RESUMO
OBJECTIVES: Adherence is critical for maximizing the effectiveness of pre-exposure prophylaxis (PrEP) in preventing HIV infection. Strategies for promoting adherence to HIV treatment, and their potential application to PrEP adherence, have received considerable attention. However, adherence promotion strategies for prevention medications have not been well characterized and may be more applicable to PrEP. We aimed to identify adherence support interventions that have been effective in other prevention fields and could be applied in the HIV prevention context to support pill taking among PrEP users. METHODS: To identify adherence support interventions that could be evaluated and applied in the PrEP context, we conducted a systematic review across the following prevention fields: hypertension, latent tuberculosis infection, hyperlipidaemia, oral contraceptives, osteoporosis, malaria prophylaxis, and post-exposure prophylaxis for HIV infection. We included randomized controlled trials that evaluated the efficacy of interventions to improve adherence to daily oral medications prescribed for primary prevention in healthy individuals or for secondary prevention in asymptomatic individuals. RESULTS: Our searches identified 585 studies, of which 48 studies met the eligibility criteria and were included in the review; nine evaluated multiple strategies, yielding 64 separately tested interventions. Interventions with the strongest evidence for improving adherence included complex, resource-intensive interventions, which combined multiple adherence support approaches, and low-cost, low-intensity interventions that provided education or telephone calls for adherence support. CONCLUSIONS: Our review identified adherence interventions with strong evidence of efficacy across prevention fields and provides recommendations for evaluating these interventions in upcoming PrEP studies.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/prevenção & controle , Adesão à Medicação , Prevenção Primária , Promoção da Saúde/métodos , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
We measured CD8(+) T-cell responses in 12 potentially exposed but uninfected men who have sex with men by using cytokine flow cytometry. Four of the individuals screened exhibited polyfunctional immune responses to human immunodeficiency virus type 1 Gag or Vif. The minimum cytotoxic T lymphocyte epitope was mapped in one Gag responder.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Epitopos de Linfócito T/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Citocinas/biossíntese , Mapeamento de Epitopos , Homossexualidade Masculina , Humanos , Masculino , Produtos do Gene gag do Vírus da Imunodeficiência Humana/imunologia , Produtos do Gene vif do Vírus da Imunodeficiência Humana/imunologiaRESUMO
BACKGROUND: Studies relating certain chemokine and chemokine receptor gene alleles with the outcome of HIV-1 infection have yielded inconsistent results. OBJECTIVE: To examine postulated associations of genetic alleles with HIV-1 disease progression. DESIGN: Meta-analysis of individual-patient data. SETTING: 19 prospective cohort studies and case-control studies from the United States, Europe, and Australia. PATIENTS: Patients with HIV-1 infection who were of European or African descent. MEASUREMENTS: Time to AIDS, death, and death after AIDS and HIV-1 RNA level at study entry or soon after seroconversion. Data were combined with fixed-effects and random-effects models. RESULTS: Both the CCR5-Delta32 and CCR2-64I alleles were associated with a decreased risk for progression to AIDS (relative hazard among seroconverters, 0.74 and 0.76, respectively; P = 0.01 for both), a decreased risk for death (relative hazard among seroconverters, 0.64 and 0.74; P < 0.05 for both), and lower HIV-1 RNA levels after seroconversion (difference, -0.18 log(10) copies/mL and -0.14 log(10) copies/mL; P < 0.05 for both). Having the CCR5-Delta32 or CCR2-64I allele had no clear protective effect on the risk for death after development of AIDS. The results were consistent between seroconverters and seroprevalent patients. In contrast, SDF-1 3'A homozygotes showed no decreased risk for AIDS (relative hazard for seroconverters and seroprevalent patients, 0.99 and 1.03, respectively), death (relative hazard, 0.97 and 1.00), or death after development of AIDS (relative hazard, 0.81 and 0.97; P > 0.5 for all). CONCLUSIONS: The CCR5-Delta32 and CCR2-64I alleles had a strong protective effect on progression of HIV-1 infection, but SDF-1 3'A homozygosity carried no such protection.
Assuntos
Quimiocinas CXC/genética , Infecções por HIV/genética , HIV-1 , Receptores CCR5/genética , Receptores de Quimiocinas/genética , Síndrome da Imunodeficiência Adquirida/genética , Síndrome da Imunodeficiência Adquirida/mortalidade , Alelos , Quimiocina CXCL12 , Progressão da Doença , HIV-1/genética , Heterozigoto , Humanos , Modelos de Riscos Proporcionais , RNA/metabolismo , Receptores CCR2 , Análise de RegressãoRESUMO
To evaluate cofactors for progression of HIV infection, the authors identified 370 men with well-defined seroconversion dates and cofactor data among participants in the San Francisco City Clinic Cohort (SFCCC). Postseroconversion substance use, sexual behavior, and sexually transmitted diseases were assessed using multivariate proportional hazards models. Weekly use of hallucinogens strongly and independently predicted death (relative hazard [RH], 2.59; 95% confidence interval [CI], 1.56-4.28), as well as diagnosis of AIDS; weekly cocaine use also predicted mortality. Receptive anal intercourse with ejaculation was independently associated with mortality risk (RH, 1.45; 95% CI, 1.02-2.04) and AIDS. The associations of accelerated progression with weekly use of recreational drugs and unprotected receptive anal intercourse need to be confirmed in other prospective cohorts.
Assuntos
Bissexualidade , Infecções por HIV/mortalidade , Homossexualidade Masculina , Infecções Sexualmente Transmissíveis/complicações , Transtornos Relacionados ao Uso de Substâncias/complicações , Adulto , Estudos de Coortes , Progressão da Doença , Infecções por HIV/complicações , Soropositividade para HIV/complicações , Soropositividade para HIV/diagnóstico , Soropositividade para HIV/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Comportamento Sexual , Infecções Sexualmente Transmissíveis/mortalidade , Transtornos Relacionados ao Uso de Substâncias/mortalidadeRESUMO
Cytotoxic T lymphocytes (CTL) target multiple epitopes in human immunodeficiency virus (HIV)-infected persons, and are thought to influence the viral set point. The extent to which HLA class I allele expression predicts the epitopes targeted has not been determined, nor have the relative contributions of responses restricted by different class I alleles within a given individual. In this study, we performed a detailed analysis of the CTL response to optimally defined CTL epitopes restricted by HLA class I A and B alleles in individuals who coexpressed HLA A2, A3, and B7. The eight HIV-1-infected subjects studied included two subjects with acute HIV infection, five subjects with chronic HIV infection, and one long-term nonprogressor. Responses were heterogeneous with respect to breadth and magnitude of CTL responses in individuals of the same HLA type. Of the 27 tested epitopes that are presented by A2, A3, and B7, 25 were targeted by at least one person. However, there was wide variation in the number of epitopes targeted, ranging from 2 to 17. The A2-restricted CTL response, which has been most extensively studied in infected persons, was found to be narrowly directed in most individuals, and in no cases was it the dominant contributor to the total HIV-1-specific CTL response. These results indicate that HLA type alone does not predict CTL responses and that numerous potential epitopes may not be targeted by CTL in a given individual. These data also provide a rationale for boosting both the breadth and the magnitude of HIV-1-specific CTL responses by immunotherapy in persons with chronic HIV-1 infection.
Assuntos
Epitopos de Linfócito T/imunologia , Infecções por HIV/imunologia , HIV-1 , Antígenos de Histocompatibilidade Classe I/imunologia , Linfócitos T Citotóxicos/imunologia , Alelos , Doença Crônica , Epitopos de Linfócito T/genética , Infecções por HIV/virologia , Antígeno HLA-A1/análise , Antígeno HLA-A2/análise , Antígeno HLA-B7/análise , HumanosRESUMO
Questions exist about whether testing of preventive human immunodeficiency virus (HIV)-1 vaccines, which will require rapid recruitment and retention of cohorts with high HIV-1 seroincidence, is feasible in the United States. A prospective cohort study was conducted in 1995-1997 among 4,892 persons at high risk for HIV infection in nine US cities. At 18 months, with an 88% retention rate, 90 incident HIV-1 infections were observed (1.31/100 person-years (PY), 95% confidence interval (CI): 1.06, 1.61). HIV-1 seroincidence rates varied significantly by baseline eligibility criteria--1.55/100 PY among men who had sex with men, 0.38/100 PY among male intravenous drug users, 1.24/100 PY among female intravenous drug users, and 1.13/100 PY among women at heterosexual risk-and by enrollment site, from 0.48/100 PY to 2.18/100 PY. HIV-1 incidence was highest among those men who had sex with men who reported unprotected anal intercourse (2.01/100 PY, 95% CI: 1.54, 2.63), participants who were definitely willing to enroll in an HIV vaccine trial (1.96/100 PY, 95% CI: 1.41, 2.73), and women who used crack cocaine (1.62/100 PY, 95% CI: 0.92, 2.85). Therefore, cohorts with HIV-1 seroincidence rates appropriate for HIV-1 vaccine trials can be recruited, enrolled, and retained.
Assuntos
Vacinas contra a AIDS/administração & dosagem , Ensaios Clínicos como Assunto/estatística & dados numéricos , Surtos de Doenças/prevenção & controle , Infecções por HIV/epidemiologia , Seleção de Pacientes , Síndrome da Imunodeficiência Adquirida/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Estudos de Coortes , Intervalos de Confiança , Projetos de Pesquisa Epidemiológica , Estudos de Viabilidade , Feminino , Soropositividade para HIV , Humanos , Incidência , Masculino , Estudos Prospectivos , Análise de Regressão , Fatores de Risco , Distribuição por Sexo , Estados Unidos/epidemiologiaRESUMO
We longitudinally measured T-cell receptor transcript frequencies of human immunodeficiency virus type 1 (HIV-1) specific cytotoxic T lymphocytes (CTL) in an individual with rapidly progressive disease and high levels of viremia. CTL clones elicited during acute HIV-1 infection were present at the time of death, despite absent functional CTL responses, arguing against clonal deletion as a mechanism for the decline of CTL responses observed during HIV-1 infection.
Assuntos
Infecções por HIV/imunologia , HIV-1/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Linfócitos T Citotóxicos/imunologia , Doença Crônica , Células Clonais , Progressão da Doença , Infecções por HIV/sangue , Infecções por HIV/virologia , Humanos , Estudos Longitudinais , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Fatores de TempoRESUMO
Risk behaviors, symptoms, and virologic characteristics were studied among 103 human immunodeficiency virus (HIV) seroconverters in vaccine preparedness cohorts during 1995-1998. Overall, 83% of subjects were men who had sex with men; most reported multiple risk episodes and symptoms (84%, > or =1 symptom) during seroconversion. Acute HIV was diagnosed in only 8 of 50 who sought medical care. Median initial pretreatment plasma virus load was 25,800 copies/mL (range, undetectable-262,000 copies/mL) a mean of 4 months after seroconversion, and 9.7% had nucleoside-associated mutations; none had multidrug resistance. Semen virus load was more variable, 1.3 log(10) lower and modestly correlated (r=.28; 95% confidence interval, 0.16-0.42) with plasma among untreated men. When the plasma RNA level was <5000 copies/mL, 32% of untreated men, 13% on nucleoside regimens, and 7% on protease inhibitor-containing regimens had detectable seminal RNA. Acute HIV was seldom diagnosed, representing missed opportunities for early treatment and prevention. Most subjects had several relatively stable virus loads before initiation of antiretrovirals, indicating feasibility of assessing HIV vaccines on virus set point in efficacy trials.
Assuntos
Infecções por HIV/virologia , HIV-1 , Sêmen/virologia , Infecções Sexualmente Transmissíveis/virologia , Doença Aguda , Adulto , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Colo do Útero/virologia , Estudos de Coortes , Demografia , Quimioterapia Combinada , Feminino , Infecções por HIV/sangue , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Soropositividade para HIV/sangue , Soropositividade para HIV/tratamento farmacológico , Soropositividade para HIV/virologia , HIV-1/isolamento & purificação , Homossexualidade Masculina , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , RNA Viral/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco , Comportamento Sexual , Infecções Sexualmente Transmissíveis/sangue , Infecções Sexualmente Transmissíveis/epidemiologia , Fatores de Tempo , Carga ViralRESUMO
Administration of antiretroviral medications-recommended to prevent HIV infection after occupational exposure-has not been evaluated for safety or efficacy following nonoccupational exposure. HIV-seronegative persons at increased risk for HIV exposure completed a self-administered questionnaire assessing their willingness to join studies of this approach. Of 4,572 respondents, 60% were willing to join a study of a "morning-after" pill; dosing three times a day and mild side effects reduced willingness to 30%. Men who have sex with men (MSM) who reported unprotected anal intercourse in the prior 6 months were significantly more likely to be willing to join a morning-after study than MSM who did not (p = 0.006). MSM favored a preventive HIV vaccine over oral chemoprophylaxis; other populations preferred oral chemoprophylaxis. Interest in studies declined as the hypothetical regimen became more demanding. Studies must emphasize the unknown efficacy of this approach, given increased interest among MSM at greater risk of exposure.
Assuntos
Vacinas contra a AIDS/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/prevenção & controle , Soronegatividade para HIV/efeitos dos fármacos , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Coleta de Dados , Estudos de Viabilidade , Feminino , Homossexualidade Masculina , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Assunção de RiscosRESUMO
OBJECTIVES: This study assessed use of Reality "female condoms" for anal sex by HIV-seronegative men who have sex with men and are at high risk for HIV infection. METHODS: Self-administered questionnaires were completed by 2277 participants in a 6-city prospective cohort study. RESULTS: Of the 1084 (48%) men who had heard of using the female condom for anal sex, 145 (13%) reported using it in the prior 6 months. Users were at greater risk than nonusers: 47 receptive and 35 insertive users reported problems, including bleeding by the receptive partner (4). CONCLUSIONS: Redesign of the female condom could increase acceptability and use by men who have sex with men and could address possible safety concerns.
Assuntos
Preservativos/estatística & dados numéricos , Comportamento Sexual/estatística & dados numéricos , Adulto , Desenho de Equipamento , Humanos , Masculino , Razão de Chances , Inquéritos e Questionários , Estados Unidos/epidemiologiaRESUMO
Information on long-term survival after infection with human immunodeficiency virus type 1 (HIV-1) is limited. In hepatitis B vaccine trials in Amsterdam, New York City, and San Francisco, 362 gay men were followed up to 18 years (1978-1995). The median survival time from seroconversion was 12.1 years (95% confidence interval: 11.4, 12.9). The annual risk of dying increased at a constant rate until 8 years after seroconversion and then leveled off, suggesting a group that is relatively resistant to progression. These data provide a picture of the natural history of HIV-1 infection, especially in the era prior to widespread use of highly effective treatments.
Assuntos
Infecções por HIV/mortalidade , Soropositividade para HIV , HIV-1 , Vacinas contra Hepatite B , Homossexualidade Masculina , Adulto , Estudos de Coortes , Vacinas contra Hepatite B/administração & dosagem , Humanos , Expectativa de Vida , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Medição de Risco , São Francisco/epidemiologia , Análise de SobrevidaRESUMO
We evaluated recent trends in the incidence of AIDS-related malignancies using Cox proportional hazards analysis in 622 men with well-characterized dates of HIV seroconversion in the San Francisco City Clinic cohort. By the end of 1996, 182 men had been diagnosed with Kaposi's sarcoma (KS), and 45 men had been diagnosed with lymphoma. The incidence of KS dropped from 3.5 to 0 per 100 person-years between 1993 through 1995 and 1996 (p = .07), whereas lymphoma incidence remained stable between these periods (1.4-1.8, p = .2). Combination antiretroviral therapy increased from 13% to 23% in 1993 through 1995 to 49% in 1996 and 79% in 1997. The decline in KS cannot be explained by earlier declines in HIV incidence, and concurrent increases in antiretroviral therapy suggests that control of viral replication may lead to a direct or indirect effect on KS pathogenesis. Failure to see such a trend for AIDS-related lymphoma may reflect inadequate follow-up time after widespread use of therapy or a need to treat earlier in the course of HIV infection to prevent HIV-associated lymphomagenesis.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Fármacos Anti-HIV , Linfoma/epidemiologia , Fármacos Anti-HIV/administração & dosagem , Neoplasias do Sistema Nervoso Central/epidemiologia , Quimioterapia Combinada , Humanos , Incidência , Linfoma Relacionado a AIDS/epidemiologia , Linfoma não Hodgkin/epidemiologia , Masculino , PrevalênciaRESUMO
The risk of human immunodeficiency virus (HIV) transmission from various types of homosexual contact, including oral sex, is of biologic, epidemiologic, and public health importance. The per-contact risk of acquiring HIV infection from specific acts was estimated in a prospective cohort study of 2,189 high-risk homosexual and bisexual men, conducted in San Francisco, California; Denver, Colorado; and Chicago, Illinois, in 1992-1994. During 2,633 person-years of follow-up, 60 seroconversions were observed. The estimated per-contact risk of acquiring HIV from unprotected receptive anal intercourse (URA) was 0.82 percent (95% confidence interval: 0.24, 2.76 percent) when the partner was known to be HIV+ and 0.27 percent (95% confidence interval: 0.06, 0.49 percent) when partners of unknown serostatus were included. There was heterogeneity in per-contact risk, with nine seroconversions occurring after only one or two episodes of URA. The per-contact risk associated with unprotected insertive anal and receptive oral sex with HIV-positive or unknown serostatus partners was 0.06 and 0.04 percent, respectively. URA accounted for only 15 percent of all reported sexual activity by seroconverters. As lower-risk practices become more common, they may play a larger role in propagating the epidemic and should also be addressed by interventions targeting high-risk homosexual and bisexual men.
Assuntos
Transmissão de Doença Infecciosa/estatística & dados numéricos , Infecções por HIV/transmissão , Homossexualidade Masculina/estatística & dados numéricos , Comportamento Sexual/estatística & dados numéricos , Estudos de Coortes , Preservativos/estatística & dados numéricos , Infecções por HIV/epidemiologia , Soropositividade para HIV , Soroprevalência de HIV , Humanos , Masculino , Fatores de Risco , Inquéritos e Questionários , Estados Unidos/epidemiologiaRESUMO
Cellular immune responses are thought to be an important antiviral host defense, but the relationship between virus-specific T-helper and cytotoxic-T-lymphocyte (CTL) responses has not been defined. To investigate a potential link between these responses, we examined functional human immunodeficiency virus type 1 (HIV-1)-specific memory CTL precursor frequencies and p24-specific proliferative responses in a cohort of infected untreated persons with a wide range of viral loads and CD4 cell counts. Levels of p24-specific proliferative responses positively correlated with levels of Gag-specific CTL precursors and negatively correlated with levels of plasma HIV-1 RNA. These data linking the levels of HIV-specific CTL with virus-specific helper cell function during chronic viral infection provide cellular immunologic parameters to guide therapeutic and prophylactic vaccine development.
Assuntos
Infecções por HIV/imunologia , HIV-1/imunologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Divisão Celular , Doença Crônica , Estudos de Coortes , Produtos do Gene gag/imunologia , Proteína do Núcleo p24 do HIV/imunologia , Infecções por HIV/virologia , Humanos , ViremiaRESUMO
Condom failure (slippage or breakage) has been shown to be associated with HIV seroconversion among men who have sex with men (MSM), but predictors of failure have been poorly elucidated. Of 2592 HIV-seronegative MSM participants in the HIV Network for Prevention Trials (HIVNET) multisite Vaccine Preparedness Study who reported condom use for anal sex in the 6 months before enrollment, condom failure was reported by 16.6%, with failure rates of 2.1/100 episodes of condom usage (2.5 failures/100 episodes for receptive anal sex and 1.9/100 episodes for insertive anal sex). In separate multivariate models evaluating predictors of condom failure reported by the insertive and receptive partners, more frequent condom use was associated with a decreased per-condom failure rate and amphetamine and heavy alcohol use with increased rates in both models. Being employed, having private medical insurance, and using lubricants for >80% of anal sex acts were significantly associated with decreased failure rates in the insertive model. Safer sex counseling should particularly target men of lower socioeconomic status, promote proper and consistent use of condoms with appropriate lubricants, and address the impact of drug use, especially amphetamines and alcohol, on condom failure.
PIP: Although the extent of condom use during anal intercourse has increased considerably among men who have sex with men (MSM) in response to the HIV/AIDS pandemic, condom failure through both slippage and breakage limits the effectiveness of such method use. Condom failure is associated with HIV seroconversion among MSM. 16.6% of the 2592 HIV-seronegative MSM participants in the HIV Network for Prevention Trials (HIVNET) multi-site Vaccine Preparedness Study who reported condom use for anal sex in the 6 months before enrollment reported condom failure. The overall failure rate was 2.1/100 episodes of condom use, with 2.5 failures/100 episodes for receptive anal sex and 1.9/100 episodes for insertive anal sex. Almost half of the men were aged 30 years or younger, 25% were non-White, 60.6% attended college, and 85.7% were employed either part- or full-time. Multivariate analysis of reported failures found more frequent condom use to be associated with a decreased per condom failure rate, and amphetamine and heavy alcohol use with increased rates in both models. Being employed, having private medical insurance, and using lubricants for more than 80% of anal sex acts were significantly associated with decreased failure rates in the insertive model. These findings suggest that safer sex counseling should therefore target men of lower socioeconomic status, promote the proper and consistent use of condoms with appropriate lubricants, and address the impact of drug use upon condom failure.
Assuntos
Preservativos , Homossexualidade Masculina , Adulto , Estudos de Coortes , Humanos , MasculinoRESUMO
Neutralization-escape variants of human immunodeficiency virus type 1 (HIV-1) were sought in persons who had persistent low virus loads and who remained asymptomatic for at least 12-16 years of infection without antiretroviral therapy. Viruses were isolated from 3 persons at two or three time points during the course of infection and were assessed for neutralization by sequential autologous serum samples. Virus neutralization was poor or undetectable with contemporaneous autologous serum but improved with later serum samples for each person. In particular, later isolates resisted neutralization by autologous serum samples that neutralized an earlier isolate. Strain-specific neutralizing antibodies remained detectable for up to 4.2 years without diminishing in titer. The results demonstrate that neutralization-escape variants arise periodically in HIV-1-infected long-term nonprogressors.
Assuntos
Anticorpos Anti-HIV/imunologia , Infecções por HIV/imunologia , Sobreviventes de Longo Prazo ao HIV , HIV-1/imunologia , HIV-1/isolamento & purificação , Infecções por HIV/virologia , Humanos , Testes de Neutralização , Carga ViralRESUMO
The reasons for recent declines in AIDS incidence and mortality may include advances in treatment, but these may be confounded by earlier declines in the incidence of human immunodeficiency virus (HIV) infection. To determine whether the declines in AIDS and mortality may, in part, stem from wider use of combination antiretroviral therapy, 622 HIV-positive men with well-characterized dates of seroconversion were followed. In this group, combination therapy came into widespread use in only 1996. In a Cox proportional hazards model, the 1996 calendar period was significantly associated with slower progression to AIDS (relative hazard [RH]=0. 19, 95% confidence interval [CI], 0.05-0.69, P=.01) and death (RH=0. 45, 95% CI, 0.21-0.95, P=.04). Declines in incidence of HIV infection, changes in HIV virulence, and end-point underreporting cannot fully explain the decline in AIDS and death in 1996. The introduction of combination antiretroviral therapy as the standard of care may already have had measurable effects.
Assuntos
Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/epidemiologia , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Síndrome da Imunodeficiência Adquirida/mortalidade , Intervalos de Confiança , Progressão da Doença , Quimioterapia Combinada , Infecções por HIV/mortalidade , Soropositividade para HIV/epidemiologia , Homossexualidade Masculina , Humanos , Incidência , Masculino , Modelos de Riscos Proporcionais , São Francisco/epidemiologiaRESUMO
The relationship between peripheral lymphocyte apoptosis and human immunodeficiency virus disease progression was studied in infected subgroups with distinct profiles of progression. Long-term nonprogressors (LTNP) and seronegative controls had levels of spontaneous apoptosis significantly lower than those for recent seroconverters who had CD4 cell counts similar to those of nonprogressors but with a high likelihood of disease progression. Lymphocytes from nonprogressors and seronegative controls also showed negligible spontaneous caspase-3 activity, a biochemical indicator for apoptosis, whereas early progressors exhibited substantial activity. In contrast, when activated with mitogens, the lymphocytes from both LTNP and progressors displayed indistinguishable levels of heightened apoptosis. Spontaneous apoptosis and plasma viremia levels correlated positively in progressors, but not in LTNP. These findings demonstrate that increased lymphocyte apoptosis is evident prior to CD4 T cell decline and that LTNP are relatively resistant to the factors that induce accentuated levels of spontaneous but not mitogen-induced cell death.
Assuntos
Apoptose , Caspases , Inibidores de Dissociação do Nucleotídeo Guanina , Infecções por HIV/imunologia , HIV-1 , Linfócitos/patologia , Caspase 3 , Células Cultivadas , Cisteína Endopeptidases/metabolismo , Progressão da Doença , Ativação Enzimática , Proteínas de Ligação ao GTP/metabolismo , Infecções por HIV/metabolismo , Infecções por HIV/virologia , HIV-1/genética , Humanos , Especificidade por Substrato , Sobreviventes , Fatores de Tempo , Carga Viral , Inibidores da Dissociação do Nucleotídeo Guanina rho-EspecíficoRESUMO
BACKGROUND AND OBJECTIVES: Incomplete condom use during anal sex persists among gay men; microbicides may provide additional protection. Despite the absence of efficacy or safety data, many gay men use sexual lubricants containing nonoxynol-9 (N-9), a detergent-based spermicide under evaluation for efficacy as a vaginal microbicide. GOAL: Evaluate unprotected sex, lubricant use, and attitudes regarding possible participation in clinical trials of rectal microbicides among high-risk human immunodeficiency virus-(HIV) seronegative U.S. gay men in six cities. STUDY DESIGN: A total of 3,257 gay men were interviewed and responded to a self-administered questionnaire at enrollment into a longitudinal cohort study of HIV seroincidence. RESULTS: Among 2,216 men who practiced receptive anal intercourse in the previous 6 months, 438 (20%) reported they never used condoms. More than three fourths of 3,093 men who had anal sex used lubricants more than 80% of the time. 41% of whom actively sought N-9 containing products. About two thirds said they were definitely or probably willing to participate in rectal microbicide clinical trials. CONCLUSION: Condom use is imperfect among men who report anal sex. N-9 lubricants are popular. Most gay men in this cohort indicate willingness to participate in rectal microbicide studies.
Assuntos
Anti-Infecciosos/uso terapêutico , Preservativos , Conhecimentos, Atitudes e Prática em Saúde , Homossexualidade Masculina , Nonoxinol/uso terapêutico , Adolescente , Adulto , Ensaios Clínicos como Assunto , Humanos , Estudos Longitudinais , Lubrificação , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Estados UnidosRESUMO
Despite detailed analysis of the HIV-1-specific cytotoxic T lymphocyte response by various groups, its relation to viral load and viral sequence variation remains controversial. We analyzed HLA-A*0201 restricted cytotoxic T lymphocyte responses in 17 HIV-1-infected individuals with viral loads ranging from < 400 to 221,000 HIV RNA molecules per milliliter of plasma. In 13 out of 17 infected subjects, CTL responses against the SLYNTVATL epitope (p17 Gag; aa 77-85) were detectable, whereas two other HLA-A*0201 restricted epitopes (ILKEPVHGV, IV9; and VIYQYMDDL, VL9) were only recognized by six and five individuals out of 17 individuals tested, respectively. Naturally occurring variants of the SL9 epitope were tested for binding to HLA-A*0201 and for recognition by specific T cell clones generated from five individuals. Although these variants were widely recognized, they differed by up to 10,000-fold in terms of variant peptide concentrations required for lysis of target cells. A comparison of viral sequences derived from 10 HLA-A*0201-positive individuals to sequences obtained from 11 HLA-A*0201-negative individuals demonstrated only weak evidence for immune selective pressure and thus question the in vivo efficacy of immunodominant CTL responses present during chronic HIV-1 infection.