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1.
Clin Infect Dis ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38663013

RESUMO

BACKGROUND: Mortality among people with HIV declined with the introduction of combination antiretroviral therapy. We investigated trends over time in all-cause and cause-specific mortality in people with HIV from 1999-2020. METHODS: Data were collected from the D:A:D cohort from 1999 through January 2015 and RESPOND from October 2017 through 2020. Age-standardized all-cause and cause-specific mortality rates, classified using Coding Causes of Death in HIV (CoDe), were calculated. Poisson regression models were used to assess mortality trends over time. RESULTS: Among 55716 participants followed for a median of 6 years (IQR 3-11), 5263 participants died (crude mortality rate [MR] 13.7/1000 PYFU; 95%CI 13.4-14.1). Changing patterns of mortality were observed with AIDS as the most common cause of death between 1999- 2009 (n = 952, MR 4.2/1000 PYFU; 95%CI 4.0-4.5) and non-AIDS defining malignancy (NADM) from 2010 -2020 (n = 444, MR 2.8/1000 PYFU; 95%CI 2.5-3.1). In multivariable analysis, all-cause mortality declined over time (adjusted mortality rate ratio [aMRR] 0.97 per year; 95%CI 0.96, 0.98), mostly from 1999 through 2010 (aMRR 0.96 per year; 95%CI 0.95-0.97), and with no decline shown from 2011 through 2020 (aMRR 1·00 per year; 95%CI 0·96-1·05). Mortality due all known causes except NADM also declined over the entire follow-up period. CONCLUSION: Mortality among people with HIV in the D:A:D and/or RESPOND cohorts decreased between 1999 and 2009 and was stable over the period from 2010 through 2020. The decline in mortality rates was not fully explained by improvements in immunologic-virologic status or other risk factors.

2.
New Microbiol ; 46(4): 407-411, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38252053

RESUMO

People aging with 4 antiretroviral class resistant HIV are a very challenging population. It is difficult to build up a fully suppressive regimen, and the high prevalence of comorbidities and polypharmacy may cause drug-drug interactions and put adherence at risk. We herein present the case of an 80-year-old man, participating in the PRESTIGIO registry, asking for a reduction in his antiretroviral burden while on polypharmacy for his comorbidities.


Assuntos
Envelhecimento , Infecções por HIV , Masculino , Humanos , Idoso de 80 Anos ou mais , Antirretrovirais , Infecções por HIV/tratamento farmacológico
3.
New Microbiol ; 47(1): 116-122, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38700893

RESUMO

Management of virological failure in heavily treatment-experienced people with multidrug-resistant (MDR) HIV infection is a serious clinical challenge. New drugs with novel mechanisms of action have recently been approved, and their use has improved the outcome of subjects with limited treatment options (LTO). In this setting, the choice of antiretroviral therapy (ART) should be tailored based on the pattern of resistance, treatment history and patients' individual characteristics. While genotypic resistance testing is the reference method for analysing residual drug susceptibility, phenotypic resistance testing can provide additional support when facing LTO. Herein, we present the case of a patient with MDR HIV-1 infection on virological failure enrolled in the PRESTIGIO Registry. The salvage ART regimen, which included drugs with novel mechanisms of action (MoA), was tailored to the patient's clinical characteristics and on the resistance pattern explored with genotypic and phenotypic investigation, allowing the achievement of viro-immunological success. The use of recently approved drugs with novel MoA, combined with an optimized background regimen, may also achieve virological suppression in people with LTO.


Assuntos
Fármacos Anti-HIV , Cobicistat , Farmacorresistência Viral Múltipla , Genótipo , Infecções por HIV , HIV-1 , Compostos Heterocíclicos com 3 Anéis , Piperazinas , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Masculino , HIV-1/efeitos dos fármacos , HIV-1/genética , Pessoa de Meia-Idade , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/farmacologia , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Farmacorresistência Viral Múltipla/genética , Piperazinas/uso terapêutico , Cobicistat/uso terapêutico , Cobicistat/administração & dosagem , Sulfato de Atazanavir/uso terapêutico , Rilpivirina/uso terapêutico , Piridonas/uso terapêutico , Oxazinas/uso terapêutico , Testes de Sensibilidade Microbiana , Fenótipo
4.
Sex Transm Infect ; 99(2): 120-123, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35523576

RESUMO

OBJECTIVES: To explore different sexual behaviours as risk factors for STI among men who have sex with men (MSM) living with HIV. METHODS: This is a cross-sectional study on MSM living with HIV followed at the Infectious Diseases Unit of San Raffaele Hospital, Milan, with at least one diagnosis of gonorrhoea, syphilis, chlamydia or anal human papilloma virus (HPV), between July 2016 and February 2021. We conducted a survey on high-risk sexual behaviours with regard to (1) mean number of partners per month, (2) estimated percentage of condom use and (3) most frequent type of sexual intercourse during 2016-2021. Data on these variables were grouped as follows: (1a) ≤5 vs >5, (1b) >10 vs ≤10, (2a) 0% vs >0%, (2b) ≤50% vs >50%, (2c) 100% vs <100%, (3a) ≥50% vs <50% receptive, (3b) 100% vs <100% insertive, and (3c) 100% vs <100% receptive. A high-risk group was defined as >5 partners, <100% use of condom and ≥50% receptive intercourse. Univariate logistic regressions were applied to assess the association between sexual behaviours and the risk of each STI. RESULTS: Out of 1051 MSM with at least one STI diagnosis, 580 (55%) answered the survey. The risk of chlamydia was lower among individuals with ≤5 partners (≤5 partners vs >5 partners: OR=0.43, 95% CI 0.28 to 0.66, p=0.001) and among those using condoms more frequently (≤50% use of condom vs >50% use of condom: OR=1.55, 95% CI 1.06 to 2.27, p=0.025; 100% vs <100%: OR=0.35, 95% CI 0.20 to 0.59, p=0.001). Individuals using condoms more frequently also had lower risk of gonorrhoea (100% use of condom vs <100% use of condom: OR=0.37, 95% CI 0.17 to 0.79, p=0.011). The risks of chlamydia (OR=3.07, 95% CI 1.92 to 4.90, p<0.001) and gonorrhoea (OR=2.05, 95% CI 1.12 to 3.75, p=0.020) were higher among individuals belonging to the high-risk group. CONCLUSIONS: Chlamydia and gonorrhoea are more likely associated with high-risk sexual behaviours than syphilis and anal HPV among MSM living with HIV.


Assuntos
Gonorreia , Infecções por HIV , Infecções por Papillomavirus , Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Sífilis , Masculino , Humanos , Homossexualidade Masculina , Gonorreia/diagnóstico , Coito , Estudos Transversais , Parceiros Sexuais , Comportamento Sexual , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções por HIV/epidemiologia
5.
Sex Transm Dis ; 50(5): 247-251, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36728240

RESUMO

BACKGROUND: We assessed the vaccination effectiveness (VE) of multicomponent meningococcal serogroup B (4CMenB) vaccine against gonorrhea among people living with HIV (PLWH) with a previous diagnosis of sexually transmitted infection. METHODS: Unmatched case-control study on men who have sex with men living with HIV, in care at San Raffaele Scientific Institute, Milan, Italy, with gonorrhea, syphilis, chlamydia, or anal human papillomavirus between July 2016 (beginning of 4CMenB vaccination) and February 2021 (date of freezing). For the analysis, cases were people with ≥1 gonorrhea infection since July 2016, and controls were people with ≥1 syphilis, chlamydia, or anal human papillomavirus infection since July 2016. Logistic regression was used to provide the estimate of 4CMenB VE against gonorrhea. RESULTS: Included people living with HIV were 1051 (103 cases, 948 controls); 349 of 1051 (33%) received 2 doses of 4CMenB vaccination. The median follow-up was 3.8 years (2.1-4.3 years). The unadjusted estimate for VE against gonorrhea was 42% (95% confidence interval, 6%-64%; P = 0.027). Logistic regression showed that VE against gonorrhea remained significant (44%; 95% confidence interval, 9%-65%; P = 0.020) after adjusting for some factors that might have a potential influence on VE or those with significant unbalanced distributions between cases and controls at univariable analysis. CONCLUSIONS: 4CMenB vaccination is associated with a lower risk of gonorrhea in the setting of men who have sex with men living with HIV with a previous sexually transmitted infection.


Assuntos
Gonorreia , Infecções por HIV , Infecções Meningocócicas , Vacinas Meningocócicas , Neisseria meningitidis , Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Sífilis , Masculino , Humanos , Gonorreia/epidemiologia , Gonorreia/prevenção & controle , Gonorreia/diagnóstico , Homossexualidade Masculina , Estudos de Casos e Controles , Infecções Meningocócicas/epidemiologia , Infecções Meningocócicas/prevenção & controle , Infecções Sexualmente Transmissíveis/diagnóstico , Vacinação , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Neisseria gonorrhoeae
6.
New Microbiol ; 46(2): 226-230, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37247247

RESUMO

Management of heavily treatment experienced (HTE) people with HIV remains a challenge. Tailored antiretroviral therapy (ART) is needed in this fragile population who almost invariably harbor viral quasispecies with resistance-associated mutations (RAMs). The reference method for HIV genotypic resistance testing (GRT) has long been Sanger sequencing (SS), but next-generation sequencing (NGS), following recent progress in workflow and cost-effectiveness, is replacing SS because of higher sensitivity. From the PRESTIGIO Registry, we present a case of a 59-year-old HTE woman who failed darunavir/ritonavir plus raltegravir at low-viremia levels due mainly to high pill burden and poor adherence. NGS-GRT was performed on HIV-RNA at failure and the results were compared to all past SS-GRT data available (historical genotype). In this case, NGS-GRT did not detect any minority drug-resistant variants. After discussing several therapeutic options, the treatment was changed to dolutegravir 50 mg twice daily plus doravirine 100 mg once a day, based on clinical history, adherence issues, and pill burden, as well as the historical SS-GRT and the latest NGS-GRT results. At six months follow-up visit, the patient had HIV-RNA below 30 copies/ml and CD4+ T cell count increased from 673 cells/ mm3 to 688 cells/ mm3. Close follow-up of this patient is ongoing.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Soropositividade para HIV , HIV-1 , Humanos , Raltegravir Potássico/uso terapêutico , Darunavir/uso terapêutico , Ritonavir/uso terapêutico , HIV-1/genética , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Soropositividade para HIV/tratamento farmacológico , RNA , Carga Viral , Farmacorresistência Viral , Resultado do Tratamento
7.
New Microbiol ; 46(1): 65-67, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36853821

RESUMO

Weight gain following the initiation or the switch of antiretroviral therapy (ART) is well documented and mainly associated with some of the most recent drugs, such as integrase strand transfer inhibitors and tenofovir alafenamide. However, limited data have been published on weight trends in ART-experienced people living with HIV (PLWH) with a long exposure to HIV infection and antiretroviral drugs. In our study, we assessed changes in weight after switching ART among PLWH who reported weight gain under a previous regimen.


Assuntos
Infecções por HIV , Humanos , Infecções por HIV/tratamento farmacológico , Antirretrovirais/uso terapêutico , Aumento de Peso
8.
HIV Med ; 23(8): 895-910, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35233903

RESUMO

OBJECTIVE: To compare the incidence of hypertension in people living with HIV receiving integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) versus non-nucleoside reverse transcriptase inhibitors (NNRTIs) or boosted protease inhibitors (PIs) in the RESPOND consortium of HIV cohorts. METHODS: Eligible people with HIV were aged ≥18 years who initiated a new three-drug ART regimen for the first time (baseline), did not have hypertension, and had at least two follow-up blood pressure (BP) measurements. Hypertension was defined as two consecutive systolic BP measurements ≥140 mmHg and/or diastolic BP ≥90 mmHg or initiation of antihypertensives. Multivariable Poisson regression was used to determine adjusted incidence rate ratios (aIRRs) of hypertension, overall and in those who were ART naïve or experienced at baseline. RESULTS: Overall, 4606 people living with HIV were eligible (INSTIs 3164, NNRTIs 807, PIs 635). The median baseline systolic BP, diastolic BP, and age were 120 (interquartile range [IQR] 113-130) mmHg, 78 (70-82) mmHg, and 43 (34-50) years, respectively. Over 8380.4 person-years (median follow-up 1.5 [IQR 1.0-2.7] years), 1058 (23.0%) participants developed hypertension (incidence rate 126.2/1000 person-years, 95% confidence interval [CI] 118.9-134.1). Participants receiving INSTIs had a higher incidence of hypertension than those receiving NNRTIs (aIRR 1.76; 95% CI 1.47-2.11), whereas the incidence was no different in those receiving PIs (aIRR 1.07; 95% CI 0.89-1.29). The results were similar when the analysis was stratified by ART status at baseline. CONCLUSION: Although unmeasured confounding and channelling bias cannot be excluded, INSTIs were associated with a higher incidence of hypertension than were NNRTIs, but rates were similar to those of PIs overall, in ART-naïve and ART-experienced participants within RESPOND.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Inibidores de Integrase de HIV , Hipertensão , Adolescente , Adulto , Idoso de 80 Anos ou mais , Fármacos Anti-HIV/efeitos adversos , Antirretrovirais/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/efeitos adversos , Humanos , Hipertensão/induzido quimicamente , Hipertensão/epidemiologia , Incidência , Inibidores de Integrase/uso terapêutico , Inibidores da Transcriptase Reversa/efeitos adversos
9.
Ann Clin Microbiol Antimicrob ; 21(1): 57, 2022 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-36494813

RESUMO

BACKGROUND: Disseminated Mycobacterium chimaera infection is an emerging disease in people undergone to cardiothoracic surgery, which need to be suspected also with atypical presentations. CASE PRESENTATION: We report the case of a 74-year-old man with fever of unknown origin, purple nodules on both feet and a history of open-heart surgery. Imaging investigations showed an abscess near aortic bioprosthesis but screening for endocarditis resulted negative and pyrexia did not respond to antibiotic therapy. A biopsy of cutaneous lesions showed HHV8-related Kaposi's sarcoma, so bone marrow biopsy was executed with evidence of HHV8 localization. Bone marrow and urine mycobacterial cultures resulted positive for M. chimaera and a specific antimicrobial therapy was started, with apyrexia after 7 weeks. CONCLUSIONS: M. chimaera infection should be always investigated as a possible etiology of fever of unknow origin in people with a history of open-heart surgical intervention, even with negative mycobacterial blood cultures. The possible role of disseminated infection in inducing immunodepression with the occurrence of other opportunistic diseases (such as Kaposi's sarcoma) cannot be excluded.


Assuntos
Infecções por Mycobacterium não Tuberculosas , Mycobacterium , Sarcoma de Kaposi , Masculino , Humanos , Idoso , Sarcoma de Kaposi/diagnóstico , Sarcoma de Kaposi/patologia
10.
Clin Infect Dis ; 73(7): e2323-e2333, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-33354721

RESUMO

BACKGROUND: Limited data exist that compare clinical outcomes of 2-drug regimens (2DRs) and 3-drug regimens (3DRs) in people living with human immunodeficiency virus. METHODS: Antiretroviral treatment-experienced individuals in the International Cohort Consortium of Infectious Diseases (RESPOND) who switched to a new 2DR or 3DR from 1 January 2012-1 October 2018 were included. The incidence of clinical events (AIDS, non-AIDS cancer, cardiovascular disease, end-stage liver and renal disease, death) was compared between regimens using Poisson regression. RESULTS: Of 9791 individuals included, 1088 (11.1%) started 2DRs and 8703 (88.9%) started 3DRs. The most common 2DRs were dolutegravir plus lamivudine (22.8%) and raltegravir plus boosted darunavir (19.8%); the most common 3DR was dolutegravir plus 2 nucleoside reverse transcriptase inhibitors (46.9%). Individuals on 2DRs were older (median, 52.6 years [interquartile range, 46.7-59.0] vs 47.7 [39.7-54.3]), and a higher proportion had ≥1 comorbidity (81.6% vs 73.9%). There were 619 events during 27 159 person-years of follow-up (PYFU): 540 (incidence rate [IR] 22.5/1000 PYFU; 95% confidence interval [CI]: 20.7-24.5) on 3DRs and 79 (30.9/1000 PYFU; 95% CI: 24.8-38.5) on 2DRs. The most common events were death (7.5/1000 PYFU; 95% CI: 6.5-8.6) and non-AIDS cancer (5.8/1000 PYFU; 95% CI: 4.9-6.8). After adjustment for baseline demographic and clinical characteristics, there was a similar incidence of events on both regimen types (2DRs vs 3DRs IR ratio, 0.92; 95% CI: .72-1.19; P = .53). CONCLUSIONS: This is the first large, international cohort to assess clinical outcomes on 2DRs. After accounting for baseline characteristics, there was a similar incidence of events on 2DRs and 3DRs. 2DRs appear to be a viable treatment option with regard to clinical outcomes. Further research on resistance barriers and long-term durability of 2DRs is needed.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Preparações Farmacêuticas , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , HIV , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos
11.
New Microbiol ; 44(3): 135-144, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34783348

RESUMO

Neutralizing monoclonal antibody therapies against the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) play a significant role both in the prevention and treatment of the coronavirus disease 2019 (COVID-19). In this review we discuss the monoclonal antibody therapies that have received preliminary authorization for use in COVID-19 patients by the U.S. Food and Drug Administration or the European Medicines Agency. We review here their mechanisms of action, their efficacy in prophylaxis and treatment, their indications for use, and the impact of SARS-CoV-2 variants of concern on their activity.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes , Anticorpos Antivirais , Humanos , Testes de Neutralização , Glicoproteína da Espícula de Coronavírus/genética
12.
Int J Cancer ; 146(3): 601-609, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31215037

RESUMO

We compared invasive cervical cancer (ICC) incidence rates in Europe, South Africa, Latin and North America among women living with HIV who initiated antiretroviral therapy (ART) between 1996 and 2014. We analyzed cohort data from the International Epidemiology Databases to Evaluate AIDS (IeDEA) and the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord. We used flexible parametric survival models to determine regional ICC rates and risk factors for incident ICC. We included 64,231 women from 45 countries. During 320,141 person-years (pys), 356 incident ICC cases were diagnosed (Europe 164, South Africa 156, North America 19 and Latin America 17). Raw ICC incidence rates per 100,000 pys were 447 in South Africa (95% confidence interval [CI]: 382-523), 136 in Latin America (95% CI: 85-219), 76 in North America (95% CI: 48-119) and 66 in Europe (95% CI: 57-77). Compared to European women ICC rates at 5 years after ART initiation were more than double in Latin America (adjusted hazard ratio [aHR]: 2.43, 95% CI: 1.27-4.68) and 11 times higher in South Africa (aHR: 10.66, 95% CI: 6.73-16.88), but similar in North America (aHR: 0.79, 95% CI: 0.37-1.71). Overall, ICC rates increased with age (>50 years vs. 16-30 years, aHR: 1.57, 95% CI: 1.03-2.40) and lower CD4 cell counts at ART initiation (per 100 cell/µl decrease, aHR: 1.25, 95% CI: 1.15-1.36). Improving access to early ART initiation and effective cervical cancer screening in women living with HIV should be key parts of global efforts to reduce cancer-related health inequities.


Assuntos
Infecções por HIV/complicações , Disparidades nos Níveis de Saúde , Neoplasias do Colo do Útero/epidemiologia , Adolescente , Adulto , Fatores Etários , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Comparação Transcultural , Detecção Precoce de Câncer , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Humanos , Incidência , América Latina/epidemiologia , Pessoa de Meia-Idade , América do Norte/epidemiologia , Fatores de Risco , África do Sul/epidemiologia , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/prevenção & controle , Adulto Jovem
13.
J Antimicrob Chemother ; 75(10): 2994-2997, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32585684

RESUMO

BACKGROUND: HIV-DNA is a marker of HIV reservoirs. Objectives of the study were to determine prevalence of HIV-DNA < 100 copies/106 PBMCs in blood and to identify factors associated with this in a cohort of HIV-1-infected subjects treated with ART and with undetectable viral load (VL). METHODS: This was a cross-sectional study on chronic HIV-1-infected people living with HIV (PLWH) followed up at the Department of Infectious Diseases of San Raffaele Scientific Institute on current ART without change for 12 months, with available pre-ART HIV-RNA and with undetectable VL for ≥12 months. HIV-DNA was amplified and quantified by real-time PCR (ABI Prism 7900); limit of detectability was 100 copies/106 PBMCs. Logistic regression was used to identify predictive factors for HIV-DNA < 100 copies/106 PBMCs. RESULTS: Four hundred and sixty-eight PLWH were considered in the analyses, 119 (25%) with HIV-DNA < 100 copies/106 PBMCs. At multivariate analysis, we found that PLWH with lower zenith HIV-RNA, higher nadir CD4 and a shorter time between HIV diagnosis and ART start were more likely to have HIV-DNA < 100 copies/106 PBMCs, after adjustment for age, gender, calendar year of ART start, type of current ART regimen, percentage time spent with undetectable VL since ART start, current CD4 and CD4/CD8 ratio. CONCLUSIONS: In our chronic PLWH on virological suppression for 4 years, the prevalence of HIV-DNA < 100 copies/106 PBMCs was found to be 25%. Lower zenith HIV-RNA, shorter time between HIV diagnosis and starting ART and higher CD4 nadir were independently associated with low HIV-DNA.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Estudos Transversais , DNA , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Carga Viral
14.
J Antimicrob Chemother ; 74(7): 2039-2046, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31225610

RESUMO

OBJECTIVES: Despite the fact that there are individuals who have chronic HIV infection, few studies have investigated ART interruption in this setting. The aim of this study was to evaluate the ability to spontaneously control viral replication during analytical treatment interruption (ATI) in adults with chronic HIV-1 infection, on ART, with suppressed viraemia for >10 years and with a low reservoir. PATIENTS AND METHODS: This was a prospective, open-label, single-arm, non-randomized, proof-of-concept study (NCT03198325) of subjects with chronic HIV-1 infection, HIV-RNA <50 copies/mL for ≥10 years, without residual viraemia for ≥5 years, CD4+ >500 cells/mm3, HIV-DNA <100 copies/106 PBMCs and without comorbidities or AIDS-defining diseases. Enrolled patients were strictly monitored. The ART regimen in use at ATI was resumed in the case of confirmed viral rebound (CVR, two consecutive HIV-RNA >50 copies/mL). Results are reported as median (IQR). RESULTS: Nine patients underwent ATI. All participants experienced CVR [4.84 (IQR: 3.47-6.47) HIV-RNA log10 copies/mL] after ATI at a median time of 21 days (range 14-56) and restarted ART. After ART resumption, all the subjects achieved HIV-RNA <50 copies/mL in a median of 88 days (range 15-197). No serious adverse event occurred; one subject experienced acute retroviral syndrome. No significant correlation between baseline factors and time to viral rebound was observed, while the magnitude of viral rebound was significantly associated with pre-ART HIV-1 RNA (Spearman r = 0.786, P = 0.036), nadir CD4+ (Spearman r = -0.800, P = 0.010), baseline CD4+ (Spearman r = -0.667, P = 0.049) and years with undetectable viral load (Spearman r = -0.717, P = 0.030). CONCLUSIONS: Despite a long period of HIV viral load suppression and a low viral reservoir, early and consistent viral rebound was observed during ATI in all subjects.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Relação CD4-CD8 , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Carga Viral
15.
J Med Virol ; 91(11): 1937-1943, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31286527

RESUMO

OBJECTIVE: To describe the trajectories of the homeostatic model assessment for insulin resistance (HOMA-IR) index in a cohort of HIV-1 infected patients during their first-line antiretroviral (ART) regimen. METHODS: Retrospective analysis of naïve patients who started ART from 2007 at the Infectious Diseases Unit of the San Raffaele Hospital, Milan. We included patients treated with two nucleoside reverse transcriptase inhibitors (NRTIs, tenofovir, abacavir, lamivudine or emtricitabine), and one anchor drug (ritonavir-boosted protease inhibitor [PI/r], non-NRTI [NNRTI], or integrase strand transfer inhibitor [InSTI]), and with HOMA-IR assessed both before and after the start of ART. Univariate and multivariate mixed linear models estimated HOMA-IR changes during ART. RESULTS: Among 618 patients included in the study, 218 received InSTI-, 210 PI/r-, and 190 NNRTI-based regimens. Median follow-up was 27.4 (16.3-41.2) months. Adjusted mean change in HOMA-IR index was significantly higher (P = .041) in patients treated with InSTI-based regimens [0.160 (95% CI: 0.003-0.321) units per year] compared with NNRTI-based regimens [-0.005 (95% CI: -0.184-0.074) units per year]; no difference was observed between patients treated with NNRTI- and PI/r-based regimens or between INSTI-based and PI/r-based regimens. CONCLUSION: InSTI-based first-line ARTs were independently associated with greater increases in HOMA-IR index.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Homeostase , Resistência à Insulina , Adulto , Terapia Antirretroviral de Alta Atividade , Feminino , Infecções por HIV/complicações , Inibidores da Protease de HIV/uso terapêutico , Humanos , Inibidores de Integrase/uso terapêutico , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Inibidores da Transcriptase Reversa/uso terapêutico , Carga Viral
19.
Ann Intern Med ; 166(1): 9-17, 2017 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-27750294

RESUMO

Background: Non-Hodgkin lymphoma (NHL) is the most common AIDS-defining condition in the era of antiretroviral therapy (ART). Whether chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection promote NHL in HIV-infected patients is unclear. Objective: To investigate whether chronic HBV and HCV infection are associated with increased incidence of NHL in HIV-infected patients. Design: Cohort study. Setting: 18 of 33 cohorts from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). Patients: HIV-infected patients with information on HBV surface antigen measurements and detectable HCV RNA, or a positive HCV antibody test result if HCV RNA measurements were not available. Measurements: Time-dependent Cox models to assess risk for NHL in treatment-naive patients and those initiating ART, with inverse probability weighting to control for informative censoring. Results: A total of 52 479 treatment-naive patients (1339 [2.6%] with chronic HBV infection and 7506 [14.3%] with HCV infection) were included, of whom 40 219 (77%) later started ART. The median follow-up was 13 months for treatment-naive patients and 50 months for those receiving ART. A total of 252 treatment-naive patients and 310 treated patients developed NHL, with incidence rates of 219 and 168 cases per 100 000 person-years, respectively. The hazard ratios for NHL with HBV and HCV infection were 1.33 (95% CI, 0.69 to 2.56) and 0.67 (CI, 0.40 to 1.12), respectively, in treatment-naive patients and 1.74 (CI, 1.08 to 2.82) and 1.73 (CI, 1.21 to 2.46), respectively, in treated patients. Limitation: Many treatment-naive patients later initiated ART, which limited the study of the associations of chronic HBV and HCV infection with NHL in this patient group. Conclusion: In HIV-infected patients receiving ART, chronic co-infection with HBV and HCV is associated with an increased risk for NHL. Primary Funding Source: European Union Seventh Framework Programme.


Assuntos
Infecções por HIV/complicações , Hepatite B Crônica/complicações , Hepatite C Crônica/complicações , Linfoma não Hodgkin/complicações , Adulto , Fármacos Anti-HIV/uso terapêutico , Biomarcadores/sangue , Estudos de Coortes , Feminino , Infecções por HIV/tratamento farmacológico , Anticorpos Anti-Hepatite/sangue , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/imunologia , Hepatite B Crônica/diagnóstico , Hepatite C/imunologia , Hepatite C Crônica/diagnóstico , Humanos , Imunoglobulina G/sangue , Linfoma não Hodgkin/mortalidade , Masculino , RNA Viral/sangue , Fatores de Risco
20.
New Microbiol ; 41(4): 256-261, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30252923

RESUMO

As dolutegravir (DTG), rilpivirine (RPV) and cobicistat affect creatinine, but not cystatin C, tubular transport or serum concentration, the aim of the study was to compare estimated glomerular filtration rates (eGFRs) calculated by means of a standard creatinine formula with those calculated by means of the cystatin C formula in patients receiving these drugs. This was a cross-sectional study of HIV-1 infected patients with eGFR <90 ml/min/1.73 m2 (CKD-EPI-creatinine formula) on-treatment with regimens including DTG, RVP or cobicistat; cystatin C was measured after the switch to these regimens. eGFR was calculated by means of the CKD-EPI formulas (CKD-EPI-creatinine: eGFRcrea; CKD-EPI-cystatin C: eGFRcyst). eGFRcyst was compared with the last eGFR assessed before (eGFRcrea pre) and after the switch (eGFRcrea post). The primary end-point of the study was the difference between eGFRcyst and eGFRcrea post. One hundred and twenty patients were included. eGFRcrea pre was 80 (70-92) ml/min/1.73 m2. eGFRcrea post was significantly lower than eGFRcyst (65 [59-75] vs. 80 [69-95] mL/ min/1.73m2; p<0.001); eGFRcyst did not differ from eGFRcrea pre (p=0.544). The difference between eGFRcyst and eGFRcrea post was not significantly different among regimen groups (p=0.056). In HIV-patients with reduced eGFR treated with DTG, RPV or cobicistat, measuring eGFR by means of the CKD-EPI cystatin C formula is probably more relevant.


Assuntos
Cistatina C , Taxa de Filtração Glomerular , HIV-1 , Fármacos Anti-HIV/uso terapêutico , Cobicistat/uso terapêutico , Creatinina/urina , Estudos Transversais , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Oxazinas , Piperazinas , Piridonas , Rilpivirina/uso terapêutico
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