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1.
Lancet HIV ; 10(12): e790-e806, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38040478

RESUMO

BACKGROUND: HIV pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV acquisition. To enable routine commissioning of PrEP in England, we aimed to establish population need, duration of need, PrEP uptake, and duration of use in attendees of sexual health services (SHS) in England. METHODS: The Impact Trial was a prospective, open-label, single-arm, multicentre trial conducted at 157 SHS across England between Oct 13, 2017, and July 12, 2020. Clinicians assessed HIV-negative attendees for their risk of HIV acquisition to identify those who were eligible to participate and receive either daily or event-based oral PrEP (tenofovir disoproxil maleate with emtricitabine), as appropriate. Eligible participants were aged 16 years or older, considered HIV-negative on the day of enrolment, and willing to adhere to the trial procedures. Non-trial attendees are mutually exclusive of trial participants and included SHS attendees who were not recruited to the Impact Trial at any point. They include HIV-negative individuals aged 16 years or older who attended a participating SHS at least once after recruitment at that SHS had begun and before Feb 29, 2020. The main outcomes assessed were PrEP need, uptake, and use, and HIV and sexually transmitted infection (STI) incidence. Data are presented up to Feb 29, 2020, before the introduction of COVID-19 control measures. The study is registered with ClinicalTrials.gov, NCT03253757. FINDINGS: In this analysis, we include 21 356 of 24 268 participants enrolled before Feb 29, 2020. 20 403 participants (95·5%) were men who have sex with men (MSM). Uptake of PrEP among SHS attendees clinically assessed and coded as eligible was 21 292 (57·1%) of 37 289. 18 400 trial participants had at least one post-enrolment visit and a median of 361 days of follow-up (IQR 143-638); 14 039 (75·9%) of these had enough PrEP prescribed to provide protection for 75% of their follow-up time. Among MSM, HIV incidence was 0·13 (95% CI 0·08-0·19) per 100 person-years in trial participants (27 seroconversions) and 0·95 (95% CI 0·88-1·03) per 100 person-years in non-trial attendees (587 seroconversions; proportionate reduction of 86·8%, 95% CI 80·2-91·6). 18 607 bacterial STIs were recorded (incidence 68·1 per 100 person-years in trial participants who were MSM). 4343 (24·4%) MSM participants were diagnosed with two or more STIs, accounting for 14 800 (79·5%) of all 18 607 diagnoses. INTERPRETATION: PrEP need was higher than initially estimated by an expert stakeholder group. The high proportion of follow-up time protected by PrEP suggests that the need for protection persisted throughout trial participation for most participants. HIV incidence among MSM trial participants was low. The large unmet need for PrEP suggests that greater provision is required to maximise the potential of a national programme. The high incidence of bacterial STIs among participants, concentrated within a subgroup of PrEP users, presents an opportunity for tailored STI control measures. FUNDING: NHS England.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Masculino , Humanos , Feminino , Homossexualidade Masculina , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Infecções por HIV/diagnóstico , Profilaxia Pré-Exposição/métodos , Fármacos Anti-HIV/uso terapêutico , Estudos Prospectivos , Avaliação da Tecnologia Biomédica , Infecções Sexualmente Transmissíveis/epidemiologia , Inglaterra/epidemiologia
2.
AIDS ; 27(16): 2551-7, 2013 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-23736152

RESUMO

OBJECTIVE: Liver disease secondary to hepatitis C virus (HCV) infection in the context of HIV infection is one of the leading non-AIDS causes of death. Sexual transmission of HCV infection among HIV-positive MSM appears to be leading to increased reports of acute HCV infection. Reinfection after successful treatment or spontaneous clearance is reported among HIV-positive MSM but the scale of reinfection is unknown. We calculate and compare HCV reinfection rates among HIV-positive MSM after spontaneous clearance and successful medical treatment of infection. DESIGN: Retrospective analysis of HIV-positive MSM with sexually acquired HCV who subsequently spontaneously cleared or underwent successful HCV treatment between 2004 and 2012. RESULTS: Among 191 individuals infected with HCV, 44 were reinfected over 562 person-years (py) of follow-up with an overall reinfection rate of 7.8/100 py [95% confidence interval (CI) 5.8-10.5]. Eight individuals were subsequently reinfected a second time at a rate of 15.5/100 py (95% CI 7.7-31.0). Combining all reinfections, 20% resulted in spontaneous clearance and treatment sustained viral response rates were 73% (16/22) for genotypes one and four and 100% (2/2) for genotypes two and three. Among 145 individuals with a documented primary infection, the reinfection rate was 8.0 per 100 py (95% CI 5.7-11.3) overall, 9.6/100 py (95% CI 6.6-14.1) among those successfully treated and 4.2/100 py (95% CI 1.7-10.0) among those who spontaneously cleared. The secondary reinfection rate was 23.2/100 py (95% CI 11.6-46.4). CONCLUSION: Despite efforts at reducing risk behaviour, HIV-positive MSM who clear HCV infection remain at high risk of reinfection. This emphasizes the need for increased sexual education, surveillance and preventive intervention work.


Assuntos
Infecções por HIV/complicações , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Homossexualidade Masculina , Adulto , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Medição de Risco , Resultado do Tratamento
3.
AIDS Res Hum Retroviruses ; 29(1): 84-8, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22920222

RESUMO

Chronic HIV-1 infection results in the expansion of both NKG2C+ and CD16+CD56- human natural killer cells. NKG2C+ cells proliferate in response to human cytomegalovirus (HCMV) and expansion of the dysfunctional CD56-CD16+ natural killer (NK) cells is associated with HIV-1 viremia. Here we report an association between increased proportions of CD56-CD16+ NK cells in viremic HIV-1+ individuals and an increased contribution of NKG2C+ cells to this subset. These data, in addition to anti-HCMV IgG serology, indicate a potential contribution of both HCMV and HIV-1 to NK cell dysfunction in HIV-1-infected individuals.


Assuntos
Antígeno CD56/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Células Matadoras Naturais/imunologia , Subfamília C de Receptores Semelhantes a Lectina de Células NK/imunologia , Receptores de IgG/imunologia , Carga Viral/imunologia , Adulto , Idoso , Humanos , Subpopulações de Linfócitos/imunologia , Pessoa de Meia-Idade , Adulto Jovem
4.
JAMA ; 308(4): 353-61, 2012 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-22820788

RESUMO

CONTEXT: Therapies to decrease immune activation might be of benefit in slowing HIV disease progression. OBJECTIVE: To determine whether hydroxychloroquine decreases immune activation and slows CD4 cell decline. DESIGN, SETTING, AND PATIENTS: Randomized, double-blind, placebo-controlled trial performed at 10 HIV outpatient clinics in the United Kingdom between June 2008 and February 2011. The 83 patients enrolled had asymptomatic HIV infection, were not taking antiretroviral therapy, and had CD4 cell counts greater than 400 cells/µL. INTERVENTION: Hydroxychloroquine, 400 mg, or matching placebo once daily for 48 weeks. MAIN OUTCOME MEASURES: The primary outcome measure was change in the proportion of activated CD8 cells (measured by the expression of CD38 and HLA-DR surface markers), with CD4 cell count and HIV viral load as secondary outcomes. Analysis was by intention to treat using mixed linear models. RESULTS: There was no significant difference in CD8 cell activation between the 2 groups (-4.8% and -4.2% in the hydroxychloroquine and placebo groups, respectively, at week 48; difference, -0.6%; 95% CI, -4.8% to 3.6%; P = .80). Decline in CD4 cell count was greater in the hydroxychloroquine than placebo group (-85 cells/µL vs -23 cells/µL at week 48; difference, -62 cells/µL; 95% CI, -115 to -8; P = .03). Viral load increased in the hydroxychloroquine group compared with placebo (0.61 log10 copies/mL vs 0.23 log10 copies/mL at week 48; difference, 0.38 log10 copies/mL; 95% CI, 0.13 to 0.63; P = .003). Antiretroviral therapy was started in 9 patients in the hydroxychloroquine group and 1 in the placebo group. Trial medication was well tolerated, but more patients reported influenza-like illness in the hydroxychloroquine group compared with the placebo group (29% vs 10%; P = .03). CONCLUSION: Among HIV-infected patients not taking antiretroviral therapy, the use of hydroxychloroquine compared with placebo did not reduce CD8 cell activation but did result in a greater decline in CD4 cell count and increased viral replication. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN30019040.


Assuntos
Anti-Inflamatórios/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Hidroxicloroquina/uso terapêutico , Ativação Linfocitária/efeitos dos fármacos , Adolescente , Adulto , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos , Progressão da Doença , Método Duplo-Cego , Feminino , Humanos , Inflamação/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Resultado do Tratamento , Carga Viral , Adulto Jovem
5.
PLoS One ; 7(2): e29844, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22363409

RESUMO

Define and identify long-term non-progressors (LTNP) and HIV controllers (HIC), and estimate time until disease progression. LTNP are HIV-1(+) patients who maintain stable CD4(+) T-cell counts, with no history of opportunistic infection or antiretroviral therapy (ART). HIC are a subset of LTNP who additionally have undetectable viraemia. These individuals may provide insights for prophylactic and therapeutic development. Records of HIV-1(+) individuals attending Chelsea and Westminster Hospital (1988-2010), were analysed. LTNP were defined as: HIV-1(+) for >7 years; ART-naïve; no history of opportunistic infection and normal, stable CD4(+) T-cell counts. MIXED procedure in SAS using random intercept model identified long-term stable CD4(+) T-cell counts. Survival analysis estimated time since diagnosis until disease progression. Subjects exhibiting long-term stable CD4(+) T-cell counts with history below the normal range (<450 cells/µl blood) were compared to LTNP whose CD4(+) T-cell count always remained normal. Within these two groups subjects with HIV-1 RNA load below limit of detection (BLD) were identified. Of 14,227 patients, 1,204 were diagnosed HIV-1(+) over 7 years ago and were ART-naïve. Estimated time until disease progression for the 20% (239) whose CD4(+) T-cell counts remained within the normal range, was 6.2 years (IQR: 2.0 to 9.6); significantly longer than 4.0 years (IQR: 1.0 to 7.3) for patients with historical CD4(+) T-cell count below normal (Logrank chi-squared = 21.26; p<0.001). Within a subpopulation of 312 asymptomatic patients, 50 exhibited long-term stable CD4(+) T-cell counts. Of these, 13 were LTNP, one of whom met HIC criteria. Of the remaining 37 patients with long-term stable low CD4(+) T-cell counts, 3 controlled HIV-1 RNA load BLD. Individuals with stable, normal CD4(+) T-cell counts progressed less rapidly than those with low CD4(+) T-cell counts. Few LTNP and HIC identified in this and other studies, endorse the need for universal definitions to facilitate comparison.


Assuntos
Progressão da Doença , Infecções por HIV/patologia , Sobreviventes de Longo Prazo ao HIV , Adulto , Contagem de Linfócito CD4 , Estudos de Coortes , Demografia , Feminino , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/fisiologia , Humanos , Londres , Masculino , Fatores de Tempo
6.
J Allergy Clin Immunol ; 128(4): 838-846.e5, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21745684

RESUMO

BACKGROUND: In HIV-1-infected patients impaired IFN-γ responses to purified protein derivative (PPD) are associated with an increased risk of active tuberculosis. Tuberculosis antigen-specific cells are found in the T(H)1/T(H)17 subset of CD4 T cells, which support HIV-1 replication. Selective loss of T(H)1/T(H)17 cells in patients with HIV-1 infection might contribute to reduced tuberculosis-induced immune responses and an increased susceptibility to active tuberculosis. OBJECTIVES: We sought to investigate the association between T(H)1/T(H)17 cells and PPD-specific cytokine responses in HIV-1-infected patients. METHODS: A cross-sectional study was performed on healthy control subjects, HIV-1-infected patients receiving successful antiretroviral therapy (ART(+)), and ART-naive HIV-1-infected patients (ART(-)). All patients studied had evidence of BCG vaccination. Four discrete CD4 T-cell subsets were assessed by flow cytometry: T(H)1/T(H)17 cells (CXCR3(+)CCR6(+)CCR4(-)), T(H)1 cells (CXCR3(+)CCR6(-)CCR4(-)), T(H)17 cells (CXCR3(-)CCR6(+)CCR4(+)), and T(H)2 cells (CXCR3(-)CCR6(-)CCR4(+)). IFN-γ and IL-2 PPD-specific cytokine responses were assessed in PBMCs by using the enzyme-linked immunospot assay. RESULTS: Twenty-nine healthy control subjects, 34 ART(+) patients, and 26 ART(-) patients were recruited. The number and frequency of T(H)1/T(H)17 and T(H)1/T(H)17 CCR5(+) CD4 T cells were significantly reduced in HIV-1-infected patients. IFN-γ and IL-2 PPD responses were significantly lower in ART(-) patients and were partially reconstituted with successful ART. Loss of T(H)1/T(H)17 CCR5(+) cells was associated with reduced IFN-γ and IL-2 PPD responses. CONCLUSIONS: Selective loss of T(H)1/T(H)17 cells may be a risk factor for the development of active tuberculosis in patients with HIV-1 infection and might be a useful biomarker in the development of tuberculosis vaccines.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/imunologia , HIV-1/imunologia , Interferon gama/imunologia , Interleucina-2/imunologia , Células Th1/imunologia , Células Th17/imunologia , Tuberculina/imunologia , Tuberculose/imunologia , Adulto , Biomarcadores , Contagem de Linfócito CD4 , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Células Th2/imunologia
7.
Clin Infect Dis ; 52(5): 671-3, 2011 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-21292672

RESUMO

CCR5 antagonists may provide a well-tolerated switch option for patients experiencing tolerability or toxicity of their antiretroviral regimen. We analyzed stored samples from patients undergoing planned treatment interruptions for reasons other than virological failure, in order to analyze tropism evolution during fully suppressive antiretroviral therapy (ART). Two of 37 patients showed evidence of switching. Tropism switching after suppressive ART was uncommon in this cohort. Pretreatment human immunodeficiency virus (HIV) RNA tropism testing may help guide the switch to CCR5 antagonists in patients with undetectable HIV RNA.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Terapia Antirretroviral de Alta Atividade , Inibidores da Fusão de HIV/administração & dosagem , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV/patogenicidade , Tropismo Viral , Adulto , Feminino , Humanos , Masculino , Gravidez , Suspensão de Tratamento
8.
Br J Nutr ; 102(7): 1038-46, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19480729

RESUMO

Mechanisms underlying the lipodystrophy syndrome associated with antiretroviral therapy (ART) for HIV infection are not completely understood. We investigated the effect of ART on blood lipid concentrations in the fasting state and after consumption of a meal containing [1-13C]palmitic acid in HIV-positive men receiving nucleoside reverse transcriptase inhibitors (NRTI, n 7), NRTI combined with protease inhibitors (PI; NRTIPI, n 6), in HIV-positive but therapy-naïve men (noART, n 5) and in HIV-seronegative men (controls, n 6). HIV-positive subjects had higher fasting TAG concentrations and resting energy expenditure than controls. Subjects receiving NRTIPI therapy had higher fasting NEFA concentrations than the other groups. There were no significant differences in postprandial lipid metabolism between noART subjects and controls. NRTI therapy impaired hydrolysis of meal-derived TAG, most evidently when combined with PI (the NRTIPI group). Accumulation of 13C-label in the NEFA fraction was not different between groups. In the NRTIPI group, fasting and postprandial NEFA concentrations were significantly higher than other groups. Postprandial glucose and insulin responses in HIV-positive subjects did not differ from controls. These findings suggest that ART dyslipidaemia is associated with impaired postprandial TAG clearance, which is exacerbated by NRTIPI therapy. If dyslipidaemia is to be minimised in ART, the specific adverse effects of particular combinations during the fed state should be considered.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , HIV-1 , Hipertrigliceridemia/induzido quimicamente , Adulto , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Terapia Antirretroviral de Alta Atividade/métodos , Glicemia/metabolismo , Metabolismo Energético/efeitos dos fármacos , Infecções por HIV/sangue , Inibidores da Protease de HIV/efeitos adversos , Inibidores da Protease de HIV/uso terapêutico , Humanos , Hidrólise/efeitos dos fármacos , Hipertrigliceridemia/sangue , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Oxirredução/efeitos dos fármacos , Período Pós-Prandial/fisiologia , Inibidores da Transcriptase Reversa/efeitos adversos , Inibidores da Transcriptase Reversa/uso terapêutico , Triglicerídeos/sangue , Adulto Jovem
9.
J Acquir Immune Defic Syndr ; 51(2): 140-6, 2009 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-19352201

RESUMO

OBJECTIVES: We wished to determine the efficacy of nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens in antiretroviral-naive patients commencing highly active antiretroviral therapy (HAART) and to evaluate the effect of calendar year, nucleoside analogue reverse transcriptase inhibitor (NRTI) backbone, sex, and ethnicity on treatment outcome. METHODS: Antiretroviral-naive individuals commencing efavirenz or nevirapine with dual-nucleoside analogue backbones were identified from a prospective database. Virological success was defined as HIV viral load <500 copies per milliliter. Treatment failure was defined as a switch or discontinuation of NNRTI or documented virological failure (2 measurements with viral load >500 copies/mL). RESULTS: From a cohort of 994 individuals, 73% commenced efavirenz- and 27% nevirapine-containing regimens. We found no differences between the 2 treatment groups for the time to virological success (proportion with virological success: efavirenz 71%, nevirapine 72%, P = 0.77) or treatment failure (proportion failing treatment: efavirenz 23%, nevirapine 26%, P = 0.58). There was a significant difference in the calendar year for commencing HAART for the time to virological success and treatment failure (P < 0.001). In the multivariable model, the likelihood of virological success for stavudine/lamivudine was 52% [relative hazard (RH) 1.52, 95% confidence interval (CI) 1.17 to 1.97, P = 0.002]. The nonthymidine analogue backbones as a group seemed to be least likely associated with virological success (RH 0.62, 95% CI 0.48 to 0.80, P < 0.001). This was however largely driven by tenofovir/didanosine being significantly associated with treatment failure (RH 6.48, 95% CI 3.81 to 11.0, P < 0.001). Sex and ethnicity were not associated with treatment outcome. CONCLUSIONS: We found no significant differences between nevirapine and efavirenz for the time to virological success or treatment failure. Calendar year of commencing HAART and NRTI backbones were significant predictors of virological success and treatment failure, explaining differences in data to the 2NN study. The weaker the NNRTI (or the weaker the protease inhibitor) the more important the NRTI backbone becomes.


Assuntos
Terapia Antirretroviral de Alta Atividade , Benzoxazinas/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Nevirapina/uso terapêutico , Adulto , Alcinos , Benzoxazinas/administração & dosagem , Estudos de Coortes , Ciclopropanos , Etnicidade , Feminino , Humanos , Masculino , Nevirapina/administração & dosagem
10.
AIDS ; 23(1): 29-34, 2009 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-19050383

RESUMO

BACKGROUND: Lipopolysaccharide (LPS) is elevated in the plasma of individuals chronically infected with HIV-1 and is thought to contribute to chronic immune activation of myeloid cells and T-cells. Natural killer (NK) cells can also be stimulated by LPS in vitro. OBJECTIVES: To measure plasma LPS levels in individuals with HIV-1 infection, with or without suppressed plasma viral load, and in individuals with or without inflammatory bowel diseases (IBD). To compare the expression of NK cell receptors and activation markers in individuals with HIV-1 infection and in HIV-1-negative individuals with active IBD. METHODS: NK cells were studied by flow cytometry in treatment-naïve viraemic HIV-1-positive individuals (n = 14), aviraemic HIV-1-positive individuals (n = 19), HIV-1-negative individuals with inflammatory bowel disease (n = 10) and HIV-1-negative healthy control individuals (n = 17). Plasma endotoxin (LPS) was measured using the limulus amoebocyte assay. RESULTS: Viraemic and aviraemic HIV-1-positive individuals and patients with IBD have elevated levels of plasma LPS compared with HIV-1-negative individuals.HIV-1-positive individuals had significant changes in activation marker or NK cell receptor expression, whereas NK cells from IBD patients had similar levels to HIV-1-negative controls. NK cells from HIV-1-positive individuals are refractory to further stimulation by LPS in vitro. CONCLUSION: Elevated plasma LPS alone does not account for the chronic activation and receptor loss in NK cells from HIV-1-infected individuals.


Assuntos
Infecções por HIV/imunologia , HIV-1 , Células Matadoras Naturais/imunologia , Lipopolissacarídeos/sangue , Ativação Linfocitária/imunologia , Adulto , Células Cultivadas , Infecções por HIV/virologia , Humanos , Doenças Inflamatórias Intestinais/imunologia , Pessoa de Meia-Idade , Receptores de Células Matadoras Naturais/sangue , Carga Viral , Adulto Jovem
12.
J Interferon Cytokine Res ; 28(2): 89-100, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18279104

RESUMO

We sought to determine the safety, maximum tolerated dose, optimal dose, and preliminary dose efficacy of intermittent subcutaneously (s.c.) administered BAY 50-4798 among patients with HIV infection receiving highly active antiretroviral therapy (HAART) compared with patients receiving HAART alone. A phase I/II randomized, double-blind, dose-escalation study was conducted of the safety, tolerability, pharmacokinetics, and efficacy of s.c. BAY 50-4798 administered to HIV-infected patients already receiving stable HAART. There were no unexpected safety findings in a population of HIV-infected patients receiving HAART plus SC BAY 50-4798 as adjunctive therapy. BAY 50-4798 exhibited nearly dose-proportional pharmacokinetics, and accumulation was minimal during multiple-dose treatment. Limited efficacy data indicated that treatment with BAY 50-4798 caused at least a transient increase in CD4(+) T cell counts in some recipients, particularly at the early time points. In general, this effect appeared to increase with increasing dose. Bay 50-4798 was generally well tolerated across the dose range tested, but a lack of potent, sustained immunologic activity suggests that further optimization of dose and schedule will be necessary.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Interleucina-2/análogos & derivados , Adulto , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/farmacocinética , Citocinas/metabolismo , Método Duplo-Cego , Feminino , Infecções por HIV/imunologia , Infecções por HIV/metabolismo , Humanos , Injeções Subcutâneas , Interleucina-2/administração & dosagem , Interleucina-2/efeitos adversos , Interleucina-2/agonistas , Interleucina-2/farmacocinética , Contagem de Linfócitos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/farmacocinética
13.
AIDS ; 21(16): 2177-82, 2007 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-18090044

RESUMO

BACKGROUND: HIV-1 infection is known to have a detrimental impact on peripheral blood natural killer cell phenotype and function. Chronic HIV-1 also causes a substantial depletion of CD4+ T cells in the gastrointestinal tract and the blood. OBJECTIVE: To investigate the impact of chronic HIV-1 infection with on natural killer cell populations in the gastrointestinal tract and the effect of suppression of plasma viraemia with antiretroviral therapy. METHODS: Lymphocyte populations were extracted from the lamina propria of biopsies taken from the sigmoid colon of HIV-1-infected and uninfected individuals. The proportions of natural killer cell subsets were compared in viraemic (n = 15) and aviraemic HIV-1-positive, HAART-treated individuals (n = 27) and HIV-1 negative control individuals (n = 26) using flow cytometry on gated subsets. RESULTS: Natural killer cells are depleted in colonic biopsies from HIV-1-infected individuals with detectable plasma virus in comparison with HIV-1-negative individuals. A significant increase in the proportion of both natural killer and CD4+ T cells in the colonic lamina propria is observed in aviraemic individuals compared to viraemic individuals. CONCLUSIONS: Chronic HIV-1 infection results in depletion of both natural killer cells and CD4+ T cells in colonic tissue and antiretroviral therapy results in a recovery of these subsets in individuals with undetectable plasma viral load.


Assuntos
Colo Sigmoide , Infecções por HIV/imunologia , HIV-1 , Mucosa Intestinal/imunologia , Células Matadoras Naturais/imunologia , Mucosa/imunologia , Adulto , Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Estudos de Casos e Controles , Citometria de Fluxo , Infecções por HIV/tratamento farmacológico , Humanos , Contagem de Linfócitos , Pessoa de Meia-Idade , Estatísticas não Paramétricas , Carga Viral , Viremia/imunologia
14.
Antivir Ther ; 12(6): 971-5, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17926652

RESUMO

OBJECTIVES: To determine if the expression of CD38 on CD8+ T-cells could be used as a marker of viral replication <50 copies/ml in peripheral blood. METHODS: In a cross-sectional study of patients attending a single HIV clinic in London, an ultra-sensitive HIV RNA viral load assay, with a limit of detection of 3 copies/ml, was used to determine HIV-1 replication in plasma in 70 patients who had sustained viral suppression <50 copies/ml by bDNA assays. Immune activation using the expression of CD38 on CD8+ T-cells was also assessed in patients on antiretroviral therapy (ART) with sustained viral suppression, individuals with persistent low-level viraemia <400 copies/ml and subjects failing ART (viral load >400 copies/mi). RESULTS: There was no significant difference in the percentage of CD8+CD38++ T-cells between patients with <50 copies or <3 copies/ml. Immune activation was significantly increased in patients with persistent low-level viraemia and in subjects failing ART. CD4+ T-cell counts in patients on long-term successful ART are inversely associated with CD8+ T-cell activation. CONCLUSIONS: T-cell activation in patients on long-term successful ART is not due to residual low-level viral replication in the blood compartment of HIV-1. CD8+ T-cell activation in this patient group appears to be associated with poor CD4+ T-cell recovery.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Linfócitos T CD8-Positivos/imunologia , Infecções por HIV/tratamento farmacológico , HIV-1/fisiologia , ADP-Ribosil Ciclase 1/análise , Adulto , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Estudos Transversais , Feminino , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Humanos , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Subpopulações de Linfócitos T/imunologia , Carga Viral , Replicação Viral/efeitos dos fármacos
17.
Top HIV Med ; 14(3): 827-43, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17016878

RESUMO

CONTEXT: Guidelines for antiretroviral therapy are important for clinicians worldwide given the complexity of the field and the varied clinical situations in which these agents are used. The International AIDS Society-USA panel has updated its recommendations as warranted by new developments in the field. OBJECTIVE: To provide physicians and other human immunodeficiency virus (HIV) clinicians with current recommendations for the use of antiretroviral therapy in HIV-infected adults in circumstances for which there is relatively unrestricted access to drugs and monitoring tools. The recommendations are centered on 4 key issues: when to start antiretroviral therapy; what to start; when to change; and what to change. Antiretroviral therapy in special circumstances is also described. DATA SOURCES AND STUDY SELECTION: A 16-member noncompensated panel was appointed, based on expertise in HIV research and patient care internationally. Data published or presented at selected scientific conferences from mid 2004 through May 2006 were identified and reviewed by all members of the panel. DATA EXTRACTION AND SYNTHESIS: Data that might change previous guidelines were identified and reviewed. New guidelines were drafted by a writing committee and reviewed by the entire panel. CONCLUSIONS: Antiretroviral therapy in adults continues to evolve rapidly, making delivery of state-of-the-art care challenging. Initiation of therapy continues to be recommended in all symptomatic persons and in asymptomatic persons after the CD4 cell count falls below 350/microL and before it declines to 200/microL. A nonnucleoside reverse transcriptase inhibitor or a protease inhibitor boosted with low-dose ritonavir each combined with 2 nucleoside (or nucleotide) reverse transcriptase inhibitors is recommended with choice being based on the individual patient profile. Therapy should be changed when toxicity or intolerance mandate it or when treatment failure is documented. The virologic target for patients with treatment failure is now a plasma HIV-1 RNA level below 50 copies/mL. Adherence to antiretroviral therapy in the short-term and the long-term is crucial for treatment success and must be continually reinforced.

18.
JAMA ; 296(7): 827-43, 2006 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-16905788

RESUMO

CONTEXT: Guidelines for antiretroviral therapy are important for clinicians worldwide given the complexity of the field and the varied clinical situations in which these agents are used. The International AIDS Society-USA panel has updated its recommendations as warranted by new developments in the field. OBJECTIVE: To provide physicians and other human immunodeficiency virus (HIV) clinicians with current recommendations for the use of antiretroviral therapy in HIV-infected adults in circumstances for which there is relatively unrestricted access to drugs and monitoring tools. The recommendations are centered on 4 key issues: when to start antiretroviral therapy; what to start; when to change; and what to change. Antiretroviral therapy in special circumstances is also described. DATA SOURCES AND STUDY SELECTION: A 16-member noncompensated panel was appointed, based on expertise in HIV research and patient care internationally. Data published or presented at selected scientific conferences from mid 2004 through May 2006 were identified and reviewed by all members of the panel. DATA EXTRACTION AND SYNTHESIS: Data that might change previous guidelines were identified and reviewed. New guidelines were drafted by a writing committee and reviewed by the entire panel. CONCLUSIONS: Antiretroviral therapy in adults continues to evolve rapidly, making delivery of state-of-the-art care challenging. Initiation of therapy continues to be recommended in all symptomatic persons and in asymptomatic persons after the CD4 cell count falls below 350/microL and before it declines to 200/microL. A nonnucleoside reverse transcriptase inhibitor or a protease inhibitor boosted with low-dose ritonavir each combined with 2 nucleoside (or nucleotide) reverse transcriptase inhibitors is recommended with choice being based on the individual patient profile. Therapy should be changed when toxicity or intolerance mandate it or when treatment failure is documented. The virologic target for patients with treatment failure is now a plasma HIV-1 RNA level below 50 copies/mL. Adherence to antiretroviral therapy in the short-term and the long-term is crucial for treatment success and must be continually reinforced.


Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Adulto , Terapia Antirretroviral de Alta Atividade/normas , Monitoramento de Medicamentos , Farmacorresistência Viral , Feminino , HIV/efeitos dos fármacos , HIV/genética , Infecções por HIV/complicações , Infecções por HIV/imunologia , Hepatite B/complicações , Hepatite C/complicações , Humanos , Masculino , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Tuberculose/complicações , Carga Viral
20.
Expert Opin Pharmacother ; 7(6): 793-802, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16556093

RESUMO

With the continuing spread of HIV infection, particularly in developing countries, cost-effective treatment for its management is a high priority. Truvada (Gilead Sciences) is a single combination pill of the nucleotide reverse transcriptase inhibitors tenofovir disoproxil fumarate and emtricitabine, which is used once daily. It is anticipated to be a clinically potent combination that is free of short-term irritating toxicity. The drug has recently been licensed but there are currently little clinical efficacy data regarding its use. The limited published data have indicated that emtricitabine and lamivudine have equivalent potency, and randomised controlled trials have produced evidence of the efficacy of lamivudine combined with tenofovir disoproxil fumarate in a regimen containing either the non-nucleoside reverse transcriptase inhibitor efavirenz or a protease inhibitor lopinavir/ritonavir. In these trials, long-term durability data are available for < or = 96 weeks.


Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/administração & dosagem , Desoxicitidina/análogos & derivados , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Organofosfonatos/administração & dosagem , Adenina/administração & dosagem , Desoxicitidina/administração & dosagem , Quimioterapia Combinada , Emtricitabina , Infecções por HIV/epidemiologia , Humanos , Tenofovir
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