RESUMO
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) lower atherosclerotic cardiovascular disease (ASCVD) event risk. OBJECTIVE: Analyze patient characteristics associated with time to PCSK9i initiation following an acute myocardial infarction (AMI). METHODS: We analyzed characteristics of patients ≥21 years of age in the Marketscan or Medicare databases who initiated a PCSK9i 0-89 days, 90-179 days, or 180-365 days after an AMI between July 2015 and December 2018 (n=1,705). We estimated the cumulative incidence of recurrent ASCVD events before PCSK9i initiation. RESULTS: Overall, 42%, 25%, and 33% of patients who initiated a PCSK9i did so 0-89 days, 90-179 days, and 180-365 days following AMI hospital discharge, respectively. Taking ezetimibe prior to AMI hospitalization and initiating ezetimibe within 30 days after AMI hospital discharge were each associated with a higher likelihood of PCSK9i initiation in the 0-89 days versus 180-365 days post-discharge (adjusted odds ratio [OR] 1.83, 95% confidence interval [95%CI] 1.35-2.49 and 1.76, 95%CI 1.11-2.80, respectively). Statin use before and statin initiation within 30 days after AMI hospitalization were associated with a lower likelihood of PCSK9i initiation 0-89 days versus 180-365 days post-discharge (adjusted OR 0.64, 95%CI 0.49-0.84 and 0.39, 95%CI 0.28-0.54, respectively). Overall, 8.0%, 10.5%, and 12.5% of patients had an ASCVD event at 90, 180, and 365 days following AMI hospital discharge and before initiating a PCSK9i, respectively. CONCLUSION: Among patients initiating a PCSK9i after AMI, a low proportion did so within 89 days of hospital discharge. Many patients had a recurrent ASCVD event before treatment initiation.
Assuntos
Anticolesterolemiantes , Aterosclerose , Inibidores de Hidroximetilglutaril-CoA Redutases , Infarto do Miocárdio , Assistência ao Convalescente , Idoso , Anticolesterolemiantes/efeitos adversos , Ezetimiba , Hospitais , Humanos , Medicare , Infarto do Miocárdio/tratamento farmacológico , Inibidores de PCSK9 , Alta do Paciente , Pró-Proteína Convertase 9 , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Herpes simplex virus type 2 (HSV-2) infection increases acquisition and transmission of HIV, but the results of trials measuring the impact of HSV-2 therapy on HIV genital shedding and HIV acquisition are mixed, and the potential impact of HSV-2 therapy on the incidence of HIV at the population level is unknown. METHODS: The effects of episodic and suppressive HSV-2 therapy were simulated using the individual-level model STDSIM fitted to data from Cotonou, Benin (relatively low HIV prevalence) and Kisumu, Kenya (high HIV prevalence). Clinician- and patient-initiated episodic therapy, started when symptomatic, were assumed to reduce ulcer duration. Suppressive therapy, given regardless of symptoms, was also assumed to reduce ulcer frequency and HSV-2 infectiousness. RESULTS: Clinician-initiated episodic therapy in the general population had almost no effect on the incidence of HIV. The impact of patient-initiated therapy was higher because of earlier treatment initiation, but still low (<5%) unless symptom recognition and treatment-seeking behaviour were very high. Suppressive therapy given to female sex workers (FSW) in Kisumu had little effect on population HIV incidence. In Cotonou, suppressive therapy in FSW with high coverage and long duration reduced population HIV incidence by >20% in the long term. Impact was increased in both cities by also treating a proportion of their clients. Long-term suppressive therapy with high coverage in the general population could reduce HIV incidence by more than 30%. CONCLUSIONS: These results show that HSV-2 therapy could potentially have a population-level impact on the incidence of HIV, especially in more concentrated epidemics. However, a substantial impact requires high coverage and long duration therapy, or very high symptom recognition and treatment-seeking behaviour.
Assuntos
Infecções por HIV/epidemiologia , HIV-1 , Herpes Genital/tratamento farmacológico , Herpes Genital/epidemiologia , Herpesvirus Humano 2 , Adolescente , Adulto , África Subsaariana/epidemiologia , Distribuição por Idade , Feminino , Infecções por HIV/complicações , Infecções por HIV/prevenção & controle , Herpes Genital/complicações , Humanos , Incidência , Masculino , PrevalênciaRESUMO
Community-randomized trials in Mwanza, Tanzania, and Rakai and Masaka, Uganda, suggested that population characteristics were an important determinant of the impact of sexually transmitted infection (STI) treatment interventions on incidence of human immunodeficiency virus (HIV) infection. We performed simulation modeling of HIV and STI transmission, which confirmed that the low trial impact in Rakai and Masaka could be explained by low prevalences of curable STI resulting from lower-risk sexual behavior in Uganda. The mature HIV epidemics in Uganda, with most HIV transmission occurring outside core groups with high STI rates, also contributed to the low impact on HIV incidence. Simulated impact on HIV was much greater in Mwanza, although the observed impact was larger than predicted from STI reductions, suggesting that random error also may have played some role. Of proposed alternative explanations, increasing herpetic ulceration due to HIV-related immunosuppression contributed little to the diminishing impact of antibiotic treatment during the Ugandan epidemics. The strategy of STI treatment also was unimportant, since syndromic treatment and annual mass treatment showed similar effectiveness in simulations of each trial population. In conclusion, lower-risk behavior and the mature HIV epidemic explain the limited impact of STI treatment on HIV incidence in Uganda in the 1990s. In populations with high-risk sexual behavior and high STI rates, STIs treatment interventions may contribute substantially to prevention of HIV infection.
Assuntos
Infecções por HIV/prevenção & controle , Infecções Sexualmente Transmissíveis/tratamento farmacológico , Infecções Sexualmente Transmissíveis/epidemiologia , Adolescente , Adulto , Feminino , Gonorreia/tratamento farmacológico , Gonorreia/epidemiologia , Gonorreia/prevenção & controle , Infecções por HIV/epidemiologia , Herpes Genital/tratamento farmacológico , Herpes Genital/epidemiologia , Herpes Genital/prevenção & controle , Humanos , Masculino , Prevalência , Assunção de Riscos , Comportamento Sexual , Infecções Sexualmente Transmissíveis/prevenção & controle , Síndrome , Tanzânia/epidemiologia , Resultado do Tratamento , Uganda/epidemiologiaRESUMO
OBJECTIVES: To assess bias in estimates of STD prevalence in population based surveys resulting from diagnostic error and selection bias. To evaluate the effects of such biases on STD prevalence estimates from three community randomised trials of STD treatment for HIV prevention in Masaka and Rakai, Uganda and Mwanza, Tanzania. METHODS: Age and sex stratified prevalences of gonorrhoea, chlamydia, syphilis, HSV-2 infection, and trichomoniasis observed at baseline in the three trials were adjusted for sensitivity and specificity of diagnostic tests and for sample selection criteria. RESULTS: STD prevalences were underestimated in all three populations because of diagnostic errors and selection bias. After adjustment, gonorrhoea prevalence was higher in men and women in Mwanza (2.8% and 2.3%) compared to Rakai (1.1% and 1.9%) and Masaka (0.9% and 1.8%). Chlamydia prevalence was higher in women in Mwanza (13.0%) compared to Rakai (3.2%) and Masaka (1.6%) but similar in men (2.3% in Mwanza, 2.7% in Rakai, and 2.2% in Masaka). Prevalence of trichomoniasis was higher in women in Mwanza compared to women in Rakai (41.9% versus 30.8%). Herpes simplex virus type 2 (HSV-2) seroprevalence and prevalence of serological syphilis (TPHA+/RPR+) were similar in the three populations but the prevalence of high titre syphilis (TPHA+/RPR >/=1:8) in men and women was higher in Mwanza (5.6% and 6.3%) than in Rakai (2.3% and 1.4%) and Masaka (1.2% and 0.7%). CONCLUSIONS: Limited sensitivity of diagnostic and screening tests led to underestimation of STD prevalence in all three trials but especially in Mwanza. Adjusted prevalences of curable STD were higher in Mwanza than in Rakai and Masaka.
Assuntos
Infecções Sexualmente Transmissíveis/epidemiologia , Erros de Diagnóstico , Feminino , Humanos , Masculino , Prevalência , Ensaios Clínicos Controlados Aleatórios como Assunto , Viés de Seleção , Tanzânia/epidemiologiaRESUMO
OBJECTIVES: To compare the proportion of HIV seroconversions attributable to other sexually transmitted diseases in the intervention and comparison arms of the Mwanza sexually transmitted diseases (STD) intervention trial. DESIGN: Case-control study of 96 cases of HIV seroconversion and 974 HIV-negative controls, nested within the Mwanza trial cohort. METHODS: Data on reported STD symptoms during 2 years of follow-up, and serological evidence of recent syphilis, were used to obtain odds ratios (ORs) for HIV seroconversion, adjusted for community, age, marital status, sex partners and travel. Population-attributable fractions (PAF) of HIV seroconversions associated with these STD exposures were calculated separately for the intervention and comparison arms, and for men and women. RESULTS: In men in the comparison arm, adjusted ORs for ulcers (14.8), discharge (3.3), any symptom (4.1) and any STD (4.0) were highly significant. There were no significant associations between HIV incidence and STD exposures in the intervention arm. The PAF were consistently higher in the comparison arm than the intervention arm. In men, the PAF for any STD was 39.6% [95% confidence interval (CI), 12.4-58.3)] in the comparison arm but only 12.0% (CI, 0.0-35.9) in the intervention arm. The PAF for women were lower than for men. CONCLUSIONS: These are minimal PAF estimates and they do not account for STD effects on HIV infectiousness. Nevertheless, a substantial proportion of new HIV infections in men in the comparison arm were attributable to STD. Lower PAF in the intervention arm than in the comparison arm for men provide further evidence of the role of STD cofactors in HIV transmission, supporting the hypothesis that the Mwanza intervention reduced the duration of symptomatic STD, thus reducing the HIV risk associated with such STD.