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1.
MMWR Morb Mortal Wkly Rep ; 69(1): 1-5, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31917782

RESUMO

In May 2018, a study of birth defects in infants born to women with diagnosed human immunodeficiency virus (HIV) infection in Botswana reported an eightfold increased risk for neural tube defects (NTDs) among births with periconceptional exposure to antiretroviral therapy (ART) that included the integrase inhibitor dolutegravir (DTG) compared with other ART regimens (1). The World Health Organization* (WHO) and the U.S. Department of Health and Human Services† (HHS) promptly issued interim guidance limiting the initiation of DTG during early pregnancy and in women of childbearing age with HIV who desire pregnancy or are sexually active and not using effective contraception. On the basis of additional data, WHO now recommends DTG as a preferred treatment option for all populations, including women of childbearing age and pregnant women. Similarly, the U.S. recommendations currently state that DTG is a preferred antiretroviral drug throughout pregnancy (with provider-patient counseling) and as an alternative antiretroviral drug in women who are trying to conceive.§ Since 1981 and 1994, CDC has supported separate surveillance programs for HIV/acquired immunodeficiency syndrome (AIDS) (2) and birth defects (3) in state health departments. These two surveillance programs can inform public health programs and policy, linkage to care, and research activities. Because birth defects surveillance programs do not collect HIV status, and HIV surveillance programs do not routinely collect data on occurrence of birth defects, the related data have not been used by CDC to characterize birth defects in births to women with HIV. Data from these two programs were linked to estimate overall prevalence of NTDs and prevalence of NTDs in HIV-exposed pregnancies during 2013-2017 for 15 participating jurisdictions. Prevalence of NTDs in pregnancies among women with diagnosed HIV infection was 7.0 per 10,000 live births, similar to that among the general population in these 15 jurisdictions, and the U.S. estimate based on data from 24 states. Successful linking of data from birth defects and HIV/AIDS surveillance programs for pregnancies among women with diagnosed HIV infection suggests that similar data linkages might be used to characterize possible associations between maternal diseases or maternal use of medications, such as integrase strand transfer inhibitors used to manage HIV, and pregnancy outcomes. Although no difference in NTD prevalence in HIV-exposed pregnancies was found, data on the use of integrase strand transfer inhibitors in pregnancy are needed to understand the safety and risks of these drugs during pregnancy.


Assuntos
Infecções por HIV/diagnóstico , Defeitos do Tubo Neural/epidemiologia , Complicações Infecciosas na Gravidez/diagnóstico , Adolescente , Adulto , Antirretrovirais/efeitos adversos , Antirretrovirais/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Recém-Nascido , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Estados Unidos/epidemiologia , Adulto Jovem
2.
Hu Li Za Zhi ; 67(1): 55-65, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-31960397

RESUMO

BACKGROUND: Early antiretroviral therapy (ART) is recommended as an intervention for HIV by the World Health Organization. However, the association between the CD4 count at ART initiation and the risk of adverse drug reactions (ADRs) remains unclear. PURPOSE: This study aimed to describe the trends related to symptom number and intensity among patients newly diagnosed with HIV in three different CD4-count-based groups and then to investigate the ADR trends for these three groups at different points in time. METHODS: This multi-center cohort study recruited newly diagnosed HIV/AIDS patients who had not previously used ART from AIDS-designated hospitals in Taiwan from March 2015 to December 2016. Study measures were assessed at the time of case enrollment (T0) and during the 1st month (T1), 4-6th month (T2), and 7-9th month (T3) of ART treatment. Patients were stratified into three groups according to initial CD4 count: ≤ 350 cells/mm3, >350-500 cells/mm3 and >500 cells/mm3. Repeated measures ANOVA and generalized estimating equations were used to estimate the relationships between the level of initial CD4 count and ADRs. RESULTS: A total of 207 patients completed the study. Mean symptom numbers and symptom intensities decreased significantly over time in all three groups (p < .01). The largest mean reduction in both symptom number and intensity was achieved by the CD4 count >500 cells/mm3 group. Overall, at least one ADR was reported by 85.7% of the participants at the first month of ART use, and the incidence of ADR had decreased by an average of 22% at the 7-9th month assessment (p < .001). ARDs decreased significantly over time in the CD4 count > 500 cells/mm3 group, with the degrees of ADRs in systematic side effect most significantly decreased in this group (p = .03). CONCLUSIONS / IMPLICATIONS FOR PRACTICE: Number and intensity of symptoms significantly improved over time in all three CD4 count groups. The percentage of systematic side effects was most reduced in the CD4 count > 500 cells/mm3 group. The results of this study may be referenced by HIV care providers when discussing with patients the initiation of ART and the potential risks of experiencing ADRs.


Assuntos
Antirretrovirais/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Contagem de Linfócito CD4/estatística & dados numéricos , Estudos de Coortes , Infecções por HIV/diagnóstico , Humanos , Taiwan/epidemiologia , Fatores de Tempo
3.
BMC Infect Dis ; 19(1): 1043, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31823736

RESUMO

BACKGROUND: The implementation of national antiretroviral therapy (ART) and expanded ART policies results in that more and more HIV-infected patients receive ART in Kunming, Yunnan province, China. At the same time, however, the number of patients, who drop-out from ART, are also increasing. In this study, we explored the factors that may account for drop-out. METHODS: Four hundred and thirty-nine HIV-infected patients, who received or used to receive ART, were recruited in this study. Their age is among 18 and 75. All patients were divided into two group: ART group (187 patients) and drop-out group (252 patients). Appropriate bio-statistics analysis, including univariate analysis and Multivariate analysis, were used to identify factors associated with drop-out. RESULTS: Data from all patients were analyzed. Univariate analysis suggested that the factors associated with drop-out may include age, residential area, educational level, occupation, monthly income, the access to minimum living allowance, HIV transmission route, and living status. On the other hand, factors including area, monthly income, the access to minimum living allowance, and referral methods of follow-up institutions account for drop-out in multivariate analysis. CONCLUSIONS: This study identified a number of factors associated with drop out from ART. Based on our findings,appropriate interventions should be introduced decrease drop-out.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Adolescente , Adulto , Idoso , Antirretrovirais/efeitos adversos , China , Feminino , Infecções por HIV/economia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Inquéritos e Questionários , Adulto Jovem
4.
Artigo em Inglês | MEDLINE | ID: mdl-31859848

RESUMO

Mycobacterium haemophilum is a nontuberculous mycobacterium that causes localized or disseminated disease, mainly in immunocompromised hosts. We report the case of a 35-year-old HIV-infected woman who presented with several enlarging cutaneous lesions over the arms and legs. Histopathological examination revealed the diagnosis of a cutaneous mycobacterial disease. Mycobacterial analyses unveiled M. haemophilum infection. Six months after completion of a successful antimycobacterial treatment, she developed an immune reconstitution inflammatory syndrome (IRIS). This paradoxical relapse presented as tenderness, redness and swelling at the precise sites of the healed lesions and took place in the setting of significant recovery of the CD4 cell count (from 05 to 318 cells/mm 3 ). Microbiological analyses of these worsening lesions were negative, and they spontaneously remitted without the initiation of a novel antimycobacterial treatment cycle. M. haemophilum infection should always be considered as a cause of skin lesions in immunocompromised subjects. Physicians should be aware of the possibility of IRIS as a complication of successful antiretroviral therapy in HIV-infected patients with M. haemophilum infection.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Antirretrovirais/efeitos adversos , Síndrome Inflamatória da Reconstituição Imune/microbiologia , Infecções por Mycobacterium/microbiologia , Mycobacterium haemophilum/isolamento & purificação , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Adulto , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Feminino , Humanos , Síndrome Inflamatória da Reconstituição Imune/imunologia , Síndrome Inflamatória da Reconstituição Imune/metabolismo , Hospedeiro Imunocomprometido , Masculino , Infecções por Mycobacterium/imunologia
5.
Rev Soc Bras Med Trop ; 52: e20180441, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31596347

RESUMO

Hepatitis B is a major public health problem worldwide and associated with significant mortality. To prevent or delay the deleterious effects of chronic infection by the hepatitis B virus, patients should be carefully followed, and antiviral therapy indicated according to specific recommendations. Currently, available drugs inhibit viral replication and slow or stop the progression of inflammation and fibrosis of the liver. However, the drugs for oral use in the treatment of hepatitis B, jointly referred to as nucleoside/nucleotide analogs, are indicated for prolonged use and have potential side effects. The reduction in bone mineral density was associated with the use of tenofovir, already evaluated in patients infected with HIV because the drug is also part of the therapeutic arsenal for this viral infection. There are few studies on the effects of tenofovir in patients with mono hepatitis B. Therefore, this literature review proposes to examine how hepatitis B acts in the body and the mechanisms by which antiretroviral drugs (especially tenofovir) can affect bone metabolism.


Assuntos
Antirretrovirais/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Antirretrovirais/administração & dosagem , Humanos , Replicação Viral/efeitos dos fármacos
6.
Life Sci ; 235: 116851, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31499070

RESUMO

AIMS: We performed a systematic review and meta-analysis on the effect of HIV infection and antiretroviral therapy (ART) on carotid intima-media thickness (cIMT) to elucidate the role of HIV infection and ART. Also, an analysis on the role of ethnicity and gender on cIMT in HIV-infected populations was performed. MAIN METHODS: We searched the PubMed, Web of Science, the WHO websites and International AIDS Society for published observational studies were conducted by two independent reviewers for studies comparing HIV-infected antiretroviral-experienced patients and/or inexperienced with healthy controls on cIMT. The primary outcome was the standardized mean difference (SMD) of cIMT. FINDINGS: Twenty studies (five cohort, 15 cross-sectional, and two both cohort and cross-sectional studies) were identified comprising 7948 subjects (4656 HIV-infected; 3292 controls). In cohort studies, the standardized mean 1-year change in cIMT between HIV-infected patients and uninfected controls was not significantly different (0.16 mm/yr; 95% CI, -0.16, 0.49; p = 0.326). In 17 cross-sectional studies, the SMD in cIMT was significantly higher in HIV-infected than uninfected persons (0.27 mm; 95% CI, 0.04, 0.49; p = 0.027). HIV-infected patients on ART exhibited significantly higher SMD in cIMT compared to those not on ART (0.75 mm; 95% CI, 0.30, 1.19; p = 0.001). No confounding effect of gender and ethnicity could be established using meta-regression p > 0.05. SIGNIFICANCE: HIV infection itself and ART appear to influence the progression of cIMT and hence may be risk factors for cardiovascular events. No firm conclusions could be drawn on the effect of ethnic/race and gender differences on cIMT in HIV-infected populations.


Assuntos
Antirretrovirais/efeitos adversos , Espessura Intima-Media Carotídea , Infecções por HIV/dietoterapia , Infecções por HIV/patologia , Grupos Étnicos , Humanos , Caracteres Sexuais
7.
Przegl Epidemiol ; 73(2): 249-255, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31385682

RESUMO

INTRODUCTION: Chronic kidney disease is a significant cause of morbidity and mortality among patients infected with human immunodeficiency virus (HIV). Tenofovir disoproxil fumarate (TDF) is widely used as the part of combination antiretroviral therapy (cART) and may cause renal function impairment. AIM: The primary objective of this analysis was to determine the rate of reversibility of kidney dysfunction and factors correlated with eGFR improvement in patients treated with TDF. MATERIALS AND METHODS: All patients who discontinued TDF between 2003 and 2015 were screened and included in the study if the reason for withdrawal was nephrotoxicity. Kidney function (eGFR, proteinuria, haematuria) was assessed on treatment and one year after discontinuation. Factors associated with not achieving eGFR recovery one year after discontinuing TDF were assessed. RESULTS: A total of 69 patients out of 1625 screened discontinued TDF due to nephrotoxicity and were included in the analysis. At the end of the study period eGFR (CKD-EPI) improved in 52 (75,4%) patients. The eGFR difference was 11,7 ml/min/1,73m2 (95% CI: 6,0 ­ 14,5). Two factors were associated with kidney function improvement: the length of TDF treatment and baseline eGFR. Better recovery was observed in patients treated with shorter (difference: 15,6 ml/min/1,73m2, 95% CI: 5,99 ­ 23,0) and in those with impaired renal function at baseline (difference: 21 ml/min/1,73m2, 95% CI: 11,0 ­ 27,99). CONCLUSIONS: In majority of patients who discontinue TDF therapy, kidney function improves during oneyear period. The drug withdrawal in case of eGFR deterioration should not be postponed.


Assuntos
Nefropatias/induzido quimicamente , Tenofovir/efeitos adversos , Adulto , Antirretrovirais/efeitos adversos , Antirretrovirais/uso terapêutico , Antirretrovirais/toxicidade , Feminino , Taxa de Filtração Glomerular , Infecções por HIV/tratamento farmacológico , Hematúria , Humanos , Masculino , Pessoa de Meia-Idade , Proteinúria , Estudos Retrospectivos , Tenofovir/uso terapêutico , Tenofovir/toxicidade
8.
Infect Dis Clin North Am ; 33(3): 787-805, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31395145

RESUMO

Antiretroviral therapy has advanced significantly since zidovudine was first approved. Although 31 antiretrovirals have been approved by the FDA, only about half of those are commonly used. Newer, more tolerable agents have made human immunodeficiency virus into a chronic condition, which can be managed with medication. The most common antiretroviral regimens consist of 2 nucleoside reverse transcriptase inhibitors plus a third agent, often an integrase inhibitor because of better tolerability and fewer drug interactions than other regimens. Understanding the dosage forms, adverse effects, and drug interactions of antiretrovirals allow clinicians to choose the most appropriate regimen for their patient. New developments, such as branded generic regimens and long-acting intramuscular injections, may play a larger role in the future.


Assuntos
Antirretrovirais/administração & dosagem , Terapia Antirretroviral de Alta Atividade/métodos , Infecções por HIV/tratamento farmacológico , Antirretrovirais/efeitos adversos , Antirretrovirais/farmacocinética , Antirretrovirais/farmacologia , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Interações de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos
10.
N Engl J Med ; 381(9): 803-815, 2019 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-31339677

RESUMO

BACKGROUND: Two drugs under consideration for inclusion in antiretroviral therapy (ART) regimens for human immunodeficiency virus (HIV) infection are dolutegravir (DTG) and tenofovir alafenamide fumarate (TAF). There are limited data on their use in low- and middle-income countries. METHODS: We conducted a 96-week, phase 3, investigator-led, open-label, randomized trial in South Africa, in which we compared a triple-therapy combination of emtricitabine (FTC) and DTG plus either of two tenofovir prodrugs - TAF (TAF-based group) or tenofovir disoproxil fumarate (TDF) (TDF-based group) - against the local standard-of-care regimen of TDF-FTC-efavirenz (standard-care group). Inclusion criteria included an age of 12 years or older, no receipt of ART in the previous 6 months, a creatinine clearance of more than 60 ml per minute (>80 ml per minute in patients younger than 19 years of age), and an HIV type 1 (HIV-1) RNA level of 500 copies or more per milliliter. The primary end point was the percentage of patients with a 48-week HIV-1 RNA level of less than 50 copies per milliliter (as determined with the Snapshot algorithm from the Food and Drug Administration; noninferiority margin, -10 percentage points). We report the primary (48-week) efficacy and safety data. RESULTS: A total of 1053 patients underwent randomization from February 2017 through May 2018. More than 99% of the patients were black, and 59% were female. The mean age was 32 years, and the mean CD4 count was 337 cells per cubic millimeter. At week 48, the percentage of patients with an HIV-1 RNA level of less than 50 copies per milliliter was 84% in the TAF-based group, 85% in the TDF-based group, and 79% in the standard-care group, findings that indicate that the DTG-containing regimens were noninferior to the standard-care regimen. The number of patients who discontinued the trial regimen was higher in the standard-care group than in the other two groups. In the per-protocol population, the standard-care regimen had equivalent potency to the other two regimens. The TAF-based regimen had less effect on bone density and renal function than the other regimens. Weight increase (both lean and fat mass) was greatest in the TAF-based group and among female patients (mean increase, 6.4 kg in the TAF-based group, 3.2 kg in the TDF-based group, and 1.7 kg in the standard-care group). No resistance to integrase inhibitors was identified in patients receiving the DTG-containing regimens. CONCLUSIONS: Treatment with DTG combined with either of two tenofovir prodrugs (TAF and TDF) showed noninferior efficacy to treatment with the standard-care regimen. There was significantly more weight gain with the DTG-containing regimens, especially in combination with TAF, than with the standard-care regimen. (ADVANCE ClinicalTrials.gov number, NCT03122262.).


Assuntos
Adenina/análogos & derivados , Antirretrovirais/administração & dosagem , Infecções por HIV/tratamento farmacológico , HIV-1 , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Ácidos Fosforosos/administração & dosagem , Adenina/administração & dosagem , Adenina/efeitos adversos , Adolescente , Adulto , Antirretrovirais/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Contagem de Linfócito CD4 , Quimioterapia Combinada , Feminino , Inibidores de Integrase de HIV/administração & dosagem , HIV-1/genética , HIV-1/isolamento & purificação , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Ácidos Fosforosos/efeitos adversos , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Pró-Fármacos/administração & dosagem , RNA Viral/sangue , Uracila/administração & dosagem , Uracila/análogos & derivados , Carga Viral , Adulto Jovem
11.
N Engl J Med ; 381(9): 827-840, 2019 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-31329379

RESUMO

BACKGROUND: A preliminary safety signal for neural-tube defects was previously reported in association with dolutegravir exposure from the time of conception, which has affected choices of antiretroviral treatment (ART) for human immunodeficiency virus (HIV)-infected women of reproductive potential. The signal can now be evaluated with data from follow-up of additional pregnancies. METHODS: We conducted birth-outcomes surveillance at hospitals throughout Botswana, expanding from 8 to 18 sites in 2018. Trained midwives performed surface examinations of all live-born and stillborn infants. Research assistants photographed abnormalities after maternal consent was obtained. The prevalence of neural-tube defects and major external structural defects according to maternal HIV infection and ART exposure status was determined. In the primary analyses, we used the Newcombe method to evaluate differences in prevalence with 95% confidence intervals. RESULTS: From August 2014 through March 2019, surveillance captured 119,477 deliveries; 119,033 (99.6%) had an infant surface examination that could be evaluated, and 98 neural-tube defects were identified (0.08% of deliveries). Among 1683 deliveries in which the mother was taking dolutegravir at conception, 5 neural-tube defects were found (0.30% of deliveries); the defects included two instances of myelomeningocele, one of anencephaly, one of encephalocele, and one of iniencephaly. In comparison, 15 neural-tube defects were found among 14,792 deliveries (0.10%) in which the mother was taking any non-dolutegravir ART at conception, 3 among 7959 (0.04%) in which the mother was taking efavirenz at conception, 1 among 3840 (0.03%) in which the mother started dolutegravir treatment during pregnancy, and 70 among 89,372 (0.08%) in HIV-uninfected mothers. The prevalence of neural-tube defects was higher in association with dolutegravir treatment at conception than with non-dolutegravir ART at conception (difference, 0.20 percentage points; 95% confidence interval [CI], 0.01 to 0.59) or with other types of ART exposure. Major external structural defects were found in 0.95% of deliveries among women exposed to dolutegravir at conception and 0.68% of those among women exposed to non-dolutegravir ART at conception (difference, 0.27 percentage points; 95% CI, -0.13 to 0.87). CONCLUSIONS: The prevalence of neural-tube defects was slightly higher in association with dolutegravir exposure at conception than with other types of ART exposure at conception (3 per 1000 deliveries vs. 1 per 1000 deliveries). (Funded by the National Institutes of Health.).


Assuntos
Antirretrovirais/efeitos adversos , Anormalidades Congênitas/epidemiologia , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Defeitos do Tubo Neural/induzido quimicamente , Complicações Infecciosas na Gravidez/tratamento farmacológico , Adulto , Antirretrovirais/uso terapêutico , Botsuana/epidemiologia , Quimioterapia Combinada , Feminino , Feto/efeitos dos fármacos , Inibidores de Integrase de HIV/efeitos adversos , Inibidores de Integrase de HIV/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Recém-Nascido , Defeitos do Tubo Neural/epidemiologia , Vigilância da População , Gravidez , Prevalência , Fatores Socioeconômicos
12.
Zhonghua Liu Xing Bing Xue Za Zhi ; 40(7): 770-774, 2019 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-31357796

RESUMO

Objective: To evaluate the influence of antiretroviral prophylaxis on the growth and development of HIV-exposed uninfected infants in Guangzhou. Methods: Data were from the national information system for prevention of mother-to-child transmission of HIV infection, syphilis and hepatitis B. After excluding death and perinatal HIV infection cases, 564 HIV-exposed uninfected infants were included. The infants were divided into three groups, nevirapine (NVP) group, zidovudine (AZT) group and untreated group. The influences of antiretroviral prophylaxis on the body weight and height of the HIV-exposed uninfected infants were analyzed by using generalized estimating equations. Results: The HIV-exposed uninfected infants at 1-month old had lower Z scores of body weight-for-age and body height-for-age than the World Health Organization's reference standard. The prevalence of wasting in AZT group (17.5%) was higher than that in NVP group (6.2%) for 1-month old infants. Taking NVP or AZT was a protective factor for Z score of body length-for-age (P<0.05). Intrauterine exposure to triple antiviral drugs was a risk factor for the Z scores of body weight-for-age and body length-for-age (P<0.05). Conclusion: The physical growth and development of HIV-exposed uninfected infants at 1-month old was not well, and HIV-exposed uninfected infants who taking AZT had a higher incidence of wasting. Attention should be paid to these infants.


Assuntos
Antirretrovirais/efeitos adversos , Crescimento e Desenvolvimento/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Complicações Infecciosas na Gravidez/tratamento farmacológico , China/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Síndrome de Emaciação/epidemiologia
13.
Drug Des Devel Ther ; 13: 1667-1685, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190745

RESUMO

Background: The protease inhibitor (PI) darunavir (DRV) has proven to be highly effective and well tolerated for HIV treatment. The DAD (Data collection on Adverse Effects of Anti-HIV Drugs) cohort showed an increased 5-year cumulative cardiovascular (CV) risk in patients given various PIs, including DRV, whereas two other recent studies found no association between DRV and CV diseases. Methods: We performed a post-hoc analysis of CV adverse events (CVAEs) in an Italian cohort, the TMC114-HIV4042 observational study, where 875 patients treated with ritonavir-boosted DRV-based regimens were followed for a total of 1,566 patient-years. Results: We observed 23 CVAEs of any type, including 17 [12 (95%CI, 7-19) per 1,000 patient-years] primary; 14 [10 (95%CI, 5-17) per 1,000 patient-years] were primary Framingham-type general CVAEs, close to what expected according to the Framingham algorithm based on traditional risk factors. Age and systolic blood pressure (SBP) at the time of study enrolment were the only relevant (p<0.01) independent predictors of CVAEs in all models; patients with any CVAE were on average 10 years older and had an SBP 14 mmHg higher than patients without CVAEs. When controlling for age and SBP, the association with other traditional factors, including serum lipids, and with HIV-specific factors was not statistically significant (p>0.05). Models that also adjusted for previous ARV exposure showed no statistically significant association between any-type CVAEs and either DRV doses, 1,200 or 800 mg/daily (as also suggested by propensity score stratification), or previous DRV exposure duration. Conclusion : We found no evidence of a relationship between DRV use and increased CV risk.


Assuntos
Antirretrovirais/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Darunavir/efeitos adversos , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/efeitos adversos , Adulto , Antirretrovirais/farmacologia , Estudos de Coortes , Darunavir/farmacologia , Relação Dose-Resposta a Droga , Feminino , Inibidores da Protease de HIV/farmacologia , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Fatores de Risco
14.
JAMA ; 321(23): 2349-2360, 2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-31184704

RESUMO

Importance: Prenatal screening for HIV can inform use of interventions to reduce the risk of mother-to-child transmission. The US Preventive Services Task Force (USPSTF) previously found strong evidence that prenatal HIV screening reduced risk of mother-to-child transmission. The previous evidence review was conducted in 2012. Objective: To update the 2012 review on prenatal HIV screening to inform the USPSTF. Data Sources: Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews from 2012 to June 2018, with surveillance through January 2019. Study Selection: Pregnant persons 13 years and older; randomized clinical trials and cohort studies of screening vs no screening; risk of mother-to-child transmission or maternal or infant harms associated with antiretroviral therapy (ART) during pregnancy; screening yield at different intervals or in different risk groups. Data Extraction and Synthesis: One investigator abstracted data; a second checked accuracy. Two investigators independently rated study quality. Main Outcomes and Measures: Mother-to-child transmission; harms of screening and treatment; screening yield. Results: Sixty-two studies were included in this review, including 29 new studies. There remains no direct evidence on effects of prenatal screening vs no screening on risk of mother-to-child HIV transmission, maternal or infant clinical outcomes, or the yield of repeat or alternative screening strategies. New evidence confirms that combination ART is highly effective at reducing the risk of mother-to-child transmission, with some new cohort studies reporting rates of mother-to-child transmission less than 1% when combination ART was started early in pregnancy (when begun in first trimester, 0%-0.4%; when begun after first trimester, or at any time if timing of ART initiation not reported, 0.4%-2.8%). New evidence on harms of ART was also largely consistent with the previous review. Evidence from primarily observational studies found prenatal combination ART with a boosted protease inhibitor associated with increased risk of preterm delivery (range, 14.4%-26.1%). For other birth outcomes (low birth weight, small for gestational age, stillbirth, birth defects, neonatal death), results were mixed and depended on the specific antiretroviral drug or drug regimen given and timing of prenatal therapy. Conclusions and Relevance: Combination ART was highly effective at reducing risk of mother-to-child HIV transmission. Use of certain ART regimens during pregnancy was associated with increased risk of harms that may be mitigated by selection of ART regimen. The 2012 review found that avoidance of breastfeeding and cesarean delivery in women with viremia also reduced risk of transmission and that prenatal screening accurately diagnosed HIV infection.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/diagnóstico , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Programas de Rastreamento , Complicações Infecciosas na Gravidez/diagnóstico , Adolescente , Adulto , Antirretrovirais/efeitos adversos , Contagem de Linfócito CD4 , Feminino , Feto/efeitos dos fármacos , HIV , Infecções por HIV/tratamento farmacológico , Infecções por HIV/transmissão , Humanos , Programas de Rastreamento/efeitos adversos , Guias de Prática Clínica como Assunto , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Diagnóstico Pré-Natal , Carga Viral
15.
JAMA ; 321(23): 2337-2348, 2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-31184705

RESUMO

Importance: Untreated HIV infection can result in significant morbidity, mortality, and HIV transmission. A 2012 review for the US Preventive Services Task Force (USPSTF) found antiretroviral therapy (ART) associated with improved clinical outcomes and decreased transmission risk in persons with CD4 cell counts less than 500/mm3. Objective: To update the 2012 review on HIV screening to inform the USPSTF. Data Sources: Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews from 2012 to June 2018, with surveillance through January 2019. Study Selection: Nonpregnant individuals 12 years and older; randomized clinical trials (RCTs) and controlled observational studies of screening vs no screening, alternative screening strategies, earlier vs later initiation of ART, and long-term harms of ART. Data Extraction and Synthesis: One investigator abstracted data; a second checked accuracy. Two investigators independently rated study quality. Main Outcomes and Measures: Mortality, AIDS events, quality of life, function, and HIV transmission; harms of screening and long-term (≥2 years) harms of ART; screening yield. Results: Eighteen new studies (5 RCTs, 11 cohort studies, and 2 systematic reviews; N = 266 563) were included, and 11 studies (2 RCTs and 9 cohort studies; N = 218 542) were carried forward from the prior USPSTF report. No study directly evaluated effects of HIV screening vs no screening on clinical outcomes or harms, or the yield of alternative screening strategies. Two newly identified RCTs conducted completely or partially in low-resource settings found ART initiation at CD4 cell counts greater than 500/mm3 associated with lower risk of a composite outcome of mortality, AIDS-defining events, or serious non-AIDS events (relative risk [RR], 0.44 [95% CI, 0.31-0.63] and RR, 0.57 [95% CI, 0.35-0.95]); results were consistent with those from a large observational study. Early ART was not associated with increased risk of cardiovascular events. Early ART initiation was associated with sustained reduction in risk of HIV transmission at 5.5 years (RR, 0.07 [95% CI, 0.02-0.22] for linked transmission). New evidence regarding the association between abacavir use and risk of cardiovascular events was inconsistent. Certain antiretroviral regimens were associated with increased risk of long-term neuropsychiatric, renal, hepatic, and bone adverse events. Conclusions and Relevance: In nonpregnant adolescents and adults there was no direct evidence on the clinical benefits and harms of screening for HIV infections vs no screening, or the yield of repeat or alternative screening strategies. New evidence extends effectiveness of ART to asymptomatic individuals with CD4 cell counts greater than 500/mm3 and shows sustained reduction in risk of HIV transmission at longer-term follow-up, although certain ART regimens may be associated with increased risk of long-term harms.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/diagnóstico , Programas de Rastreamento , Adolescente , Adulto , Antirretrovirais/efeitos adversos , Contagem de Linfócito CD4 , Criança , Transmissão de Doença Infecciosa/prevenção & controle , Feminino , HIV , Infecções por HIV/tratamento farmacológico , Infecções por HIV/transmissão , Humanos , Masculino , Programas de Rastreamento/efeitos adversos , Guias de Prática Clínica como Assunto , Tempo para o Tratamento
16.
JAMA ; 321(22): 2214-2230, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31184746

RESUMO

Importance: Effective prevention strategies for HIV infection are an important public health priority. Preexposure prophylaxis (PrEP) involves use of antiretroviral therapy (ART) daily or before and after sex to decrease risk of acquiring HIV infection. Objective: To synthesize the evidence on the benefits and harms of PrEP, instruments for predicting incident HIV infection, and PrEP adherence to inform the US Preventive Services Task Force. Data Sources: Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and EMBASE through June 2018, with surveillance through January 2019. Study Selection: English-language placebo-controlled randomized clinical trials of oral PrEP with tenofovir disoproxil fumarate/emtricitabine or tenofovir disoproxil fumarate monotherapy; studies on the diagnostic accuracy of instruments for predicting incident HIV infection; and studies on PrEP adherence. Data Extraction and Synthesis: Dual review of titles and abstracts, full-text articles, study quality, and data abstraction. Data were pooled using the Dersimonian and Laird random-effects model for effects of PrEP on HIV infection, mortality, and harms. Main Outcomes and Measures: HIV acquisition, mortality, and harms; adherence to PrEP; and diagnostic test accuracy and discrimination. Results: Fourteen RCTs (N = 18 837), 8 observational studies (N = 3884), and 7 studies of diagnostic accuracy (N = 32 279) were included. PrEP was associated with decreased risk of HIV infection vs placebo or no PrEP after 4 months to 4 years (11 trials; relative risk [RR], 0.46 [95% CI, 0.33-0.66]; I2 = 67%; absolute risk reduction [ARD], -2.0% [95% CI, -2.8% to -1.2%]). Greater adherence was associated with greater efficacy (RR with adherence ≥70%, 0.27 [95% CI, 0.19-0.39]; I2 = 0%) in 6 trials. PrEP was associated with an increased risk of renal adverse events (12 trials; RR, 1.43 [95% CI, 1.18-1.75]; I2 = 0%; ARD, 0.56% [95% CI, 0.09%-1.04%]) and gastrointestinal adverse events (12 trials; RR, 1.63 [95% CI, 1.26-2.11]; I2 = 43%; ARD, 1.95% [95% CI, 0.48%-3.43%]); most adverse events were mild and reversible. Instruments for predicting incident HIV infection had moderate discrimination (area under the receiver operating characteristic curve, 0.49-0.72) and require further validation. Adherence to PrEP in the United States in men who have sex with men varied widely (22%-90%). Conclusions and Relevance: In adults at increased risk of HIV infection, PrEP with oral tenofovir disoproxil fumarate monotherapy or tenofovir disoproxil fumarate/emtricitabine was associated with decreased risk of acquiring HIV infection compared with placebo or no PrEP, although effectiveness decreased with suboptimal adherence.


Assuntos
Antirretrovirais/uso terapêutico , Emtricitabina/uso terapêutico , Infecções por HIV/prevenção & controle , Profilaxia Pré-Exposição , Tenofovir/uso terapêutico , Administração Oral , Antirretrovirais/efeitos adversos , Quimioterapia Combinada , Emtricitabina/efeitos adversos , Feminino , Infecções por HIV/epidemiologia , Humanos , Masculino , Adesão à Medicação , Risco , Tenofovir/efeitos adversos
17.
JAMA ; 321(22): 2203-2213, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31184747

RESUMO

Importance: An estimated 1.1 million individuals in the United States are currently living with HIV, and more than 700 000 persons have died of AIDS since the first cases were reported in 1981. In 2017, there were 38 281 new diagnoses of HIV infection reported in the United States; 81% of these new diagnoses were among males and 19% were among females. Although treatable, HIV infection has no cure and has significant health consequences. Objective: To issue a new US Preventive Services Task Force (USPSTF) recommendation on preexposure prophylaxis (PrEP) for the prevention of HIV infection. Evidence Review: The USPSTF reviewed the evidence on the benefits of PrEP for the prevention of HIV infection with oral tenofovir disoproxil fumarate monotherapy or combined tenofovir disoproxil fumarate and emtricitabine and whether the benefits vary by risk group, population subgroup, or regimen or dosing strategy; the diagnostic accuracy of risk assessment tools to identify persons at high risk of HIV acquisition; the rates of adherence to PrEP in primary care settings; the association between adherence and effectiveness of PrEP; and the harms of PrEP when used for HIV prevention. Findings: The USPSTF found convincing evidence that PrEP is of substantial benefit in decreasing the risk of HIV infection in persons at high risk of HIV acquisition. The USPSTF also found convincing evidence that adherence to PrEP is highly associated with its efficacy in preventing the acquisition of HIV infection; thus, adherence to PrEP is central to realizing its benefit. The USPSTF found adequate evidence that PrEP is associated with small harms, including kidney and gastrointestinal adverse effects. The USPSTF concludes with high certainty that the magnitude of benefit of PrEP with oral tenofovir disoproxil fumarate-based therapy to reduce the risk of acquisition of HIV infection in persons at high risk is substantial. Conclusions and Recommendation: The USPSTF recommends offering PrEP with effective antiretroviral therapy to persons at high risk of HIV acquisition. (A recommendation).


Assuntos
Antirretrovirais/uso terapêutico , Emtricitabina/uso terapêutico , Infecções por HIV/prevenção & controle , Profilaxia Pré-Exposição , Tenofovir/uso terapêutico , Síndrome de Imunodeficiência Adquirida/epidemiologia , Administração Oral , Comitês Consultivos , Antirretrovirais/efeitos adversos , Quimioterapia Combinada , Emtricitabina/efeitos adversos , Feminino , Humanos , Masculino , Adesão à Medicação , Medição de Risco , Fatores de Risco , Tenofovir/efeitos adversos , Estados Unidos/epidemiologia
18.
Expert Opin Pharmacother ; 20(14): 1719-1729, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31232617

RESUMO

Introduction: Cardiovascular disease is an important cause of morbidity and mortality in persons with human immunodeficiency virus (PWH). The risk of atherosclerotic cardiovascular disease (ASCVD) is higher in PWH compared to uninfected persons. Dyslipidemia is a critical link in the pathogenesis of ASCVD in PWH. Chronic inflammation associated with HIV infection may drive both dyslipidemia and ASCVD. Areas covered: The authors review the evidence for using lipid-lowering therapy in PWH and includes an overview of the utility and complexity of using statins in PWH, in particular, drug interactions, safety, and efficacy. In addition, data covering alternate therapies like omega-3 fatty acids, fibrates, niacin, ezetimibe, and PCSK-9 inhibitors are reviewed. Expert opinion: Dyslipidemia is a common problem in PWH. The risk of ASCVD is higher in PWH. Lipid-lowering therapy reduces the risk of ASCVD, but clinical endpoint trials are lacking in PWH. Statin therapy is the mainstay of primary prevention for ASCVD. The timing of when to initiate primary prevention with statins in PWH is unclear. Beyond statins, there are limited data that other lipid-lowering agents have utility in PWH. Ongoing trials like the REPRIEVE trial will inform the community about the optimal approach to lipid-lowering therapy in PWH.


Assuntos
Dislipidemias/tratamento farmacológico , Infecções por HIV/patologia , Hipolipemiantes/uso terapêutico , Antirretrovirais/efeitos adversos , Antirretrovirais/química , Antirretrovirais/uso terapêutico , Interações de Medicamentos , Dislipidemias/etiologia , Ezetimiba/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/química , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Niacina/uso terapêutico , Medição de Risco
19.
BMC Infect Dis ; 19(1): 537, 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31215397

RESUMO

BACKGROUND: Treatment failure has become a significant challenge in patients taking antiretroviral therapy (ART). The aim of the present study was to identify risk factors for first-line ART failure among patients attending clinical follow-up. METHODS: A 1:2 matched case-control study (by age, sex, and treatment duration since initiated on ART) was conducted from June 2015 to July 2017 on adult patients (aged ≥15 years) who were on ART for at least 6 months. Cases were selected from patients who were switched to second-line ART after first-line ART failure (viral load ≥1000 copies/mL). Controls were randomly selected from patients on first-line ART with viral load < 50 copies/mL. Data were collected using an interview questionnaire, reviewing chart and electronic health records and laboratory tests. Multivariate logistic regression analysis was performed to identify risk factors for treatment failure. RESULTS: Of the 273 patients who participated in this study, 55% were males. Ninety-one cases were compared with 182 controls. The median age of participants was 40 years and the median duration of treatment since initiated on ART was 69 months. Independent risk factors associated with first-line antiretroviral treatment failure were discontinuation of ART (adjusted odds ratio (AOR) = 9.8, 95% confidence interval (CI): 4.0-23.8), baseline CD4 lymphocyte count ≤50 cells/mm3 (AOR = 3.8, 95% CI: 1.5-9.6) and persistent diarrhea (AOR = 4.4, 95% CI: 1.5-13.2). The risk of ART failure was high and comparable whether the duration of ART discontinuation was greater or less than 1 month (crude odds ratio (COR) = 6.3 and 8. 5 respectively, p-value < 0.001). Frequent eating of a diet containing wheat or barley (AOR = 2.3, 95% CI: 0.9-5.4) showed a trend to be a risk factor for first-line ART failure (p-value = 0.064). CONCLUSIONS: Our findings underscore the importance of avoiding ART discontinuation of any duration, early initiation of ART and diarrhea management to prevent first-line ART failure.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adolescente , Adulto , Antirretrovirais/efeitos adversos , Contagem de Linfócito CD4 , Estudos de Casos e Controles , Diarreia/etiologia , Dieta , Etiópia , Feminino , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Falha de Tratamento , Adulto Jovem
20.
Int J Mycobacteriol ; 8(2): 113-117, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31210151

RESUMO

Background: Nonsuppression of viral load (VL) in HIV-infected patients on antiretroviral therapy (ART) is associated with increased HIV transmission and poor survival. The objective of this work was to evaluate the factors associated with the unsuppressed VL (VL >400 copies/ml) in HIV-1-infected patients after 6 months of the first-line ART. Methods: This was a retrospective cohort study of 181 patients living with HIV-1 on ART in Dermatology and Venereology Department of Mohamed V Military Teaching Hospital of Rabat, during the period between January 1, 2007, and January 1, 2017. Associated factors were identified through a logistic regression model. Results: Of the 181 patients, 76% were men. At inclusion, the median age was 35 years. Five variables (male sex, initial fasting glucose >1.1 g/l, alcoholism, smoking, and initial VL >10,000 copies/ml) were significantly associated (P < 0.05) with unsuppressed VL. In multivariate analysis, smoking (relative risk [RR]: 4.27, 95% confidence interval [CI]: 1.67-10.89) and initial VL >10,000 (RR: 9.78, 95% CI: 2.40-39.73) were associated independently with unsuppressed VL. Conclusion: Approximately 83% of the patients in the cohort had been able to suppress VL after 6 months of the first-line ART. Smoking and high initial VL were independent risk factors of unsuppressed VL. This work highlights the importance of developing and evaluating targeted interventions for patients at risk of unsuppressed VL on ART.


Assuntos
Antirretrovirais/efeitos adversos , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Resposta Viral Sustentada , Carga Viral , Adulto , Alcoolismo/complicações , Feminino , HIV-1/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Marrocos , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Fumar/efeitos adversos
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