RESUMEN

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.

Asunto(s)

Infecciones por VIH , Síndrome Inflamatorio de Reconstitución Inmune , Tuberculosis , Carga Viral , Humanos , Síndrome Inflamatorio de Reconstitución Inmune/epidemiología , Masculino , Adulto , Femenino , Incidencia , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Infecciones por VIH/complicaciones , Infecciones por VIH/inmunología , Recuento de Linfocito CD4 , Tuberculosis/epidemiología , Tuberculosis/tratamiento farmacológico , Tuberculosis/inmunología , India/epidemiología , Persona de Mediana Edad , Antirretrovirales/uso terapéutico , Antirretrovirales/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/efectos adversos , Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Infecciones Oportunistas Relacionadas con el SIDA/inmunología , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico

RESUMEN

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.

Asunto(s)

Infecciones por VIH , Humanos , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Incidencia , Antirretrovirales/efectos adversos , Antirretrovirales/uso terapéutico , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/epidemiología

Asunto(s)

Infecciones por VIH , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/complicaciones , Niño , Masculino , Femenino , Antirretrovirales/uso terapéutico , Antirretrovirales/efectos adversos , Enfermedades Metabólicas , Adolescente , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Preescolar

RESUMEN

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.

Asunto(s)

Barrera Hematoencefálica , Compuestos Heterocíclicos con 3 Anillos , Oxazinas , Piperazinas , Piridonas , Animales , Ratones , Piperazinas/farmacología , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/efectos de los fármacos , Compuestos Heterocíclicos con 3 Anillos/farmacología , Humanos , Oxazinas/farmacología , Inflamación/inducido químicamente , Inflamación/metabolismo , Ratones Endogámicos C57BL , Femenino , Inhibidores de Integrasa VIH/farmacología , Inhibidores de Integrasa VIH/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/metabolismo , Masculino , Antirretrovirales/efectos adversos , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos

RESUMEN

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.

Asunto(s)

Infecciones por VIH , Aumento de Peso , Humanos , Aumento de Peso/efectos de los fármacos , Masculino , Femenino , Infecciones por VIH/tratamiento farmacológico , Adulto , Persona de Mediana Edad , Antirretrovirales/uso terapéutico , Antirretrovirales/efectos adversos , Terapia Antirretroviral Altamente Activa/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/efectos adversos , Estudios de Cohortes , Índice de Masa Corporal , Tenofovir/uso terapéutico , Tenofovir/efectos adversos

RESUMEN

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.

Asunto(s)

Infecciones por VIH , Aumento de Peso , Humanos , Aumento de Peso/efectos de los fármacos , Infecciones por VIH/tratamiento farmacológico , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Obesidad , Antirretrovirales/uso terapéutico , Antirretrovirales/efectos adversos , Terapia Antirretroviral Altamente Activa/efectos adversos

RESUMEN

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.

Asunto(s)

Anomalías Inducidas por Medicamentos , Antirretrovirales , Infecciones por VIH , Complicaciones Infecciosas del Embarazo , Primer Trimestre del Embarazo , Humanos , Femenino , Embarazo , Infecciones por VIH/tratamiento farmacológico , Estados Unidos/epidemiología , Adulto , Anomalías Inducidas por Medicamentos/epidemiología , Anomalías Inducidas por Medicamentos/etiología , Recién Nacido , Estudios Longitudinales , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Antirretrovirales/efectos adversos , Antirretrovirales/uso terapéutico , Lactante , Masculino , Adulto Joven , Prevalencia , Anomalías Congénitas/epidemiología

RESUMEN

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.

Asunto(s)

Terapia Antirretroviral Altamente Activa , Dislipidemias , Infecciones por VIH , Humanos , Dislipidemias/tratamiento farmacológico , Dislipidemias/inducido químicamente , Terapia Antirretroviral Altamente Activa/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipolipemiantes/efectos adversos , Hipolipemiantes/uso terapéutico , Antirretrovirales/efectos adversos , Antirretrovirales/uso terapéutico , Sustitución de Medicamentos

RESUMEN

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.

Asunto(s)

Tejido Adiposo , Infecciones por VIH , Humanos , Infecciones por VIH/tratamiento farmacológico , Tejido Adiposo/efectos de los fármacos , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Inhibidores de la Transcriptasa Inversa/efectos adversos , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Síndrome de Lipodistrofia Asociada a VIH/inducido químicamente , Antirretrovirales/efectos adversos , Antirretrovirales/uso terapéutico , Tenofovir/uso terapéutico , Tenofovir/efectos adversos

RESUMEN

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.

Asunto(s)

Antirretrovirales , Agentes Anticonceptivos Hormonales , Interacciones Farmacológicas , Humanos , Femenino , Antirretrovirales/efectos adversos , Agentes Anticonceptivos Hormonales/administración & dosificación , Agentes Anticonceptivos Hormonales/farmacocinética , Embarazo , Benzoxazinas/administración & dosificación , Benzoxazinas/efectos adversos , Alquinos , Anticoncepción Hormonal , Tenofovir/farmacocinética , Tenofovir/efectos adversos , Citocromo P-450 CYP2B6/genética , Infecciones por VIH/tratamiento farmacológico , Ciclopropanos/administración & dosificación , Índice de Embarazo , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/administración & dosificación

RESUMEN

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.

Asunto(s)

Fármacos Anti-VIH , Interacciones Farmacológicas , Infecciones por VIH , Polifarmacia , Humanos , Infecciones por VIH/tratamiento farmacológico , Anciano , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/farmacología , Comorbilidad , Factores de Edad , Relación Dosis-Respuesta a Droga , Esperanza de Vida , Antirretrovirales/efectos adversos , Antirretrovirales/administración & dosificación , Monitoreo de Drogas/métodos

RESUMEN

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.

Asunto(s)

Infecciones por VIH , Aumento de Peso , Humanos , Infecciones por VIH/tratamiento farmacológico , Aumento de Peso/efectos de los fármacos , Femenino , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/efectos adversos , Tenofovir/uso terapéutico , Tenofovir/efectos adversos , Masculino , Antirretrovirales/uso terapéutico , Antirretrovirales/efectos adversos

RESUMEN

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.

Asunto(s)

Antirretrovirales , Endotelio Vascular , Infecciones por VIH , Animales , Humanos , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Antirretrovirales/efectos adversos , Antirretrovirales/uso terapéutico , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/patología , Endotelio Vascular/virología , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico

RESUMEN

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.

Asunto(s)

Antituberculosos , Interacciones Farmacológicas , Infecciones por VIH , Síndrome Inflamatorio de Reconstitución Inmune , Tuberculosis , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/complicaciones , Tuberculosis/tratamiento farmacológico , Tuberculosis/complicaciones , Antituberculosos/uso terapéutico , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/efectos adversos , Antirretrovirales/uso terapéutico , Antirretrovirales/efectos adversos , Terapia Antirretroviral Altamente Activa , Resultado del Tratamiento

RESUMEN

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.

Asunto(s)

Exodesoxirribonucleasas , Infecciones por VIH , VIH-1 , Reconstitución Inmune , Fosfoproteínas , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anticuerpos Antinucleares/sangre , Linfocitos T CD4-Positivos/inmunología , Exodesoxirribonucleasas/genética , Exodesoxirribonucleasas/metabolismo , Genotipo , Infecciones por VIH/inmunología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/genética , Infecciones por VIH/virología , VIH-1/inmunología , Reconstitución Inmune/genética , Reconstitución Inmune/inmunología , Interferón-alfa/sangre , Interferón-alfa/metabolismo , Fosfoproteínas/genética , Polimorfismo de Nucleótido Simple , Carga Viral , Antirretrovirales/efectos adversos , Antirretrovirales/uso terapéutico

RESUMEN

BACKGROUND: Infants born with HIV-1 require lifelong antiretroviral therapy (ART). We aimed to assess whether very early ART in neonates might restrict HIV-1 reservoirs, an important step towards ART-free remission. METHODS: IMPAACT P1115 is an ongoing, phase 1/2, proof-of-concept study in which infants were enrolled at 30 research clinics in 11 countries (Brazil, Haiti, Kenya, Malawi, South Africa, Tanzania, Thailand, Uganda, the USA, Zambia, and Zimbabwe) into two cohorts. Infants at least 34 weeks' gestational age at high risk for in-utero HIV-1 with either untreated maternal HIV-1 (cohort 1) or who were receiving pre-emptive triple antiretroviral prophylaxis outside of the study (maternal ART permissible; cohort 2) were included. All infants initiated treatment within 48 h of life. Cohort 1 initiated three-drug nevirapine-based ART, and cohort 2 initiated three-drug nevirapine-based prophylaxis then three-drug nevirapine-based ART following HIV diagnosis by age 10 days. We added twice-daily coformulated oral ritonavir 75 mg/m2 and lopinavir 300 mg/m2 from 14 days of life and 42 weeks postmenstrual age. We discontinued nevirapine 12 weeks after two consecutive plasma HIV-1 RNA levels below limit of detection. We tracked virological suppression, safety outcomes, and meeting a predetermined biomarker profile at age 2 years (undetectable RNA since week 48, HIV-1 antibody-negative, HIV-1 DNA not detected, and normal CD4 count and CD4 percentage) to assess qualification for analytical treatment interruption. This study is registered with ClinicalTrials.gov, NCT02140255. FINDINGS: Between Jan 23, 2015, and Dec 14, 2017, 440 infants were included in cohort 1 and 20 were included in cohort 2. 54 of these infants (34 from cohort 1 and 20 from cohort 2) had confirmed in-utero HIV-1 and were enrolled to receive study ART. 33 (61%) of 54 infants were female and 21 (39%) were male. The estimated probability of maintaining undetectable plasma RNA through to 2 years was 33% (95% CI 17-49) in cohort 1 and 57% (28-78) in cohort 2. Among infants maintaining protocol-defined virological control criteria through to study week 108, seven of 11 (64%, 95% CI 31-89) in cohort 1 and five of seven (71%, 29-96) in cohort 2 had no detected HIV-1 DNA. Ten of 12 (83%, 52-100) in cohort 1 and all seven (100%, 59-100) in cohort 2 tested HIV-1 antibody-negative at week 108. Among 54 infants initiated on very early ART, ten (19%; six in cohort 1 and four in cohort 2) met all criteria for possible analytical treatment interruption. Reversible grade 3 or 4 adverse events occurred in 15 (44%) of 34 infants in cohort 1 and seven (35%) of 20 infants in cohort 2. INTERPRETATION: Very early ART for in-utero HIV-1 can achieve sustained virological suppression in association with biomarkers indicating restricted HIV-1 reservoirs by age 2 years, which might enable potential ART-free remission. FUNDING: National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health.

Asunto(s)

Fármacos Anti-VIH , Infecciones por VIH , Seropositividad para VIH , VIH-1 , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Antirretrovirales/efectos adversos , ADN/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Seropositividad para VIH/tratamiento farmacológico , VIH-1/genética , Nevirapina/uso terapéutico , ARN/uso terapéutico , Prueba de Estudio Conceptual

RESUMEN

BACKGROUND: Rilpivirine (RPV) is an antiretroviral drug characterized by good tolerability and a favorable liver safety profile. Recent research has shown that RPV ameliorates liver fibrosis in animal models of various chronic liver diseases. Our study aimed to analyze the effect of RPV on liver fibrosis by assessing changes in liver stiffness using transient elastography. METHODS: Retrospective cohort study of HIV-infected patients who were exposed and not exposed to RPV. The change in liver stiffness during the period between two transient elastography measurements was analyzed and compared for patients exposed and not exposed to RPV. RESULTS: We selected 118 RPV-exposed and 118 non-RPV-exposed HIV-infected patients. Median time between transient elastography (TE) measurements was 50 (29-68) months. A repeated-measures general linear model based on the main clinical characteristics revealed a significant decrease in the TE value of -0.8kPa in non-RPV-exposed patients (p=0.254) and -1.6kPa in the RPV-exposed group (p<0.001). The subgroup analysis showed a significant reduction in the TE value only patients cured of hepatitis C (RPV-exposed, -2.8kPa [p<0.001]; non-RPV-exposed, -1.1kPa [p=0.22]). CONCLUSION: RPV-based antiretroviral regimens significantly reduced liver stiffness, as measured by TE, in patients cured of chronic hepatitis C.

Asunto(s)

Fármacos Anti-VIH , Coinfección , Infecciones por VIH , Hepatitis C , Animales , Humanos , Rilpivirina/uso terapéutico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Fármacos Anti-VIH/efectos adversos , Estudios Retrospectivos , Coinfección/tratamiento farmacológico , Antirretrovirales/efectos adversos , Hepatitis C/tratamiento farmacológico , Hepacivirus , Cirrosis Hepática/tratamiento farmacológico

RESUMEN

INTRODUÇÃO: O HIV-1 é um vírus que apresenta em seu envelope viral a glicoproteína gp120, capaz de se ligar aos receptores CD4+ dos linfócitos T do hospedeiro, inviabilizando o funcionamento normal ou levando à destruição das células do sistema imune da pessoa vivendo com esse agente infeccioso. No contexto do tratamento contra o vírus, as quasispécies de HIV-1 podem sofrer uma ou mais mutações genéticas que afetam a atividade de um ou mais ARVs que já foram efetivos anteriormente, processo que é denominado resistência. Segundo a Organização Mundial de Saúde (OMS), observa-se em diversos países que a resistência atinge mais de 10% dos indivíduos em início ou reinício do tratamento contra o HIV. PERGUNTA: Fostensavir 600 mg é eficaz, custo-efetivo e seguro no tratamento de pessoas adultas vivendo com HIV-1 multirresistente aos ARVs? EVIDÊNCIAS CLÍNICAS: A partir da pergunta de pesquisa, foi desenvolvida estratégia de busca nas bases de dados MEDLINE via PubMed e EMBASE. A busca realizada resultou em 318 publicações. Foram inicialmente excluídas 72 por serem duplicatas. Posteriormente, foram excluídas outras 220 após triagem. Após leitura dos textos completos, chegou-se ao resultado de cinco publicações elegíveis, todas fruto do ensaio clínico randomizado de fase III, BRIGHTE. Foram relatados os desfechos de média de redução de carga viral, resposta virológica, falha virológica, variação média de linfócitos T CD4+, eventos adversos, morte, qualidade de vida e adesão ao tratamento. Em geral, o nível de certeza das evidências foi classificado como baixo, com risco de viés grave. AVALIAÇÃO ECONÔMICA: Utilizando um modelo de árvore de decisão, foi realizada uma análise para estimar a razão de custo-efetividade incremental (RCEI) do fostensavir 600 mg para pessoas vivendo com HIV-Aids, adultos e com multirresistência a pelo menos quatro classes terapêuticas de antirretrovirais desde que combinado a pelo menos um ARV totalmente ativo para um ano. O modelo comparou o fostensavir à terapia de base otimizada (TBO) apresentada no estudo pivotal BRIGHTE. ANÁLISE DE IMPACTO ORÇAMENTÁRIO: Foram projetados dois cenários de incorporação para a difusão do fostensavir: conservador e moderado. No cenário de difusão conservador (market share 10% ao ano), o impacto da incorporação do fostensavir em cinco anos variou entre R$ 10.975.053,60 e R$ 65.109.874,58, de 2024 a 2028 respectivamente. O impacto orçamentário acumulado em cinco anos no cenário conservador foi R$ 185.241.468,80. No cenário de difusão moderado (market share 20% ao ano), o impacto da incorporação em cinco anos variou entre R$ 10.975.053,60 e R$ 117.197.774,25, de 2024 a 2028. O impacto orçamentário acumulado em cinco anos no cenário de difusão moderado foi R$ 310.435.446,95. Monitoramento do horizonte tecnológico: Foram identificadas duas tecnologias para o tratamento de pessoas adultas convivendo com HIV multirresistente. Lenacapavir, que está registrado nas agências EMA e FDA, e ibalizumabe, com registro na FDA. PERSPECTIVA DO PACIENTE: A chamada pública nº 30/2023 ficou aberta entre 14 e 24 de agosto de 2023. Duas pessoas se inscreveram. O representante titular contou que tem 50 anos e há 25 vive com HIV. Acredita já ter usado todas as classes de medicamentos por conta da multirresistência do HIV aos ARV, chegando a ficar sem opção terapêutica por cinco ou seis anos. Atualmente utiliza a combinação maraviroque, dolutegravir, tenofovir, lamivudina, darunavir e ritonavir, com a qual consegue obter a supressão da carga viral. Ressaltou que quem vive com HIV há muito tempo corre o risco de ficar sem opção de medicamentos e que a incorporação de novas tecnologias pode beneficiar pessoas como ele. RECOMENDAÇÃO PRELIMINAR DA CONITEC: Os membros do Comitê de Medicamentos presentes na 125ª Reunião Ordinária, realizada no dia 6 de dezembro de 2023, deliberaram, por unanimidade, encaminhar o tema para consulta pública com recomendação preliminar favorável à incorporação do fostensavir trometamol 600 mg para o tratamento de pessoas vivendo com HIV-Aids multirresistentes a terapia antirretroviral. Considerou-se a oportunidade de uma opção terapêutica aos indivíduos multirresitentes, a capacidade das Câmaras Técnicas Estaduais e da área técnica do Ministério da Saúde no monitoramento dos benefícios clínicos e dos eventos adversos do fostensavir e a expectativa de uma nova proposta de preço encaminhada pela empresa durante a consulta pública. CONSULTA PÚBLICA: A consulta pública (CP) nº 69/2023 foi realizada entre os dias 29/12/2023 e 17/01/2024. Foram recebidas 11 contribuições, sendo sete pelo formulário para contribuições técnico-científico e quatro pelo formulário pra contribuições sobre experiência ou opinião de pacientes, familiares, amigos ou cuidadores de pacientes, profissionais de saúde ou pessoas interessadas no tema. Sobre as contribuições técnicas, todas foram favoráveis às recomendações preliminares da Conitec e uma possuía referencial teórico para a abordagem técnico-científica. Entretanto, não se identificou nenhuma evidência científica adicional que pudesse modificar o entendimento preliminar da Conitec. Nas contribuições de experiência ou opinião, todos os participantes manifestaram-se favoráveis à recomendação preliminar da tecnologia avaliada. Os argumentos relevantes foram classificados em "Sobrevida do paciente", uma vez que a abordagem foi especificamente quanto às falhas terapêuticas do uso de outros antirretrovirais e a evolução para complicações e óbito. Metade dos respondedores apontaram ter experiência com o fostensavir. No que diz respeito à experiência com outras tecnologias, um dos três respondentes, o paciente, mencionou o uso de medicamentos, como tenofovir, lamivudina, efavirenz e dolutegravir e apontou como evento negativo os seus efeitos colaterais. Além disso, destacaram o valor elevado da aquisição do fostensavir como uma das principais dificuldades para acesso a este tratamento. NOVA PROPOSTA COMERCIAL: Foi submetida ao DGITS/SECTICS/MS o valor de USD 38,67 por comprimido, com uma quantidade mínima de aquisição estabelecida em 360.000 (trezentos e sessenta mil) unidades. Considerando o novo valor proposto, o custo mensal do tratamento será de R$ 11.513,40, representando aproximadamente 65,59% de desconto em relação ao preço CMED PMVG 18% e uma redução de 1,66% em relação à proposta apresentada em 2023. Ainda com base no novo valor proposto, atualizou-se a avaliação econômica e a AIO. Os critérios considerados englobam os termos da recente proposta comercial e a taxa de câmbio do dólar no dia 15 de fevereiro de 2024, fixada em 1 USD = R$ 4,9624. A RCEI foi estimada em R$ 257.370,65, apresentando uma efetividade incremental de 0,54. No cenário conservador da nova AIO, levando em consideração uma participação de mercado de 10% ao ano, o impacto orçamentário incremental em cinco anos foi R$ 100.714.577,75. Já no cenário moderado, com um aumento de 20% após o primeiro ano, o impacto orçamentário acumulado em cinco anos foi R$ 247.300.234,85. RECOMENDAÇÃO FINAL DA CONITEC: Os membros do Comitê de Medicamentos presentes na 127ª Reunião Ordinária, realizada no dia 6 de março de 2024, deliberaram, por unanimidade, recomendar a incorporação do fostensavir trometamol 600 mg para o tratamento de indivíduos adultos vivendo com HIV multirresistentes aos antirretrovirais, conforme Protocolo Clínico do Ministério da Saúde. Considerou-se as expectativas da ampliação das opções terapêuticas e da redução da carga viral aos pacientes multirresistentes. Foi assinado o Registro de Deliberação nº 881/2024. DECISÃO: incorporar, no âmbito do Sistema Único de Saúde - SUS, o fostensavir trometamol 600 mg para o tratamento de indivíduos adultos vivendo com HIV multirresistente aos antirretrovirais, conforme Protocolo Clínico do Ministério da Saúde, publicada no Diário Oficial da União nº 77, seção 1, página 177, em 22 de abril de 2024.

Asunto(s)

Humanos , Profármacos/administración & dosificación , Proteína gp120 de Envoltorio del VIH/antagonistas & inhibidores , Infecciones por VIH/tratamiento farmacológico , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Antirretrovirales/efectos adversos , Evaluación en Salud/economía , Sistema Único de Salud , Brasil , Análisis Costo-Beneficio/economía

RESUMEN

INTRODUCTION: The incidence of metabolic syndrome (MetS) in people living with HIV is significantly higher than in people without HIV. MetS is not only a major driver of cardiovascular disease (CVD) but is also closely related to the development of chronic kidney disease (CKD). The aim of this study was to investigate the prevalence of and risk factors for MetS and to further understand the degree of damage to target organs. METHODS: This was a cross-sectional descriptive study conducted at Chongqing Public Health Medical Center, China. Information was collected via questionnaire survey, physical examination, and laboratory tests. We used the China Diabetes Society guidelines to define MetS. Pooled cohort equations were calculated to compare CVD risk in the next 10 years in people living with HIV aged ≥40 years with or without MetS. We used Student's t-test, the chi-squared test, Fisher's exact test, binary logistic regression, and multiple linear regression in the statistical analysis. RESULTS: The study included 979 people living with HIV, including 13 who have experienced CVD, receiving antiretroviral therapy (ART). The median age was 43.0 years, 20.9% were female, and the median ART time was 45.0 months. The prevalence of MetS was 33.9%. The components of MetS criteria were hyperglycaemia (50.4%), hypertriglyceridaemia (48.4%), hypertension (46.8%), low concentrations of high-density lipoprotein cholesterol (28.2%), and abdominal obesity (25.0%). Higher body mass index (odds ratio [OR] 1.266; 95% confidence interval [CI] 1.203-1.333), higher total cholesterol (OR 1.267; 95% CI 1.011-1.588), high alcohol consumption (OR 1.973; 95% CI 1.009-3.859), and family history of diabetes (OR 1.726; 95% CI 1.075-2.770) were independent risk factors for MetS. Compared with the non-MetS group, the MetS group had a higher rate of urine albumin (23.8% vs 14.8%, p = 0.001), and the estimated glomerular filtration rate <90 mL/min/1.73 m2 (18.37% vs. 12.8%, p = 0.020) and ß2-microglobin (p = 0.004) increased more markedly in the MetS group. Regarding the risk of developing CVD events in the next 10 years, 38.5% of those in the MetS group were at high or very high risk, which was significantly higher than in the non-MetS group (p < 0.001). In addition, age (p < 0.001) and sex (p = 0.002) are independent risk factors for developing CVD events in the next 10 years. CONCLUSIONS: The prevalence of MetS in people living with HIV on ART is high in Chongqing, China. Risk factors for the development of MetS are high alcohol consumption, family history of diabetes, higher body mass index, and higher total cholesterol levels. In addition, MetS is associated with a risk of CKD and the incidence of 10-year CVD.

Asunto(s)

Infecciones por VIH , Síndrome Metabólico , Humanos , Femenino , Masculino , Estudios Transversales , Síndrome Metabólico/epidemiología , Adulto , China/epidemiología , Persona de Mediana Edad , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Prevalencia , Factores de Riesgo , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/complicaciones , Antirretrovirales/uso terapéutico , Antirretrovirales/efectos adversos

RESUMEN

OBJECTIVES: To evaluate carotid intima media thickness (CIMT) in children with Human immunodeficiency virus (HIV) on anti-retroviral therapy (ART) and in controls. Also, to compare body mass index (BMI), body fat percentage, skin-fold thickness (SFT), waist-to-height ratio (WHtR), lipid profile, blood pressure, lipodystrophy syndrome (LDS), non-alcoholic fatty liver disease (NAFLD) in children with HIV and in controls and to determine association between lipid profile, LDS, liver amino-transferases, NAFLD, BMI, body fat percentage, SFT, WHtR and CIMT. METHODS: This cross-sectional study was done in 7 to 12 y old children attending the ART clinic and receiving ART for ≥6 mo according to 2018 National Aids Control Organization (NACO) guidelines. Thirty age and gender matched controls were enrolled from the pediatrics OPD. Weight, height, BMI, waist circumference, skin fold thickness and blood pressure were recorded. Lipid profile, liver amino-transferases, USG abdomen and CIMT were done with prior appointment. RESULTS: The present study had 43% females and 57% males (mean age of 9.33 ± 1.65 y). All cases were on combination ART (mean treatment duration: 59.1 mo). CIMT was significantly increased in cases as compared to controls 0.481 ± 0.087 mm vs. 0.418 ± 0.072 mm (p = 0.003). However, CIMT did not correlate with any other parameter. Cases had significantly higher body fat percentage (17% vs. 13.15%), systolic blood pressure (SBP), SFT, total cholesterol (TC) and low density lipoprotein- cholesterol (LDL-C) as compared to controls. NAFLD was seen in 3 cases (1%), lipohypertrophy in 7 (23%) cases and 5 (16%) controls. CONCLUSIONS: Children with HIV on ART have significantly higher CIMT and increased metabolic abnormalities.

Asunto(s)

Grosor Intima-Media Carotídeo , Infecciones por VIH , Humanos , Masculino , Femenino , Estudios Transversales , Niño , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/complicaciones , Enfermedad del Hígado Graso no Alcohólico , Índice de Masa Corporal , Antirretrovirales/uso terapéutico , Antirretrovirales/efectos adversos , Estudios de Casos y Controles