RESUMO
Substance use in people with HIV (PWH) negatively impacts antiretroviral therapy (ART) adherence. However, less is known about this in the current treatment era and the impact of specific substances or severity of substance use. We examined the associations of alcohol, marijuana, and illicit drug use (methamphetamine/crystal, cocaine/crack, illicit opioids/heroin) and their severity of use with adherence using multivariable linear regression in adult PWH in care between 2016 and 2020 at 8 sites across the US. PWH completed assessments of alcohol use severity (AUDIT-C), drug use severity (modified ASSIST), and ART adherence (visual analogue scale). Among 9400 PWH, 16% reported current hazardous alcohol use, 31% current marijuana use, and 15% current use of ≥1 illicit drugs. In multivariable analysis, current methamphetamine/crystal use, particularly common among men who had sex with men, was associated with 10.1% lower mean ART adherence (p < 0.001) and 2.6% lower adherence per 5-point higher severity of use (ASSIST score) (p < 0.001). Current and more severe use of alcohol, marijuana, and other illicit drugs were also associated with lower adherence in a dose-dependent manner. In the current HIV treatment era, individualized substance use treatment, especially for methamphetamine/crystal, and ART adherence should be prioritized.
Assuntos
Infecções por HIV , Drogas Ilícitas , Metanfetamina , Transtornos Relacionados ao Uso de Substâncias , Adulto , Masculino , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/complicações , Transtornos Relacionados ao Uso de Substâncias/complicações , Antirretrovirais/uso terapêutico , Etanol/uso terapêutico , Metanfetamina/uso terapêutico , Adesão à MedicaçãoRESUMO
BACKGROUND: Anemia is common among people living with HIV infection (PLWH) and is associated with adverse health outcomes. Information on risk factors for anemia incidence in the current antiretroviral therapy (ART) era is lacking. METHODS: Within a prospective clinical cohort of adult PLWH receiving care at eight sites across the United States between 1/2010-3/2018, Cox proportional hazards regression analyses were conducted among a) PLWH free of anemia at baseline and b) PLWH free of severe anemia at baseline to determine associations between time-updated patient characteristics and development of anemia (hemoglobin < 10 g/dL), or severe anemia (hemoglobin < 7.5 g/dL). Linear mixed effects models were used to examine relationships between patient characteristics and hemoglobin levels during follow-up. Hemoglobin levels were ascertained using laboratory data from routine clinical care. Potential risk factors included: age, sex, race/ethnicity, body mass index, smoking status, hazardous alcohol use, illicit drug use, hepatitis C virus (HCV) coinfection, estimated glomerular filtration rate (eGFR), CD4 cell count, viral load, ART use and time in care at CNICS site. RESULTS: This retrospective cohort study included 15,126 PLWH. During a median follow-up of 6.6 (interquartile range [IQR] 4.3-7.6) years, 1086 participants developed anemia and 465 participants developed severe anemia. Factors that were associated with incident anemia included: older age, female sex, black race, HCV coinfection, lower CD4 cell counts, VL ≥400 copies/ml and lower eGFR. CONCLUSION: Because anemia is a treatable condition associated with increased morbidity and mortality among PLWH, hemoglobin levels should be monitored routinely, especially among PLWH who have one or more risk factors for anemia.
Assuntos
Anemia/epidemiologia , Anemia/etiologia , Infecções por HIV/complicações , Hemoglobinas/análise , Adulto , Antirretrovirais/efeitos adversos , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Coinfecção/complicações , Feminino , Seguimentos , Taxa de Filtração Glomerular , HIV , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Hepatite C/complicações , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Transtornos Relacionados ao Uso de Substâncias/complicações , Estados Unidos/epidemiologia , Carga ViralRESUMO
People aging with HIV face social stressors which may negatively affect their overall nutrition. Here, we assess relationships between self-reported measures of depression, perceived stress, social support, and food insecurity with diet quality in older adults with HIV. A retrospective analysis of self-reported data from parent study at The University of Alabama at Birmingham 1917 HIV Clinic was performed. The study sample consisted of sixty people living with HIV (PLWH) with controlled HIV infection (<50 copies/mL), aged 50 years or older who participated in a cross-sectional microbiome study. Dietary intake was measured using the NHANES 12-month Food Frequency Questionnaire (FFQ) and three Automated Self-Administered (ASA) 24-hr diet recalls to calculate diet quality scores using the Mediterranean Diet Score (MDS); alternative Healthy Eating Index (aHEI); and the Recommended Food Score (RFS) indices. Food insecurity was measured with the Food Security Questionnaire (FSQ). Participants completed the following psychosocial scales: (1) depression - Patient Health Questionnaire-8 (PHQ8); (2) perceived stress - Perceived Stress Scale (PSS-10); (3) social support - Multidimensional Scale of Perceived Social Support (MSPSS). Linear regression models were used to investigate relationships among variables controlling for gender and income. The cohort was characterized as follows: Mean age 56 ± 4.6 years, 80% African-American, and 32% women. Mean body mass index (BMI) was 28.4 ± 7.2 with 55% reporting food insecurity. Most participants reported having post-secondary education (53%), although 77% reported annual incomes <$20,000. Food insecurity was independently associated with measures of poor dietary intake: aHEI (ß = -0.08, p = .02) and MDS (ß = -0.23, p < 0.01) and with low dietary intake of fibre (ß = -0.27, p = .04), vitamin E (ß = -0.35, p = .01), folate (ß = -0.31, p = .02), magnesium (ß = -0.34, p = .01) and copper (ß = -0.36, p = .01). These data indicate food insecurity is associated with poor diet quality among PLWH. Clinical interventions are needed to improve food access for PLWH of low SES.
Assuntos
Dieta , Comportamento Alimentar , Abastecimento de Alimentos/estatística & dados numéricos , Infecções por HIV/psicologia , Estresse Psicológico , Idoso , Alabama , Fármacos Anti-HIV/uso terapêutico , Estudos de Coortes , Depressão , Fibras na Dieta , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Inquéritos Nutricionais , Estado Nutricional , Estudos Retrospectivos , Apoio Social , Inquéritos e QuestionáriosRESUMO
We developed, implemented, and evaluated a myocardial infarction (MI) adjudication protocol for cohort research of human immunodeficiency virus. Potential events were identified through the centralized Centers for AIDS Research Network of Integrated Clinical Systems data repository using MI diagnoses and/or cardiac enzyme laboratory results (1995-2012). Sites assembled de-identified packets, including physician notes and results from electrocardiograms, procedures, and laboratory tests. Information pertaining to the specific antiretroviral medications used was redacted for blinded review. Two experts reviewed each packet, and a third review was conducted if discrepancies occurred. Reviewers categorized probable/definite MIs as primary or secondary and identified secondary causes of MIs. The positive predictive value and sensitivity for each identification/ascertainment method were calculated. Of the 1,119 potential events that were adjudicated, 294 (26%) were definite/probable MIs. Almost as many secondary (48%) as primary (52%) MIs occurred, often as the result of sepsis or cocaine use. Of the patients with adjudicated definite/probable MIs, 78% had elevated troponin concentrations (positive predictive value = 57%, 95% confidence interval: 52, 62); however, only 44% had clinical diagnoses of MI (positive predictive value = 45%, 95% confidence interval: 39, 51). We found that central adjudication is crucial and that clinical diagnoses alone are insufficient for ascertainment of MI. Over half of the events ultimately determined to be MIs were not identified by clinical diagnoses. Adjudication protocols used in traditional cardiovascular disease cohorts facilitate cross-cohort comparisons but do not address issues such as identifying secondary MIs that may be common in persons with human immunodeficiency virus.
Assuntos
Técnicas de Apoio para a Decisão , Projetos de Pesquisa Epidemiológica , Infecções por HIV/complicações , Infarto do Miocárdio/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Reações Falso-Positivas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Método Simples-CegoRESUMO
The self-rating scale item (SRSI) is a single-item self-report adherence measure that uses adjectives in a 5-point Likert scale, from "very poor" to "excellent," to describe medication adherence over the past 4 weeks. This study investigated the SRSI in 2,399 HIV-infected patients in routine care at two outpatient primary HIV clinics. Correlations between the SRSI and four commonly used adherence items ranged from 0.37 to 0.64. Correlations of adherence barriers, such as depression and substance use, were comparable across all adherence items. General estimating equations suggested the SRSI is as good as or better than other adherence items (p's <0.001 vs. <0.001-0.99) at predicting adherence-related clinical outcomes, such as HIV viral load and CD4(+) cell count. These results and the SRSI's low patient burden suggest its routine use could be helpful for assessing adherence in clinical care and should be more widespread, particularly where more complex instruments may be impractical.
Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Autorrelato , Inquéritos e Questionários , Adulto , Consumo de Bebidas Alcoólicas/psicologia , Contagem de Linfócito CD4 , Depressão/complicações , Depressão/psicologia , Feminino , Infecções por HIV/psicologia , Infecções por HIV/virologia , Humanos , Entrevistas como Assunto , Masculino , Adesão à Medicação/psicologia , Pessoa de Meia-Idade , Medição da Dor , Testes Psicológicos , Sensibilidade e Especificidade , Fatores Socioeconômicos , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/psicologia , Resultado do Tratamento , Carga ViralRESUMO
Plasma HIV RNA determinations are an important prognostic marker of disease progression and, when used appropriately, provide a valuable tool for the management of individual patients. But what constitutes appropriate use?
Assuntos
Infecções por HIV/etiologia , Infecções por HIV/genética , RNA Viral/sangue , Antivirais/uso terapêutico , Coleta de Amostras Sanguíneas , Infecções por HIV/terapia , Humanos , Valor Preditivo dos Testes , Prognóstico , RNA Viral/efeitos dos fármacos , Resultado do TratamentoRESUMO
T-20, a synthetic peptide corresponding to a region of the transmembrane subunit of the HIV-1 envelope protein, blocks cell fusion and viral entry at concentrations of less than 2 ng/ml in vitro. We administered intravenous T-20 (monotherapy) for 14 days to sixteen HIV-infected adults in four dose groups (3, 10, 30 and 100 mg twice daily). There were significant, dose-related declines in plasma HIV RNA in all subjects who received higher dose levels. All four subjects receiving 100 mg twice daily had a decline in plasma HIV RNA to less than 500 copies/ml, by bDNA assay. A sensitive RT-PCR assay (detection threshold 40 copies/ml) demonstrated that, although undetectable levels were not achieved in the 14-day dosing period, there was a 1.96 log10 median decline in plasma HIV RNA in these subjects. This study provides proof-of-concept that viral entry can be successfully blocked in vivo. Short-term administration of T-20 seems safe and provides potent inhibition of HIV replication comparable to anti-retroviral regimens approved at present.
Assuntos
Fármacos Anti-HIV/farmacocinética , Fármacos Anti-HIV/uso terapêutico , Proteína gp41 do Envelope de HIV/sangue , Proteína gp41 do Envelope de HIV/fisiologia , Proteína gp41 do Envelope de HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/fisiologia , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/uso terapêutico , Replicação Viral/efeitos dos fármacos , Adulto , Fármacos Anti-HIV/sangue , Contagem de Linfócito CD4 , Relação Dose-Resposta a Droga , Enfuvirtida , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/isolamento & purificação , Meia-Vida , Humanos , Taxa de Depuração MetabólicaRESUMO
OBJECTIVES: To define the incidence of clinically-detected COVID-19 in people with HIV (PWH) in the US and evaluate how racial and ethnic disparities, comorbidities, and HIV-related factors contribute to risk of COVID-19. DESIGN: Observational study within the CFAR Network of Integrated Clinical Systems cohort in 7 cities during 2020. METHODS: We calculated cumulative incidence rates of COVID-19 diagnosis among PWH in routine care by key characteristics including race/ethnicity, current and lowest CD4 count, and geographic area. We evaluated risk factors for COVID-19 among PWH using relative risk regression models adjusted with disease risk scores. RESULTS: Among 16,056 PWH in care, of whom 44.5% were Black, 12.5% were Hispanic, with a median age of 52 years (IQR 40-59), 18% had a current CD4 count < 350, including 7% < 200; 95.5% were on antiretroviral therapy, and 85.6% were virologically suppressed. Overall in 2020, 649 PWH were diagnosed with COVID-19 for a rate of 4.94 cases per 100 person-years. The cumulative incidence of COVID-19 was 2.4-fold and 1.7-fold higher in Hispanic and Black PWH respectively, than non-Hispanic White PWH. In adjusted analyses, factors associated with COVID-19 included female sex, Hispanic or Black identity, lowest historical CD4 count <350 (proxy for CD4 nadir), current low CD4/CD8 ratio, diabetes, and obesity. CONCLUSIONS: Our results suggest that the presence of structural racial inequities above and beyond medical comorbidities increased the risk of COVID-19 among PWHPWH with immune exhaustion as evidenced by lowest historical CD4 or current low CD4:CD8 ratio had greater risk of COVID-19.
RESUMO
Quantitative analysis of the relationship between virus expression and disease outcome has been critical for understanding HIV-1 pathogenesis. Yet the amount of viral RNA contained within an HIV-expressing cell and the relationship between the number of virus-producing cells and plasma virus load has not been established or reflected in models of viral dynamics. We report here a novel strategy for the coordinated analysis of virus expression in lymph node specimens. The results obtained for patients with a broad range of plasma viral loads before and after antiretroviral therapy reveal a constant mean viral (v)RNA copy number (3.6 log10 copies) per infected cell, regardless of plasma virus load or treatment status. In addition, there was a significant but nonlinear direct correlation between the frequency of vRNA+ lymph node cells and plasma vRNA. As predicted from this relationship, residual cells expressing this same mean copy number are detectable (frequency <2/10(6) cells) in tissues of treated patients who have plasma vRNA levels below the current detectable threshold (<50 copies/ml). These data suggest that fully replication-active cells are responsible for sustaining viremia after initiation of potent antiretroviral therapy and that plasma virus titers correlate, albeit in a nonlinear fashion, with the number of virus-expressing cells in lymphoid tissue.
Assuntos
Infecções por HIV/sangue , HIV-1/patogenicidade , Linfonodos/virologia , RNA Viral/sangue , Antivirais/uso terapêutico , Biópsia , Contagem de Células , Humanos , Linfonodos/efeitos dos fármacos , Monócitos , RNA Viral/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Carga Viral , Viremia/genética , Replicação Viral/genéticaRESUMO
Little is known about the psychometric properties of depression instruments among persons infected with HIV. We analyzed data from a large sample of patients in usual care in two US cities (n=1467) using the nine-item Patient Health Questionnaire (PHQ-9) from the PRIME-MD. The PHQ-9 had curvilinear scaling properties and varying levels of measurement precision along the continuum of depression measured by the instrument. In our cohort, the scale showed a prominent floor effect and a distribution of scores across depression severity levels. Three items had differential item functioning (DIF) with respect to race (African-American vs. white); two had DIF with respect to sex; and one had DIF with respect to age. There was minimal individual-level DIF impact. Twenty percent of the difference in mean depression levels between African-Americans and whites was due to DIF. While standard scores for the PHQ-9 may be appropriate for use with individual HIV-infected patients in cross-sectional settings, these results suggest that investigations of depression across groups and within patients across time may require a more sophisticated analytic framework.
Assuntos
Transtorno Depressivo/diagnóstico , Infecções por HIV/psicologia , Inquéritos e Questionários , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Saúde Mental , Pessoa de Meia-Idade , Psicometria , Adulto JovemRESUMO
Quantitative competitive polymerase chain reaction (QC-PCR) methods were used to quantify virion-associated human immunodeficiency virus type-1 (HIV-1) RNA in plasma from 66 patients with Centers for Disease Control stage I to IVC1 infection. HIV-1 RNA, ranging from 100 to nearly 22,000,000 copies per milliliter of plasma (corresponding to 50 to 11,000,000 virions per milliliter), was readily quantified in all subjects, was significantly associated with disease stage and CD4+ T cell counts, and decreased by as much as 235-fold with resolution of primary infection or institution of antiretroviral therapy. Plasma virus levels determined by QC-PCR correlated with, but exceeded by an average of 60,000-fold, virus titers measured by endpoint dilution culture. Quantitation of HIV-1 in plasma by QC-PCR may be useful in assessing the efficacy of antiretroviral agents, especially in early stage disease when conventional viral markers are often negative.
Assuntos
Síndrome da Imunodeficiência Adquirida/microbiologia , HIV-1/isolamento & purificação , Reação em Cadeia da Polimerase , RNA Viral/sangue , Síndrome da Imunodeficiência Adquirida/sangue , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Linfócitos T CD4-Positivos/patologia , HIV-1/genética , HIV-1/fisiologia , Humanos , Contagem de Leucócitos , Ultracentrifugação , Replicação Viral , Zidovudina/uso terapêuticoRESUMO
It has now been some 25 years since the initial description of AIDS. Following these observations, the epidemiology, natural history and manifestations of this disease have been well characterised. Intense investigation has better characterised HIV, resulting in the development of effective drug therapies to arrest disease progression. These multidrug combinations, termed highly active antiretroviral therapy or HAART, can suppress the viral load to the undetectable range and secondarily halt the destruction of CD4 T lymphocytes. This virological response is associated with a marked improvement in survival and absence of the many complications related to immunodeficiency. For patients who respond to HAART, the current emphasis is on treating side effects from the medications as well as treating other non-AIDS-related disorders. However, given the cost and complexities of these regimens, there are many patients who continue to present with the classic manifestations of AIDS, and, especially in the developing world, we will continue to see these patients for years to come.
Assuntos
Terapia Antirretroviral de Alta Atividade , Gastroenteropatias/virologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Algoritmos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Diarreia/etiologia , Endoscopia Gastrointestinal , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/diagnóstico , HumanosRESUMO
During the initial year of HIV diagnosis, while patients are often overwhelmed adjusting to this life changing diagnosis, they must develop self-care behaviors for attending regular medical care visits and antiretroviral therapy (ART) adherence to achieve and sustain viral suppression (VS). Maintaining "HIV adherence" and integrating it into one's daily life is required to sustain VS over time. The HIV care continuum or "treatment cascade," an epidemiological snapshot of the national epidemic in the United States (US), indicates that a minority of persons living with HIV (PLWH) have achieved VS. Little evidence exists regarding the effects of interventions focusing on PLWH newly initiating outpatient HIV care. An intervention that focuses on both retention in care and ART adherence skills delivered during the pivotal first year of HIV care is lacking. To address this, we developed a theory-based intervention evaluated in the Integrating Engagement and Adherence Goals upon Entry (iENGAGE) study, a National Institute of Allergy and Infectious Diseases (NIAID) funded randomized behavioral intervention trial. Here we present the study objectives, design and rationale, as well as the intervention components, targeting rapid and sustained VS through retention in HIV care and ART adherence during participants' first year of HIV care. The primary outcome of the study is 48-week VS (<200â¯c/mL). The secondary outcomes are retention in care, including HIV visit adherence and visit constancy, as well as ART adherence.
Assuntos
Antirretrovirais/administração & dosagem , Terapia Comportamental/métodos , Infecções por HIV , Adesão à Medicação , Cooperação do Paciente , Retenção nos Cuidados , Autocuidado/psicologia , Carga Viral/métodos , Adulto , Atitude Frente a Saúde , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/psicologia , Infecções por HIV/terapia , Humanos , Masculino , Adesão à Medicação/psicologia , Adesão à Medicação/estatística & dados numéricos , Avaliação de Resultados em Cuidados de Saúde , Cooperação do Paciente/psicologia , Cooperação do Paciente/estatística & dados numéricos , Resposta Viral Sustentada , Estados UnidosRESUMO
Previous studies proposed a dynamic, steady-state relationship between HIV-mediated cell killing and T-cell proliferation, whereby highly active antiretroviral therapy (HAART) blocks viral replication and tips the balance toward CD4(+) cell repopulation. In this report, we have analyzed blood and lymph node tissues obtained concurrently from HIV-infected patients before and after initiation of HAART. Activated T cells were significantly more frequent in lymph node tissue compared with blood at both time points. Ten weeks after HAART, the absolute number of lymphocytes per excised lymph node decreased, whereas the number of lymphocytes in the blood tended to increase. The relative proportions of lymphoid subsets were not significantly changed in tissue or blood by HAART. The expression levels of mRNA for several proinflammatory cytokines (IFN-gamma, IL-1beta, IL-6, and macrophage inflammatory protein-1alpha) were lower after HAART. After therapy, the expression of VCAM-1 and ICAM-1 -- adhesion molecules known to mediate lymphocyte sequestration in lymphoid tissue -- was also dramatically reduced. These data provide evidence suggesting that initial increases in blood CD4(+) cell counts on HAART are due to redistribution and that this redistribution is mediated by resolution of the immune activation that had sequestered T cells within lymphoid tissues.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Linfócitos T CD4-Positivos/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Linfonodos/efeitos dos fármacos , Adulto , Sequência de Bases , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/imunologia , Citocinas/genética , Primers do DNA/genética , Expressão Gênica/efeitos dos fármacos , Infecções por HIV/genética , Humanos , Imuno-Histoquímica , Molécula 1 de Adesão Intercelular/metabolismo , Linfonodos/imunologia , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Molécula 1 de Adesão de Célula Vascular/metabolismoRESUMO
Optimal adherence is essential for successful antiretroviral therapy. We analyzed the relation between minimum plasma drug concentration (Cmin) and total drug exposure over 24 hr (AUC24) with virologic failure for therapy-adherent patients in the nevirapine (NVP) and efavirenz (EFV) groups of the double nonnucleoside study (2NN), which compared the efficacy of NVP and/or EFV together with stavudine and lamivudine. The objective was to find cutoff values of the Cmin and AUC24 below which the risk of virologic failure increased. The relation between Cmin and AUC24 with virologic failure (never a plasma viral load [pVL] < 50 copies/ml or a rebound to two consecutive pVL > 50 copies/ml) was analyzed with proportional hazard analyses. Data were censored at end of study or change of allocated treatment. The risk of virologic failure with NVP (n = 511) started to increase at a Cmin < 3.1 mg/L (hazard ratio [HR], 1.33; 95% confidence interval [CI], 0.89-1.97), but there was no cutoff value below which a statistically significant increased risk occurred. Neither was such a cutoff point identified for the AUC24. The risk of virologic failure with EFV (n = 312) was significantly increased at a Cmin < 1.1 mg/L (HR, 1.95; 95% CI, 1.08-3.54) and an AUC24 < 40 mg x hr x L1 (HR, 1.95; 95% CI, 1.07-3.54). Both cutoff values represent the median values for adherent patients. These associations were driven by patients from Thailand. Adjusting for geographical region made the association between Cmin and AUC24 with virologic failure statistically nonsignificant. The sensitivity of the Cmin values was too low (29% for NVP, 64% for EFV) to be an adequate predictor for virologic failure. We conclude that identifying the Cmin value for the sole purpose of predicting virologic failure in patients who report to be adherent to NVP or EFV is questionable because of the absence of a concentration-response relation (NVP) or the low sensitivity for such a cutoff value (NVP and EFV).
Assuntos
Fármacos Anti-HIV/farmacocinética , Fármacos Anti-HIV/uso terapêutico , Nevirapina/farmacocinética , Nevirapina/uso terapêutico , Oxazinas/farmacocinética , Oxazinas/uso terapêutico , Inibidores da Transcriptase Reversa/farmacocinética , Inibidores da Transcriptase Reversa/uso terapêutico , Adulto , Alcinos , Fármacos Anti-HIV/sangue , Área Sob a Curva , Benzoxazinas , Ciclopropanos , Feminino , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Humanos , Lamivudina/sangue , Lamivudina/farmacocinética , Lamivudina/uso terapêutico , Masculino , Nevirapina/sangue , Oxazinas/sangue , Cooperação do Paciente , Modelos de Riscos Proporcionais , Estudos Prospectivos , RNA Viral/sangue , Curva ROC , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores da Transcriptase Reversa/sangue , Estavudina/sangue , Estavudina/farmacocinética , Estavudina/uso terapêuticoAssuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , HIV-1/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Animais , Fármacos Anti-HIV/farmacologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Ensaios Clínicos como Assunto , Humanos , RNA Viral/sangue , RNA Viral/efeitos dos fármacos , Resultado do TratamentoRESUMO
Highly active antiretroviral therapy (HAART) can suppress HIV type 1 plasma viremia to undetectable levels for up to 3 years or more. When the therapy is discontinued, viral rebound occurs in a majority of patients, indicating that HAART is unable to completely eradicate the virus. Initial calculations of the half-lives of the infected cells (estimated to be 14-21 days) suggested that only 3 years continuous HAART therapy would be necessary to achieve complete eradication; however, several studies have determined that the half-lives of chronically infected cells are in the order of 6-44 months. New estimates indicate that it may take as long as 60 years to eradicate the virus. Thus, there has been movement toward combining HAART with various means of augmenting and/or reconstituting the host's immune system, especially HIV-1-specific immune responses. The long-term goal is to discontinue HAART and permit the reconstituted immune system to contain whatever small amounts of the virus remain.
Assuntos
Síndrome da Imunodeficiência Adquirida/imunologia , Fármacos Anti-HIV/farmacologia , Terapia Antirretroviral de Alta Atividade/métodos , HIV-1/crescimento & desenvolvimento , Imunoterapia/métodos , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/virologia , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Humanos , Viremia/imunologiaRESUMO
BACKGROUND: Current potent antiretroviral therapy (using a protease inhibitor and two nucleoside reverse transcriptase inhibitors) produces a durable suppression of HIV replication in less than 75% of treated patients. Identification of predictors of successful therapy might allow the development of improved strategies to increase response rates. METHODS: We analyzed retrospectively the results from a multicenter, randomized, double-blind Phase III study of combination anti-HIV therapy with nelfinavir, zidovudine, and lamivudine to evaluate the relationship between virological response over 48 weeks of treatment to variables which could potentially serve as early predictors of long-term response. The goal was to produce long-term suppression of viral load to sensitive (<400 copies HIV RNA/ml) and ultrasensitive (<50 copies HIV RNA/ml) limits of quantification with the Amplicor PCR assay. FINDINGS: Baseline viral load, the change in viral load over the first 4 weeks of treatment, the 2 h post-dose nelfinavir levels and the time to respond to HIV RNA levels of <400 copies/ml and <50 copies/ml have the best predictive value in determining response and response duration. Patients who achieved very low viral nadirs (<50 copies HIV RNA/ml) had significantly longer responses than those who achieved nadirs of 50-400 copies HIV RNA/ml. INTERPRETATION: Parameters that can be measured easily at baseline or early after therapy is started can identify patients at high risk of failure with standard treatment. Such patients may be candidates for more aggressive therapy or for alternative strategies designed to improve outcome. In addition, these results support the use of ultra-sensitive HIV RNA assays to predict long-term outcome of anti-HIV therapy.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Inibidores da Protease de HIV/uso terapêutico , Soropositividade para HIV/tratamento farmacológico , Lamivudina/uso terapêutico , Nelfinavir/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Zidovudina/uso terapêutico , Adulto , Ensaios Clínicos como Assunto , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Soropositividade para HIV/sangue , Soropositividade para HIV/virologia , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Valor Preditivo dos Testes , RNA Viral/sangue , Estudos Retrospectivos , Fatores de Tempo , Carga ViralRESUMO
OBJECTIVES: To better characterize viral load profiles through the course of HIV-1 disease and in response to treatment, and to further evaluate quantitative competitive polymerase chain reaction for measurement of viral load, we extended our comparative evaluation of this and other viral load measurements to a total of 118 patients, representing all stages of HIV-1 disease. DESIGN: For cross-sectional analysis across the spectrum of HIV-1 disease, plasma viral load was evaluated in 112 HIV-1-infected patients by quantitative competitive polymerase chain reaction analysis, plasma p24 antigen assay, plasma immune complex-dissociated p24 antigen assay and an endpoint dilution viral culture. Longitudinal specimens from six additional patients were analyzed, extending from the time of presentation with symptomatic acute HIV-1 infection through up to more than 2 years of follow-up. Longitudinal specimens were also studied for three patients over the period of initiation of zidovudine treatment, for 6 weeks of treatment and following temporary withdrawal of the treatment. METHODS: All measurement techniques were assessed in replicate aliquots of plasma. RESULTS: Quantitative competitive polymerase chain reaction was the most sensitive measure of viral load, and was best correlated with CD4+ T-cell counts. In longitudinally studied patients, this technique also allowed measurement of plasma virus levels throughout the period of follow-up, even when culture and p24 assays became negative following resolution of acute HIV-1 infection. The quantitative competitive polymerase chain reaction was also able to detect rapid and substantial changes in viral load associated with initiation and temporary withdrawal of antiviral treatment. CONCLUSIONS: The quantitative competitive polymerase chain reaction is promising as a sensitive and accurate method for measuring plasma viral load in HIV-1-infected patients, and is useful for following changes in viral load over the natural history of infection and following treatment intervention. The technique is particularly useful for patients with > 200 x 10(6) CD4+ T cells/l, in whom other viral markers are typically negative.