RESUMO
BACKGROUND: Chlamydia remains the most notified bacterial sexually transmissible infection in Australia with guidelines recommending testing for re-infection at 3months post treatment. This paper aimed to determine chlamydia retesting and repeat positivity rates within 2-4months among young women in Australia, and to evaluate what factors increase or decrease the likelihood of retesting. METHODS: Chlamydia retesting rates among 16-29-year-old women were analysed from Australian Collaboration for Coordinated Enhanced Sentinel Surveillance of sexually transmissible infection and bloodborne virus (ACCESS) sentinel surveillance data (n =62 sites). Among women with at least one positive test between 1 January 2018 and 31 August 2022, retesting counts and proportions within 2-4months were calculated. Logistic regression was performed to assess factors associated with retesting within 2-4months. RESULTS: Among 8758 women who were positive before 31 August 2022 to allow time for follow up, 1423 (16.2%) were retested within 2-4months, of whom 179 (12.6%) tested positive. The odds of retesting within 2-4months were 25% lower if tested in a coronavirus disease 2019 (COVID-9) pandemic year (2020-2022) (aOR=0.75; 95% CI 0.59-0.95). Among 9140 women with a positive test before 30 November 2022, 397 (4.3%) were retested too early (within 7days to 1month) and 81 (20.4%) of those were positive. CONCLUSIONS: Chlamydia retesting rates remain low with around a sixth of women retested within 2-4months in line with guidelines. Re-infection is common with around one in eight retesting positive. An increase in retesting is required to reduce the risk of reproductive complications and onward transmission.
Assuntos
Infecções por Chlamydia , Chlamydia , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/epidemiologia , Infecções por Chlamydia/microbiologia , Vigilância de Evento Sentinela , Reinfecção , Austrália/epidemiologia , Programas de Rastreamento , Chlamydia trachomatisRESUMO
BACKGROUND: Overwhelming evidence highlights the negative impact of substance use on HIV care and treatment outcomes. Yet, the extent to which alcohol use disorder (AUD) and other substance use disorders (SUD) services have been integrated within HIV clinical settings is limited. We describe AUD/SUD screening and treatment availability in HIV clinical sites participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. METHODS: In 2020, 223 IeDEA HIV clinical sites from 41 countries across seven geographic regions completed a survey on capacity and practices related to management of AUD/ SUD. Sites provided information on AUD and other SUD screening and treatment practices. RESULTS: Sites were from low-income countries (23%), lower-middle-income countries (38%), upper-middle income countries (17%) and high-income counties (23%). AUD and SUD screening using validated instruments were reported at 32% (n=71 located in 12 countries) and 12% (n=27 located in 6 countries) of the 223 sites from 41 countries, respectively. The North American region had the highest proportion of clinics that reported AUD screening (76%), followed by East Africa (46%); none of the sites in West or Central Africa reported AUD screening. 31% (n=69) reported both AUD screening and counseling, brief intervention, psychotherapy, or Screening, Brief Intervention, and Referral to Treatment; 8% (n=18) reported AUD screening and detox hospitalization; and 10% (n=24) reported both AUD screening and medication. While the proportion of clinics providing treatment for SUD was lower than those treating AUD, the prevalence estimates of treatment availability were similar. CONCLUSIONS: Availability of screening and treatment for AUD/SUD in HIV care settings is limited, leaving a substantial gap for integration into ongoing HIV care. A critical understanding is needed of the multilevel implementation factors or feasible implementation strategies for integrating screening and treatment of AUD/SUD into HIV care settings, particularly for resource-constrained regions.
Assuntos
Alcoolismo , Infecções por HIV , Transtornos Relacionados ao Uso de Substâncias , Humanos , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/terapia , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/terapia , Programas de Rastreamento , AconselhamentoRESUMO
BACKGROUND: Microelimination of hepatitis C virus (HCV) among people living with human immunodeficiency virus (HIV) may be feasible in Australia, given unrestricted access to direct-acting antiviral (DAA) therapy from 2016. Our aim was to evaluate progress towards elimination goals within HIV/HCV-coinfected adults in Australia following universal DAA access. METHODS: The CEASE prospective cohort study enrolled adults with HIV/HCV, irrespective of viremic status, from 14 primary and tertiary clinics in Australia. Annual and cumulative HCV treatment uptake, outcome, and HCV RNA prevalence were evaluated, with follow-up through May 2018 (median follow-up, 2.63 years). Factors associated with DAA uptake were analyzed. RESULTS: Between July 2014 and March 2017, 402 participants who were HIV/HCV antibody positive were enrolled (95% male [80% gay and bisexual men,], 13% cirrhosis, 80% history of injecting drug use [39% currently injecting]). Following universal DAA access, annual HCV treatment uptake in those eligible increased from 7% and 11% per year in 2014 and 2015, respectively, to 80% in 2016. By 2018, cumulative HCV treatment uptake in those ever eligible for treatment was 91% (336/371). HCV viremic prevalence declined from 82% (95% CI, 78-86%) in 2014 to 8% (95% CI, 6-12%) in 2018. Reinfection was reported in only 5 participants for a reinfection incidence of 0.81 per 100 person-years (95% CI, 0.34-1.94). CONCLUSIONS: High uptake and effectiveness of unrestricted DAA therapy in Australia have permitted rapid treatment scale-up, with a dramatic reduction in HCV infection burden and low reinfection rate among people living with HIV, suggesting that microelimination is feasible. CLINICAL TRIALS REGISTRATION: NCT02102451.
Assuntos
Infecções por HIV , Hepatite C Crônica , Hepatite C , Adulto , Antivirais/uso terapêutico , Austrália/epidemiologia , Feminino , HIV , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Hepacivirus , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Humanos , Masculino , Estudos ProspectivosRESUMO
Background The aim of this study is to estimate the reduction in new HIV infections and resultant cost outcomes of providing antiretroviral treatment (ART) through Australia's 'universal access' health scheme to all temporary residents with HIV infection living legally in Australia, but currently deemed ineligible to access subsidised ART via this scheme. METHODS: A mathematical model to estimate the number of new HIV infections averted and the associated lifetime costs over 5 years if all HIV-positive temporary residents in Australia had access to ART and subsidised medical care was developed. Input data came from a cohort of 180 HIV-positive temporary residents living in Australia who are receiving free ART donated by pharmaceutical companies for up to 4 years. RESULTS: Expanding ART access to an estimated total 450 HIV+ temporary residents in Australia for 5 years could avert 80 new infections. The model estimated the total median discounted (5%) cost for ART and associated care to be A$36million, while the total savings in lifetime-discounted costs for the new infections averted was A$22million. CONCLUSIONS: It is estimated that expanded access to ART for all HIV-positive temporary residents in Australia will substantially reduce HIV transmission to their sexual partners at little additional cost. In the context of Australia's National HIV strategy and Australia's endorsement of global goals to provide universal access to ART for all people with HIV, this is an important measure to remove inequities in the provision of HIV-related treatment and care.
Assuntos
Fármacos Anti-HIV/economia , Terapia Antirretroviral de Alta Atividade/economia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde/economia , Adulto , Assistência Ambulatorial/economia , Fármacos Anti-HIV/uso terapêutico , Austrália , Análise Custo-Benefício , Humanos , Masculino , Programas de Rastreamento/economia , Programas Nacionais de Saúde/economiaRESUMO
OBJECTIVE: To assess the performance and acceptability of the OraQuick Advance Rapid HIV-1/2 Antibody Test (ORT) in Australia. DESIGN, PARTICIPANTS AND SETTING: Cross-sectional study of 1074 men who have sex with men (MSM) and individuals aged 18 years or older at high risk of acquiring HIV infection who attended five public HIV or sexual health services, two general practices and one community clinic in Sydney from 1 January to 31 December 2013. INTERVENTION: One ORT confirmed by fourth-generation HIV enzyme immunoassay (EIA). MAIN OUTCOME MEASURES: ORT sensitivity and specificity compared with EIA; acceptabiity of the ORT to participants. RESULTS: 83.5% of participants were MSM, 90.3% were aged under 50 years, and 9% had never been tested for HIV. There were 11 true-positive ORT results, two false-negative (non-reactive) results (both were early infections), and one false-positive (reactive) result (due to reader error). Sensitivity and specificity were 84.6% and 99.8%, respectively (compared with a sensitivity of 99.3% and specificity of 99.8% listed by the manufacturer). Three quarters of participants (74.0%; 730/987) found the ORT less stressful than venous sampling. Those who usually had tests at intervals of greater than 3 months deemed the ORT less stressful than those who had quarterly tests (77.5% v 64.8%; P<0.001). Nearly all participants (99.2%; 998/1006) would have an ORT again and 99.4% (994/1000) would recommend it to peers. Most participants (69.1%; 720/1042) felt ORT approval by Australia's Therapeutic Goods Administration (TGA) would encourage testing. CONCLUSION: ORT sensitivity is reduced in early HIV infection. The test is highly acceptable and less stressful than venous sampling. Participants are keen to be tested with the ORT in future, would recommend it to peers and would have tests more frequently if the ORT were licensed. TGA approval of this test might slow increasing HIV infection rates among MSM and others by facilitating diagnosis and treatment.
Assuntos
Infecções por HIV/diagnóstico , Testes Imunológicos/métodos , Programas de Rastreamento/métodos , Aceitação pelo Paciente de Cuidados de Saúde , Adulto , Austrália , Estudos Transversais , Anticorpos Anti-HIV/metabolismo , Infecções por HIV/psicologia , Homossexualidade Masculina , Humanos , Testes Imunológicos/psicologia , Masculino , Programas de Rastreamento/psicologia , Fatores de Risco , Saliva , Sensibilidade e Especificidade , Estresse Psicológico/etiologiaRESUMO
BACKGROUND: A 55-year-old male presented with severe pain and functional limitations as a result of left hip osteoarthritis. He had failed multiple treatments while waiting for a hip arthroplasty, including physical therapy, medications, and various intra-articular injections. Thermal radiofrequency lesioning of the obturator and femoral articular branches to the hip joint was offered in the interim. OBJECTIVES: To our knowledge, this is the first report to describe an inferior-lateral approach for lesioning the obturator branch, the clinical application of successive lesions to increase denervation area, and outcomes in a patient receiving a second treatment with previously good results. METHODS: To discuss relevant and technical factors for this specific case, we reviewed previous literature on hip joint radiofrequency and critically evaluated previous anatomic studies in the context of radiofrequency. RESULTS: The first treatment provided significant benefit for a period of 6 months. A second treatment was employed providing only mild to moderate benefit until his joint replacement surgery 4 months later. Literature review revealed studies of low quality secondary to small sample sizes, patient selection methodology, inclusion of patients with heterogenous etiologies for pain, variable needle placement techniques, and lack of measurement of functional outcomes. LIMITATIONS: Case report and low quality studies in existing literature. CONCLUSIONS: Hip joint radiofrequency denervation is a promising avenue for adjunctive treatment of hip pain. Further cadaveric studies are required to clarify a multitude of technical parameters. Once these are well defined, future clinical studies should consider pain, functional, and economic outcomes in their design.
Assuntos
Artralgia/cirurgia , Denervação/métodos , Articulação do Quadril/inervação , Articulação do Quadril/cirurgia , Manejo da Dor/métodos , Denervação/instrumentação , Nervo Femoral/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Manejo da Dor/instrumentaçãoRESUMO
The fine control of T-cell differentiation and its impact on HIV disease states is poorly understood. In this study, we demonstrate that B-lymphocyte-induced maturation protein-1 (Blimp-1/Prdm1) is highly expressed in CD4(+) T cells from chronically HIV-infected (CHI) patients compared to cells from long-term nonprogressors or healthy controls. Stimulation through the T-cell receptor in the presence of IL-2 induces Blimp-1 protein expression. We show here that Blimp-1 levels are translationally regulated by microRNA-9 (miR-9). Overexpression of miR-9 induces Blimp-1 repression, restoring IL-2 secretion in CD4(+) T cells via reduction in the binding of Blimp-1 to the il-2 promoter. In CHI patients where IL-2 expression is reduced and there is generalized T-cell dysfunction, we show differential expression of both miR-9 and Blimp-1 in CD4(+) cells compared with levels in long-term nonprogressors. These data identify a novel miR-9/Blimp-1/IL-2 axis that is dysregulated in progressive HIV infection.
Assuntos
Linfócitos B/metabolismo , Infecções por HIV/metabolismo , Interleucina-2/metabolismo , MicroRNAs/genética , Proteínas Repressoras/metabolismo , Adulto , Linfócitos B/imunologia , Linfócitos B/virologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/virologia , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Linhagem Celular Tumoral , Regulação para Baixo/genética , Regulação para Baixo/imunologia , Feminino , Infecções por HIV/genética , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Interleucina-2/genética , Interleucina-2/imunologia , Células Jurkat , Masculino , MicroRNAs/imunologia , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Fator 1 de Ligação ao Domínio I Regulador Positivo , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/imunologia , Regulação para Cima/genética , Regulação para Cima/imunologia , Adulto JovemRESUMO
BACKGROUND: Previous studies have demonstrated that hepatitis B virus (HBV) infection increases the risk for ALT elevations in HIV-HBV co-infected patients during the first year of HAART; however, there is limited data on the prevalence of ALT elevations with prolonged HAART in this patient group. METHODS/PRINCIPAL FINDINGS: To identify factors associated with ALT elevations in an HIV-HBV co-infected cohort receiving prolonged HAART, data from 143 co-infected patients on HAART enrolled in an international HIV-HBV co-infected cohort where ALT measurements were obtained every 6 months was analysed. A person-visit analysis was used to determine frequency of ALT elevation (≥ 2.5×ULN) at each visit. Factors associated with ALT elevation were determined using multivariate logistic regression with generalized estimating equations to account for correlated data. The median time on HAART at the end of follow-up was 5.6 years (range 0.4-13.3) years. During follow-up, median ALT was 36 U/L with 10.6% of person-visits classified as having ALT elevation. Most ALT elevations were grade 2 (86.5%), with only 13.5% of all ALT elevations grade 3 or higher. Univariate associations with ALT elevation (p<0.05) included history of AIDS, HBV DNA ≥ 2,000 IU/ml, HBeAg positive, study visit CD4 <200 cells/ml and nadir CD4 <200 cells/ml. In the multivariate analysis, only study visit CD4 <200 cells/ml (OR 2.07, 95%CI 1.04-4.11, pâ=â0.04) and HBeAg positive status (OR 2.22, 95%CI 1.03-4.79, pâ=â0.04) were independently associated with ALT elevation. CONCLUSIONS: In this HIV-HBV co-infected cohort, elevated ALT after >1 year of HAART was uncommon, and severe ALT elevations were rare. HIV-HBV co-infected patients on long-term HAART who are either HBeAg positive or have a CD4 count of <200 cells/ml are at increased risk for ALT elevations.
Assuntos
Alanina Transaminase/sangue , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , HIV/fisiologia , Vírus da Hepatite B/fisiologia , Hepatite B/sangue , Hepatite B/tratamento farmacológico , Adulto , Terapia Antirretroviral de Alta Atividade , DNA Viral/genética , Feminino , Infecções por HIV/virologia , Hepatite B/virologia , Antígenos E da Hepatite B/metabolismo , Humanos , Estudos Longitudinais , Masculino , Reação em Cadeia da Polimerase , Prognóstico , Estudos Prospectivos , RNA Viral/genética , Carga ViralRESUMO
Gene transfer has potential as a once-only treatment that reduces viral load, preserves the immune system and avoids lifetime highly active antiretroviral therapy. This study, which is to our knowledge the first randomized, double-blind, placebo-controlled, phase 2 cell-delivered gene transfer clinical trial, was conducted in 74 HIV-1-infected adults who received a tat-vpr-specific anti-HIV ribozyme (OZ1) or placebo delivered in autologous CD34+ hematopoietic progenitor cells. There were no OZ1-related adverse events. There was no statistically significant difference in viral load between the OZ1 and placebo group at the primary end point (average at weeks 47 and 48), but time-weighted areas under the curve from weeks 40-48 and 40-100 were significantly lower in the OZ1 group. Throughout the 100 weeks, CD4+ lymphocyte counts were higher in the OZ1 group. This study indicates that cell-delivered gene transfer is safe and biologically active in individuals with HIV and can be developed as a conventional therapeutic product.
Assuntos
Antígenos CD34/imunologia , Terapia Genética , Infecções por HIV/terapia , HIV-1/genética , RNA Catalítico/genética , Adulto , Sequência de Bases , Método Duplo-Cego , Feminino , HIV-1/isolamento & purificação , Humanos , Masculino , Placebos , RNA Catalítico/uso terapêutico , Carga ViralRESUMO
In human recurrent cutaneous herpes simplex, there is a sequential infiltrate of CD4 and then CD8 lymphocytes into lesions. CD4 lymphocytes are the major producers of the key cytokine IFN-gamma in lesions. They recognize mainly structural proteins and especially glycoproteins D and B (gD and gB) when restimulated in vitro. Recent human vaccine trials using recombinant gD showed partial protection of HSV seronegative women against genital herpes disease and also, in placebo recipients, showed protection by prior HSV1 infection. In this study, we have defined immunodominant peptide epitopes recognized by 8 HSV1(+) and/or 16 HSV2(+) patients using (51)Cr-release cytotoxicity and IFN-gamma ELISPOT assays. Using a set of 39 overlapping 20-mer peptides, more than six immunodominant epitopes were defined in gD2 (two to six peptide epitopes were recognized for each subject). Further fine mapping of these responses for 4 of the 20-mers, using a panel of 9 internal 12-mers for each 20-mers, combined with MHC II typing and also direct in vitro binding assay of these peptides to individual DR molecules, showed more than one epitope per 20-mers and promiscuous binding of individual 20-mers and 12-mers to multiple DR types. All four 20-mer peptides were cross-recognized by both HSV1(+)/HSV2(-) and HSV1(-)/HSV2(+) subjects, but the sites of recognition differed within the 20-mers where their sequences were divergent. This work provides a basis for CD4 lymphocyte cross-recognition of gD2 and possibly cross-protection observed in previous clinical studies and in vaccine trials.
Assuntos
Apresentação de Antígeno/imunologia , Linfócitos T CD4-Positivos/imunologia , Herpes Genital/imunologia , Herpesvirus Humano 1/imunologia , Herpesvirus Humano 2/imunologia , Epitopos Imunodominantes/metabolismo , Proteínas do Envelope Viral/imunologia , Adolescente , Sequência de Aminoácidos , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/virologia , Linhagem Celular Transformada , Células Clonais , Técnicas de Cocultura , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito T/metabolismo , Feminino , Antígenos HLA-DR/imunologia , Antígenos HLA-DR/metabolismo , Cadeias HLA-DRB1 , Cadeias HLA-DRB3 , Herpes Genital/epidemiologia , Herpes Genital/prevenção & controle , Herpesvirus Humano 1/metabolismo , Herpesvirus Humano 2/metabolismo , Humanos , Epitopos Imunodominantes/imunologia , Dados de Sequência Molecular , Ligação Proteica/imunologia , Estomatite Herpética/imunologia , Estomatite Herpética/prevenção & controle , Proteínas do Envelope Viral/metabolismoRESUMO
We recently found that human immunodeficiency virus (HIV)-specific CD4+ T cells express coreceptor CCR5 and activation antigen CD38 during early primary HIV-1 infection (PHI) but then rapidly disappear from the circulation. This cell loss may be due to susceptibility to infection with HIV-1 but could also be due to inappropriate apoptosis, an expansion of T regulatory cells, trafficking out of the circulation, or dysfunction. We purified CD38+++CD4+ T cells from peripheral blood mononuclear cells, measured their level of HIV-1 DNA by PCR, and found that about 10% of this population was infected. However, a small subset of HIV-specific CD4+) T cells also expressed CD127, a marker of long-term memory cells. Purified CD127+CD4+ lymphocytes contained fivefold more copies of HIV-1 DNA per cell than did CD127-negative CD4+ cells, suggesting preferential infection of long-term memory cells. We observed no apoptosis of antigen-specific CD4+ T cells in vitro and only a small increase in CD45RO+CD25+CD127dimCD4+ T regulatory cells during PHI. However, 40% of CCR5+CD38+++ CD4+ T cells expressed gut-homing integrins, suggesting trafficking through gut-associated lymphoid tissue (GALT). Furthermore, 80% of HIV-specific CD4+ T cells expressed high levels of the negative regulator CTLA-4 in response to antigen stimulation in vitro, which was probably contributing to their inability to produce interleukin-2 and proliferate. Taken together, the loss of HIV-specific CD4+ T cells is associated with a combination of an infection of CCR5+ CD127+ memory CD4+ T cells, possibly in GALT, and a high expression of the inhibitory receptor CTLA-4.
Assuntos
Antígenos de Diferenciação/biossíntese , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Infecções por HIV/imunologia , HIV-1/imunologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/virologia , ADP-Ribosil Ciclase 1/análise , Adulto , Antígenos CD , Antígeno CTLA-4 , DNA Viral/análise , DNA Viral/genética , Citometria de Fluxo , HIV-1/genética , HIV-1/fisiologia , Humanos , Antígenos Comuns de Leucócito/análise , Masculino , Reação em Cadeia da Polimerase , Proteína Tirosina Fosfatase não Receptora Tipo 1 , Receptores CCR5/análise , Receptores de Interleucina-2/análise , Receptores de Interleucina-7/análise , Linfócitos T Reguladores/imunologiaRESUMO
BACKGROUND: Structured treatment interruptions (STIs) have been postulated to improve virologic control in primary HIV infection (PHI) by stimulating HIV-specific T-lymphocyte immunity. The addition of hydroxyurea (HU) may reduce viral production from activated CD4 cells. METHODS: Patients with PHI received a standardized antiretroviral (ARV) regimen consisting of indinavir 800 mg twice daily (BID), ritonavir 100 mg BID, didanosine 400 mg (QD), and either stavudine 40 mg BID or lamivudine 150 mg BID, for up to 12 months and were randomized to HU 500 mg BID or not. If viral suppression (<50 copies/mL) was achieved, up to 3 STIs were undertaken. Two ARV cycles were allowed after each interruption if virologic rebound to more than 5000 RNA copies/mL occurred. Treatment success was defined as maintaining viral loads below 5000 copies/mL for 6 months after ARV interruption. RESULTS: Sixty-eight male homosexual patients were randomized: 35 to ARV + HU and 33 to ARV-alone. Median baseline HIV RNA was 5.73 log10 copies/mL, and median CD4 T-lymphocyte count was 517 cells/microL. Treatment success was not significantly different between those receiving and not receiving HU, with 9 (26%) and 9 (27%), respectively, maintaining viral load at less than 5000 copies/mL in each group (P = 0.88). Virologic control was achieved by 11 (19%) of 59 after 1 STI, 1 (2%) of 41 after 2 STIs, and 6 (17%) of 36 after the third STI. Serious adverse events were recorded for 9 (26%) of 35 of patients using HU and 3 (9%) of 33 in the ARV-only group (P = 0.28). CD4 cell increases were significantly blunted for the HU group compared to the ARV-alone group after the initial treatment phase (+101 cells vs. +196 cells, respectively, P = 0.006). CONCLUSIONS: Hydroxyurea was not found to be beneficial when used in association with STIs in patients during PHI.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Hidroxiureia/uso terapêutico , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/farmacologia , Contagem de Linfócito CD4 , Esquema de Medicação , Quimioterapia Combinada , HIV/efeitos dos fármacos , Homossexualidade , Humanos , Hidroxiureia/administração & dosagem , Hidroxiureia/efeitos adversos , Hidroxiureia/farmacologia , Masculino , RNA Viral/sangue , Resultado do Tratamento , Carga ViralRESUMO
A 54-year-old HIV-positive homosexual man presented with erythematous and pigmented plaques on background erythema in the perianal region, histologically consistent with Bowen's disease. Perianal Bowen's disease represents high-grade anal intraepithelial neoplasia, which is considered a precursor lesion of invasive anal squamous cell carcinoma. This patient's anal intraepithelial neoplasia was unresponsive to multiple treatment modalities including cryotherapy, serial curettage and cautery, topical 5-fluorouracil and 5-aminolaevulinic acid photodynamic therapy. He progressed to develop a poorly differentiated squamous cell carcinoma of the anus three and a half years after the Bowen's disease was diagnosed. The squamous cell carcinoma was treated with combined chemoradiation. A recurrence of high-grade anal intraepithelial neoplasia was noted 6 months after completion of chemoradiation.
Assuntos
Doença de Bowen/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Infecções por HIV , Recidiva Local de Neoplasia/diagnóstico , Neoplasias Cutâneas/diagnóstico , Canal Anal , Doença de Bowen/complicações , Doença de Bowen/patologia , Doença de Bowen/terapia , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Terapia Combinada , Diagnóstico Diferencial , Homossexualidade Masculina , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/complicações , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapiaRESUMO
We investigated whether HIV-1 antigen-specific CD4(+) T cells expressed the viral coreceptor CCR5 during primary HIV-1 infection (PHI). In the peripheral blood of subjects with very early PHI (< 22 days after onset of symptoms), there was a 10- to 20-fold increase in the proportion of highly activated (CD38(+++)) and proliferating (Ki-67(+)) CD4(+) T cells that expressed CCR5(+), and were mostly T-cell intracellular antigen-1 (TIA-1)(+) perforin(+) granzyme B(+). Inthe same patient samples, CD4(+) T cells producing interferon (IFN)-gamma in response to HIV group-specific antigen (Gag) peptides were readily detected (median, 0.58%) by intracellular cytokine assay-these cells were again predominantly CD38(+++), Ki-67(+), and TIA-(++), as well as Bcl-2(low). On average, 20% of the Gag-specific CD4(+) T cells also expressed interleukin-2 (IL-2) and were CD127 (IL-7R)(+). Taken together, these results suggest that Gag-specific T-helper 1 (Th1) effector cells express CCR5 during the primary response and may include precursors of long-term self-renewing memory cells. However, in PHI subjects with later presentation, antigen-specific CD4(+) T cells could not be readily detected (median, 0.08%), coinciding with a 5-fold lower level of the CCR5(+)CD38(+++) CD4(+) T cells. These results suggest that the antiviral response to HIV-1 infection includes highly activated CCR5(+)CD4(+) cytotoxic effector cells, which are susceptible to both apoptosis and cytopathic infection with HIV-1, and rapidly decline.