RESUMO
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.
Assuntos
Infecções por HIV , Doença de Hodgkin , Humanos , Doença de Hodgkin/tratamento farmacológico , Masculino , Adulto , Infecções por HIV/tratamento farmacológico , Índia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Contagem de Linfócito CD4 , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Bleomicina/efeitos adversos , Bleomicina/administração & dosagem , Dacarbazina/efeitos adversos , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vimblastina/uso terapêutico , Antirretrovirais/uso terapêutico , Antirretrovirais/efeitos adversosRESUMO
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.
Assuntos
Infecções por HIV , Síndrome Inflamatória da Reconstituição Imune , Tuberculose , Carga Viral , Humanos , Síndrome Inflamatória da Reconstituição Imune/epidemiologia , Masculino , Adulto , Feminino , Incidência , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/imunologia , Contagem de Linfócito CD4 , Tuberculose/epidemiologia , Tuberculose/tratamento farmacológico , Tuberculose/imunologia , Índia/epidemiologia , Pessoa de Meia-Idade , Antirretrovirais/uso terapêutico , Antirretrovirais/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológicoRESUMO
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.
Assuntos
Infecções por HIV , Humanos , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Incidência , Antirretrovirais/efeitos adversos , Antirretrovirais/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/epidemiologiaAssuntos
Infecções por HIV , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/complicações , Criança , Masculino , Feminino , Antirretrovirais/uso terapêutico , Antirretrovirais/efeitos adversos , Doenças Metabólicas , Adolescente , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Pré-EscolarRESUMO
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.
Assuntos
Barreira Hematoencefálica , Compostos Heterocíclicos com 3 Anéis , Oxazinas , Piperazinas , Piridonas , Animais , Camundongos , Piperazinas/farmacologia , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/farmacologia , Humanos , Oxazinas/farmacologia , Inflamação/induzido quimicamente , Inflamação/metabolismo , Camundongos Endogâmicos C57BL , Feminino , Inibidores de Integrase de HIV/farmacologia , Inibidores de Integrase de HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/metabolismo , Masculino , Antirretrovirais/efeitos adversos , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacosRESUMO
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 3âyears 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 +â1.9âkg/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.
Assuntos
Infecções por HIV , Aumento de Peso , Humanos , Aumento de Peso/efeitos dos fármacos , Masculino , Feminino , Infecções por HIV/tratamento farmacológico , Adulto , Pessoa de Meia-Idade , Antirretrovirais/uso terapêutico , Antirretrovirais/efeitos adversos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Estudos de Coortes , Índice de Massa Corporal , Tenofovir/uso terapêutico , Tenofovir/efeitos adversosRESUMO
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.
Assuntos
Infecções por HIV , Aumento de Peso , Humanos , Aumento de Peso/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Obesidade , Antirretrovirais/uso terapêutico , Antirretrovirais/efeitos adversos , Terapia Antirretroviral de Alta Atividade/efeitos adversosRESUMO
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.
Assuntos
Tecido Adiposo , Infecções por HIV , Humanos , Infecções por HIV/tratamento farmacológico , Tecido Adiposo/efeitos dos fármacos , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Inibidores da Transcriptase Reversa/efeitos adversos , Inibidores da Transcriptase Reversa/uso terapêutico , Síndrome de Lipodistrofia Associada ao HIV/induzido quimicamente , Antirretrovirais/efeitos adversos , Antirretrovirais/uso terapêutico , Tenofovir/uso terapêutico , Tenofovir/efeitos adversosRESUMO
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.
Assuntos
Terapia Antirretroviral de Alta Atividade , Dislipidemias , Infecções por HIV , Humanos , Dislipidemias/tratamento farmacológico , Dislipidemias/induzido quimicamente , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Infecções por HIV/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipolipemiantes/efeitos adversos , Hipolipemiantes/uso terapêutico , Antirretrovirais/efeitos adversos , Antirretrovirais/uso terapêutico , Substituição de MedicamentosRESUMO
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 â=â43) and musculoskeletal ( n â=â37) 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.
Assuntos
Anormalidades Induzidas por Medicamentos , Antirretrovirais , Infecções por HIV , Complicações Infecciosas na Gravidez , Primeiro Trimestre da Gravidez , Humanos , Feminino , Gravidez , Infecções por HIV/tratamento farmacológico , Estados Unidos/epidemiologia , Adulto , Anormalidades Induzidas por Medicamentos/epidemiologia , Anormalidades Induzidas por Medicamentos/etiologia , Recém-Nascido , Estudos Longitudinais , Complicações Infecciosas na Gravidez/tratamento farmacológico , Antirretrovirais/efeitos adversos , Antirretrovirais/uso terapêutico , Lactente , Masculino , Adulto Jovem , Prevalência , Anormalidades Congênitas/epidemiologiaRESUMO
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.
Assuntos
Antirretrovirais , Contraceptivos Hormonais , Interações Medicamentosas , Humanos , Feminino , Antirretrovirais/efeitos adversos , Contraceptivos Hormonais/administração & dosagem , Contraceptivos Hormonais/farmacocinética , Gravidez , Benzoxazinas/administração & dosagem , Benzoxazinas/efeitos adversos , Alcinos , Contracepção Hormonal , Tenofovir/farmacocinética , Tenofovir/efeitos adversos , Citocromo P-450 CYP2B6/genética , Infecções por HIV/tratamento farmacológico , Ciclopropanos/administração & dosagem , Taxa de Gravidez , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/administração & dosagemRESUMO
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.
Assuntos
Fármacos Anti-HIV , Interações Medicamentosas , Infecções por HIV , Polimedicação , Humanos , Infecções por HIV/tratamento farmacológico , Idoso , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/farmacologia , Comorbidade , Fatores Etários , Relação Dose-Resposta a Droga , Expectativa de Vida , Antirretrovirais/efeitos adversos , Antirretrovirais/administração & dosagem , Monitoramento de Medicamentos/métodosRESUMO
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.
Assuntos
Antirretrovirais , Endotélio Vascular , Infecções por HIV , Animais , Humanos , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/efeitos adversos , Antirretrovirais/uso terapêutico , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Endotélio Vascular/virologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológicoRESUMO
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.
Assuntos
Infecções por HIV , Aumento de Peso , Humanos , Infecções por HIV/tratamento farmacológico , Aumento de Peso/efeitos dos fármacos , Feminino , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Tenofovir/uso terapêutico , Tenofovir/efeitos adversos , Masculino , Antirretrovirais/uso terapêutico , Antirretrovirais/efeitos adversosRESUMO
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.
Assuntos
Antituberculosos , Interações Medicamentosas , Infecções por HIV , Síndrome Inflamatória da Reconstituição Imune , Tuberculose , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/complicações , Tuberculose/tratamento farmacológico , Tuberculose/complicações , Antituberculosos/uso terapêutico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Antirretrovirais/uso terapêutico , Antirretrovirais/efeitos adversos , Terapia Antirretroviral de Alta Atividade , Resultado do TratamentoRESUMO
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.
Assuntos
Exodesoxirribonucleases , Infecções por HIV , HIV-1 , Reconstituição Imune , Fosfoproteínas , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anticorpos Antinucleares/sangue , Linfócitos T CD4-Positivos/imunologia , Exodesoxirribonucleases/genética , Exodesoxirribonucleases/metabolismo , Genótipo , Infecções por HIV/imunologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Infecções por HIV/virologia , HIV-1/imunologia , Reconstituição Imune/genética , Reconstituição Imune/imunologia , Interferon-alfa/sangue , Interferon-alfa/metabolismo , Fosfoproteínas/genética , Polimorfismo de Nucleotídeo Único , Carga Viral , Antirretrovirais/efeitos adversos , Antirretrovirais/uso terapêuticoRESUMO
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.