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1.
AIDS Care ; 26(12): 1555-61, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25029599

RESUMO

CRANIum, a cross-sectional epidemiology study in Western Europe and Canada, was conducted to describe and compare the prevalence of a positive screen for neurocognitive impairment (NCI), depressive symptoms, and anxiety in an HIV-positive population either receiving combination antiretroviral therapy (cART) or who were naive to antiretroviral therapy (ART). HIV-positive patients ≥18 years of age attending a routine medical follow-up visit and able to complete the designated screening tools were eligible for study inclusion. The Brief Neurocognitive Screen was used to assess NCI; depressive and anxiety symptoms were assessed using the Hospital Anxiety and Depression Scale. The evaluable patient population (N = 2863) included 1766 men (61.7%) and 1096 (38.3%) women. A total of 1969 patients were cART-experienced (68.8%), and 894 were ART-naive (31.2%). A positive screen for NCI was found in 41.5% of patients (cART-experienced, 42.5%; ART-naive, 39.4%; p = 0.12). A positive screen for depressive symptoms was found in 15.7% of patients (cART-experienced, 16.8%; ART-naive, 13.3%; p = 0.01), whereas 33.3% of patients screened positive for anxiety (cART-experienced, 33.5%; ART-naive, 32.8%; p = 0.71). A greater percentage of women compared with men screened positive for NCI (51.78% vs. 35.1%; p < 0.0001) and depressive symptoms (17.9% vs. 14.3%; p = 0.01). These data suggest that neurocognitive and mood disorders remain highly prevalent in HIV-infected patients. Regular mental health screening in this population is warranted.


Assuntos
Ansiedade/psicologia , Depressão/psicologia , Infecções por HIV/psicologia , Complexo AIDS Demência/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Antirretroviral de Alta Atividade/métodos , Ansiedade/epidemiologia , Canadá , Transtornos Cognitivos/psicologia , Estudos Transversais , Depressão/epidemiologia , Europa (Continente) , Feminino , Seguimentos , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Testes Neuropsicológicos , Prevalência , Inquéritos e Questionários
2.
Artigo em Inglês | MEDLINE | ID: mdl-22713685

RESUMO

This study was conducted to assess the prevalence of depressive symptoms, sleep disturbances, and subjective cognitive complaints in patients with HIV receiving highly active antiretroviral therapy. Participants completed the "Center for Epidemiological Studies Depression Scale" (CES-D) and a questionnaire on sleep disturbances and subjective cognitive complaints. Mean age of the 799 participants was 43.7 years and 67% were men. Adjusted prevalence of CES-D was 35.4% (95% confidence interval [CI]: 32.0-38.7), with no significant differences between gender and age groups. Sleep disturbances were more prevalent in older versus younger participants (74.0% [95% CI: 70.4-77.7] versus 63.3% [95% CI: 56.8-69.8]). Cognitive complaints were more prevalent in women (52.3% [95% CI: 46.4-58.2]) when compared with men (48.2% [95% CI: 44.7-51.6]). Hepatitis C virus coinfection was a strong predictor of depressive symptoms. Male gender and detectable viral load were independent risk factors for sleep disturbance. A higher CES-D score was an independent risk factor for sleep disturbance and cognitive complaints.


Assuntos
Transtornos Cognitivos/epidemiologia , Depressão/epidemiologia , Dissonias/epidemiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Adulto , Fatores Etários , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Coinfecção/epidemiologia , Coinfecção/psicologia , Dissonias/virologia , Feminino , Infecções por HIV/psicologia , Hepatite C/epidemiologia , Hepatite C/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Escalas de Graduação Psiquiátrica , Fatores de Risco , Fatores Sexuais , Espanha/epidemiologia , Inquéritos e Questionários , Carga Viral
3.
AIDS Res Hum Retroviruses ; 21(5): 398-406, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15929702

RESUMO

We evaluated the effect of salvage antiretroviral therapy with lopinavir/ritonavir (LPV/r) on the immune system of heavily antiretroviral pretreated HIV-infected children. We carried out a longitudinal study in 20 antiretroviral experienced HIV-infected children to determine the changes in several immunological parameters (T cell subsets, thymic function) every 3 months during 18 months of follow-up on salvage therapy with LPV/r. Statistical analyses were performed with the Wilcoxon test, taking as a reference the basal value at the entry in the study. HIV-infected children showed an increase of CD4+ T cells, a decrease in CD8+ T cells, and an increase in T cell rearrangement excision circle (TRECs) levels. The percentage of HIV children with undetectable viral load (VL < or = 400 copies/ml) increased significantly (p = 0.007) and the percentage with SI viral phenotype decreased significantly (p = 0.002) at the end of the study. Thus, the viral phenotype changed to NSI/R5 after salvage therapy with LPV/r. Interestingly, we observed a significant decrease of memory (CD4+ CD45RO+) and a moderate decrease of activated (CD4+ HLA-DR+, CD4+ HLA-DR+CD38, CD4+, CD45RO+HLA-DR+) CD4+ T cells during the follow-up. On the other hand, memory (CD8+ CD45RO+ and CD8+ CD45RO+CD38+), activated (CD8+ HLA-DR+CD38+, CD8+ HLA-DR+, CD8+ CD38+), and effector (CD8+ CD57+, CD8+ CD28(-)CD57+) CD8+ T cells had a very significant decrease during follow-up. Our data indicate an immune system reconstitution in heavily pretreated HIV-infected children in response to salvage therapy with LPV/r as a consequence of a decrease in immune system activation and an increase in thymic function.


Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Inibidores da Protease de HIV/uso terapêutico , Pirimidinonas/uso terapêutico , Ritonavir/uso terapêutico , Adolescente , Criança , Pré-Escolar , Feminino , Infecções por HIV/virologia , Humanos , Memória Imunológica , Lactente , Lopinavir , Masculino , Estudos Prospectivos , Terapia de Salvação , Subpopulações de Linfócitos T/imunologia , Timo/imunologia , Resultado do Tratamento
4.
Pediatr Infect Dis J ; 24(10): 867-73, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16220083

RESUMO

INTRODUCTION: Many human immunodeficiency virus type 1 (HIV-1)-infected children have already failed treatment with 2 or even 3 classes of antiretrovirals. Coformulation of lopinavir with low dose ritonavir exhibits a potent antiretroviral effect. However, the data in heavily pretreated children are still scarce. This study evaluated the safety and effectiveness of combination therapy including lopinavir/ritonavir in children with prior exposure to all classes of oral antiretrovirals. METHODS: This was an open label multicenter observational study, in which data were reviewed according to a standardized protocol. The study population included all HIV-1-infected children with virologic failure (HIV-1 RNA >5000 copies/mL) followed in 12 Spanish hospitals for >12 months, experienced with the 3 classes of oral antiretrovirals, in whom a lopinavir/ritonavir-containing regimen was started. RESULTS: By March 2003, 45 patients had been treated with lopinavir/ritonavir for a median of 18 months (range, 3-28). The median age at baseline was 9.7 years (range, 4.3-17.1). The median times of prior treatment were 88 months (range, 31-145) with nucleoside reverse transcription inhibitors and 42 months (range, 19-63) with protease inhibitors. Twenty-five patients were classified as Centers for Disease Control and Prevention clinical category C. Median values for absolute and percentage CD4 at baseline were 501 (range, 6-1512) and 19% (range, 0.5-49), respectively, and plasma HIV-RNA was 5.0 log10 copies/mL (range, 4.1-6.1). During follow-up, 11 (24%) children switched from liquid to solid formulation. At 48 weeks, the median values for absolute and percentage CD4 increased by 199 cells/microL and 3%, respectively, and median plasma viral load declined 1.75 log10 copies/mL. Forty-two percent of children achieved a plasma RNA of <400 copies/mL (intent to treat analysis). Baseline genotypic resistance was available in 40 children. Nonresponders had 7.0 +/- 1.6 protease inhibitor-associated mutations at baseline compared with 4.8 +/- 1.7 in children achieving virologic suppression (P = 0.06). Adverse events were described in 18 children. Three children permanently discontinued and 4 transiently withdrew lopinavir/ritonavir. At 12 months, there were mild but not significant increases in plasma cholesterol and triglycerides. CONCLUSIONS: Lopinavir/ritonavir when given as part of salvage regimen is well-tolerated, although switching to pills is frequently required. The regimen has a potent and durable antiretroviral activity in most heavily pretreated children, despite the presence of multiple mutations to all classes of oral antiretrovirals.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Pirimidinonas/efeitos adversos , Inibidores da Transcriptase Reversa/uso terapêutico , Ritonavir/efeitos adversos , Adolescente , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Infecções por HIV/virologia , Humanos , Lopinavir , Masculino , Pirimidinonas/uso terapêutico , RNA Viral/sangue , Ritonavir/uso terapêutico , Terapia de Salvação , Resultado do Tratamento
5.
AIDS ; 18(2): 247-55, 2004 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-15075542

RESUMO

OBJECTIVE: To investigate the effects of salvage therapy with lopinavir-ritonavir on HIV-1 phenotype in heavily antiretroviral experienced HIV-infected children. DESIGN: Twenty antiretroviral experienced HIV-infected children were studied during a mean of time of 16.1 months from initiation of the treatment with lopinavir-ritonavir. METHODS: Besides CD4 T cells, viral load and clinical status, we analyzed 91 serial viral isolates to study the phenotype, and biological clones derived from co-cultivation techniques. RESULTS: We observed an increase in CD4 T cells, a statistically significant decrease in viral load and clinical benefits from 3 months after treatment. Ninety per cent of children had SI/X4 bulk isolates in peripheral blood mononuclear cells at study entry. The viral phenotype changed to non syncitium-inducing (NSI)/R5 in 94% of the children after a mean of 5.7 months (95% confidence interval, 2.1-9.3 months) of salvage therapy. The remaining 10% of children had NSI/R5 isolates at entry and at all follow-up study. Similar results were found at the clonal level. Thus, at study entry in PBMC of three children with bulk syncitium-inducing (SI) phenotype, we recovered 65 biologic clones, 56 being SI and nine NSI. After salvage therapy bulk isolates changed to NSI and of 40 biologic clones recovered only five were SI and the rest were NSI. CONCLUSIONS: Our data suggest that lopinavir-ritonavir salvage therapy led not only to a viral load decrease but also to a phenotypic change. X4 virus appeared to be preferentially suppressed. Shifts in co-receptor usage may thereby contribute to the clinical efficacy of anti-HIV drugs in vertically infected infants.


Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , HIV-1/fisiologia , Pirimidinonas/uso terapêutico , Ritonavir/uso terapêutico , Combinação de Medicamentos , Feminino , Infecções por HIV/transmissão , Humanos , Lactente , Transmissão Vertical de Doenças Infecciosas , Leucócitos Mononucleares/virologia , Lopinavir , Masculino , Fenótipo , Terapia de Salvação , Subpopulações de Linfócitos T , Carga Viral , Replicação Viral/efeitos dos fármacos
6.
Pediatr Infect Dis J ; 23(10): 923-30, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15602192

RESUMO

OBJECTIVE: To study the control of viral replication in human immunodeficiency virus (HIV)-infected children on different salvage therapies. DESIGN AND SETTING: A retrospective observational study in 120 HIV-infected children was conducted. The children were divided into 3 groups according to their salvage therapies: (1) children receiving first line highly active antiretroviral therapy (HAART); (2) protease inhibitor-experienced children receiving second line HAART; (3) protease inhibitor-experienced children receiving HAART including lopinavir-ritonavir (LPV/r). The outcome variables examined were time to achieve viral load (VL) < or =400 copies/mL, success in achieving VL < or =400 copies/mL and time to virologic failure (VL >400 copies/mL). METHODS: VL (HIV-RNA copies/mL) was quantified with reverse transcription-polymerase chain reaction molecular assay. For each protocol, survival analyses were conducted to determine the probability of achieving VL < or =400 copies/mL and rebound of VL. RESULTS: VL < or =400 copies/mL was achieved by 52.4% of children receiving first line HAART, 48.3% receiving second line HAART and 71.5% receiving HAART including LPV/r. Children receiving HAART including LPV/r reached VL < or =400 copies/mL in a shorter time than children receiving second line HAART (P = 0.017), but quite similar to children receiving first line HAART. In terms of adjusted relative risk, children receiving HAART including LPV/r were 3.36 [95% confidence interval (95% CI), 1.59, 7.07] more likely to achieve VL < or =400 copies/mL than children receiving a different second line HAART. VL rebound occurred in 68.2% children receiving first line HAART, 73.4% receiving second line HAART and 32.4% receiving HAART including LPV/r. Children receiving HAART that includes LPV/r has less incidence of VL rebound (P=0.013) and 3.29 (95% CI 1.04, 10.3) times less risk to achieve a VL rebound than children receiving a different second line HAART. CONCLUSIONS: HAART that includes LPV/r is able to control HIV replication more efficiently than other classic salvage antiretroviral therapies.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Pirimidinonas/uso terapêutico , Ritonavir/uso terapêutico , Terapia de Salvação , Sequência de Aminoácidos , Fármacos Anti-HIV/administração & dosagem , Terapia Antirretroviral de Alta Atividade , Criança , Farmacorresistência Viral , Quimioterapia Combinada , Genes Virais , Genótipo , HIV-1/efeitos dos fármacos , HIV-1/genética , Humanos , Lopinavir , Mutação/efeitos dos fármacos , Pirimidinonas/administração & dosagem , Ritonavir/administração & dosagem , Carga Viral
7.
AIDS Patient Care STDS ; 24(1): 5-13, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20095903

RESUMO

Patients infected with HIV treated with highly active antiretroviral therapy (HAART) frequently develop body physical changes (BPC) that have an important psychosocial burden. The purpose of this study was to determine the prevalence of BPC observed by HIV-infected patients and their attending physicians and to assess the impact BPC had on daily life. In this epidemiologic multicenter study, patients with HIV infection and their treating physicians filled out parallel questionnaires about their perceptions of specific BPC and their impact on daily activities. A total of 965 patient-physician questionnaires were collected across 98 health centers. Patient's mean age was 43.7 +/- 8.5 years and 72.6% were men. Adjusted prevalence of perceived BPC by patients and physicians was 55.1% (95% confidence interval [CI]: 52.0-58.1) and 55.2% (95% CI: 52.1-58.2), respectively (p = 1.000). Overall patient-physician agreement concerning perception of BPC was 83% (p < 0.0005). The most common BPC was lipoatrophy, described by 46.8% (95% CI: 43.7-49.8) of patients and 49.4% (95% CI: 46.3-52.5) of physicians (p = 0.033) followed by lipohypertrophy. No gender differences were observed in the global prevalence of BPC (p = 0.649). However, significantly more women reported lipoatrophy of the lower limbs (p = 0.009) and buttocks (p = 0.007), as well as lipohypertrophy (p = 0.007), than men; 58.2% (95% CI: 54.0-62.4) patients noted that BPC negatively affected their daily activities. This study reflects the high prevalence of patient and physician-perceived BPC in the HIV population, and the adverse impact on daily life. Physicians should be aware of the psychosocial consequences of BPC in HIV patients in order to improve patient well-being.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Distribuição da Gordura Corporal , Infecções por HIV/tratamento farmacológico , Adulto , Antropometria , Fármacos Anti-HIV/efeitos adversos , Distribuição da Gordura Corporal/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Caracteres Sexuais
8.
AIDS ; 22(2): F1-9, 2008 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-18097218

RESUMO

BACKGROUND: Prior attempts to reduce the number of drugs needed to maintain viral suppression in patients with suppressed HIV replication while receiving three antiretroviral drugs have been unsuccessful. METHODS: In 205 patients with suppressed HIV replication on lopinavir-ritonavir and two nucleosides, this randomized, open-label, non-inferiority clinical trial compared the strategies of continuation of triple therapy versus lopinavir-ritonavir monotherapy followed by reinduction with two nucleosides if virological rebound occurred without genotypic resistance to lopinavir-ritonavir. The primary endpoint was proportion of patients without therapeutic failure, defined as confirmed HIV RNA higher than 500 copies/mL (with exclusion of patients receiving monotherapy who resuppressed to < 50 copies/mL after resuming baseline nucleosides), or loss to follow-up, or change of randomized therapy other than reinduction. RESULTS: At week 48, the percentage of patients without therapeutic failure was 94% in the monotherapy group versus 90% in the triple therapy group (difference,-4%; upper limit of 95% confidence interval for difference, 3.4%). The percentage of patients with HIV RNA 50 copies/mL at 48 weeks by intention-to-treat, missing data or reinductions considered as failures, were 85% in the monotherapy group versus 90% in the triple therapy group (P = 0.31; 95% upper limit of 95% confidence interval for difference, 14%). CONCLUSION: In this trial, 48 weeks of lopinavir-ritonavir monotherapy with reintroduction of nucleosides as needed was non-inferior to continuation of two nucleosides and lopinavir-ritonavir in patients with prior stable suppression. However, episodes of low level viremia were more common in patients receiving monotherapy.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , HIV-1 , Nucleosídeos/uso terapêutico , Pirimidinonas/uso terapêutico , Ritonavir/uso terapêutico , Adulto , Idoso , Fármacos Anti-HIV/administração & dosagem , Terapia Antirretroviral de Alta Atividade , Esquema de Medicação , Feminino , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Lopinavir , Masculino , Pessoa de Meia-Idade , Nucleosídeos/efeitos adversos , Pirimidinonas/administração & dosagem , RNA Viral/genética , Ritonavir/administração & dosagem , Espanha , Resultado do Tratamento , Carga Viral
9.
J Antimicrob Chemother ; 54(5): 921-31, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15472006

RESUMO

BACKGROUND: Lopinavir/ritonavir has demonstrated antiviral activity in the HIV-infected patient. OBJECTIVE: To analyse virological response to lopinavir/ritonavir therapy in previously protease inhibitor (PI)-experienced HIV-1-infected children. MATERIALS AND METHODS: Sixty-seven HIV-1-children on lopinavir/ritonavir were studied in a multicentre prospective cohort observational study. The outcome variables were undetectable viral load (uVL; VL < or =400 copies/mL) and virological failure after uVL with a rebound of VL >400 copies/mL. VL and genotype of HIV-1-isolates were measured using standard assays. RESULTS: 83.5% of children had a 1 log10 VL decrease including 65.6% who reached uVL. Children with >2 changes of antiretroviral therapy (ART) or >5 drugs needed a median time of 3-4 months higher than children with < or =2 changes of ART or < or =5 drugs previous to lopinavir/ritonavir, to reach those values, and the relative proportions (RP) were 2.2 (P =0.038) and 1.9 (P=0.050), respectively. Children with CD4+>15% (P=0.122), VL < or =30,000 (P < 0.001) copies/mL, and age >12 years (P=0.096) achieved an earlier control of VL during the follow-up. The children with virological failure or rebound of VL had higher baseline VL and lower CD4+ T-lymphocytes/mm3 and had taken a greater number of drugs previous to lopinavir/ritonavir. HIV-children with a new nucleoside reverse transcriptase inhibitor (NRTI), or protease inhibitor (PI) or PI plus non-nucleoside reverse transcriptase inhibitors (NNRTI) in the current regimen had a better virological response than children without these new drugs. Also, children with <6 protease mutations had an RP of 2.31 of achieving uVL. CONCLUSIONS: Highly active antiretroviral therapy (HAART) including lopinavir/ritonavir induces beneficial effects in terms of virological outcome responses, and it is an effective option for salvage therapy in PI-experienced HIV-1-infected children.


Assuntos
Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , HIV-1 , Pirimidinonas/administração & dosagem , Ritonavir/administração & dosagem , Síndrome da Imunodeficiência Adquirida/imunologia , Síndrome da Imunodeficiência Adquirida/virologia , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Estudos de Coortes , Quimioterapia Combinada , Humanos , Lopinavir , Estudos Prospectivos , Pirimidinonas/efeitos adversos , Ritonavir/efeitos adversos , Terapia de Salvação
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