H3K4me3)-specific demethylase KDM5A/B play a role in suppressing HIV-1 Tat/LTR-mediated viral transcription in HIV-1 latent cells. Furthermore, we evaluated the potential of KDM5-specific inhibitor JQKD82 as an HIV-1 "shock and kill" agent. Our results showed that JQKD82 increases the H3K4me3 level at HIV-1 5' LTR promoter regions, HIV-1 reactivation, and the cytopathic effects in an HIV-1-latent T cell model. In addition, we identified that the combination of JQKD82 and AZD5582, a non-canonical NF-κB activator, generates a synergistic impact on inducing HIV-1 lytic reactivation and cell death in the T cell. The latency-reversing potency of the JQKD82 and AZD5582 pair was also confirmed in peripheral blood mononuclear cells (PBMCs) isolated from HIV-1 aviremic patients and in an HIV-1 latent monocyte. In latently infected microglia (HC69) of the brain, either deletion or inhibition of KDM5A/B results in a reversal of the HIV-1 latency. Overall, we concluded that KDM5A/B function as a host repressor of the HIV-1 lytic reactivation and thus promote the latency and the survival of HIV-1 infected reservoirs.
PubMed: 38925368
DOI: 10.1016/j.antiviral.2024.105947 -
Journal of Clinical Virology : the... Jun 2024Human Immunodeficiency virus type 1 (HIV-1) remains a significant global health threat partly due to its ability to develop resistance to anti-retroviral therapies....
BACKGROUND
Human Immunodeficiency virus type 1 (HIV-1) remains a significant global health threat partly due to its ability to develop resistance to anti-retroviral therapies. HIV-1 genotype and drug resistance analysis of the polymerase (pol) sequence is a mainstay of its clinical and public health management. However, as new treatments and resistances evolve, analysis methods must change accordingly. In this study, we outline the development and implementation of a direct whole-genome sequencing approach (dWGS) using probe-capture target-enrichment for HIV-1 genotype and drug resistance analysis.
METHODS
We implemented dWGS and performed parallel pol Sanger sequencing for clinical samples, followed by comparative genotype and drug-resistance analysis. These HIV-1 WGS sequences were also utilised for a novel partitioned phylogenetic analysis.
RESULTS
Optimised nucleic acid extraction and DNAse I treatment significantly increased HIV-1 whole-genome coverage and depth, and improved recovery of high-quality genomes from low viral load clinical samples, enabling routine sequencing of viral loads as low as 1000 copies/mL. Overall, dWGS was robust, accurate and more sensitive for detecting low-frequency variants at drug-resistance sites compared to Sanger sequencing. Analysis of multiple sequence regions improved phylogenetic reconstruction for recombinant HIV-1 sequences compared to analysis of pol sequence alone.
CONCLUSIONS
These findings demonstrate dWGS enhances HIV-1 drug-resistance analysis by quantitative variant detection and improves reconstruction of HIV-1 phylogenies compared to traditional pol sequencing. This work supports that HIV-1 dWGS is a viable option to replace Sanger sequencing for clinical and public health applications.
PubMed: 38924832
DOI: 10.1016/j.jcv.2024.105709 -
Journal of the International AIDS... Jun 2024As access to effective antiretroviral therapy (ART) has improved globally, tobacco-related illnesses, including cardiovascular disease, cancer and chronic respiratory...
INTRODUCTION
As access to effective antiretroviral therapy (ART) has improved globally, tobacco-related illnesses, including cardiovascular disease, cancer and chronic respiratory conditions, account for a growing proportion of deaths among people with HIV (PWH). We estimated the impact of tobacco smoking and smoking cessation on life expectancy among PWH in South Africa.
METHODS
In a microsimulation model, we simulated 18 cohorts of PWH with virologic suppression, each homogenous by sex, initial age (35y/45y/55y) and smoking status (current/former/never). Input parameters were from data sources published between 2008 and 2022. We used South African data to estimate age-stratified mortality hazard ratios: 1.2-2.3 (females)/1.1-1.9 (males) for people with current versus never smoking status; and 1.0-1.3 (females)/1.0-1.5 (males) for people with former versus never smoking status, depending on age at cessation. We assumed smoking status remains unchanged during the simulation; people who formerly smoked quit at model start. Simulated PWH face a monthly probability of disengagement from care and virologic non-suppression. In sensitivity analysis, we varied smoking-associated and HIV-associated mortality risks. Additionally, we estimated the total life-years gained if a proportion of all virologically suppressed PWH stopped smoking.
RESULTS
Forty-five-year-old females/males with HIV with virologic suppression who smoke lose 5.3/3.7 life-years compared to PWH who never smoke. Smoking cessation at age 45y adds 3.4/2.4 life-years. Simulated PWH who continue smoking lose more life-years from smoking than from HIV (females, 5.3 vs. 3.0 life-years; males, 3.7 vs. 2.6 life-years). The impact of smoking and smoking cessation increase as smoking-associated mortality risks increase and HIV-associated mortality risks, including disengagement from care, decrease. Model results are most sensitive to the smoking-associated mortality hazard ratio; varying this parameter results in 1.0-5.1 life-years gained from cessation at age 45y. If 10-25% of virologically suppressed PWH aged 30-59y in South Africa stopped smoking now, 190,000-460,000 life-years would be gained.
CONCLUSIONS
Among virologically suppressed PWH in South Africa, tobacco smoking decreases life expectancy more than HIV. Integrating tobacco cessation interventions into HIV care, as endorsed by the World Health Organization, could substantially improve life expectancy.
Topics: Humans; Male; Life Expectancy; Female; HIV Infections; South Africa; Adult; Smoking Cessation; Middle Aged; Tobacco Smoking; Computer Simulation
PubMed: 38924347
DOI: 10.1002/jia2.26315