RESUMEN
In a nonrandomized study of nonoccupational postexposure prophylaxis (PEP), a cross-sectional evaluation of subjects who were the source of human immunodeficiency (HIV) exposure was performed to characterize partners of index subjects seeking nonoccupational PEP against HIV. Among 401 index subjects, 64 (16%) recruited a source subject. Those in a steady relationship and those who knew that the source subject was HIV antibody positive were more likely to recruit their source subject. Source subjects reported high rates of past (78%) and current (69%) antiretroviral use; 46% of those using antiretroviral drugs had detectable plasma HIV-1 RNA levels. Antiretroviral resistance was detected in many source subjects who reported any use of antiretrovirals and was rare among source subjects who reported no history of antiretroviral use. Clinicians often make treatment decisions on the basis of incomplete knowledge of the source subject's HIV status or antiretroviral treatment history. The treatment history, particularly nonuse of a class of antiretroviral drugs, can be used to predict drug resistance.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Trazado de Contacto , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Conducta Sexual , Abuso de Sustancias por Vía Intravenosa , Adulto , Fármacos Anti-VIH/farmacología , Estudios Transversales , Farmacorresistencia Viral/genética , Femenino , Anticuerpos Anti-VIH/sangre , Infecciones por VIH/transmisión , VIH-1/genética , VIH-1/inmunología , Humanos , Masculino , ARN Viral/sangreRESUMEN
Antiretroviral monotherapy for initial drug characterization risks the selection of resistant virus, yet monotherapy is the only setting where many fundamental properties of a new drug can be reliably determined. Using data on viral replication kinetics and dynamics, we designed an accelerated (14 day) open-label study of single agent emtricitabine (formerly known as FTC)--a nucleoside reverse transcriptase inhibitor--to select a dosing regimen for further therapeutic study. Five regimens (25 mg bd, 100 mg od, 200 mg od, 100 mg bd and 200 mg bd) were evaluated in HIV-1-infected subjects over a 14 day dosing period to determine the optimal dose and pharmacokinetics. Serial blood samples for virological, pharmacokinetic and intracellular FTC-triphosphate measurements were drawn frequently. A dose-response relationship for the antiviral activity of emtricitabine was established, with total daily doses of 200 mg or more producing the greatest median HIV-1 viral load suppression: 1.72-1.92 log10. Based on virological outcomes, dose-response analysis and intracellular triphosphate levels, a once-daily dose of 200 mg was selected for further long-term clinical study. Adverse events possibly related to emtricitabine were unremarkable. The antiviral activity of emtricitabine correlated well with intracellular FTC-triphosphate concentrations. This study design is a safe, useful tool for early dose selection for drugs with potent antiretroviral activity and linear pharmacokinetics.
Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Ensayos Clínicos como Asunto/métodos , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , Proyectos de Investigación/normas , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Adulto , Fármacos Anti-VIH/farmacocinética , Fármacos Anti-VIH/uso terapéutico , Ensayos Clínicos como Asunto/normas , Desoxicitidina/farmacocinética , Desoxicitidina/uso terapéutico , Relación Dosis-Respuesta a Droga , Emtricitabina , Femenino , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , VIH-1/fisiología , Humanos , Masculino , Inhibidores de la Transcriptasa Inversa/farmacocinética , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Carga ViralRESUMEN
Tenofovir DF is an antiviral nucleotide with activity against human immunodeficiency virus type 1 (HIV-1). The pharmacokinetics, safety, and activity of oral tenofovir DF in HIV-1-infected adults were evaluated in a randomized, double-blind, placebo-controlled, escalating-dose study of four doses (75, 150, 300, and 600 mg given once daily). Subjects received a single dose of tenofovir DF or a placebo, followed by a 7-day washout period. Thereafter, subjects received their assigned study drug once daily for 28 days. Pharmacokinetic parameters were dose proportional and demonstrated no change with repeated dosing. Reductions in plasma HIV-1 RNA were dose related at tenofovir DF doses of 75 to 300 mg, but there was no increase in virus suppression between the 300- and 600-mg dose cohorts, despite dose-proportional increases in drug exposure. Grade III or IV adverse events were limited to laboratory abnormalities, including elevated creatine phosphokinase and liver function tests, which resolved with or without drug discontinuation and without sequelae. No patients developed detectable sequence changes in the reverse transcriptase gene.
Asunto(s)
Adenina/análogos & derivados , Adenina/farmacocinética , Fármacos Anti-VIH/farmacocinética , Infecciones por VIH/metabolismo , Organofosfonatos , Compuestos Organofosforados/farmacocinética , Adenina/efectos adversos , Adulto , Fármacos Anti-VIH/efectos adversos , Método Doble Ciego , Tolerancia a Medicamentos , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Compuestos Organofosforados/efectos adversos , ARN Viral/sangre , ARN Viral/efectos de los fármacos , TenofovirRESUMEN
We use a mathematical model to understand (from 1996 to 2001) and to predict (from 2001 to 2005) the evolution of the epidemic of drug-resistant HIV in San Francisco. We predict the evolutionary trajectories for 1,000 different drug-resistant strains with each strain having a different fitness relative to a drug-sensitive strain. We calculate that the current prevalence of resistance is high, and predict it will continue to rise. In contrast, we calculate that transmission of resistance is currently low, and predict it will remain low. We show that the epidemic of resistance is being generated mainly by the conversion of drug-sensitive cases to drug-resistant cases, and not by the transmission of resistant strains. We also show that transmission of resistant strains has not increased the overall number of new HIV infections. Our results indicate that transmission of resistant strains is, and will remain, a relatively minor public health problem.
Asunto(s)
Farmacorresistencia Microbiana , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , VIH-1/fisiología , Modelos Teóricos , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/epidemiología , Humanos , San Francisco/epidemiologíaRESUMEN
The feasibility of providing postexposure prophylaxis (PEP) after sexual or injection drug use exposures to human immunodeficiency virus (HIV) was evaluated. PEP was provided within 72 h to individuals with exposures from partners known to have or to be at risk for HIV infection. PEP consisted of 4 weeks of antiretroviral medications and individually tailored risk-reduction and medication-adherence counseling. Among 401 participants seeking PEP, sexual exposures were most common (94%; n=375). Among sexual exposures, receptive (40%) and insertive (27%) anal intercourse were the most common sexual acts. The median time from exposure to treatment was 33 h. Ninety-seven percent of participants were treated exclusively with dual reverse-transcriptase inhibitors, and 78% completed the 4-week treatment. Six months after the exposure, no participant developed HIV antibodies, although a second PEP course for a subsequent exposure was provided to 12%. PEP, after nonoccupational HIV exposure, is feasible for persons at risk for HIV infection.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/prevención & control , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Enfermedades Virales de Transmisión Sexual/prevención & control , Abuso de Sustancias por Vía Intravenosa/complicaciones , Adolescente , Adulto , Anciano , Trazado de Contacto , Consejo , Didanosina/uso terapéutico , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Lamivudine/uso terapéutico , Masculino , Persona de Mediana Edad , Nelfinavir/uso terapéutico , Cooperación del Paciente , Factores de Riesgo , Asunción de Riesgos , Enfermedades Virales de Transmisión Sexual/tratamiento farmacológico , Factores de Tiempo , Zidovudina/uso terapéuticoRESUMEN
Immune responses induced during the early stages of chronic viral infections are thought to influence disease outcome. Using HIV as a model, we examined virus-specific cytotoxic T lymphocytes (CTLs), T helper cells, and viral genetic diversity in relation to duration of infection and subsequent response to antiviral therapy. Individuals with acute HIV-1 infection treated before seroconversion had weaker CTL responses directed at fewer epitopes than persons who were treated after seroconversion. However, treatment-induced control of viremia was associated with the development of strong T helper cell responses in both groups. After 1 yr of antiviral treatment initiated in acute or early infection, all epitope-specific CTL responses persisted despite undetectable viral loads. The breadth and magnitude of CTL responses remained significantly less in treated acute infection than in treated chronic infection, but viral diversity was also significantly less with immediate therapy. We conclude that early treatment of acute HIV infection leads to a more narrowly directed CTL response, stronger T helper cell responses, and a less diverse virus population. Given the need for T helper cells to maintain effective CTL responses and the ability of virus diversification to accommodate immune escape, we hypothesize that early therapy of primary infection may be beneficial despite induction of less robust CTL responses. These data also provide rationale for therapeutic immunization aimed at broadening CTL responses in treated primary HIV infection.
Asunto(s)
Infecciones por VIH/inmunología , Infecciones por VIH/virología , VIH-1/genética , Inmunidad Celular , Enfermedad Aguda , Secuencia de Aminoácidos , Terapia Antirretroviral Altamente Activa , Secuencia de Bases , Estudios de Cohortes , Cartilla de ADN/genética , Epítopos/genética , Femenino , Variación Genética , Infecciones por VIH/tratamiento farmacológico , Seropositividad para VIH/inmunología , Seropositividad para VIH/virología , Humanos , Estudios Longitudinales , Masculino , Datos de Secuencia Molecular , ARN Viral/sangre , ARN Viral/genética , Linfocitos T Citotóxicos/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Factores de TiempoRESUMEN
The effects of early antiretroviral therapy on the peripheral CD8(+) T-cell population were assessed by sequentially determining the T-cell receptor (TCR) repertoire complexity in a cohort of 15 individuals recently diagnosed with human immunodeficiency virus infection. Analysis was based on quantitative TCR variable B gene (TCRBV) usage and complementary-determining region 3 length assessment. Repertories were assessed at baseline and at weeks 2, 4, 12, 24, and 72 after initiation of therapy. Early administration of highly active antiretroviral therapy has a positive effect on the preservation and homeostasis of the CD8(+) cell repertoire. Nevertheless, differences from average baseline and control TCR profiles and initial development of repertoire perturbations were observed. The findings suggest that additional therapeutic protocols will be required during primary infection to significantly prevent long-term erosion of the T-cell-mediated immune response.
Asunto(s)
Fármacos Anti-VIH/farmacología , Linfocitos T CD8-positivos/inmunología , Genes Codificadores de los Receptores de Linfocitos T/inmunología , Infecciones por VIH/inmunología , VIH-1 , Adulto , Fármacos Anti-VIH/administración & dosificación , Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos/química , Linfocitos T CD8-positivos/citología , Estudios de Casos y Controles , Estudios de Cohortes , Regiones Determinantes de Complementariedad/análisis , Regiones Determinantes de Complementariedad/efectos de los fármacos , Progresión de la Enfermedad , Femenino , Reordenamiento Génico de la Cadena beta de los Receptores de Antígenos de los Linfocitos T/efectos de los fármacos , Genes Codificadores de los Receptores de Linfocitos T/efectos de los fármacos , Humanos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , ARN Mensajero/análisis , ARN Mensajero/efectos de los fármacos , Grupos Raciales , Receptores de Antígenos de Linfocitos T alfa-beta/análisis , Receptores de Antígenos de Linfocitos T alfa-beta/efectos de los fármacos , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Factores de Tiempo , Carga ViralRESUMEN
CONTEXT: Despite enormous improvements achieved through the use of antiretroviral therapies (ARTs), the risk for eventual human immunodeficiency virus (HIV) disease progression remains high. Agents that enhance the immunologic mechanism for viral recognition might reduce disease progression. OBJECTIVE: To determine whether the addition of HIV-1 Immunogen would confer added clinical efficacy to that achievable by ARTs. DESIGN AND SETTING: Multicenter, double-blind, placebo-controlled, randomized trial beginning March 1996 and ending May 1999 conducted at 77 centers in the United States providing primary care or referral care for persons infected with HIV. PATIENTS: Adults infected with HIV who have baseline CD4 cell counts between 300 x 10(6)/L and 549 x 10(6)/L without prior acquired immunodeficiency syndrome-defining conditions receiving stable ART (or no therapy) were screened and 2527 were randomized. INTERVENTIONS: Ten units of HIV-1 Immunogen, derived from a Zairian HIV isolate, inactivated and formulated with incomplete Freund adjuvant, was administered intramuscularly every 12 weeks. The placebo was incomplete Freund adjuvant. Changes in ARTs were allowed. MAIN OUTCOME MEASURES: HIV progression-free survival; secondary end points included overall survival, changes in HIV RNA, CD4 cell counts, CD4 percentage, body weight, and immunogenicity. RESULTS: The overall event rate was 1.8 per 100 person-years of follow-up. Fifty-three subjects developed clinical progression in each treatment group (relative risk [RR], 0.97; 95% confidence interval [CI], 0.66-1.42; P =.89). There were 19 and 23 deaths in the placebo and HIV-1 Immunogen groups, respectively (RR, 0.81; 95% CI, 0.44-1. 48; P =.49). There were no statistically significant differences between the groups with respect to changes in HIV RNA (P =.59), CD4 percentage (P =.63), or body weight (P =.89). Subjects in the HIV-1 Immunogen group had an increase in average CD4 cell count of approximately 10 x 10(6)/L greater than the placebo group (P =.02). CONCLUSION: HIV-1 Immunogen with unrestricted ART failed to demonstrate an increase in HIV progression-free survival. JAMA. 2000;284:2193-2202.
Asunto(s)
Vacunas contra el SIDA/uso terapéutico , Adyuvantes Inmunológicos/uso terapéutico , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Adulto , Recuento de Linfocito CD4 , Progresión de la Enfermedad , Método Doble Ciego , Femenino , Infecciones por VIH/inmunología , Humanos , Masculino , Análisis de Supervivencia , Carga ViralAsunto(s)
Infecciones por VIH/prevención & control , Síndrome de Inmunodeficiencia Adquirida , Adulto , California , Ensayo de Inmunoadsorción Enzimática , Femenino , Infecciones por VIH/diagnóstico , Infecciones por VIH/terapia , Humanos , Masculino , Persona de Mediana Edad , Investigación , Factores de Riesgo , Factores SocioeconómicosRESUMEN
CONTEXT: While interleukin 2 (IL-2) is capable of inducing a marked expansion of the CD4 T-lymphocyte pool, limited data exist on whether IL-2 treatment can add significantly to the immunologic and virologic effects of potent antiretroviral therapy (ART). OBJECTIVE: To determine the rate and magnitude of CD4 cell recovery and viral suppression when using a combination therapy of IL-2 and ART compared with ART alone. DESIGN AND SETTING: Randomized, controlled multicenter trial conducted from April 1996 through April 1998 at 8 clinical sites in the United States. PATIENTS: Eighty-two adult outpatients who were infected with human immunodeficiency virus (HIV) and had baseline CD4 cell counts of 200 x 10(6)/L to 500 x 10(6)/L and baseline RNA levels of fewer than 10,000 copies/mL were randomized; 78 completed the study. INTERVENTIONS: Thirty-nine patients were randomly assigned to receive a combination therapy of subcutaneous IL-2 (administered in 5-day courses every 8 weeks at a starting dosage of 7.5 mIU twice per day) and ART; 43 were to receive ART therapy alone. MAIN OUTCOME MEASURES: Interleukin 2 safety and differential effects on CD4 cell counts, CD4 cell percentages, and plasma HIV RNA levels. RESULTS: The mean (SD) percentage increase in CD4 cell counts at 1 year for patients who received IL-2 was 112% (113%) compared with 18% (35%) in recipients of ART alone (P<.001). Both groups had mean (SD) increases in CD4 cell percentage: from 20.4% (6.3%) to 32.3% (12.4%) for the combination therapy group compared with 20.4% (5.1%) to 23.0% (7.2%) for recipients of ART alone (P<.001). Using a sensitive viral RNA assay, mean viral load changes were -0.28 and 0.09 log(10) copies for IL-2 recipients and control patients, respectively (P=.03). Twenty (67%) of 30 evaluable patients receiving IL-2 achieved final viral loads of fewer than 50 copies/mL compared with 13 (36%) of 36 control patients (P=.02). Toxic effects were common among patients who received IL-2 and were managed with antipyretics, hydration, rest, and dosage reduction as needed. CONCLUSIONS: Intermittent therapy with IL-2 and ART produced a substantially greater increase in CD4 cells and was associated with a larger decrease in viral load than ART alone. Clinical end-point trials will be necessary to determine whether the enhanced viral suppression and CD4 cell increases associated with IL-2 therapy will translate into improved clinical outcomes. JAMA. 2000;284:183-189
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Interleucina-2/uso terapéutico , Adulto , Anciano , Análisis de Varianza , Fármacos Anti-VIH/administración & dosificación , Formación de Anticuerpos , Recuento de Linfocito CD4 , Quimioterapia Combinada , Femenino , Infecciones por VIH/inmunología , Infecciones por VIH/virología , VIH-1/genética , Humanos , Inmunoglobulina G/biosíntesis , Inmunoglobulina M/biosíntesis , Interleucina-2/administración & dosificación , Interleucina-2/efectos adversos , Interleucina-2/inmunología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , ARN Viral/sangre , Carga ViralRESUMEN
HIV-specific antibodies and CD8+ T cell antiviral responses were evaluated in three human immunodeficiency virus 1 (HIV-1) gp120 vaccine recipients who later became infected with HIV-1. Titers of neutralizing antibody to the HIV-1(SF2) vaccine isolate were boosted, but titers of antibody to the autologous infecting viruses were never high and required at least 6 months after HIV infection to develop. Similarly, a marginal noncytotoxic CD8+ T cell antiviral response was observed only in one of the three vaccinees 3 months after HIV-1 infection. The infecting virus isolates had several amino acid substitutions in the HIV-1 envelope V3 region but were similar to other regional HIV-1 clade B isolates. Viral loads were similar to those of other HIV-1-infected individuals who had not been vaccinated and transient CD4+ T cell declines were observed in each person, suggesting that the vaccine was not effective at controlling these prognostic markers early in infection.
Asunto(s)
Vacunas contra el SIDA/inmunología , Anticuerpos Anti-VIH/biosíntesis , Proteína gp120 de Envoltorio del VIH/inmunología , Infecciones por VIH/inmunología , VIH-1/inmunología , Linfocitos T Citotóxicos/inmunología , Vacunas Sintéticas/inmunología , Secuencia de Aminoácidos , Estudios de Cohortes , Secuencia de Consenso , Ensayo de Inmunoadsorción Enzimática , Humanos , Inmunización Secundaria , Activación de Linfocitos , Datos de Secuencia Molecular , Pruebas de Neutralización , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Factores de Tiempo , Insuficiencia del Tratamiento , Carga ViralAsunto(s)
Antivirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/fisiopatología , Antivirales/administración & dosificación , Esquema de Medicación , Infecciones por VIH/fisiopatología , VIH-1 , Humanos , Guías de Práctica Clínica como Asunto , Garantía de la Calidad de Atención de Salud , Ensayos Clínicos Controlados Aleatorios como Asunto/normas , Estados UnidosRESUMEN
OBJECTIVE: The primary objective was to compare the effects of dual or triple combinations of HIV-1 reverse transcriptase inhibitors with respect to survival. The time to new HIV disease progression or death, toxicities, the change in CD4 cells, and plasma HIV-1 RNA concentrations in a subset of study subjects were evaluated. DESIGN: This was a multicenter randomized, double-blind, placebo-controlled study. SETTING: The study was conducted among 42 adult AIDS Clinical Trials Group sites and 7 National Hemophilia Foundation centers. PATIENTS: 1313 HIV-infected patients with CD4 counts < or = 50 cells/mm3 participated in this study, which was conducted from June 1993 to June 1996. INTERVENTION: Patients were randomized to one of four daily regimens containing 600 mg of zidovudine: zidovudine alternating monthly with 400 mg didanosine; zidovudine plus 2.25 mg of zalcitabine; zidovudine plus 400 mg of didanosine; or zidovudine plus 400 mg of didanosine plus 400 mg of nevirapine (triple therapy). MAIN OUTCOME MEASURES: The main outcome was survival (i.e., time to death). RESULTS: A significant difference in survival time was found between the four treatment groups, favoring those assigned to triple therapy (p = .02). A significant difference was also found in the delay of disease progression or death among the four treatment arms favoring the group assigned to triple therapy (p = .002). Baseline CD4 cell counts and plasma HIV-1 RNA concentrations as well as changes of CD4 counts at week 8 predicted survival for subjects in the virology substudy. CONCLUSIONS: In the pre-protease inhibitor era, a combination of triple reverse transcriptase inhibitors prolonged life and delayed disease progression in AIDS patients with advanced immune suppression.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Fármacos Anti-VIH/uso terapéutico , Didanosina/uso terapéutico , Nevirapina/uso terapéutico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Zalcitabina/uso terapéutico , Zidovudina/uso terapéutico , Síndrome de Inmunodeficiencia Adquirida/inmunología , Síndrome de Inmunodeficiencia Adquirida/mortalidad , Adulto , Recuento de Linfocito CD4 , Didanosina/administración & dosificación , Supervivencia sin Enfermedad , Método Doble Ciego , Esquema de Medicación , Quimioterapia Combinada , Femenino , VIH/genética , VIH/aislamiento & purificación , Humanos , Masculino , Nevirapina/administración & dosificación , Placebos , ARN Viral/sangre , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Tasa de Supervivencia , Factores de Tiempo , Zalcitabina/administración & dosificación , Zidovudina/administración & dosificaciónRESUMEN
9-[2-(R)-(Phosphonomethoxy)propyl]adenine (PMPA) is a nucleotide analogue with potent antiretroviral activity in vitro and in simian models. A randomized, double-blind, placebo-controlled, dose-escalation clinical trial of intravenous PMPA monotherapy was conducted in 20 human immunodeficiency virus (HIV)-infected adults with CD4 cell counts of >/=200 cells/mm3 and plasma HIV RNA levels of >/=10,000 copies/ml. Two dose levels were evaluated (1 and 3 mg/kg of body weight/day). Ten subjects were enrolled at each dose level (eight randomized to receive PMPA and two randomized to receive placebo). On day 1, a single dose of PMPA or placebo was administered by intravenous infusion. Beginning on study day 8, PMPA or placebo was administered once daily for an additional 7 consecutive days. All subjects tolerated dosing without significant adverse events. Mean peak serum PMPA concentrations were 2.7 +/- 0.9 and 9.1 +/- 2.1 microgram/ml in the 1- and 3-mg/kg cohorts, respectively. Serum concentrations declined in a biexponential fashion, with a terminal half-life of 4 to 8 h. At 3 mg/kg/day, a single infusion of PMPA resulted in a 0.4 log10 median decline in plasma HIV RNA by study day 8. Following 7 consecutive days of study drug administration thereafter, the median changes in plasma HIV RNA from baseline were -1.1, -0.6, and 0.1 log10 in the 3-mg/kg/day, 1-mg/kg/day, and placebo dose groups, respectively. Following the final dose in the 3-mg/kg/day cohort, the reduction in HIV RNA was sustained for 7 days before returning toward baseline. Further studies evaluating an oral prodrug of PMPA are under way.
Asunto(s)
Adenina/análogos & derivados , Antivirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Organofosfonatos , Compuestos Organofosforados/uso terapéutico , Adenina/efectos adversos , Adenina/farmacocinética , Adenina/uso terapéutico , Adolescente , Adulto , Método Doble Ciego , Femenino , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Humanos , Masculino , Persona de Mediana Edad , Compuestos Organofosforados/efectos adversos , Compuestos Organofosforados/farmacocinética , ARN Viral/sangre , Linfocitos T/inmunología , TenofovirAsunto(s)
Infecciones por VIH , VIH-1 , Enfermedad Aguda , Fármacos Anti-VIH/uso terapéutico , Quimioterapia Combinada , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/etiología , Infecciones por VIH/fisiopatología , Humanos , Inhibidores de Proteasas/uso terapéutico , ARN Viral/sangre , Inhibidores de la Transcriptasa Inversa/uso terapéutico , ViremiaRESUMEN
CONTEXT: Differentiating individuals with early human immunodeficiency virus 1 (HIV-1) infection from those infected for longer periods is difficult but important for estimating HIV incidence and for purposes of clinical care and prevention. OBJECTIVE: To develop and validate a serologic testing algorithm in which HIV-1-positive persons with reactive test results on a sensitive HIV-1 enzyme immunoassay (EIA) but nonreactive results on a less sensitive (LS) EIA are identified as having early infection. DESIGN: Diagnostic test and testing strategy development, validation, and application. Specimens were tested with both a sensitive HIV-1 EIA (3A11 assay) and a less sensitive modification of the same EIA (3A11-LS assay). SETTINGS AND PARTICIPANTS: For assay development: 104 persons seroconverting to HIV-1 comprising 38 plasma donors, 18 patients of a sexually transmitted disease clinic in Trinidad, and 48 participants in the San Francisco Men's Health Study (SFMHS); 268 men without the acquired immunodeficiency syndrome (AIDS) in the SFMHS who had been infected for at least 2.5 years; and 207 persons with clinical AIDS; for testing strategy validation: 488 men in the SFMHS from 1985 through 1990 and 1275449 repeat blood donors at 3 American Red Cross blood centers from 1993 through 1995; and for HIV-1 incidence estimates: 2717910 first-time blood donors. We retrospectively identified persons eligible for a study of early infection. MAIN OUTCOME MEASURE: Ability to identify early HIV infection. RESULTS: Estimated mean time from being 3A11 reactive/3A11-LS nonreactive to being 3A11 reactive/3A11-LS reactive was 129 days (95% confidence interval [CI], 109-149 days) [corrected]. Our testing strategy accurately diagnosed 95% of persons with early infection; however, 0.4% (1/268) of men with established infection and 2% (5/207) of persons with late-stage AIDS were misdiagnosed as having early HIV-1 infection. Average yearly incidence estimates in SFMHS subjects were 1.5% per year vs observed average incidence of 1.4 per 100 person-years. Incidence in repeat blood donors using the sensitive/less sensitive assay testing strategy was 2.95 per 100000 per year (95% CI, 1.14-6.53/100000) vs observed incidence of 2.60 per 100000 person-years (95% CI, 1.49-4.21/100000). Overall incidence in first-time blood donors was 7.18 per 100000 per year (95% CI, 4.51-11.20/100000) and did not change statistically significantly between 1993 and 1996. Use of the sensitive/less sensitive testing strategy alone would have identified all 17 persons with antibodies to HIV-1 eligible for a study of early HIV-1 infection and would have increased enrollment. CONCLUSIONS: The sensitive/less sensitive testing strategy provides accurate diagnosis of early HIV-1 infection, provides accurate estimates of HIV-1 incidence, can facilitate clinical studies of early HIV-1 infection, and provides information on HIV-1 infection duration for care planning.
Asunto(s)
Serodiagnóstico del SIDA , Infecciones por VIH/diagnóstico , VIH-1 , Algoritmos , Anticuerpos Anti-VIH/sangre , Infecciones por VIH/epidemiología , VIH-1/inmunología , Humanos , Técnicas para Inmunoenzimas , Incidencia , Masculino , Modelos Teóricos , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Estadísticas no ParamétricasAsunto(s)
Transmisión de Enfermedad Infecciosa , Resistencia a Múltiples Medicamentos/genética , Infecciones por VIH/transmisión , Infecciones por VIH/virología , VIH-1/clasificación , Inhibidores de Proteasas/uso terapéutico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Fármacos Anti-VIH/uso terapéutico , Quimioterapia Combinada , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , VIH-1/genética , Humanos , Masculino , Persona de Mediana Edad , Mutación , Inhibidores de Proteasas/farmacología , ARN Viral/sangre , ADN Polimerasa Dirigida por ARN/genética , Inhibidores de la Transcriptasa Inversa/farmacología , Conducta SexualRESUMEN
Post-exposure prevention of human immunodeficiency virus type 1 (HIV-1) infection involves a combined modality approach to subjects exposed to the HIV-1 virus through sexual or occupational contact or intravenous drug use. Identification of those at highest risk of transmission, which involves patient factors as well as the infectivity of the partner and the local prevalence of HIV-1, will help to determine appropriate candidates for post-exposure treatment. Early institution of therapy (within 72 h) should be followed with education and counselling to help maximize therapeutic adherence while reinforcing safer behaviour for the future.
Asunto(s)
Infecciones por VIH/prevención & control , VIH-1 , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Personal de Salud , Humanos , Exposición Profesional , Embarazo , Complicaciones Infecciosas del Embarazo , Factores de RiesgoRESUMEN
We conducted a longitudinal study of participants in phase I and II HIV vaccine safety and immunogenicity trials to examine changes in sexual risk behavior that are associated with risk of HIV transmission. The participants were 48 HIV-negative men and women enrolled in one of two placebo-controlled HIV vaccine trials conducted at San Francisco General Hospital. There was a significant increase in insertive unprotected anal intercourse (UAI) from 9% at baseline (trial entry), to 13% at the month 6 assessment, to 20% at the month 12 assessment (p = .02). The primary predictor of either insertive or receptive UAI during the vaccine trials was having engaged in this behavior prior to entry (p = .001). Higher-risk behavior was also seen among participants who were younger and had multiple sexual partners (each, p = .06) and who indicated that one of their reasons for participation in the vaccine trial was hope of protection from HIV infection (p = .07). These findings indicate that despite instructions otherwise, participants with a history of high-risk behavior or who express hope of protection from HIV infection by enrolling in vaccine trials may be candidates for more intensive risk-behavior counseling prior to and during their participation.
Asunto(s)
Vacunas contra el SIDA/administración & dosificación , Ensayos Clínicos Controlados como Asunto/psicología , Infecciones por VIH/prevención & control , Infecciones por VIH/psicología , Participación del Paciente/psicología , Adulto , Femenino , Infecciones por VIH/inmunología , Seropositividad para VIH/psicología , Homosexualidad Masculina , Humanos , Estudios Longitudinales , Masculino , Recuerdo Mental , Selección de Paciente , Asunción de Riesgos , Conducta Sexual , Percepción Social , Factores Socioeconómicos , VoliciónRESUMEN
The objective of this study was to identify prognostic factors for survival in patients with pretreatment CD4 < or =50 cells/mm3 treated with nucleoside analogs, and to develop and validate a mortality risk model based on these factors. The design of the study consisted of retrospective analysis of AIDS Clinical Trials Group (ACTG) protocols 116a, 116b/117, 155, and 118. The setting was the multicenter AIDS Clinical Trials Group. The patients were HIV-infected with pretreatment CD4 < or =50 cells/mm3 and various degrees of prior zidovudine (ZDV) use. Double-blind, three-arm randomized control trials ACTG 116a and ACTG 116b/117 compared ZDV with didanosine (ddI). ACTG 155 compared ZDV with zalcitabine or combination therapy. Our validation study, ACTG 118, compared the effects of three different doses of ddI on survival. The main outcome measures were survival and mortality. The three studies combined enrolled 699 patients with entry CD4 T-lymphocyte counts of < or =50 cells/mm3. Forty percent of patients died during follow-up, with a median survival of 19.7 months. Multivariate analysis showed shorter survival at p < 0.0001 with lower CD4 count (relative hazard [RH] = 0.98) and lower hemoglobin level (RH = 0.81). Other factors included older age (RH = 1.03), male gender (RH = 1.70), Hispanic ethnicity (RH = 1.68), and symptomatic disease stage (RH = 2.06). Our predictive mortality risk model differentiated well patients with differing risks of mortality. When the risk model was applied to ACTG 118, the validation data set, the identified prognostic factors could distinguish patients with varying risks of death (p < 0.001, stratified log-rank test). These results demonstrate that CD4 T-lymphocytes counts < or =50 cells/mm3 should not be considered a precursor of imminent death; considerable variability in survival exists in severely immunocompromised patients. Our identification of prognostic indicators for survival can aid clinicians and patients in management of their disease and researchers in design of future clinical trials.