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1.
HIV Med ; 23(2): 146-158, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34605153

RESUMO

OBJECTIVES: The aim of the study was to assess the feasibility of a national pre-exposure prophylaxis (PrEP) programme using smartphone-compatible data collection. METHODS: This was a multicentre cohort study (NCT03893188) enrolling individuals interested in PrEP in Switzerland. All centres participate in the SwissPrEPared programme, which uses smartphone-compatible data collection. Feasibility was assessed after centres had enrolled at least one participant. Participants were HIV-negative individuals presenting for PrEP counselling. Outcomes were participation (number enrolled/number eligible), enrolment rates (number enrolled per month), retention at first follow-up (number with first follow-up/number enrolled), and uptake (proportion attending first visit as scheduled). Participant characteristics were compared between those retained after baseline assessment and those who dropped out. RESULTS: Between April 2019 and January 2020, 987 individuals were assessed for eligibility, of whom 969 were enrolled (participation: 98.2%). The median enrolment rate was 86 per month [interquartile range (IQR) 52-137]. Retention at first follow-up and uptake were both 80.7% (782/969 and 532/659, respectively). At enrolment, the median age was 40 (IQR 33-47) years, 95% were men who have sex with men, 47% had a university degree, and 75.5% were already taking PrEP. Most reported multiple casual partners (89.2%), previous sexually transmitted infections (74%) and sexualized drug use (73.1%). At baseline, 25.5% tested positive for either syphilis, gonorrhoea or chlamydia. Participants who dropped out were at lower risk of HIV infection than those retained after baseline assessment. CONCLUSIONS: In a national PrEP programme using smartphone-compatible data collection, participation, retention and uptake were high. Participants retained after baseline assessment were at considerable risk of HIV infection. Younger, less educated individuals were underrepresented in the SwissPrEPared cohort.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Adulto , Fármacos Anti-HIV/uso terapêutico , Estudos de Coortes , Coleta de Dados , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Humanos , Masculino , Smartphone
2.
HIV Med ; 22(5): 346-359, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33368946

RESUMO

OBJECTIVES: Understanding the drivers of HIV-1 transmission is of importance for curbing the ongoing epidemic. Phylogenetic methods based on single viral sequences allow us to assess whether two individuals are part of the same viral outbreak, but cannot on their own assess who potentially transmitted the virus. We developed and assessed a molecular epidemiology method with the main aim to screen cohort studies for and to characterize individuals who are 'potential HIV-1 transmitters', in order to understand the drivers of HIV-1 transmission. METHODS: We developed and validated a molecular epidemiology approach using longitudinally sampled viral Sanger sequences to characterize potential HIV-1 transmitters in the Swiss HIV Cohort Study. RESULTS: Our method was able to identify 279 potential HIV-1 transmitters and allowed us to determine the main epidemiological and virological drivers of transmission. We found that the directionality of transmission was consistent with infection times for 72.9% of 85 potential HIV-1 transmissions with accurate infection date estimates. Being a potential HIV-1 transmitter was associated with risk factors including viral load [adjusted odds ratiomultivariable (95% confidence interval): 1.86 (1.49-2.32)], syphilis coinfection [1.52 (1.06-2.19)], and recreational drug use [1.45 (1.06-1.98)]. By contrast for the potential HIV-1 recipients, this association was weaker or even absent [1.18 (0.82-1.72), 0.89 (0.52-1.55) and 1.53 (0.98-2.39), respectively], indicating that inferred directionality of transmission is useful at the population level. CONCLUSIONS: Our results indicate that longitudinally sampled Sanger sequences do not provide sufficient information to identify transmitters with high certainty at the individual level, but that they allow the drivers of transmission at the population level to be characterized.


Assuntos
Infecções por HIV , HIV-1 , Sequência de Bases , Estudos de Coortes , HIV-1/genética , Humanos , Filogenia
3.
Infection ; 44(3): 329-35, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26661659

RESUMO

BACKGROUND: Antiretroviral treatment (ART) with ritonavir-boosted protease inhibitor monotherapy (rb-PMT) remains a potentially attractive strategy for treatment simplification in HIV-infected individuals. However, long-term follow-up in particular with respect to HIV-RNA suppression in cerebrospinal fluids (CSF) is still lacking. METHODS: Patients who participated in one of the three monotherapy trials [indinavir/r, ATARITMO (atazanavir/r), MOST (lopinavir/r)] at our HIV clinic and remained successfully suppressed during the entire trial (plasma < 50 copies/mL, CSF < 100 copies/mL) were offered to continue their monotherapy under close monitoring. While on rb-PMT, patients were asked to provide CSF samples in yearly or 2-yearly intervals. All patients fully suppressed in plasma and CSF for at least 12 months were included in the analysis. Patients demonstrating any failure in plasma or CSF resumed triple combined ART. RESULTS: A total of 27 patients (5 women and 22 men) fulfilled the entry criteria. The median follow-up time was 4.8 (1.1-10.9) years with an overall experience of 139 patient-years on monotherapy. Eleven of 27 (41 %) patients (2 women and 9 men) developed virologic failure (1 in plasma only, 4 in CSF only, 4 both in plasma and CSF and 2 in plasma with CSF not available). Plasma failure occurred in 7 patients after a median follow-up of 25 (13-32) months, and CSF failure in 8 patients after a median follow-up of 30 (14-64) months. Seven patients are still on rb-PMT with atazanavir/r. Failure was associated with shorter duration of fully suppressed plasma viral load prior to starting (p < 0.022). CONCLUSION: For selected patients, rb-PMT might be a valid long-term treatment strategy. Nevertheless, even after 12 months of full HIV-RNA suppression, more than 1/3 of patients may still develop failure in either plasma or CSF. Given the observation of isolated CSF failure, treatment monitoring with regular lumbar puncture should be recommended in rb-PMT. Only monotherapy with atazanavir/r was successful beyond 39 months. Monotherapy failure was significantly associated with a shorter duration of complete HIV-RNA suppression in plasma prior to rb-PMT start. Further investigation is needed to better identify predictors for patients that will qualify for successful long-term rb-PMT.


Assuntos
Infecções por HIV/líquido cefalorraquidiano , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , RNA Viral/líquido cefalorraquidiano , Ritonavir/uso terapêutico , Adulto , Idoso , Feminino , Infecções por HIV/virologia , HIV-1/genética , Humanos , Masculino , Pessoa de Meia-Idade , Falha de Tratamento
4.
Nature ; 458(7241): 993-5, 2009 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-19396138

RESUMO

A comparison of the laboratory reflectance spectra of meteorites with observations of asteroids revealed that the latter are much 'redder', with the spectral difference explained by 'space weathering', though the actual processes and timescales involved have remained controversial. A recent study of young asteroid families concluded that they suffered only minimal space weathering. Here we report additional observations of those families, revealing that space weathering must be a very rapid process-the final colour of a silicate-rich asteroid is acquired shortly after its 'birth' (within 10(6) years of undergoing a catastrophic collision). This rapid timescale favours solar wind implantation as the main mechanism of space weathering, as laboratory experiments have shown that it is the most rapid of several competing processes. We further demonstrate the necessity to take account of composition when evaluating weathering effectiveness, as both laboratory and asteroid data show an apparent dependence of weathering on olivine abundance. The rapid colour change that we find implies that colour trends seen among asteroids are most probably due to compositional or surface-particle-size properties, rather than to different relative ages. Apparently fresh surfaces most frequently seen among small near-Earth asteroids may be the result of tidal shaking that rejuvenates their surfaces during planetary encounters.

5.
HIV Med ; 15(8): 505-10, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24641488

RESUMO

OBJECTIVES: Tenofovir is associated with reduced renal function. It is not clear whether patients can be expected to fully recover their renal function if tenofovir is discontinued. METHODS: We calculated the estimated glomerular filtration rate (eGFR) for patients in the Swiss HIV Cohort Study remaining on tenofovir for at least 1 year after starting a first antiretroviral therapy regimen with tenofovir and either efavirenz or the ritonavir-boosted protease inhibitor lopinavir, atazanavir or darunavir. We estimated the difference in eGFR slope between those who discontinued tenofovir after 1 year and those who remained on tenofovir. RESULTS: A total of 1049 patients on tenofovir for at least 1 year were then followed for a median of 26 months, during which time 259 patients (25%) discontinued tenofovir. After 1 year on tenofovir, the difference in eGFR between those starting with efavirenz and those starting with lopinavir, atazanavir and darunavir was - 0.7 [95% confidence interval (CI) -2.3 to 0.8], -1.4 (95% CI -3.2 to 0.3) and 0.0 (95% CI -1.7 to 1.7) mL/min/1.73 m(2), respectively. The estimated linear rate of decline in eGFR on tenofovir was -1.1 (95% CI -1.5 to -0.8) mL/min/1.73 m(2) per year and its recovery after discontinuing tenofovir was 2.1 (95% CI 1.3 to 2.9) mL/min/1.73 m(2) per year. Patients starting tenofovir with either lopinavir or atazanavir appeared to have the same rates of decline and recovery as those starting tenofovir with efavirenz. CONCLUSIONS: If patients discontinue tenofovir, clinicians can expect renal function to recover more rapidly than it declined.


Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/efeitos adversos , Taxa de Filtração Glomerular/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Rim/efeitos dos fármacos , Rim/fisiopatologia , Organofosfonatos/efeitos adversos , Adenina/administração & dosagem , Adenina/efeitos adversos , Adulto , Fármacos Anti-HIV/administração & dosagem , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Terapia Antirretroviral de Alta Atividade/métodos , Feminino , Humanos , Masculino , Organofosfonatos/administração & dosagem , Estudos Prospectivos , Tenofovir , Suspensão de Tratamento
6.
Nature ; 454(7206): 858-60, 2008 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-18704080

RESUMO

Understanding the nature and origin of the asteroid population in Earth's vicinity (near-Earth asteroids, and its subset of potentially hazardous asteroids) is a matter of both scientific interest and practical importance. It is generally expected that the compositions of the asteroids that are most likely to hit Earth should reflect those of the most common meteorites. Here we report that most near-Earth asteroids (including the potentially hazardous subset) have spectral properties quantitatively similar to the class of meteorites known as LL chondrites. The prominent Flora family in the inner part of the asteroid belt shares the same spectral properties, suggesting that it is a dominant source of near-Earth asteroids. The observed similarity of near-Earth asteroids to LL chondrites is, however, surprising, as this meteorite class is relatively rare ( approximately 8 per cent of all meteorite falls). One possible explanation is the role of a size-dependent process, such as the Yarkovsky effect, in transporting material from the main belt.

7.
Internist (Berl) ; 53(10): 1179-86, 2012 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-22986541

RESUMO

Successful prevention of an HIV epidemic is still a desirable goal. As young people are mainly affected by new infections and AIDS mortality has fallen virtually to zero, the long-term total costs of HIV management are increasing. This report describes how the targeted application of HIV testing can influence the HIV epidemic. The crucial point is the early diagnosis of primary HIV infection in standard situations whereby early diagnosis and counselling result in behavioral modifications preventing new transmission.


Assuntos
Surtos de Doenças/prevenção & controle , Surtos de Doenças/estatística & dados numéricos , Infecções por HIV/mortalidade , Infecções por HIV/prevenção & controle , Vigilância da População/métodos , Infecções por HIV/diagnóstico , Humanos , Incidência , Programas de Rastreamento
8.
HIV Med ; 12(5): 279-88, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-20955356

RESUMO

BACKGROUND: The long-term outcome of antiretroviral therapy (ART) is not assessed in controlled trials. We aimed to analyse trends in the population effectiveness of ART in the Swiss HIV Cohort Study over the last decade. METHODS: We analysed the odds of stably suppressed viral load (ssVL: three consecutive values <50 HIV-1 RNA copies/mL) and of CD4 cell count exceeding 500 cells/µL for each year between 2000 and 2008 in three scenarios: an open cohort; a closed cohort ignoring the influx of new participants after 2000; and a worst-case closed cohort retaining lost or dead patients as virological failures in subsequent years. We used generalized estimating equations with sex, age, risk, non-White ethnicity and era of starting combination ART (cART) as fixed co-factors. Time-updated co-factors included type of ART regimen, number of new drugs and adherence to therapy. RESULTS: The open cohort included 9802 individuals (median age 38 years; 31% female). From 2000 to 2008, the proportion of participants with ssVL increased from 37 to 64% [adjusted odds ratio (OR) per year 1.16 (95% CI 1.15-1.17)] and the proportion with CD4 count >500 cells/µL increased from 40 to >50% [OR 1.07 (95% CI 1.06-1.07)]. Similar trends were seen in the two closed cohorts. Adjustment did not substantially affect time trends. CONCLUSIONS: There was no relevant dilution effect through new participants entering the open clinical cohort, and the increase in virological/immunological success over time was not an artefact of the study design of open cohorts. This can partly be explained by new treatment options and other improvements in medical care.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/imunologia , Antirretrovirais/uso terapêutico , Infecções por HIV/imunologia , HIV-1/imunologia , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/virologia , Adulto , Contagem de Linfócito CD4 , Relação CD4-CD8 , Estudos de Coortes , Quimioterapia Combinada , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Masculino , Cooperação do Paciente/estatística & dados numéricos , Suíça/epidemiologia , Carga Viral
9.
HIV Med ; 12(5): 299-307, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-20955357

RESUMO

OBJECTIVES: Darunavir was designed for activity against HIV resistant to other protease inhibitors (PIs). We assessed the efficacy, tolerability and risk factors for virological failure of darunavir for treatment-experienced patients seen in clinical practice. METHODS: We included all patients in the Swiss HIV Cohort Study starting darunavir after recording a viral load above 1000 HIV-1 RNA copies/mL given prior exposure to both PIs and nonnucleoside reverse transcriptase inhibitors. We followed these patients for up to 72 weeks, assessed virological failure using different loss of virological response algorithms and evaluated risk factors for virological failure using a Bayesian method to fit discrete Cox proportional hazard models. RESULTS: Among 130 treatment-experienced patients starting darunavir, the median age was 47 years, the median duration of HIV infection was 16 years, and 82% received mono or dual antiretroviral therapy before starting highly active antiretroviral therapy. During a median patient follow-up period of 45 weeks, 17% of patients stopped taking darunavir after a median exposure of 20 weeks. In patients followed beyond 48 weeks, the rate of virological failure at 48 weeks was at most 20%. Virological failure was more likely where patients had previously failed on both amprenavir and saquinavir and as the number of previously failed PI regimens increased. CONCLUSIONS: As a component of therapy for treatment-experienced patients, darunavir can achieve a similar efficacy and tolerability in clinical practice to that seen in clinical trials. Clinicians should consider whether a patient has failed on both amprenavir and saquinavir and the number of failed PI regimens before prescribing darunavir.


Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , HIV-1/efeitos dos fármacos , Sulfonamidas/uso terapêutico , Teorema de Bayes , Contagem de Linfócito CD4 , Estudos de Coortes , Darunavir , Farmacorresistência Viral , Feminino , Infecções por HIV/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Terapia de Salvação , Resultado do Tratamento , Carga Viral
10.
HIV Med ; 12(7): 394-402, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21251182

RESUMO

BACKGROUND: Using new sensitive quantitative polymerase chain reaction (PCR) assays, cytomegalovirus (CMV) DNA is often detectable in the plasma of immunosuppressed patients. We investigated the prognostic value of a positive CMV DNA test for the development of CMV end-organ disease, other AIDS-defining events and mortality. METHODS: A survival analysis was performed, using the Kaplan-Meier method and Cox proportional hazards models, for patients prospectively followed in the Swiss HIV Cohort Study, from January 1996 to December 2007, who were CMV-seropositive, had a CD4 count of ≤ 100 cells/µL, and had a plasma sample available for the measurement of baseline CMV DNA with an ultrasensitive PCR. The outcome analysed was an AIDS-defining event, including CMV end-organ disease, or death. Variables analysed at the time of CMV measurement were demographic variables, CD4 cell counts, HIV-1 RNA loads, and use and type of highly active antiretroviral therapy (HAART). RESULTS: Of 1128 patients, 208 (18%) presented an AIDS-defining event and 246 (22%) died. A total of 368 patients (34% of samples) had detectable CMV DNA at baseline, with DNA concentrations of up to 38 800 copies/mL. In the multivariate analysis, CMV DNA predicted evolution not only towards CMV end-organ disease [hazard ratio (HR) 12.6; 95% confidence interval (CI) 4.27-37.41], but also towards other AIDS-defining events (HR 2.6; 95% CI 1.60-4.33) and death (HR 1.9; 95% CI 1.10-3.34). CONCLUSION: Quantitative CMV DNA detected in the plasma of HIV-infected patients with CD4 counts ≤ 100 cells/µL is a predictor for HIV disease progression, CMV disease and death. A single low value of 80 copies/mL identifies patients at low but significantly increased risk during the following months, after the measurement.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/genética , Infecções por Citomegalovirus/genética , Citomegalovirus/isolamento & purificação , DNA Viral/análise , Insuficiência de Múltiplos Órgãos/genética , Reação em Cadeia da Polimerase/métodos , Viremia/genética , Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Infecções Oportunistas Relacionadas com a AIDS/virologia , Adulto , Infecções por Citomegalovirus/mortalidade , Infecções por Citomegalovirus/virologia , Feminino , Infecções por HIV/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/mortalidade , Insuficiência de Múltiplos Órgãos/virologia , Estudos Prospectivos , Sensibilidade e Especificidade , Suíça/epidemiologia , Carga Viral , Viremia/diagnóstico , Viremia/virologia
11.
PLoS One ; 15(9): e0237770, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32966293

RESUMO

OBJECTIVES: The aim of this proof-of-concept study is to test feasibility and efficacy of NVP plus Lamivudine (3TC) as novel simplified HIV maintenance dual therapy (DT) strategy. METHODS: Patients under combined antiretroviral treatment (cART) with fully suppressed HIV plasma viral load (pVL) >24 months-whereof >6 months on an NVP- containing regimen-were switched to oral NVP plus 3TC for 24 weeks. Patients could then decide whether to continue DT or return to the previous cART. HIV pVL was monitored monthly until week 144. The primary outcome was confirmed viral failure (RNA >100 copies/ml). Low-level detection of HIV-RNA in plasma was compared in each patient with pre-study viral load measurements. RESULTS: Twenty patients were included, switched to DT and all completed week 24. One patient decided thereafter to discontinue study participation for personal reasons. After a total of 144 observation weeks, none of the patients failed. The frequency of low- level HIV-RNA detection was not different from the period before randomization. CONCLUSIONS: Our findings are surprising but given the nature of a proof-of-concept study, the results do not support the use of this dual regimen. However, as this dual HIV maintenance strategy was feasible and effective, over a period of 144 weeks, we suggest NVP plus 3TC warrants further evaluation as potential maintenance option in patients tolerating nevirapine. A properly sized multicentre non-inferiority trial is ongoing to further evaluate the value of this DT maintenance strategy.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/fisiologia , Lamivudina/uso terapêutico , Estudo de Prova de Conceito , Fármacos Anti-HIV/farmacologia , Feminino , Infecções por HIV/sangue , HIV-1/efeitos dos fármacos , HIV-1/genética , Humanos , Lamivudina/farmacologia , Masculino , Pessoa de Meia-Idade , Nevirapina/uso terapêutico , RNA Viral/sangue
12.
HIV Med ; 10(8): 470-6, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19459990

RESUMO

OBJECTIVES: An article by the Swiss AIDS Commission states that patients with stably suppressed viraemia [i.e. several successive HIV-1 RNA plasma concentrations (viral loads, VL) below the limits of detection during 6 months or more of highly active antiretroviral therapy (HAART)] are unlikely to be infectious. Questions then arise: how reliable is the undetectability of the VL, given the history of measures? What factors determine reliability? METHODS: We assessed the probability (henceforth termed reliability) that the n+1 VL would exceed 50 or 1000 HIV-1 RNA copies/mL when the nth one had been <50 copies/mL in 6168 patients of the Swiss HIV Cohort Study who were continuing to take HAART between 2003 and 2007. General estimating equations were used to analyse potential factors of reliability. RESULTS: With a cut-off at 50 copies/mL, reliability was 84.5% (n=1), increasing to 94.5% (n=5). Compliance, the current type of HAART and the first antiretroviral therapy (ART) received (HAART or not) were predictive factors of reliability. With a cut-off at 1000 copies/mL, reliability was 97.5% (n=1), increasing to 99.1% (n=4). Chart review revealed that patients had stopped their treatment, admitted to major problems with compliance or were taking non-HAART ART in 72.2% of these cases. Viral escape caused by resistance was found in 5.6%. No explanation was found in the charts of 22.2% of cases. CONCLUSIONS: After several successive VLs at <50 copies/mL, reliability reaches approximately 94% with a cut-off of 50 copies/mL and approximately 99% with a cut-off at 1000 copies/mL. Compliance is the most important factor predicting reliability.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , Carga Viral/métodos , Viremia/diagnóstico , Adulto , Terapia Antirretroviral de Alta Atividade/métodos , Contagem de Linfócito CD4 , Estudos de Coortes , Farmacorresistência Viral , Feminino , Infecções por HIV/imunologia , Infecções por HIV/transmissão , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/genética , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Análise Multivariada , Probabilidade , RNA Viral/sangue , Reprodutibilidade dos Testes , Suíça , Carga Viral/efeitos dos fármacos , Viremia/virologia
13.
HIV Med ; 10(1): 12-8, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18795964

RESUMO

Background The principal causes of liver enzyme elevation among HIV-hepatitis B virus (HBV) co-infected patients are the hepatotoxic effects of antiretroviral therapy (ART), alcohol abuse, ART-induced immune reconstitution and the exacerbation of chronic HBV infection. Objectives To investigate the incidence and severity of liver enzyme elevation, liver failure and death following lamivudine (3TC) withdrawal in HIV-HBV co-infected patients. Methods Retrospective analysis of the Swiss HIV Cohort Study database to assess the clinical and biological consequences of the discontinuation of 3TC. Variables considered for analysis included liver enzyme, HIV virological and immunological parameters, and medication prescribed during a 6-month period following 3TC withdrawal. Results 3TC was discontinued in 255 patients on 363 occasions. On 147 occasions (109 patients), a follow-up visit within 6 months following 3TC withdrawal was recorded. Among these patients, liver enzyme elevation occurred on 42 occasions (29%), three of them (2%) with severity grade III and five of them (3.4%) with severity grade IV elevations (as defined by the AIDS Clinical Trials Group). Three patients presented with fulminant hepatitis. One death (0.7%) was recorded. Conclusions HBV reactivation leading to liver dysfunction may be an under-reported consequence of 3TC withdrawal in HIV-HBV co-infected patients. Regular monitoring of HBV markers is warranted if active therapy against HBV is discontinued.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/complicações , Fármacos Anti-HIV/uso terapêutico , HIV-1 , Hepatite B/complicações , Lamivudina/uso terapêutico , Hepatopatias/etiologia , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Adulto , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Métodos Epidemiológicos , Feminino , Hepatite B/tratamento farmacológico , Antígenos E da Hepatite B/efeitos dos fármacos , Humanos , Hepatopatias/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Recidiva , Suíça , Carga Viral
14.
Swiss Med Wkly ; 138(31-32): 453-8, 2008 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-18690558

RESUMO

QUESTION UNDER STUDY: Can additional information be obtained from recently HIV diagnosed individuals? METHODS: A 1-year prospective Swiss study, including all newly diagnosed HIV-infected patients. Information on circumstances of HIV infection was collected through physician- and patient questionnaires and patient interviews. Information on timing of infection was linked with an HIV-antibody avidity assay. RESULTS: Of 710 newly HIV diagnosed patients, 543 (76%) physician questionnaires (PhyQ) and 145 (20%) patient questionnaires (PaQ) were returned. PhyQ required fewer reminders (57% vs 28% spontaneous return). Patients whose doctors had returned the PhyQ were comparable to total population group. In contrast, a strong bias towards well educated recently infected Swiss men having sex with men (MSM) was seen in patients returning PaQ or agreeing to an interview. 83% of patients claimed that they knew the infection source and 85% infection place. Unprotected sexual contact was the most frequently cited infection source (92%; n = 404). Men mainly claimed occasional (43%) and women steady (61%) partners as the most likely source of HIV infection. Serum for timing of infection was available in 98% of patients. Recent infections (RI) were highest in MSM (51%) and intravenous drug users (IDU, 54%). Compared to women, heterosexual men were more than twice as likely to be diagnosed with a RI. CONCLUSION: Relevant additional information on circumstances of HIV infection in newly diagnosed patients can easily be collected from treating physicians. Collecting information from patients is not a feasible option, with the exception of qualitative interviews in a selected group of patients.


Assuntos
Infecções por HIV/diagnóstico , Adulto , Estudos de Viabilidade , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/fisiopatologia , Infecções por HIV/transmissão , HIV-1 , Indicadores Básicos de Saúde , Inquéritos Epidemiológicos , Humanos , Masculino , Estudos Prospectivos , Inquéritos e Questionários , Suíça/epidemiologia , Adulto Jovem
15.
J R Soc Interface ; 2(4): 349-63, 2005 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-16849193

RESUMO

We analyse data on patient adherence to prescribed regimens and surrogate markers of clinical outcome for 168 human immunodeficiency virus infected patients treated with antiretroviral therapy. Data on patient adherence consisted of dose-timing measurements collected for an average of 12 months per patient via electronic monitoring of bottle opening events. We first discuss how such data can be presented to highlight suboptimal adherence patterns and between-patient differences, before introducing two novel methods by which such data can be statistically modelled. Correlations between adherence and subsequent measures of viral load and CD4+T-cell counts are then evaluated. We show that summary measures of short-term adherence, which incorporate pharmacokinetic and pharmacodynamic data on the monitored regimen, predict suboptimal trends in viral load and CD4+T-cell counts better than measures based on adherence data alone.


Assuntos
Terapia Antirretroviral de Alta Atividade/estatística & dados numéricos , Contagem de Linfócito CD4/estatística & dados numéricos , Infecções por HIV/epidemiologia , Infecções por HIV/terapia , Avaliação de Resultados em Cuidados de Saúde/métodos , Cooperação do Paciente/estatística & dados numéricos , Medição de Risco/métodos , Simulação por Computador , Interpretação Estatística de Dados , Infecções por HIV/imunologia , Humanos , Modelos Biológicos , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Estatística como Assunto , Resultado do Tratamento , Estados Unidos/epidemiologia
16.
AIDS ; 15 Suppl 5: S161-9, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11816165

RESUMO

New HIV treatment strategies are needed. Over the past year, substantial progress has been made in the development of new antiretroviral agents, although the journey from drug discovery to wide clinical use is completed by only a small number of medications. Strategies to enhance immune control and either discontinue or decrease the need for prolonged HAART are under study. The promising preliminary results in very early PHI are in contrast with the minor successes in chronic infection.


Assuntos
Vacinas contra a AIDS/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , Desenho de Fármacos , Infecções por HIV/tratamento farmacológico , Inibidores da Transcriptase Reversa/uso terapêutico , Vacinas contra a AIDS/administração & dosagem , Vacinas contra a AIDS/imunologia , Fármacos Anti-HIV/administração & dosagem , Quimioterapia Combinada , Infecções por HIV/prevenção & controle , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/imunologia , Humanos , Inibidores da Transcriptase Reversa/administração & dosagem
17.
AIDS ; 13(18): 2547-54, 1999 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-10630524

RESUMO

OBJECTIVE: To compare the initiation of highly active antiretroviral therapy (HAART) in HIV-infected patients according to sex, route of HIV acquisition and education, and to assess the impact of differences in utilization on the probability of progression to AIDS. DESIGN AND SETTING: Swiss HIV Cohort Study, a national prospective multi-centre study. PARTICIPANTS: A total of 3342 patients, including 1007 (30%) women. HIV was acquired through injection drug use in 1155 (35%) cases and through sex between men in 1172 (35%). Twenty-eight per cent (957) of participants had attained only the minimum level of schooling. At baseline, the median CD4 cell count was 269x10(6)/l cells, median HIV-1 RNA was 4.3 log10 copies/ml and 2917 (87%) were free of AIDS. METHODS: Kaplan-Meier life tables and Cox proportional hazards regression. RESULTS: During 7007 person-years of follow-up 2285 (69%) patients started HAART and 318 (10%) developed a new AIDS event. In multivariable analysis controlling for CD4 cell count, viral load and disease stage at baseline, the probability of starting HAART was lower in injection drug users compared with men who have sex with men, hazard ratio 0.63 (95% confidence intervals 0.56-0.70) and in patients with minimum schooling compared with those with vocational training, hazard ratio 0.82 (0.75-0.91). The risk of progression to AIDS was similar among men and women, patients with a history of injecting drug use, and patients with lower educational attainment in both univariable and multivariable analysis. CONCLUSION: HIV-infected injecting drug users and those with lower levels of educational attainment start HAART later than other patient groups. The deferred initiation of therapy in these patients does not, however, appear to translate into an increased risk of clinical disease progression. This observation has important implications for treatment policy and the design of future clinical trials.


Assuntos
Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , HIV-1 , Progressão da Doença , Quimioterapia Combinada , Educação , Feminino , Humanos , Masculino , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores Sexuais , Análise de Sobrevida , Suíça , Fatores de Tempo
18.
AIDS ; 8(9): 1325-9, 1994 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-7802988

RESUMO

OBJECTIVE: Factors that influence the infectivity of an individual and the impact of antiviral treatment on infectivity are not well defined. This study investigated the value of a sensitive method for detecting infectious HIV in semen for use as a marker for infectivity. DESIGN: A cross-sectional study of infectious HIV in the semen of 33 HIV-positive men. METHODS: A sensitive method for detecting infectious HIV in semen was used. The correlation of culture in semen with clinical and laboratory data was investigated. Biological phenotypes of isolates from blood and semen were tested using an MT-2 assay. RESULTS: HIV cultures from seminal cells were positive in 18 patients (55%) and in one patient from seminal plasma. Higher recovery rates of HIV from semen correlated with a low CD4 count (80% in patients with a CD4 count > 100 x 10(6)/l versus 33% in patients with a CD4 count < 100 x 10(6) cells; P < 0.025) and symptomatic disease (78 versus 27% in asymptomatic patients; P < 0.01). Recovery of HIV from semen was independent of presence or absence of plasma viremia and the biological phenotype of blood isolates. Ten patients with syncytium-inducing (SI) isolates in their blood had positive semen cultures for HIV. Seven of the 10 patients had SI isolates recovered from their semen, whereas three had non-SI isolates only. CONCLUSION: Data from partner studies show higher rates of HIV transmission for patients with low CD4 counts and symptomatic disease. The compatibility of epidemiologic data with our finding that significantly more HIV is recovered in semen from patients with advanced disease, suggests that HIV culture of semen samples may provide a useful surrogate marker to measure infectivity in clinical studies. Further studies are needed to define the inoculum required to transmit HIV and to study the impact of sexually transmitted diseases and HIV-1 phenotype on semen infectivity.


Assuntos
Soropositividade para HIV/virologia , HIV-1/isolamento & purificação , Sêmen/virologia , Biomarcadores , Contagem de Linfócito CD4 , Efeito Citopatogênico Viral , Soropositividade para HIV/sangue , Soropositividade para HIV/transmissão , HIV-1/patogenicidade , Humanos , Leucócitos Mononucleares/virologia , Masculino , Fenótipo , Plasma/virologia , Viremia/virologia , Cultura de Vírus
19.
AIDS ; 13(14): 1857-62, 1999 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-10513643

RESUMO

OBJECTIVE: To analyse prospectively the effect of highly active antiretroviral treatment (HAART) on CD4 T-cell responses in vitro and in vivo in HIV-infected patients. DESIGN: Prospective study with 49 protease inhibitor-naive adult patients. Data were collected at baseline and after 3 and 6 months of HAART. METHODS: In vitro CD4 T-cell reactivity was analysed by stimulation of peripheral blood mononuclear cells with several antigens. In vivo CD4 T-cell reactivity (delayed type hypersensitivity) was assessed by Multitest Merieux. Both measurements were correlated to CD4 (memory) T-cell count and HIV-1 viraemia. RESULTS: Restoration of specific CD4 T-cell proliferation was observed in most patients. The in vitro T-cell response was restored more frequently against antigens to which the immune system is constantly exposed (Candida albicans, Mycobacterium tuberculosis, M. avium) as compared with a low-exposure antigen (tetanus toxoid). Overall, delayed type hypersensitivity detection rate increased under HAART. Multivariate analysis showed improvement of antigen-specific T-cell proliferation to be significantly associated with an increase in memory CD4 T-cells, whereas improvement of the delayed type hypersensitivity response was associated with a decrease in plasma HIV-1 RNA. CONCLUSIONS: HAART for 6 months restored antigen-specific CD4 T-cell response to several antigens. In vitro immune reconstitution was closely correlated with an increase in memory CD4 cells. Restoration of delayed type hypersensitivity was associated with suppression of viraemia. It appears that in addition to expansion of memory CD4 cells, suppression of viraemia following HAART may allow an improved inflammatory reaction, thus providing even stronger immune reconstitution.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Linfócitos T CD4-Positivos/imunologia , Antígenos HIV/imunologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , HIV-1/crescimento & desenvolvimento , Hipersensibilidade Tardia/imunologia , Memória Imunológica , Adulto , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/virologia , Divisão Celular , Quimioterapia Combinada , Feminino , Infecções por HIV/virologia , HIV-1/genética , HIV-1/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Carga Viral , Viremia/imunologia
20.
AIDS ; 11(8): 987-93, 1997 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9223732

RESUMO

OBJECTIVE: This study examined the concentration of HIV in semen and the effects of biological factors on HIV excretion. METHODS: Semen samples from 101 men at different stages of the disease were evaluated by quantitative HIV culture and HIV RNA detection. Blood plasma samples were available from 56 patients. The effects of CD4 and CD8 count, blood plasma RNA levels, treatment status and clinical staging on the shedding of HIV were evaluated. RESULTS: HIV RNA levels in semen correlated with quantitative HIV culture of seminal cells and a strong association of positive seminal cell culture with high RNA levels was observed. CD4 count and antiviral treatment were inversely correlated with the concentration of HIV in semen. Blood plasma HIV RNA values were correlated with HIV RNA levels in semen, although some patients had highly discrepant results. CONCLUSIONS: The strong correlation between seminal cell culture and concentration of HIV RNA in seminal plasma suggested that HIV detected in seminal plasma was released by productively infected cells in the male genital tract. The study showed that the concentration of HIV in semen, which was likely to be correlated with HIV infectivity, was a function of the immune status of the HIV-infected individual. The results suggested that antiviral therapy may have reduced the concentration of HIV in semen.


Assuntos
Soropositividade para HIV/virologia , HIV-1/isolamento & purificação , Sêmen/virologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos/citologia , Soropositividade para HIV/tratamento farmacológico , Soropositividade para HIV/imunologia , HIV-1/genética , HIV-1/crescimento & desenvolvimento , Humanos , Imunidade , Masculino , RNA Viral/análise , Eliminação de Partículas Virais
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