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1.
PLoS One ; 19(10): e0309796, 2024.
Article in English | MEDLINE | ID: mdl-39361573

ABSTRACT

BACKGROUND: Adverse drug reaction is one of the emerging challenges in antiretroviral treatment. Determining the incidence rate and predictors among children on antiretroviral treatment (ART) is essential to improve treatment outcomes and minimize harm. And also, evidence regarding the time to major adverse drug reactions and its predictors among children on antiretroviral treatment is limited in Ethiopia. OBJECTIVE: This study aimed to assess the time to major adverse drug reaction and its predictors among children on antiretroviral treatment at selected public hospitals in Northwest Amhara, Ethiopia, 2023. METHOD: A retrospective cohort study was conducted among 380 children on antiretroviral treatment who enrolled from June 27, 2017, to May 31, 2022. Data was collected using a structured data extraction checklist. Data were entered into Epidata 4.6 and analyzed using STATA 14. The incidence rate of major adverse drug reactions was determined per person/months. The Cox proportional hazards regression model was used to identify predictors of major adverse drug responses. A p-value less than 0.05 with a 95% CI was used to declare statistical significance. RESULT: The minimum and maximum follow-up time was 6 and 59 months, respectively. The study participants were followed for a total of 9916 person-months. The incidence rate of major adverse drug reactions was 3.5 /1000 person-months. Advanced clinical stages of HIV/AIDS (III and IV) [adjusted hazard ratio = 7.3, 95% CI: 2.74-19.60)], poor treatment adherence [adjusted hazard ratio = 0.33, 95% CI: 0.21-0.42], taking antiretroviral treatment twice and more [adjusted hazard ratio = 3.43, 955 CI: (1.26-9.33)] and not taking opportunistic infection prophylaxis [adjusted hazard ratio = 0.35, 95% CI: 0.23-0.52)] were predictors of major adverse drug reactions. CONCLUSION: The incidence rate of major adverse drug reactions among children on antiretroviral treatment was congruent with studies in Ethiopia. Advanced clinical stages of HIV/AIDS, poor treatment adherence, taking antiretroviral treatment medications twice or more, and not taking opportunistic infection prophylaxis were predictors of major adverse drug reactions.


Subject(s)
HIV Infections , Hospitals, Public , Humans , Ethiopia/epidemiology , Female , Male , HIV Infections/drug therapy , Child, Preschool , Retrospective Studies , Child , Infant , Incidence , Drug-Related Side Effects and Adverse Reactions/epidemiology , Anti-HIV Agents/adverse effects , Anti-HIV Agents/therapeutic use , Adolescent , Anti-Retroviral Agents/adverse effects , Anti-Retroviral Agents/therapeutic use , Time Factors
2.
BMC Infect Dis ; 24(1): 1123, 2024 Oct 08.
Article in English | MEDLINE | ID: mdl-39379848

ABSTRACT

BACKGROUND: Drug-drug interactions (DDIs) between antiretroviral therapy (ART) and commonly used co-medications in HIV patients, especially women, impact treatment efficacy and patient safety. OBJECTIVE: This study aimed to study the prevalence and types of drug-drug interactions (DDIs) between antiretroviral therapy drugs (ARTs) and comedications among a female population with HIV. Additionally, the study investigates the association of these DDIs with ART medication changes and treatment adherence. METHODS: This cross-sectional study included 632 adult women living with HIV (WLHIV). Data was retrospectively extracted from patient files. Drug.com interaction checker website was used to assess DDIs between ART and non-ART medications. Changes to the ART regimen previously attributed to ART side effects or patient non-adherence were considered drug changes. RESULTS: A total of 429 WLHIV (mean age: 44.05 ± 9.50) were eligible. The prevalence of DDIs between ART and non-ART medications was 21.4%, with 4.7% minor, 18.4% moderate, and 8.9% major interactions. The highest prevalence of DDI was among cardiovascular medication users (71.7%), followed by central nervous system drugs (69.2%). Changing medications resulted in a decrease in DDIs, with significant reductions in total and minor interactions. Participants without DDIs had better adherence to ART. DDI between ART and non-ART medications was significantly associated with ART drug change, even after accounting for side effects attributed to ARTs, indicating an independent twofold association (OR = 1.99, CI 1.04-3.77). Moreover, further adjustments for HIV viral load and CD4 + cell count did not change the significance of the association (OR = 2.01, CI 1.03-3.92). CONCLUSION: DDIs in WLHIV impact adherence to ART. Altering ART may not be directly related to ART side effects, but rather primarily due to interactions with non-ART medications. Modifying non-ART drug regimens can reduce the likelihood of DDIs.


Subject(s)
Anti-HIV Agents , Drug Interactions , HIV Infections , Medication Adherence , Humans , Female , HIV Infections/drug therapy , Adult , Cross-Sectional Studies , Middle Aged , Prevalence , Retrospective Studies , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/adverse effects , Medication Adherence/statistics & numerical data , Anti-Retroviral Agents/therapeutic use , Anti-Retroviral Agents/adverse effects
3.
Indian J Public Health ; 68(3): 454-456, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-39321241

ABSTRACT

SUMMARY: Malignancies in human immunodeficiency virus (HIV) positive individuals have a larger role in morbidity and mortality. Appropriate clinical acumen is required for a clinician to anticipate the occurrence of lymphoma after starting antiretroviral therapy, especially in patients with CD4 <100 cells/mm3. Here is a 30-year-old man with weight loss and appetite, found to be retroviral disease positive status with low CD 4 counts. He was started on antiretroviral treatment, and following that, he developed Hodgkin's lymphoma of mixed cellularity. He is planned for an ABVD regimen and received one cycle of the same without any complications. To our knowledge, we are reporting the first case of an HIV patient with a mixed cellularity form of classical Hodgkin's lymphoma from India.


Subject(s)
HIV Infections , Hodgkin Disease , Humans , Hodgkin Disease/drug therapy , Male , Adult , HIV Infections/drug therapy , India , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , CD4 Lymphocyte Count , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Bleomycin/adverse effects , Bleomycin/administration & dosage , Dacarbazine/adverse effects , Vinblastine/administration & dosage , Vinblastine/adverse effects , Vinblastine/therapeutic use , Anti-Retroviral Agents/therapeutic use , Anti-Retroviral Agents/adverse effects
5.
Indian J Tuberc ; 71(3): 291-296, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39111937

ABSTRACT

BACKGROUND: Tuberculosis-immune reconstitution inflammatory syndrome is an atypical, immoderate immune response mounted by the refurbishing immune system against the mycobacterium tuberculosis, commonly seen in HIV-infected individuals. ART significantly enhances one's immunity. However, this enhancement in immunity also sets off a number of inflammatory processes termed as Immune Reconstitution Inflammatory Syndrome (IRIS). METHODS: This observational study was conducted with the aim of assessing the incidence and pattern of TB-IRIS in people living with HIV/AIDS on ART registered at the ART Centre of S.C.B. Medical College and Hospital, Cuttack. They were evaluated for their plasma viral load and CD4 count at baseline. Thereafter, the plasma viral load was assessed every week and the CD4 count was assessed fortnightly. Each study participant was followed-up for a period of three months to look for any onset of TB-IRIS. RESULTS: A total of 286 patients were included the study. The overall incidence of TB-IRIS was 7.7%. The occurrence of paradoxical TB-IRIS was nearly double than ART-associated TB-IRIS. There was a significant rise in the CD4 cell count in the patients of both paradoxical (p = 0.001) and ART-associated (p = 0.017) TB-IRIS. The plasma viral load at baseline also showed significant differences from the levels documented at the appearance of the TB-IRIS both in both the types i.e. paradoxical (p = 0.001) and ART-associated (p = 0.012) TB-IRIS. CONCLUSION: People with HIV/TB coinfection experience high morbidity and death from all kinds of TB-IRIS, necessitating specific attention. As HIV-positive cases and implementation of ART continue to rise, it's vital to quickly rule out TB coinfection.


Subject(s)
HIV Infections , Immune Reconstitution Inflammatory Syndrome , Tuberculosis , Viral Load , Humans , Immune Reconstitution Inflammatory Syndrome/epidemiology , Male , Adult , Female , Incidence , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Infections/complications , HIV Infections/immunology , CD4 Lymphocyte Count , Tuberculosis/epidemiology , Tuberculosis/drug therapy , Tuberculosis/immunology , India/epidemiology , Middle Aged , Anti-Retroviral Agents/therapeutic use , Anti-Retroviral Agents/adverse effects , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/adverse effects , AIDS-Related Opportunistic Infections/epidemiology , AIDS-Related Opportunistic Infections/immunology , AIDS-Related Opportunistic Infections/drug therapy
6.
BMJ Open ; 14(7): e079292, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39089716

ABSTRACT

OBJECTIVE: There is limited information regarding the incidence of treatment-related adverse events (AE) following antiretroviral therapy (ART) in women. So, this review aimed to describe the incidence of AE of ART in women living with HIV/AIDS. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, Cochrane Library, Epistemonikos, Lilacs and Who Index, from inception to 9 April 2023. ELIGIBILITY CRITERIA: We included randomised controlled trials with at least 12 weeks of follow-up and evaluated AE of ART in women at any age living with HIV/AIDS, without restrictions on status, year or language of publication. We excluded post hoc or secondary analyses and open-label extensions without comparator, and trials involving pregnant or breastfeeding women or with a focus on coinfection with tuberculosis, hepatitis B or C. The primary outcomes were the incidence rate of participants with any clinical and/or laboratory AE related or not to ART and treatment discontinuation. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data and assessed the risk of bias using Cochrane's risk of bias tool 2. We used Bayesian random-effects meta-analysis to summarise event rates. Results were presented as event rates per 1000 person-years (95% credibility intervals, 95% CrI). The pooled incidence rate per 1000 person-years adjusted for duration and loss to follow-up was estimated. We assessed the certainty of the evidence using Grading of Recommendations, Assessment, Development and Evaluation. RESULTS: A total of 24 339 studies were identified for screening, of which 10 studies (2871 women) met the eligibility criteria, with 11 different antiretrovirals (ARVs) regimens. Seven studies included exclusively women, while in the remaining three, the proportion of women ranged from 11% to 46%. Nine studies received industry funding. The pooled analysis showed a mean incidence rate of ART-related clinical and laboratory AE of 341.60 events per 1000 person-years (95% CrI 133.60-862.70), treatment discontinuation of 20.78 events per 1000 person-years (95% CrI 5.58-57.31) and ART-related discontinuation of 4.31 per 1000 person-years (95% CrI 0.13-54.72). Summary estimates were subject to significant uncertainty due to the limited number of studies and sparse data. The certainty of the evidence was graded as very low for all outcomes assessed. CONCLUSION: Existing randomised trials do not provide sufficient evidence on the incidence rates of safety outcomes from antiretroviral treatment in women living with HIV/AIDS. Large comparative studies in well-characterised populations are needed to provide a more comprehensive landscape of the safety profile of these ARV therapies in women with HIV/AIDS. PROSPERO REGISTRATION NUMBER: CRD42021251051.


Subject(s)
HIV Infections , Humans , Female , HIV Infections/drug therapy , HIV Infections/epidemiology , Incidence , Anti-Retroviral Agents/adverse effects , Anti-Retroviral Agents/therapeutic use , Anti-HIV Agents/adverse effects , Anti-HIV Agents/therapeutic use , Acquired Immunodeficiency Syndrome/drug therapy , Acquired Immunodeficiency Syndrome/epidemiology
8.
FASEB J ; 38(13): e23790, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38982638

ABSTRACT

Integrase strand transfer inhibitors (INSTIs) based antiretroviral therapy (ART) is currently used as first-line regimen to treat HIV infection. Despite its high efficacy and barrier to resistance, ART-associated neuropsychiatric adverse effects remain a major concern. Recent studies have identified a potential interaction between the INSTI, dolutegravir (DTG), and folate transport pathways at the placental barrier. We hypothesized that such interactions could also occur at the two major blood-brain interfaces: blood-cerebrospinal fluid barrier (BCSFB) and blood-brain barrier (BBB). To address this question, we evaluated the effect of two INSTIs, DTG and bictegravir (BTG), on folate transporters and receptor expression at the mouse BCSFB and the BBB in vitro, ex vivo and in vivo. We demonstrated that DTG but not BTG significantly downregulated the mRNA and/or protein expression of folate transporters (RFC/SLC19A1, PCFT/SLC46A1) in human and mouse BBB models in vitro, and mouse brain capillaries ex vivo. Our in vivo study further revealed a significant downregulation in Slc19a1 and Slc46a1 mRNA expression at the BCSFB and the BBB following a 14-day DTG oral treatment in C57BL/6 mice. However, despite the observed downregulatory effect of DTG in folate transporters/receptor at both brain barriers, a 14-day oral treatment of DTG-based ART did not significantly alter the brain folate level in animals. Interestingly, DTG treatment robustly elevated the mRNA and/or protein expression of pro-inflammatory cytokines and chemokines (Cxcl1, Cxcl2, Cxcl3, Il6, Il23, Il12) in primary cultures of mouse brain microvascular endothelial cells (BBB). DTG oral treatment also significantly upregulated proinflammatory cytokines and chemokine (Il6, Il1ß, Tnfα, Ccl2) at the BCSFB in mice. We additionally observed a downregulated mRNA expression of drug efflux transporters (Abcc1, Abcc4, and Abcb1a) and tight junction protein (Cldn3) at the CP isolated from mice treated with DTG. Despite the structural similarities, BTG only elicited minor effects on the markers of interest at both the BBB and BCSFB. In summary, our current data demonstrates that DTG but not BTG strongly induced inflammatory responses in a rodent BBB and BCSFB model. Together, these data provide valuable insights into the mechanism of DTG-induced brain toxicity, which may contribute to the pathogenesis of DTG-associated neuropsychiatric adverse effect.


Subject(s)
Blood-Brain Barrier , Heterocyclic Compounds, 3-Ring , Oxazines , Piperazines , Pyridones , Animals , Mice , Piperazines/pharmacology , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/drug effects , Heterocyclic Compounds, 3-Ring/pharmacology , Humans , Oxazines/pharmacology , Inflammation/chemically induced , Inflammation/metabolism , Mice, Inbred C57BL , Female , HIV Integrase Inhibitors/pharmacology , HIV Integrase Inhibitors/adverse effects , HIV Infections/drug therapy , HIV Infections/metabolism , Male , Anti-Retroviral Agents/adverse effects , Brain/metabolism , Brain/drug effects
9.
AIDS ; 38(12): 1731-1739, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-38831733

ABSTRACT

OBJECTIVE: Antiretroviral therapy (ART) containing integrase inhibitors (INSTIs) and/or tenofovir alafenamide (TAF) has been associated with greater weight gain. Yet few studies have delineated between exposure to 'anchor' drugs [protease inhibitors (PI), nonnucleoside reverse transcriptase inhibitors (NNRTI) or INSTIs] and exposure to nucleoside reverse transcriptase inhibitors (NRTIs). DESIGN: In this cohort of antiretroviral drug-naive patients who initiated ART from 2008-2022, we analyzed BMI gain for eight contemporary 'anchor' drugs and three contemporary NRTIs during the first 3 years of ART. We censored patients if they stopped, switched, or added another antiretroviral drug to their regimen. METHODS: We used generalized estimating equations (GEE) to assess the association between BMI gain and choice of ART and a nonlinear mixed model for the marginal coefficients of determination. We adjusted for time, baseline demographic and HIV-characteristics, and time-updated HIV and substance use-related variables. RESULTS: The median BMI gain in 4 194 patients over 3 years was + 1.9 kg/m 2 [interquartile range (IQR) 0.1-4.1]. Most patients were black (55%) and men (77%). Multivariable modeling from 20 528 BMI measurements revealed that the type of ART accounted for just 9% of the predicted BMI change. Only efavirenz (EFV) and tenofovir disoproxil fumarate (TDF) were independently associated with (lower) weight gain but no differences were observed between INSTIs, PIs, and rilpivirine, or between TAF and abacavir. CONCLUSION: The choice of initial ART had little impact on weight gain. INSTIs or TAF were not independently associated with weight change after ART initiation, but EFV and TDF were.


Subject(s)
HIV Infections , Weight Gain , Humans , Weight Gain/drug effects , Male , Female , HIV Infections/drug therapy , Adult , Middle Aged , Anti-Retroviral Agents/therapeutic use , Anti-Retroviral Agents/adverse effects , Antiretroviral Therapy, Highly Active/adverse effects , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/adverse effects , Cohort Studies , Body Mass Index , Tenofovir/therapeutic use , Tenofovir/adverse effects
10.
Infect Dis Clin North Am ; 38(3): 499-515, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38871568

ABSTRACT

Antiretroviral therapy (ART) agents as a determinant of body weight in ART-naïve and ART-experienced persons with human immunodeficiency virus (HIV) (PWH) has become a major focus area in research and clinical settings. Recent studies demonstrating weight-suppressing properties of efavirenz and tenofovir disoproxil fumarate led to re-evaluation of weight gain studies, and a reassessment of whether other agents are weight promoting versus weight neutral. In this review, the authors synthesize recent literature on factors related to obesity, clinical measurements of adiposity, weight gain in ART-naïve and ART-experienced PWH, metabolic consequences of ART and weight gain, and the clinical management of weight gain in PWH.


Subject(s)
HIV Infections , Weight Gain , Humans , Weight Gain/drug effects , HIV Infections/drug therapy , Anti-HIV Agents/adverse effects , Anti-HIV Agents/therapeutic use , Obesity , Anti-Retroviral Agents/therapeutic use , Anti-Retroviral Agents/adverse effects , Antiretroviral Therapy, Highly Active/adverse effects
11.
AIDS ; 38(11): 1686-1695, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38864586

ABSTRACT

OBJECTIVE: To characterize associations of exposure to newer antiretroviral medications in the first trimester with congenital anomalies among infants born to persons with HIV in the United States. DESIGN: Longitudinal cohort of infants born 2012-2022 to pregnant persons with HIV enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study. METHODS: First-trimester exposures to newer antiretrovirals (ARVs) were abstracted from maternal medical records. Trained site staff conducted physical exams and abstracted congenital anomalies from infant medical records. Investigators classified anomalies using the Metropolitan Atlanta Congenital Defects Program classification system. The prevalence of major congenital anomalies identified by age one year was estimated for infants exposed and unexposed to each ARV. Generalized estimating equation models were used to estimate the odds ratio (OR) of major congenital anomalies for each ARV exposure, adjusting for potential confounders. RESULTS: Of 2034 infants, major congenital anomalies were identified in 135 [6.6%; 95% confidence interval (CI): 5.6-7.8%]. Cardiovascular ( n  = 43) and musculoskeletal ( n  = 37) anomalies were the most common. Adjusted ORs (95% CI) of congenital anomalies were 1.03 (0.62-1.72) for darunavir, 0.91 (0.46-1.81) for raltegravir, 1.04 (0.58-1.85) for rilpivirine, 1.31 (0.71-2.41) for elvitegravir, 0.76 (0.37-1.57) for dolutegravir, and 0.34 (0.05-2.51) for bictegravir, compared to those unexposed to each specific ARV. Findings were similar after adjustment for nucleoside/nucleotide backbones. CONCLUSIONS: The odds of congenital anomalies among infants with first-trimester exposure to newer ARVs did not differ substantially from those unexposed to these specific ARVs, which is reassuring. Continued evaluation of these ARVs with larger studies will be needed to confirm these findings.


Subject(s)
Abnormalities, Drug-Induced , Anti-Retroviral Agents , HIV Infections , Pregnancy Complications, Infectious , Pregnancy Trimester, First , Humans , Female , Pregnancy , HIV Infections/drug therapy , United States/epidemiology , Adult , Abnormalities, Drug-Induced/epidemiology , Abnormalities, Drug-Induced/etiology , Infant, Newborn , Longitudinal Studies , Pregnancy Complications, Infectious/drug therapy , Anti-Retroviral Agents/adverse effects , Anti-Retroviral Agents/therapeutic use , Infant , Male , Young Adult , Prevalence , Congenital Abnormalities/epidemiology
12.
Clin Ther ; 46(6): e114-e124, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38851959

ABSTRACT

PURPOSE: Highly active antiretroviral therapy (HAART) has brought a significant reduction in HIV/AIDS-related morbidity and mortality. However, metabolic abnormalities (eg, dyslipidemias) have continued to pose significant challenges, warranting a switch between antiretroviral agents and/or the introduction of a statin. Hence, the purposes of this study was to compare the efficacy of switching between antiretroviral agents versus introducing a statin in the long-term management of HAART-induced dyslipidemia in people living with HIV, and to identify the most potent agent in switching therapies. METHODS: A comprehensive literature search of PubMed and Medline identified articles published from the years 2000 to 2020 in the English language, resulting in 84 articles, 30 of which were selected based on inclusion and exclusion criteria. Information on primary and secondary outcomes was extracted. Statistical analysis was done on the variables, and the differences between groups were considered significant at P < 0.05. FINDINGS: Statin use was associated with significant reductions in triglycerides and total cholesterol (TC) at 6 weeks (both, P < 0.01). A switch of antiretroviral agents was associated with gradual reductions in TC and triglycerides for up to 48 weeks (both, P < 0.01). Statin use was associated with a reduced CD4 count at 24 weeks (P < 0.01). A switch of antiretroviral agents was associated with an increased CD4 count at 48 weeks (P < 0.01). IMPLICATIONS: Statins were as effective as switching antiretroviral therapies in the short-term management of TC and triglycerides in patients with HAART-induced dyslipidemia.


Subject(s)
Antiretroviral Therapy, Highly Active , Dyslipidemias , HIV Infections , Humans , Dyslipidemias/drug therapy , Dyslipidemias/chemically induced , Antiretroviral Therapy, Highly Active/adverse effects , HIV Infections/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hypolipidemic Agents/adverse effects , Hypolipidemic Agents/therapeutic use , Anti-Retroviral Agents/adverse effects , Anti-Retroviral Agents/therapeutic use , Drug Substitution
13.
Ann Endocrinol (Paris) ; 85(3): 255-258, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38871510

ABSTRACT

HIV infection has been controlled only since the introduction of triple therapy in 1996, combining, as antiretroviral agents, two nucleoside reverse transcriptase inhibitors (NRTIs) and one protease inhibitor (PI). However, among the NRTIs, the thymidine analogues stavudine and zidovudine led to lipoatrophy, either generalized or associated with visceral fat hypertrophy and buffalo hump. These molecules also increased insulin resistance and the prevalence of diabetes. They were replaced by other NRTIs or non-NRTIs (NNRTIs) that were considered to be free of adipose tissue (AT) toxicity. More recently, the NRTI tenofovir disoproxyfumarate (TDF) and the NNRTI efavirenz have been associated with inhibition of fat gain but not with clear lipoatrophy. Otherwise, the use of PIs led to a phenotype of trunk fat hypertrophy associated with cardiometabolic complications. To avoid their adverse effects, PIs have recently been replaced by a new class of antiretrovirals, the integrase inhibitors (INSTIs), which are well tolerated and effective in controlling HIV. However, this class has been associated with global weight gain, which may be important and concerning for some people living with HIV (PWH). Also, in the NRTI class, TDF has often been replaced by tenofovir alafenamide (TAF) due to bone and renal toxicities, and TAF has been associated with global fat gain. The cardiometabolic consequences of INTIs and TAF are primarily related to the associated weight gain. In the global obesogenic worldwide context, PWH are gaining weight as well in relation to poor health life conditions. Taking in charge obesity uses the same strategies as those used in the general population.


Subject(s)
Adipose Tissue , HIV Infections , Humans , HIV Infections/drug therapy , Adipose Tissue/drug effects , Anti-HIV Agents/adverse effects , Anti-HIV Agents/therapeutic use , Reverse Transcriptase Inhibitors/adverse effects , Reverse Transcriptase Inhibitors/therapeutic use , HIV-Associated Lipodystrophy Syndrome/chemically induced , Anti-Retroviral Agents/adverse effects , Anti-Retroviral Agents/therapeutic use , Tenofovir/therapeutic use , Tenofovir/adverse effects
14.
Contraception ; 138: 110490, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38762199

ABSTRACT

OBJECTIVE: To summarize and update information regarding drug-drug interactions (DDIs) between antiretrovirals (ARVs) and hormonal contraceptives (HCs). STUDY DESIGN: Systematic review. RESULTS: We included 49 articles, with clinical, ARV, or HC PK outcomes reported by 39, 25, and 30 articles, respectively, with some articles reporting outcomes in two or more categories. Fifteen of 18 articles assessing DDIs between efavirenz and progestin implants, emergency contraception, or combined hormonal intravaginal rings found higher pregnancy rates, luteal progesterone levels suggesting ovulation, or reduced progestin PK values. Five studies documented that CYP2B6 single nucleotide polymorphisms exacerbated this DDI. One cohort detected doubled bone density loss with concomitant depot medroxyprogesterone acetate (DMPA) and tenofovir disoproxil fumarate (TDF)-containing ART use versus TDF alone. No other studies described DDIs impacting clinical outcomes. Few adverse events were attributed to ARV-HC use with none exceeding Grade 2. Evidence quality was generally moderate, with dis-similar treatment and control groups, identifying and controlling for confounding, and minimizing attrition bias in the study design being the most frequent limitations. CONCLUSION: TDF-DMPA DDIs warrant longer-term study on bone health and consideration of alternate combinations. For efavirenz-based ART, client counseling on relative risks, including both potential increase in pregnancy rate with concomitant efavirenz and implant use and lower pregnancy rates compared to other HCs even with concomitant efavirenz use, should continue to allow users comprehensive method choice. IMPLICATIONS: Most ARVs and HCs may be used safely and effectively together. Efavirenz-based ART requires careful counseling and data for possible interactions between HCs and new ARV classes are anticipated.


Subject(s)
Anti-Retroviral Agents , Contraceptive Agents, Hormonal , Drug Interactions , Humans , Female , Anti-Retroviral Agents/adverse effects , Contraceptive Agents, Hormonal/administration & dosage , Contraceptive Agents, Hormonal/pharmacokinetics , Pregnancy , Benzoxazines/administration & dosage , Benzoxazines/adverse effects , Alkynes , Hormonal Contraception , Tenofovir/pharmacokinetics , Tenofovir/adverse effects , Cytochrome P-450 CYP2B6/genetics , HIV Infections/drug therapy , Cyclopropanes/administration & dosage , Pregnancy Rate , Anti-HIV Agents/adverse effects , Anti-HIV Agents/administration & dosage
15.
Expert Rev Clin Pharmacol ; 17(7): 589-614, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38753455

ABSTRACT

INTRODUCTION: People with HIV are living longer due to advances in antiretroviral therapy. With improved life expectancy comes an increased lifetime risk of comorbid conditions - such as cardiovascular disease and cancer - and polypharmacy. Older adults, particularly those living with HIV, are more vulnerable to drug interactions and adverse effects, resulting in negative health outcomes. AREA COVERED: Antiretrovirals are involved in many potential drug interactions with medications used to treat common comorbidities and geriatric conditions in an aging population of people with HIV. We review the mechanisms and management of significant drug-drug interactions involving antiretroviral medications and non-antiretroviral medications commonly used among older people living with HIV. The management of these interactions may require dose adjustments, medication switches to alternatives, enhanced monitoring, and considerations of patient- and disease-specific factors. EXPERT OPINION: Clinicians managing comorbid conditions among older people with HIV must be particularly vigilant to side effect profiles, drug-drug interactions, pill burden, and cost when optimizing treatment. To support healthier aging among people living with HIV, there is a growing need for antiretroviral stewardship, multidisciplinary care models, and advances that promote insight into the correlations between an individual, their conditions, and their medications.


Subject(s)
Anti-HIV Agents , Drug Interactions , HIV Infections , Polypharmacy , Humans , HIV Infections/drug therapy , Aged , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/adverse effects , Anti-HIV Agents/pharmacology , Comorbidity , Age Factors , Dose-Response Relationship, Drug , Life Expectancy , Anti-Retroviral Agents/adverse effects , Anti-Retroviral Agents/administration & dosage , Drug Monitoring/methods
16.
Nurs Clin North Am ; 59(2): 189-200, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38670689

ABSTRACT

Integrase inhibitors and tenofovir alafenamide have become a mainstay in modern antiretroviral therapy; more recently, they have been implicated as causing increased weight gain beyond what may be expected with the "return to health" phenomenon. Some patients, namely those assigned female at birth, of the black race, or with lower baseline CD4 counts, may be more likely to experience weight gain. This review outlines existing evidence linking the agents to excessive weight as well as ongoing efforts to combat these effects.


Subject(s)
HIV Infections , Weight Gain , Humans , HIV Infections/drug therapy , Weight Gain/drug effects , Female , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/adverse effects , Tenofovir/therapeutic use , Tenofovir/adverse effects , Male , Anti-Retroviral Agents/therapeutic use , Anti-Retroviral Agents/adverse effects
17.
Cells ; 13(8)2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38667287

ABSTRACT

Endothelial cell activation, injury, and dysfunction underlies the pathophysiology of vascular diseases and infections associated with vascular dysfunction, including human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome. Despite viral suppression with combination antiretroviral therapy (ART), people living with HIV (PLWH) are prone to many comorbidities, including neurological and neuropsychiatric complications, cardiovascular and metabolic diseases, premature aging, and malignancies. HIV and viral proteins can directly contribute to the development of these comorbidities. However, with the continued high prevalence of these comorbidities despite viral suppression, it is likely that ART or some antiretroviral (ARVs) drugs contribute to the development and persistence of comorbid diseases in PLWH. These comorbid diseases often involve vascular activation, injury, and dysfunction. The purpose of this manuscript is to review the current literature on ARVs and the vascular endothelium in PLWH, animal models, and in vitro studies. I also summarize evidence of an association or lack thereof between ARV drugs or drug classes and the protection or injury/dysfunction of the vascular endothelium and vascular diseases.


Subject(s)
Anti-Retroviral Agents , Endothelium, Vascular , HIV Infections , Animals , Humans , Anti-HIV Agents/adverse effects , Anti-HIV Agents/therapeutic use , Anti-Retroviral Agents/adverse effects , Anti-Retroviral Agents/therapeutic use , Endothelium, Vascular/drug effects , Endothelium, Vascular/pathology , Endothelium, Vascular/virology , HIV Infections/complications , HIV Infections/drug therapy
18.
Viruses ; 16(4)2024 03 23.
Article in English | MEDLINE | ID: mdl-38675837

ABSTRACT

Tuberculosis is one of the most common opportunistic infections and a prominent cause of death in patients with human immunodeficiency virus (HIV) infection, in spite of near-universal access to antiretroviral therapy (ART) and tuberculosis preventive therapy. For patients with active tuberculosis but not yet receiving ART, starting ART after anti-tuberculosis treatment can complicate clinical management due to drug toxicities, drug-drug interactions and immune reconstitution inflammatory syndrome (IRIS) events. The timing of ART initiation has a crucial impact on treatment outcomes, especially for patients with tuberculous meningitis. The principles of ART in patients with HIV-associated tuberculosis are specific and relatively complex in comparison to patients with other opportunistic infections or cancers. In this review, we summarize the current progress in the timing of ART initiation, ART regimens, drug-drug interactions between anti-tuberculosis and antiretroviral agents, and IRIS.


Subject(s)
Antitubercular Agents , Drug Interactions , HIV Infections , Immune Reconstitution Inflammatory Syndrome , Tuberculosis , Humans , HIV Infections/drug therapy , HIV Infections/complications , Tuberculosis/drug therapy , Tuberculosis/complications , Antitubercular Agents/therapeutic use , AIDS-Related Opportunistic Infections/drug therapy , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/adverse effects , Anti-Retroviral Agents/therapeutic use , Anti-Retroviral Agents/adverse effects , Antiretroviral Therapy, Highly Active , Treatment Outcome
19.
Viruses ; 16(4)2024 03 25.
Article in English | MEDLINE | ID: mdl-38675842

ABSTRACT

TREX1 acts in the initial prevention of an autoimmune response, but it may contribute to the permissiveness of retrovirus infections. This study investigated the association between the levels of TREX1 gene expression with the polymorphisms TREX1 rs3135941 (T/C) and TREX1 rs3135945 (G/A), and the presence of antinuclear antibodies (ANA) in antiretroviral therapy (ART)-naïve individuals and after 1 year of treatment. Blood samples from 119 individuals with HIV-1 were subjected to genotyping of polymorphisms and quantification of TREX1 gene expression and HIV-1 viral load by qPCR. The concentration of IFN-α and the number of CD4+/CD8+ T lymphocytes were determined by ELISA and flow cytometry, respectively; ANA was investigated by immunofluorescence. A control group of 167 seronegative individuals was used for the comparison of genotypic frequencies. The frequency of the polymorphisms were not associated with HIV infection or with variations in the expression of TREX1 and IFN-α (p > 0.05). ART-naïve individuals exhibited higher TREX1 expression and lower IFN-α expression. After 1 year of ART, TREX1 levels were reduced, while IFN-α and CD4+ T lymphocytes were elevated (p < 0.05). Some individuals on ART presented ANA. These results suggest that ART-mediated restoration of immune competence is associated with a reduction in TREX1 expression, which may induce the development of ANA, regardless of the polymorphism investigated.


Subject(s)
Exodeoxyribonucleases , HIV Infections , HIV-1 , Immune Reconstitution , Phosphoproteins , Adult , Female , Humans , Male , Middle Aged , Antibodies, Antinuclear/blood , CD4-Positive T-Lymphocytes/immunology , Exodeoxyribonucleases/genetics , Exodeoxyribonucleases/metabolism , Genotype , HIV Infections/immunology , HIV Infections/drug therapy , HIV Infections/genetics , HIV Infections/virology , HIV-1/immunology , Immune Reconstitution/genetics , Immune Reconstitution/immunology , Interferon-alpha/blood , Interferon-alpha/metabolism , Phosphoproteins/genetics , Polymorphism, Single Nucleotide , Viral Load , Anti-Retroviral Agents/adverse effects , Anti-Retroviral Agents/therapeutic use
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