RESUMO
BACKGROUND: Adherence and retention concerns raise questions about the effectiveness and cost-effectiveness of oral HIV pre-exposure prophylaxis (PrEP) in young men who have sex with men (YMSM). METHODS: Using an adolescent-focused simulation model, we compared annual HIV screening alone with tenofovir disoproxil fumarate/emtricitabine-based oral PrEP with every 3-month HIV screening in YMSM (aged 15-24) at increased risk of HIV. Data derived from published sources included: age-stratified HIV incidence/100 person-years (PY) on- or off-PrEP (0.6-10.1 or 0.4-6.4), PrEP retention at 6 years (28%), transmissions by HIV RNA level (0.0-78.4/100PY) and annual costs of antiretroviral therapy ($32 000-69 000), HIV care ($3100-34 600), and PrEP program/generic drug ($900/360). Outcomes included transmissions (percent of cohort infected), quality-adjusted life-years (QALYs), costs ($), and incremental cost-effectiveness ratios ($/QALY). We explored the sensitivity of findings to variation in HIV incidence and drug prices. RESULTS: Compared with annual screening alone, PrEP would increase QALYs (9.58 to 9.67), reduce new infections (37% to 30%), and decrease costs (by $5000) over 10 years. PrEP would remain cost-saving for HIV incidence off-PrEP ≥5.1/100PY or annual PrEP price ≤$1200. Over a lifetime horizon, PrEP would be cost-saving for HIV incidence off-PrEP ≥1.0/100PY, across all retention assumptions examined. PrEP would not be cost-effective at HIV incidence ≤0.1/100PY, regardless of drug price, due to programmatic costs. CONCLUSIONS: In US YMSM at increased risk of HIV, generic oral PrEP and every-3-month screening would be cost-saving compared with annual screening alone, even with high discontinuation and low adherence, over a range of HIV incidences.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Masculino , Adolescente , Humanos , Estados Unidos/epidemiologia , Homossexualidade Masculina , Fármacos Anti-HIV/uso terapêutico , Medicamentos Genéricos , Análise Custo-Benefício , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controleRESUMO
BACKGROUND: Men who have sex with men (MSM) are at high risk for human papillomavirus (HPV)-related anal cancer. Little is known about the prevalence of low-grade squamous intraepithelial lesions (LSILs) and the anal cancer precursor, high-grade squamous intraepithelial lesions (HSILs), among young MSM with HIV (MSMLWH). HPV vaccination is recommended in this group, but its safety, immunogenicity, and protection against vaccine-type HPV infection and associated LSILs/HSILs have not been studied. METHODS: Two hundred and sixty MSMLWH aged 18-26 years were screened at 17 US sites for a clinical trial of the quadrivalent (HPV6,11,16,18) HPV (qHPV) vaccine. Those without HSILs were vaccinated at 0, 2, and 6 months. Cytology, high-resolution anoscopy with biopsies of lesions, serology, and HPV testing of the mouth/penis/scrotum/anus/perianus were performed at screening/month 0 and months 7, 12, and 24. RESULTS: Among 260 MSMLWH screened, the most common reason for exclusion was detection of HSILs in 88/260 (34%). 144 MSMLWH were enrolled. 47% of enrollees were previously exposed to HPV16. No incident qHPV type-associated anal LSILs/HSILs were detected among men naive to that type, compared with 11.1, 2.2, 4.5, and 2.8 cases/100 person-years for HPV6,11,16,18-associated LSILs/HSILs, respectively, among those previously exposed to that type. qHPV was immunogenic and safe with no vaccine-associated serious adverse events. CONCLUSIONS: 18-26-year-old MSMLWH naive to qHPV vaccine types were protected against incident qHPV type-associated LSILs/HSILs. Given their high prevalence of HSILs, there is an urgent need to vaccinate young MSMLWH before exposure to vaccine HPV types, before initiating sexual activity, and to perform catch-up vaccination.
Assuntos
Alphapapillomavirus , Neoplasias do Ânus , Infecções por HIV , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Minorias Sexuais e de Gênero , Lesões Intraepiteliais Escamosas , Adolescente , Adulto , Canal Anal , Neoplasias do Ânus/epidemiologia , Neoplasias do Ânus/prevenção & controle , HIV , Infecções por HIV/complicações , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Humanos , Masculino , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Prevalência , Comportamento Sexual , Vacinação , Adulto JovemRESUMO
BACKGROUND: Of new HIV infections in the US, 20% occur among young men who have sex with men (YMSM, ages 13-24), but >50% of YMSM with HIV are unaware of their status. Using Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) data, we projected the clinical benefit and cost-effectiveness of frequent HIV screening among high-risk YMSM from age 15. METHODS: Using a mathematical simulation, we examined 3 screening strategies: Yearly, 6-monthly, and 3-monthly, each in addition to the Status quo (SQ, 0.7-10.3% screened/year, stratified by age). We used published data (YMSM-specific when available) including: HIV incidences (0.91-6.41/100PY); screen acceptance (80%), linkage-to-care/antiretroviral therapy (ART) initiation (76%), HIV transmission (0.3-86.1/100PY, by HIV RNA), monthly ART costs ($2290-$3780), and HIV per-screen costs ($38). Projected outcomes included CD4 count at diagnosis, primary HIV transmissions from ages 15-30, quality-adjusted life expectancy, costs, and incremental cost-effectiveness ratios (ICERs, $/quality-adjusted life-year saved [QALY]; threshold ≤$100 000/QALY). RESULTS: Compared to SQ, all strategies increased projected CD4 at diagnosis (296 to 477-515 cells/µL) and quality-adjusted life expectancy from age 15 (44.4 to 48.3-48.7 years) among YMSM acquiring HIV. Compared to SQ, all strategies increased discounted lifetime cost for the entire population ($170 800 to $178 100-$185 000/person). Screening 3-monthly was cost-effective (ICER: $4500/QALY) compared to SQ and reduced primary transmissions through age 30 by 40%. Results were most sensitive to transmission rates; excluding the impact of transmissions, screening Yearly was ≤$100 000/QALY (ICER: $70 900/QALY). CONCLUSIONS: For high-risk YMSM in the US, HIV screening 3-monthly compared to less frequent screening will improve clinical outcomes and be cost-effective.
Assuntos
Infecções por HIV , Minorias Sexuais e de Gênero , Adolescente , Adulto , Contagem de Linfócito CD4 , Análise Custo-Benefício , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Homossexualidade Masculina , Humanos , Masculino , Anos de Vida Ajustados por Qualidade de Vida , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Factors associated with prescription of smoking cessation medication (SCM), including the impact of race, have not been well described among a large population of people living with HIV (PLWH) engaged in routine clinical care. Our study investigated whether there are racial differences between African-American and White PLWH regarding SCM prescription and sought to identify other factors associated with these prescriptions at a large HIV clinic in the Southeastern United States. Among 1899 smokers, 38.8% of those prescribed SCMs were African-American and 61.2% were White. Factors associated with lower odds of SCM prescription included African-American race (AOR, 0.63 [95% CI: 0.47, 0.84]) or transferring care from another HIV provider during the study period (AOR, 0.63 [95% CI: 0.43, 0.91]). Whereas major depression (AOR, 1.54 [95% CI: 1.10, 2.15]), anxiety symptoms (AOR, 1.43 [95% CI: 1.05, 1.94]), and heavy smoking (>20 cigarettes/day) (OR, 3.50 [95% CI: 2.11, 5.98]) were associated with increased likelihood of SCM prescription. There were racial disparities in the prescription of SCM in African Americans with HIV. These findings underscore the need to increase pharmacotherapy use among African Americans to improve smoking cessation outcomes across racial groups among PLWH.
Assuntos
Infecções por HIV/terapia , Abandono do Hábito de Fumar , Negro ou Afro-Americano , Humanos , Fatores Raciais , Fumantes , Sudeste dos Estados Unidos , Estados UnidosRESUMO
PURPOSE: HIV treatment as prevention is effective for reducing the risk of HIV transmission and the messaging campaign, undetectable = untransmittable, is gaining recognition. As youth living with HIV (YLWH) who have condomless sex may acquire and potentially transmit other sexually transmitted infections (STIs), the purpose of this study was to assess potential differences in transmission risk of HIV and other STIs among YLWH to inform subsequent HIV and STI prevention efforts. METHODS: A cohort of 600 HIV behaviorally infected youth aged 13-24 years who were engaged in medical care completed an audio computer-assisted self-interview including questions about demographics, HIV disclosure, mental health, substance use, and sexual behaviors and beliefs. HIV viral loads and the presence of other STIs were abstracted from medical records. A viral load <200 copies/mL was considered undetectable. Univariate and bivariate analyses were conducted to examine differences by viral load and STIs. RESULTS: Participants were categorized into four groups: (1) undetectable without STIs (55.2%); (2) undetectable with STIs (14.2%); (3) detectable without STIs (22.8%); and (4) detectable with STIs (7.8%). In comparison to the other three groups, youth in the undetectable group with STIs reported more favorable sexual risk reduction attitudes and beliefs, internet use for finding sex partners, anal sex with male partners, and condomless anal sex with male partners. CONCLUSIONS: YLWH with undetectable viral loads and other STIs engaged in higher risk behaviors. To realize the promise of the messaging campaign, undetectable = untransmittable, efforts must focus on sustained viral suppression and prevention of STIs among YLWH.
Assuntos
Infecções por HIV , Infecções Sexualmente Transmissíveis , Adolescente , Homossexualidade Masculina , Humanos , Masculino , Comportamento Sexual , Parceiros Sexuais , Infecções Sexualmente Transmissíveis/epidemiologia , Sexo sem ProteçãoRESUMO
BACKGROUND: Young women aged 15-24 years are disproportionately affected by the HIV epidemic. Two phase III trials of a vaginal ring containing 25-mg dapivirine demonstrated HIV-1 risk reduction in adult women older than 21 years but not in those aged 18-21 years. Lack of protection was correlated with low adherence. METHODS: In this phase-IIa, randomized, double-blind, placebo-controlled, US, multicenter trial of the dapivirine ring in sexually active females, aged 15-17 years, participants were randomized 3:1 to a dapivirine or placebo ring to be inserted monthly for 6 months (NCT02028338). Primary safety end points included grade 2 product related adverse events and any grade 3 and higher adverse events. Adherence to ring use was assessed by plasma dapivirine concentrations, residual levels in used rings, and self-report. A plasma dapivirine concentration of >95 pg/mL was used to define short-term adherence; a residual ring level of <23.5 mg was used to define long-term adherence. Acceptability was assessed through computer-assisted self-interviews. RESULTS: Ninety-six participants were enrolled across 6 US sites. The median age was 16.0 years. There were no differences in safety outcomes between treatment arms. Adherence to the dapivirine ring was demonstrated by both plasma measurements (87%) and residual drug levels in rings (95%). Forty-two percent (95% confidence interval: 32 to 52) of participants reported that they never removed the ring. Participants noted no discomfort due to the ring at 87% of visits and "liking" the ring at 93% of visits. CONCLUSION: The dapivirine vaginal ring, a promising topical microbicide, was well tolerated and acceptable in young US adolescents.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Dispositivos Anticoncepcionais Femininos/efeitos adversos , Infecções por HIV/prevenção & controle , Pirimidinas/efeitos adversos , Adolescente , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/farmacocinética , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Placebos , Plasma , Pirimidinas/administração & dosagem , Pirimidinas/sangue , Pirimidinas/farmacocinética , Autorrelato , Estados Unidos , Vagina/efeitos dos fármacos , Adulto JovemRESUMO
Maintenance in HIV care is important to achieve optimal personal health and HIV viral load suppression for young people living with HIV (PLWH). We assessed the relationship between incarceration and missed visits in a longitudinal data cohort of PLWH (n = 910), ages 12-24, from 14 adolescent trial network sites across the US. The time from study entry to missed visits was modeled using Cox proportional hazards models. The cohort was mostly male (78%) and African American (75%) with a median age of 22. Prior incarceration had been experienced by 39% of the cohort, with a median number of times incarcerated of 2 (IQR: 1-3). The crude and adjusted hazard ratios for missed HIV care visits comparing those with incarceration histories to those without were 1.27 (95% CI: 1.06, 1.54) and 1.53 (95% CI: 1.26, 1.86). Among those returning to care, HIV viral loads were more likely to be unsuppressed among those with incarceration history compared to those without (RR: 1.28, 95% CI: 0.95, 1.74). This association was attenuated to the null after adjustment for suppression of viral load prior to the missed visit. Young PLWH with incarceration histories are at higher risk of missing HIV care visits.
Assuntos
Infecções por HIV , Adolescente , Criança , Estudos de Coortes , Feminino , Identidade de Gênero , Infecções por HIV/complicações , Humanos , Masculino , Modelos de Riscos Proporcionais , Carga Viral , Adulto JovemRESUMO
Human immunodeficiency virus-seronegative men aged 15-22 years who lost bone mineral density (BMD) during tenofovir disoproxil fumarate/emtricitabine preexposure prophylaxis (PrEP) showed BMD recovery 48 weeks following PrEP discontinuation. Lumbar spine and whole body BMD z-scores remained below baseline 48 weeks off PrEP in participants aged 15-19 years. Clinical Trials Registration. NCT01772823 (ATN 110) and NCT01769456 (ATN 113).
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Adolescente , Adulto , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Densidade Óssea , Emtricitabina/farmacologia , Emtricitabina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Humanos , Masculino , Tenofovir/farmacologia , Tenofovir/uso terapêutico , Adulto JovemRESUMO
BACKGROUND: People living with HIV (PLWH) have a high level of interest in quitting smoking, but only a small proportion have sustainable abstinence 6 months after cessation. Few investigations have focused on relapse to smoking among PLWH. In this investigation, we evaluated the prevalence of relapse after smoking cessation and the characteristics associated with smoking relapse using a retrospective, longitudinal cohort of PLWH during an eight-year observation. METHODS: All patients aged ≥19 years that reported current smoking during the study period and then reported not smoking on a subsequent tobacco use questionnaire (quitters) were eligible for the study. In addition, patients required at least one subsequent follow-up visit after quitting where smoking status was again reported to allow for assessment of relapse. A Cox proportional hazard model was fit to evaluate factors associated with smoking relapse in PLWH attending routine clinical care. RESULTS: Of the 473 patients who quit smoking in the study, 51% relapsed. In multivariable analysis, factors significantly associated with a higher likelihood of relapse were anxiety symptoms (HR = 1.55, 95% CI [1.11, 2.17]) and at-risk alcohol use (HR = 1.74, 95% CI [1.06, 2.85]), whereas antiretroviral therapy (ART) adherence (HR = 0.65, 95% CI [0.49, 0.99]) and longer time in care (HR = 0.94, 95% CI [0.91, 0.98]) were associated with a reduced likelihood of relapse after cessation. CONCLUSION: Our study underscores the high prevalence of smoking relapse that exists among PLWH after they quit smoking. Successful engagement in mental health care may enhance efforts to reduce relapse in the underserved populations of PLWH.
Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Infecções por HIV/epidemiologia , Transtornos Mentais/epidemiologia , Fumar/epidemiologia , Fumar/psicologia , Adulto , Alabama/epidemiologia , Feminino , Infecções por HIV/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Recidiva , Estudos Retrospectivos , Fatores de Risco , Abandono do Hábito de Fumar/psicologia , Abandono do Hábito de Fumar/estatística & dados numéricosRESUMO
People living with HIV (PLWH) have a higher prevalence of smoking and are less likely to quit smoking than the general population. Few studies involving a large sample of PLWH receiving routine care have evaluated factors associated with smoking cessation. This retrospective longitudinal cohort study evaluated factors associated with smoking cessation among PLWH from 2007 to 2018. Of 1,714 PLWH smokers included in the study, 27.6% reported quitting smoking. Suppressed plasma HIV-1 RNA (<200 copies/ml) was significantly associated with an increased likelihood of smoking cessation (HRadjusted = 1.27, 95% CI [1.03, 1.58]); whereas age/10 year increments (HRadjusted = 0.12, 95% CI [0.04, 0.38]), greater length of care at the HIV clinic (HRadjusted = 0.97, 95% CI [0.94, 0.99]), lack of insurance (HRadjusted = 0.77, 95% CI [0.61, 0.99]) or having public insurance (HRadjusted = 0.74, 95% CI [0.55, 0.97)]), current substance use (HRadjusted = 0.66, 95% CI [0.43, 0.97]) and risk of developing alcohol use disorder (HRadjusted = 0.60, 95% CI [0.43, 0.84]) were associated with a reduced likelihood of quitting smoking. These findings underscore the importance of early smoking cessation intervention among PLWH. In addition, targeted smoking cessation intervention strategies are needed for groups at risk for being less likely to quit, including older patients, and those with alcohol and substance use disorders.
Assuntos
Infecções por HIV/terapia , Abandono do Hábito de Fumar , Adulto , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fumar/epidemiologiaRESUMO
BACKGROUND: Young men who have sex with men (YMSM) experience disparities in HIV acquisition more than any other group. Daily oral pre-exposure prophylaxis (PrEP) with tenofovir/emtricitabine has been shown to effectively prevent HIV transmission in YMSM; however, recent studies suggest that young Black men who have sex with men experience subprotective levels of tenofovir diphosphate more frequently than other groups. SETTING: Combined data from Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) 110/113, 2 open-label PrEP studies that provided PrEP and evidence-based behavioral interventions to YMSM aged 15-22 years. METHODS: Bivariate and logistic regression analyses were used to examine sociodemographic and behavioral factors associated with protective tenofovir diphosphate levels (defined as ≥700 fmol/punch) in ATN 110/113 data. RESULTS: In bivariate analysis, self-identified Black participants, residential displacement due to sexual orientation, low perceived risk, and stigma with the medication were associated with subprotective levels. Hispanic ethnicity was associated with protective levels. In the final models, Black males were less likely to have subprotective levels than non-Black males at 4, 8, and 12 weeks. Self-reported displacement due to sexual orientation was associated with subprotective levels, whereas older age was as associated with protective levels. CONCLUSIONS: These findings highlight how future behavioral research and biomedical prevention efforts in YMSM will need to address PrEP disparities that may occur in young Black men who have sex with men, perception of risk, and lack of key supportive housing during this period that may be critical factors that contribute to HIV acquisition.
Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/prevenção & controle , Adesão à Medicação/estatística & dados numéricos , Organofosfatos/uso terapêutico , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Profilaxia Pré-Exposição , Adenina/uso terapêutico , Adolescente , Inquéritos Epidemiológicos , Homossexualidade Masculina , Humanos , Masculino , Adesão à Medicação/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Assunção de Riscos , Adulto JovemRESUMO
The aims of this study were to: 1) determine prevalence of anogenital and oral HPV, 2) determine concordance between HPV at anal, perianal, scrotal/penile, and oral sites; and 3) describe factors associated with anogenital HPV types targeted by the 9-valent vaccine. Data were collected from 2012 to 2015 among men who have sex with men 18-26 years of age enrolled in a vaccine trial (Nâ¯=â¯145). Penile/scrotal, perianal, anal, and oral samples were tested for 61 HPV types. Logistic regression was used to identify factors associated with types in the 9-valent vaccine. Participants' mean age was 23.0 years, 55.2% were African-American, and 26.2% were Hispanic; 93% had anal, 40% penile, and 6% oral HPV. Among those with anogenital infection, 18% had HPV16. Concordance was low between anogenital and oral sites. Factors independently associated with a 9-valent vaccine-type HPV were: race (African-American vs. White, OR=2.67, 95% CI=1.11-6.42), current smoking (yes vs. no, OR=2.37, 95% CI=1.03-5.48), and number of recent receptive anal sex partners (2+ vs. 0, OR=3.47, 95% CI=1.16-10.4). Most MSM were not infected with HPV16 or HPV18, suggesting that they may still benefit from HPV vaccination, but anogenital HPV was very common, highlighting the importance of vaccinating men before sexual initiation. CLINICAL TRIAL NUMBER: NCT01209325.
Assuntos
Canal Anal/virologia , Genitália Masculina/virologia , Infecções por HIV/complicações , Homossexualidade Masculina , Boca/virologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Adolescente , Adulto , Humanos , Masculino , Papillomaviridae/classificação , Prevalência , Adulto JovemRESUMO
We examined associations of 25-hydroxy vitamin D (25-OHD), tenofovir disoproxil fumarate (TDF), and bone toxicity. We studied TDF/emtricitabine (FTC) HIV pre-exposure prophylaxis (PrEP) in young men who have sex with men (YMSM). Bone toxicity was predefined using bone mineral density/content change from baseline to week 48. Baseline serum 25-OHD was dichotomized as <20 ng/mL (insufficient/deficient) versus ≥20 (sufficient), and week 48 dried blood spot tenofovir diphosphate (TFV-DP) as >700 fmol/punch (protective against HIV acquisition) versus ≤700. Associations were examined by univariate and multivariable logistic regression, reporting crude and adjusted odds ratios (ORs), with 95% confidence intervals (CIs). Of 101 enrolled, 69 had complete bone assessments and 25-OHD; of these, 59 had week 48 TFV-DP data. Median (Q1-Q3) age was 20 (18-21) years; 54% were black/African American. In univariate analysis, participants with baseline 25-OHD <20 ng/mL (OR = 5.4; 95% CI = 1.9-16.5) and blacks (OR = 4.9; 95% CI = 1.7-15.2) had greater odds of bone toxicity than those with 25-OHD ≥20 or other races. TFV-DP was not associated with bone toxicity (OR = 1.6; 95% CI = 0.5-5.5). In multivariable analysis, compared with those with 25-OHD ≥20 and TFV-DP ≤700, those with 25-OHD ≥20 and TFV-DP >700 (OR = 11.5; 95% CI = 1.4-169.6), 25-OHD <20 and TFV-DP ≤700 (OR = 19.4; 95% CI = 3.0-228.7), and 25-OHD <20 and TFV-DP >700 (OR = 32.3; 95% CI = 3.3-653.6) had greater odds of bone toxicity after adjusting for race. In multivariable models, 25-OHD insufficiency, protective TFV-DP concentrations, and black race were significantly associated with bone toxicity after 48 weeks of TDF/FTC PrEP in YMSM. Clinical Trials Registration: NCT01769469.
Assuntos
Fármacos Anti-HIV/toxicidade , Osso e Ossos/efeitos dos fármacos , Emtricitabina/toxicidade , Profilaxia Pré-Exposição , Tenofovir/toxicidade , Deficiência de Vitamina D , Adolescente , Fármacos Anti-HIV/administração & dosagem , Emtricitabina/administração & dosagem , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Humanos , Modelos Logísticos , Masculino , Estudos Prospectivos , Tenofovir/administração & dosagem , Vitamina D/análogos & derivados , Vitamina D/sangue , Adulto JovemRESUMO
HIV infections among adolescents and young adults continue to grow and clinical guidelines recommend the immediate start of life-saving antiretroviral therapy (ART). Unfortunately, suboptimal medication adherence among youth is common and can lead to poorer health outcomes as well as onward transmission of HIV to sexual partners. Clinical tools to assess treatment readiness are needed and can assist with adherence intervention strategies for youth. An assessment tool that we previously developed, the HIV Treatment Readiness Measure (HTRM), was administered to 595 HIV-positive youth ages 13-24 recruited from adolescent medicine clinics in the United States. Participants were followed for a minimum of 6 months and had to have at least one viral load test completed to be included in this analysis. The HTRM demonstrated high internal consistency (Chronbach's alpha = 0.86). For participants currently on ART at study entry, higher overall treatment readiness scores predicted future viral suppression (OR 1.52). Individual scores on three of the measure's factors (Psychosocial Issues, Connection with Care, and HIV Medication Beliefs) were also significant predictors of viral suppression. For those participants not on ART at study entry, the HIV Medication Beliefs factor significantly predicted who would eventually start ART (OR 2.26) but overall treatment readiness scores did not predict viral suppression in that group.
RESUMO
Malaria remains a significant public health problem worldwide with an estimated annual global incidence of 200 million and an estimated 450,000 annual deaths. Among the five known human malarial species, Plasmodium falciparum is the deadliest and most resistant to antimalarials. Hence, there is a need for new antimalarial targets. The rational design of a drug is usually based on biochemical and physiological differences between pathogens and their hosts. In view of their high rate of replication, parasites require very active nucleic acid synthesis which necessitates large supplies of the indispensable pyrimidine nucleotides. Consequently, delineation of P. falciparum pyrimidine metabolic pathways may reveal potential targets for the chemotherapy of malaria. Previous studies reported the existence of pyrimidine de novo pathways in this organism. The present results demonstrate the presence of enzymes of the pyrimidine salvage pathways in P. falciparum and indicate that this parasite is capable of pyrimidine salvage. Furthermore, some of the pyrimidine salvage enzymes, e.g., dTMP kinase, phosphoribosyltransferase, and uridine phosphorylase could be excellent targets for chemotherapeutic intervention against this parasite.
Assuntos
Plasmodium falciparum/metabolismo , Pirimidinas/metabolismo , Animais , Antimaláricos/farmacologia , Citidina Desaminase/metabolismo , Citosina Desaminase/metabolismo , DCMP Desaminase/metabolismo , Desenho de Fármacos , Eritrócitos/parasitologia , Humanos , Malária Falciparum/sangue , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia , Redes e Vias Metabólicas , Núcleosídeo-Fosfato Quinase/metabolismo , Pentosiltransferases/metabolismo , Fosfotransferases/metabolismo , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/enzimologia , Proteínas de Protozoários/metabolismo , Pirimidina Fosforilases/metabolismoRESUMO
BACKGROUND: Tenofovir disoproxil fumarate (TDF) increases serum parathyroid hormone (PTH) and 1,25 dihydroxy vitamin D (1,25-(OH)2D), and decreases bone mineral density (BMD). Optimal treatment of TDF-associated BMD loss requires an understanding of the primary cause of these abnormalities. METHODS: Secondary review of data from two studies of TDF use in youth, comparing the relationship of PTH, 25-hydroxy vitamin D (25-OHD) and 1,25-(OH)2D in three groups with varying exposures to TDF: youth without HIV enrolled in a trial of TDF/emtricitabine (FTC) for HIV pre-exposure prophylaxis (PrEP) at baseline (no TDF exposure) and after 12 weeks of TDF (short-term TDF exposure); and youth with HIV treated with TDF-containing combination antiretroviral therapy (cART) for at least 6 months at study entry (long-term TDF exposure). Relationships were evaluated by correlation analyses. RESULTS: Participants ranged in age from 17 to 24 years and >50% were Black/African American. In persons not treated with TDF, PTH had the physiologically appropriate negative correlation with 25-OHD (r=-0.3504, P=0.004). Correlations between PTH and 25-OHD in groups treated with TDF were weaker or absent. With longer term TDF treatment in persons with HIV, 25-OHD and 1,25-(OH)2D had the positive correlation similar to that found in vitamin D deficiency. CONCLUSIONS: TDF changes the relationship of 25-OHD to PTH, suggesting that in persons using TDF for PrEP or cART, a higher than usual target for serum 25-OHD concentration might be needed to reduce PTH and optimize bone health. CLINICAL TRIALS REGISTRATION: NCT01751646 (ATN 109) and NCT01769469 (ATN 117).
Assuntos
Fármacos Anti-HIV/efeitos adversos , Emtricitabina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Hormônio Paratireóideo/sangue , Tenofovir/efeitos adversos , Vitamina D/análogos & derivados , Adolescente , Negro ou Afro-Americano , Fármacos Anti-HIV/administração & dosagem , Terapia Antirretroviral de Alta Atividade , Densidade Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Estudos de Coortes , Feminino , HIV/efeitos dos fármacos , HIV/crescimento & desenvolvimento , HIV/patogenicidade , Infecções por HIV/sangue , Infecções por HIV/etnologia , Infecções por HIV/virologia , Humanos , Masculino , Profilaxia Pré-Exposição/métodos , Tenofovir/administração & dosagem , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/etnologia , Deficiência de Vitamina D/prevenção & controle , Deficiência de Vitamina D/virologia , População Branca , Adulto JovemRESUMO
OBJECTIVES: This study sought to examine the prevalence of STIs and whether substance use frequency and/or problematic use-specifically alcohol, marijuana and other drugs-was associated with having an STI diagnosis among youth living with HIV (YLWH) METHODS: A sample of 823 YLWH were recruited at 14 adolescent HIV clinics through the Adolescent Medicine Trials Network for HIV Interventions. Study staff abstracted STI data from medical records for up to 26 weeks prior to participants' completing a cross-sectional survey including the ASSIST (Alcohol, Smoking and Substance Involvement Screening Test), which measures substance use frequency and consequences. RESULTS: Almost one-third of youth had been diagnosed with an STI (30.5%) at the time of their baseline assessment. In multivariable analyses, those who engaged in weekly or greater marijuana use (adjusted OR (AOR)=10.66, 95% CI: 4.39 to 25.87, P<0.001) had an increased odds of being diagnosed with an STI. Additionally, youth who met alcohol use criteria for moderate (AOR=5.23, 95% CI: 2.50 to 10.93, P<0.001) and high risk (AOR=6.53, 95% CI: 1.20 to 35.68, P<0.05) alcohol use had an increased odds of being diagnosed with an STI compared with low-risk alcohol users. CONCLUSIONS: Study findings underscore the need to investigate the role of greater frequency of marijuana use and problematic alcohol use in STI incidence among YLWH. Given the associations between both substance use frequency and problematic use in STI diagnoses among YLWH seen in HIV care settings, clinicians should use validated substance use screening tools which capture both frequencies and consequences in order to identify YLWH who may need further evaluation and treatment.
Assuntos
Infecções por HIV/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adolescente , Consumo de Bebidas Alcoólicas/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Abuso de Maconha/epidemiologia , Prevalência , Distribuição por Sexo , Infecções Sexualmente Transmissíveis/epidemiologia , Pessoas Transgênero/estatística & dados numéricos , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Tobacco has been associated with worse HIV disease progression in adult samples of people living with HIV; however, studies have yet to examine these effects in youth living with HIV (YLWH). This study examined the association between tobacco smoking behaviors and sustained viral suppression among a sample of 820 YLWH who were recruited through the Adolescent Medicine Trials Network for HIV Interventions. Participants completed a cross-sectional survey and then staff abstracted viral suppression data from medical records for up to 26 weeks prior to enrollment. Overall, 20.4% of youth reported daily or almost daily tobacco use. In multivariable analyses, older age and daily or almost daily tobacco smoking, and ART adherence remained statistically significant in predicting sustained viral suppression over the study period. These findings underscore the need for tobacco screening and interventions in HIV care settings in order to identify youth in need of additional smoking cessation services.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV/efeitos dos fármacos , Resposta Viral Sustentada , Fumar Tabaco/epidemiologia , Adolescente , Estudos Transversais , Progressão da Doença , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Humanos , Masculino , Programas de Rastreamento , Resultado do Tratamento , Carga Viral , Adulto JovemRESUMO
Background: Young men-who-have-sex-with-men (MSM) are disproportionately impacted by human immunodeficiency virus (HIV). Preexposure prophylaxis (PrEP) could reduce HIV acquisition among youth, but suboptimal adherence threatens effectiveness. Optimal metrics of PrEP adherence among adolescents have remain undefined. Methods: The Adolescent Trials Network 110/113 studies provided daily oral PrEP with tenofovir (TFV) disoproxil fumarate/emtricitabine over 48 weeks to a diverse population of MSM (aged 15-22 years). Self-reported adherence was assessed and PrEP drug concentrations measured from hair and dried blood spot (DBS) samples; 23% of participants received Wisepill electronic monitoring devices. The average number of PrEP doses per week taken was estimated, and concordance between measures assessed. Results: Among 243 participants, hair samples were collected at 1186/1238 (96%) person-visits. The concordance of TFV levels in hair and TFV-diphosphate in DBS around thresholds consistent with taking ≥4 and 7 PrEP doses/week was high (76% and 80%). Hair and DBS concentrations correlated poorly with self-report and Wisepill metrics. Through week 12, 40%-60% of participants (by hair and DBS), ≤31% (Wisepill), and >85% (self-report) were estimated to have taken ≥4 PrEP doses/week (a threshold associated with protection among MSM). For all measures except self-report, adherence declined over time, with half of participants taking <2 doses/week by week 48. Conclusions: Among youth on PrEP, adherence waned over time. Self-report overestimated adherence, and use of Wisepill was limited. Hair collection was highly acceptable and provided similar interpretations to DBS. Incorporation of either metric in future PrEP studies among youth could identify suboptimal adherence and trigger interventions.