RESUMO
OBJECTIVES: Rapid initiation of antiretroviral therapy (ART) is important for individuals with high baseline viral loads, such as in primary HIV-1 infection (PHI). Four-drug regimens are sometimes considered; however, data are lacking on tolerability. We aimed to evaluate the tolerability of four-drug regimens used in the Research in Viral Eradication of HIV-1 Reservoirs (RIVER) study. METHODS: At enrolment, ART-naïve adult participants or those newly commenced on ART were initiated or intensified to four-drug regimens within 4 weeks of PHI. Rapid start was defined as pre-confirmation or ≤ 7 days of confirmed diagnosis. Primary and secondary outcomes were patient-reported adherence measured by 7-day recall and regimen switches between enrolment and randomization, respectively. RESULTS: Overall, 54 men were included: 72.2% were of white ethnicity, with a median age of 32 years old, 42.6% had a viral load of ≥ 100 000 HIV-1 RNA copies/mL, and in 92.6% sex with men was the mode of acquisition of HIV-1. Twenty (37%) started a four-drug regimen and 34 (63%) were intensified. Rapid ART initiation occurred in 28%, 100% started in ≤ 4 weeks. By weeks 4, 12, and 24, 37.0%, 69.0%, and 94.0% were undetectable (viral load < 50 copies/mL), respectively. Adherence rates of 100% at weeks 4, 12, 22 and 24 were reported in 88.9%, 87.0%, 82.4% and 94.1% of participants, respectively. Five individuals switched to three drugs, four changed their regimen constituents, and two switched post-randomization. CONCLUSIONS: Overall, four-drug regimens were well tolerated and had high levels of adherence. Whilst their benefit over three-drug regimens is lacking, our findings should provide reassurance if a temporarily intensified regimen is clinically indicated to help facilitate treatment.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Adulto , Fármacos Anti-HIV/efeitos adversos , Antirretrovirais/efeitos adversos , Quimioterapia Combinada , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Carga ViralRESUMO
We are not aware of a report detailing the complex obstetrical and medical management of twin pregnancy in the context of HIV infection and early post-liver transplantation period. Here we describe the successful outcome of a twin pregnancy in a 28-year-old HIV-positive female receiving antiretroviral therapy and immunosuppressive therapy who was the recipient of a liver transplant for previous drug-induced liver failure.
RESUMO
The recent success of highly active antiretroviral therapy (HAART) has altered the prognosis of patients living with HIV-1 infection. However, there are still many challenges to be addressed if we want to develop long-term therapeutic strategies for patients, in both the Western world and resource-poor countries. In this review, the potential role for HIV-1 therapeutic vaccines in the era of HAART will be discussed in the light of the present efforts at developing immune-based therapies to complement antiviral treatment and minimize the duration of exposure to antiviral drugs.
Assuntos
Vacinas contra a AIDS/farmacologia , Vacinas contra a AIDS/uso terapêutico , Infecções por HIV/prevenção & controle , HIV-1/efeitos dos fármacos , Animais , Infecções por HIV/imunologia , HIV-1/imunologia , HumanosRESUMO
In this review, we address recent advances in the understanding of the pathogenesis of human immunodeficiency type 1 virus infection, which have provided the rationale for present trials of therapeutic vaccines. We shall relate this work to lessons of the past few years both in the use of highly active antiretroviral therapy to attempt eradication of the HIV virus, and in the study of treatment interruptions.
Assuntos
Vacinas contra a AIDS/uso terapêutico , Infecções por HIV/tratamento farmacológico , Vacinas contra a AIDS/administração & dosagem , Vacinas contra a AIDS/imunologia , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/imunologia , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Doença Crônica , Esquema de Medicação , Infecções por HIV/imunologia , HIV-1/imunologia , HIV-1/patogenicidade , HumanosRESUMO
BACKGROUND: Highly active antiretroviral therapy (HAART) is now widely used in clinical practice and gives rise to a range of immunological, virological and clinical responses. OBJECTIVES: To describe the immunological, virological and clinical response to HAART and to examine the frequency of modification of the HAART regimen among patients from a single treatment centre. METHODS: Kaplan-Meier estimation and incidence rates were used to describe responses to HAART (a protease inhibitor or non-nucleoside drug in addition to at least two nucleoside analogues) among 421 patients from the Royal Free Hospital in London. RESULTS: The median CD4 cell count at starting HAART was 186 x 10(6) cells/l [interquartile range (IQR) 76-310] and viral load was 5.13 log10 copies/ml (IQR 4.66-5.56). At 6 months after starting HAART, 51.1% of patients were estimated to have experienced a 100 x 10(6) cells/l increase in CD4 cell count; the median time for viral load to fall below 400 copies/ml was 3.7 months (95% confidence interval 3.2-4.4). At 6 months after the first viral load was < 400 copies/ml, 16.4% of patients were estimated to have failed on the basis of a single viral load > 400 copies/ml and 12.4% were estimated to have failed if the more stringent definition of two viral loads above the limit of detection was used. Compared with the pre-HAART era, the incidence of death among patients on HAART was one sixth of that level; new AIDS-defining illnesses was one seventh; and hospital admissions was one fifth. In total, 141 patients (33.5%) stopped at least one of the antiretroviral agents included as part of their HAART regimen; the occurrence of side effects was the most common reason (n = 63; 44.7%). CONCLUSION: A good response occurred to an initial HAART regimen. There was a high rate of virological relapse, which varied considerably according to the definition of failure used. Even so, the rates of clinical progression and hospital admissions observed to date were low. Further follow-up of these patients is required to determine their long-term immunological, virological and clinical outcome.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Feminino , Seguimentos , Infecções por HIV/imunologia , Infecções por HIV/fisiopatologia , Infecções por HIV/virologia , Humanos , Masculino , Carga ViralAssuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Lipodistrofia/etiologia , Adulto , Fármacos Anti-HIV/efeitos adversos , Quimioterapia Combinada , Feminino , Infecções por HIV/complicações , Inibidores da Protease de HIV/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Transcriptase Reversa/uso terapêuticoRESUMO
Acute HIV-1 illness presents a wide range of clinical manifestations. We assessed a classification and data reduction of clinical features among 218 patients with acute HIV-1 infection enrolled in four prospective seroincidence studies. Factor analysis allows the definition of eight factors based on groups of symptoms and signs: gastrointestinal transit disturbances, weight loss/abdominal pain, lymphadenopathy, myalgia/arthralgia, neurologic features, constitutional and mucocutaneous features, oral candidiasis, and anorexia/pharyngitis. These groups reflected the main target systems involved at the time of acute HIV-1 disease. Grouping of symptoms and signs based on groups of patients is potentially more informative than observations made on individual patients. It might facilitate diagnosis, suggest pathogenic mechanisms and reduce the number of variables for characterizing acute HIV-1 illness.
Assuntos
Infecções por HIV/classificação , Infecções por HIV/diagnóstico , HIV-1 , Doença Aguda , Adolescente , Adulto , Anorexia , Artralgia , Austrália , Candidíase Bucal , Europa (Continente) , Análise Fatorial , Feminino , Gastroenteropatias , Infecções por HIV/fisiopatologia , Infecções por HIV/virologia , Humanos , Doenças Linfáticas , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso , Faringite , Estudos Prospectivos , Fatores de Risco , Dermatopatias , Redução de PesoRESUMO
The progression of 'naive' and 'memory' T-cells and the T-cell receptor Vbeta (TCR Vbeta) repertoire dynamics within the peripheral CD4+ T-cell compartment were studied in individuals following HIV seroconversion. Profound TCR Vbeta repertoire perturbations were observed within the CD4+ T-cell pool in treatment-naive patients regardless of their levels of viremia during the first 6-8 months after seroconversion. The ratio of 'naive' to 'memory' CD4+ T-cells as well as the TCR Vbeta repertoire dynamics did not appear to correlate with absolute numbers of CD4 T-cells.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Soropositividade para HIV/imunologia , Soropositividade para HIV/virologia , Região Variável de Imunoglobulina/imunologia , Memória Imunológica/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Adolescente , Adulto , Relação CD4-CD8 , Feminino , Humanos , Masculino , Viremia/imunologiaRESUMO
Sequences of the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) domain were determined by direct sequencing of HIV-1 RNA in successive plasma samples from eight seroconverting patients infected with virus bearing the T215Y/F amino acid substitution associated with zidovudine (ZDV) resistance. At baseline, additional mutations associated with ZDV resistance were detected. Three patients had the M41L amino acid change, which persisted. Two patients had both the D67N and the K70R amino acid substitutions; reversion to the wild type was seen at both positions in one of these patients and at codon 70 in the other one. Reversion to the wild type at codon 215 was observed in only one of eight patients. Unusual amino acids, such as aspartic acid (D) and cysteine (C), appeared at position 215 in four patients during follow-up. These variants isolated by coculturing were sensitive to ZDV. Overgrowth of these variants suggests that they have better fitness than the original T215Y variant. Intraindividual nucleoside substitutions over time were 10 times more frequent in codons associated with ZDV resistance (41, 67, 70, 215, and 219) than in other codons of the RT domain. The predominance of nonsynonymous substitutions observed over time suggests that most changes reflect adaptation of the RT function. The variance in sequence evolution observed among patients, in particular at codon 215, supports a role for chance in the evolution of the RT domain.
Assuntos
Fármacos Anti-HIV/farmacologia , Códon , Transcriptase Reversa do HIV/genética , Soropositividade para HIV/virologia , HIV-1/genética , Mutagênese Sítio-Dirigida , Inibidores da Transcriptase Reversa/farmacologia , Zidovudina/farmacologia , Aminoácidos , Células Cultivadas , Resistência Microbiana a Medicamentos , Genes Virais , Heterogeneidade Genética , Variação Genética , Transcriptase Reversa do HIV/efeitos dos fármacos , HIV-1/efeitos dos fármacos , HIV-1/enzimologia , Humanos , Testes de Sensibilidade Microbiana , Análise de Sequência de DNARESUMO
This study examined the relationship between the severity of acute human immunodeficiency virus type 1 (HIV-1) illness and disease progression and death. The population included 218 patients with acute HIV-1 illness and 41 asymptomatic patients who underwent HIV-1 seroconversion; the patients were followed up prospectively. We analyzed progression to Centers for Disease Control and Prevention clinical categories B and C (AIDS-defining conditions) and death according to an additive clinical score (CS) based on six predictive clinical features at the time of acute HIV-1 infection. Compared with patients with a CS of 0 (asymptomatic patients), those with a CS of 3-4 and 5-6 had faster progression to category B disease (adjusted hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.01-1.92; and HR, 1.80; 95% CI, 1.34-2.40; respectively); those with a CS of 5-6 had faster progression to category C disease (HR, 1.37; 95% CI, 1.01-1.89) and death (HR, 2.05; 95% CI, 1.27-3.32). Thus, the number of symptoms and signs at the time of acute HIV-1 illness affects disease progression and survival, even in symptomatic patients who have undergone seroconversion.
Assuntos
Infecções por HIV/fisiopatologia , HIV-1 , Doença Aguda , Adulto , Feminino , Seguimentos , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Masculino , Prognóstico , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
A randomized trial of 77 patients with primary HIV infection concluded that a 6-month course of zidovudine significantly reduced the incidence of opportunistic infections and improved CD4 cell counts. Follow-up was extended over a mean of 28 months to assess whether these benefits persisted beyond the trial period under conditions of routine care. In the post-trial period, antiviral drugs were prescribed with similar frequency in the zidovudine (248 treatment days per patient) and placebo arms (239 days, P=0.59). At the end of follow-up, patients initially assigned to zidovudine had still accumulated fewer disease progression events (three) than those given placebo (eight), but contrary to the initial analysis, the difference was no longer statistically significant (logrank test, P=0.07). The incidence of progression events tended to increase over time in the zidovudine group, and to decrease in the placebo group (trends tested in Weibull survival models, P=0.04). Similarly, initial gains in CD4 counts in the zidovudine arm diminished progressively after the trial, as CD4 counts declined faster in this group than in placebo-treated patients (-5.0 vs. -3.2 cells/mm3/month, P=0.06). In summary, initial clinical and immunological benefits of a 6-month course of zidovudine in patients with primary HIV infection eroded over time, suggesting that longer and more potent antiviral treatment should be given consideration.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1 , Inibidores da Transcriptase Reversa/uso terapêutico , Zidovudina/uso terapêutico , Adulto , Contagem de Linfócito CD4 , Seguimentos , Infecções por HIV/imunologia , Infecções por HIV/patologia , HumanosRESUMO
The purpose of this study was to describe the frequency and duration of clinical features at the time of acute human immunodeficiency virus type 1 (HIV-1) disease in 218 patients with documented symptomatic primary HIV-1 infection. The mean duration of acute HIV-1 disease was 25.1 days (median, 20.0 days) and did not differ by gender, age, and risk factor. The frequency and mean duration of clinical features occurring in >50% of patients were as follows: fever, 77.1% and 16.9 days; lethargy, 65.6% and 23.7 days; cutaneous rash, 56.4% and 15 days; myalgia, 54.6% and 17.7 days; and headache, 50.9% and 25.8 days. Only 15.6% of patients presented with a typical mononucleosis-like illness (MLI) defined as fever, pharyngitis or sore throat, and cervical adenopathy, and 10% had no features of an MLI. A meningitis-like syndrome occurred in 20 patients (9.2%). Acute HIV-1 disease is more diverse than previously reported, and the absence of fever or other MLI features does not rule out acute HIV-1 disease.
Assuntos
Síndrome de Fadiga Crônica/diagnóstico , Infecções por HIV/diagnóstico , HIV-1/isolamento & purificação , Doença Aguda , Adulto , Estudos de Coortes , Diagnóstico Diferencial , Síndrome de Fadiga Crônica/fisiopatologia , Feminino , Infecções por HIV/fisiopatologia , Humanos , Masculino , Prognóstico , Estudos Prospectivos , Fatores de TempoRESUMO
Zidovudine (ZDV) was the most widely used anti-HIV drug between 1987 and 1995, and, as already reported, transmission of ZDV-resistant viruses occurs. Several mutations of the reverse transcriptase gene have been identified; one of them affects the 215 codon and is associated with a high degree of resistance. We have determined, using selective PCR, the prevalence of transmission of 215 mutant isolates in 134 patients with primary HIV infection (PHI) and have identified 8 patients with 215 mutant virus between 1989 and 1995 in Switzerland. Mutant resistant viruses have been isolated from patients treated with most antiviral drugs. A systematic search for mutant viruses may provide useful information for the adaptation of treatment strategies.
Assuntos
Antivirais/farmacologia , Infecções por HIV/transmissão , HIV/efeitos dos fármacos , Zidovudina/farmacologia , Adolescente , Adulto , Sequência de Bases , DNA Viral/genética , Resistência a Medicamentos/genética , Feminino , HIV/genética , Transcriptase Reversa do HIV/genética , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Estudos RetrospectivosRESUMO
OBJECTIVE: To decrease viraemia levels in primary HIV infection by using a combination of zidovudine (ZDV) and L-697,661. DESIGN: Four primary HIV-infected patients were treated for 6 months with ZDV, 250 mg twice daily, in association with the non-nucleoside reverse transcriptase inhibitor L-697,661 500 mg three times daily. Viraemia, proviral DNA, CD4 and CD8 cell counts were measured serially during 18 months. RESULTS: Viraemia decreased to undetectable levels (< 200 RNA copies/ml) in two patients. A third patient had a marked decrease followed by a rebound during therapy; viraemia levels did not vary markedly in the fourth patient. A rebound in viraemia levels was observed within 15 days of discontinuation of therapy in the three responding patients. Proviral levels evolved in parallel with viraemia but were always detectable in all patients. In the three patients with an initial decrease of viraemia, CD4 cell counts were within the normal range 2 months after initiation of therapy and did not markedly decrease after discontinuation of therapy. In the two patients with partial or no response of viraemia, mutations associated with low level of resistance to L-697,661 appeared during treatment. CONCLUSION: A marked decrease of viraemia can be achieved in some primary HIV-infected patients with combined therapy. Six months of treatment does not prevent a rebound of viraemia, which was observed within 15 days of interruption of therapy.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Benzoxazóis/uso terapêutico , Infecções por HIV/tratamento farmacológico , Piridonas/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Zidovudina/uso terapêutico , Adulto , Fármacos Anti-HIV/administração & dosagem , Benzoxazóis/administração & dosagem , Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos , DNA Viral/sangue , Quimioterapia Combinada , Infecções por HIV/virologia , Humanos , Piridonas/administração & dosagem , RNA Viral/sangue , Inibidores da Transcriptase Reversa/administração & dosagem , Carga Viral , Viremia , Zidovudina/administração & dosagemRESUMO
BACKGROUND: It is possible that antiretroviral treatment given early during primary infection with the human immunodeficiency virus (HIV) may reduce acute symptoms, help preserve immune function, and improve the long-term prognosis. METHODS: To assess the effect of early antiviral treatment, we conducted a multicenter, double-blind, placebo-controlled trial in which 77 patients with primary HIV infection were randomly assigned to receive either zidovudine (250 mg twice daily; n = 39) or placebo (n = 38) for six months. RESULTS: The mean time from the onset of symptoms until enrollment in the study was 25.1 days. Among the 43 patients who were still symptomatic at the time of enrollment, there was no appreciable difference in the mean (+/- SE) duration of the retroviral syndrome between the zidovudine group (15.0 +/- 4.1 days) and the placebo group (15.8 +/- 3.6 days). During a mean follow-up period of 15 months, minor opportunistic infections developed in eight patients: oral candidiasis in four, herpes zoster in two, and oral hairy leukoplakia in two. Disease progression was significantly less frequent in the zidovudine group (one opportunistic infection) than in the placebo group (seven opportunistic infections; P = 0.009 by the log-rank test). After adjustment for the base-line CD4 cell count, the patients treated with zidovudine had an average gain of 8.9 CD4 cells per cubic millimeter per month (95 percent confidence interval, -1.4 to 19.1) during the first six months of the study, whereas those receiving placebo had an average loss of 12.0 CD4 cells per cubic millimeter per month (95 percent confidence interval, 5.2 to 18.7), for a between-group difference of 20.9 CD4 cells per cubic millimeter per month (95 percent confidence interval, 8.5 to 33.2; P = 0.001). CONCLUSIONS: Antiretroviral therapy administered during primary HIV infection may improve the subsequent clinical course and increase the CD4 cell count.
Assuntos
Infecções por HIV/tratamento farmacológico , Zidovudina/uso terapêutico , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Adulto , Contagem de Linfócito CD4/efeitos dos fármacos , Progressão da Doença , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Seguimentos , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/análise , Fatores de Tempo , Zidovudina/administração & dosagem , Zidovudina/efeitos adversosRESUMO
We report the history and clinical findings in 17 patients with primary HIV infection (PHI) diagnosed in the first 6 months of 1994. 9 of these patients were infected through heterosexual contacts, 5 were women with, as the only risk factor, sexual contacts with infected men. 10 of the 17 patients were symptomatic and the diagnosis of PHI was suspected in 8 of these patients at their first medical visit. However, the laboratory investigations were incomplete since p24 Ag was only requested for one patient and this led to a delay in diagnosis. Sera collected at the time of the first medical visit were available for 4 symptomatic patients, and in all of them p24 Ag was detected in the absence of HIV specific antibodies. These data underline the frequent occurrence of HIV transmission by the heterosexual route and the need to search for both specific antibodies and p24 Ag at the time of PHI.
Assuntos
Sorodiagnóstico da AIDS , Infecções por HIV/diagnóstico , Adulto , Contagem de Linfócito CD4 , Diagnóstico Diferencial , Feminino , Proteína do Núcleo p24 do HIV/sangue , Infecções por HIV/imunologia , Infecções por HIV/transmissão , Soropositividade para HIV/diagnóstico , Soropositividade para HIV/imunologia , Humanos , MasculinoAssuntos
Antivirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV/efeitos dos fármacos , Monitoramento de Medicamentos , Quimioterapia Combinada , HIV/fisiologia , Infecções por HIV/virologia , Humanos , Viremia/tratamento farmacológico , Viremia/virologia , Replicação Viral/efeitos dos fármacosRESUMO
OBJECTIVE: To evaluate the concentration of circulating RNA (viraemia) in patients with symptomatic primary HIV infection and relate it to sero-immunological parameters. METHODS: Semiquantitation of circulating HIV RNA and proviral HIV DNA was performed using the polymerase chain reaction. Circulating HIV RNA concentrations were expressed as virus equivalent (RNA copies/2) per ml serum. RESULTS: The mean CD4+ lymphocyte count for 19 patients with symptomatic primary HIV infection was 583 x 10(6)/l. Fifteen (79%) patients had detectable levels of p24 antigen (median 462 pg/ml). Circulating HIV RNA (median 2.3 x 10(7) virus equivalent/ml serum) and proviral HIV DNA (median 3630 copies/ml blood) were detected in all samples tested. Follow-up data for five patients (200-1600 days) showed a 1-3 log reduction in circulating RNA within 2 months. Later, circulating RNA concentrations were consistently greater than 10(3) virus equivalent/ml serum. Within 10 days no p24 antigen was detectable. Levels of CD4+ cells varied markedly from patient to patient during the follow-up and, in this small group, no evident correlation was observed between circulating RNA levels and CD4+ lymphocyte counts. CONCLUSIONS: High concentrations of circulating RNA (viraemia) were present in 19 patients with symptomatic primary HIV infection. Although a decrease in viraemia was observed during the following 2 months, viraemia persisted in all patients with long-term follow-up. This suggests that active viral replication is a continuous process in HIV-infected patients.