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1.
Lancet HIV ; 8(9): e531-e543, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34339628

RESUMO

BACKGROUND: Robust age-specific estimates of anal human papillomavirus (HPV) and high-grade squamous intraepithelial lesions (HSIL) in men can inform anal cancer prevention efforts. We aimed to evaluate the age-specific prevalence of anal HPV, HSIL, and their combination, in men, stratified by HIV status and sexuality. METHODS: We did a systematic review for studies on anal HPV infection in men and a pooled analysis of individual-level data from eligible studies across four groups: HIV-positive men who have sex with men (MSM), HIV-negative MSM, HIV-positive men who have sex with women (MSW), and HIV-negative MSW. Studies were required to inform on type-specific HPV infection (at least HPV16), detected by use of a PCR-based test from anal swabs, HIV status, sexuality (MSM, including those who have sex with men only or also with women, or MSW), and age. Authors of eligible studies with a sample size of 200 participants or more were invited to share deidentified individual-level data on the above four variables. Authors of studies including 40 or more HIV-positive MSW or 40 or more men from Africa (irrespective of HIV status and sexuality) were also invited to share these data. Pooled estimates of anal high-risk HPV (HR-HPV, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68), and HSIL or worse (HSIL+), were compared by use of adjusted prevalence ratios (aPRs) from generalised linear models. FINDINGS: The systematic review identified 93 eligible studies, of which 64 contributed data on 29 900 men to the pooled analysis. Among HIV-negative MSW anal HPV16 prevalence was 1·8% (91 of 5190) and HR-HPV prevalence was 6·9% (345 of 5003); among HIV-positive MSW the prevalences were 8·7% (59 of 682) and 26·9% (179 of 666); among HIV-negative MSM they were 13·7% (1455 of 10 617) and 41·2% (3798 of 9215), and among HIV-positive MSM 28·5% (3819 of 13 411) and 74·3% (8765 of 11 803). In HIV-positive MSM, HPV16 prevalence was 5·6% (two of 36) among those age 15-18 years and 28·8% (141 of 490) among those age 23-24 years (ptrend=0·0091); prevalence was 31·7% (1057 of 3337) among those age 25-34 years and 22·8% (451 of 1979) among those age 55 and older (ptrend<0·0001). HPV16 prevalence in HIV-negative MSM was 6·7% (15 of 223) among those age 15-18 and 13·9% (166 of 1192) among those age 23-24 years (ptrend=0·0076); the prevalence plateaued thereafter (ptrend=0·72). Similar age-specific patterns were observed for HR-HPV. No significant differences for HPV16 or HR-HPV were found by age for either HIV-positive or HIV-negative MSW. HSIL+ detection ranged from 7·5% (12 of 160) to 54·5% (61 of 112) in HIV-positive MSM; after adjustment for heterogeneity, HIV was a significant predictor of HSIL+ (aPR 1·54, 95% CI 1·36-1·73), HPV16-positive HSIL+ (1·66, 1·36-2·03), and HSIL+ in HPV16-positive MSM (1·19, 1·04-1·37). Among HPV16-positive MSM, HSIL+ prevalence increased with age. INTERPRETATION: High anal HPV prevalence among young HIV-positive and HIV-negative MSM highlights the benefits of gender-neutral HPV vaccination before sexual activity over catch-up vaccination. HIV-positive MSM are a priority for anal cancer screening research and initiatives targeting HPV16-positive HSIL+. FUNDING: International Agency for Research on Cancer.


Assuntos
Canal Anal/virologia , Infecções por Papillomavirus/epidemiologia , Lesões Intraepiteliais Escamosas/epidemiologia , Fatores Etários , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Masculino , Papillomaviridae/classificação , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Prevalência , Fatores de Risco , Sexualidade/estatística & dados numéricos , Lesões Intraepiteliais Escamosas/virologia
2.
Top Antivir Med ; 29(3): 361-378, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34370418

RESUMO

The 2021 Conference on Retroviruses and Opportunistic Infections included advances in therapy for HIV as well as for SARS-CoV-2. Data presented on COVID-19 therapies included trials showcasing the use of monoclonal antibodies for prevention and treatment of COVID-19. Promising new data were presented on lenacapavir, an investigational HIV capsid inhibitor given as a subcutaneous injection every 6 months. Although encouraging data from settings across the globe reported achievement of 90-90-90 HIV care cascade targets, disparities exist in care engagement and viral suppression, particularly for people of color and young people with HIV. Several interventions were associated with improved care cascade outcomes. The COVID-19 pandemic has impacted HIV care engagement, but mitigation strategies can allow programs to continue to serve people with HIV during the pandemic. Studies examining the resistance patterns of existing antiretroviral therapy (ART) agents were presented, as were resistance mechanisms of novel agents such as lenacapavir and resistance patterns among individuals who seroconverted while on preexposure prophylaxis. Data from large observational cohorts were presented on patterns of ART uptake and trends in mortality and in virologic failure. Pertinent findings relating to pediatric and maternal health issues included data on dolutegravir-based ART in children and adolescents with HIV; safety and tolerability of dolutegravir-based ART in children and pregnant women; similarly high maternal viral suppression at 50 weeks postpartum in women receiving certain ART regimens; weight gain in pregnant women receiving dolutegravir plus tenofovir alafenamide/emtricitabine; and viral suppression with dolutegravir-based ART when started during the third trimester of pregnancy.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Pesquisa Biomédica , COVID-19/tratamento farmacológico , Congressos como Assunto , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Oxazinas/uso terapêutico , Piperazinas/uso terapêutico , Piridonas/uso terapêutico , Adolescente , Adulto , Feminino , Humanos , Masculino , Gravidez , SARS-CoV-2
3.
Sex Transm Dis ; 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-34110738

RESUMO

Cervical cancer is five times more likely among women living with HIV (WHIV), likely due to higher prevalence of HPV. Despite evidence of higher rates with multiple HPV genotypes in WHIV, there are no recommendations for triage by HPV genotyping specific to WHIV. In Latin America/Caribbean (LAC) rates are high and vary significantly. To guide optimization of HPV-based cervical cancer screening among WHIV in LAC, review of current literature was completed to assess HPV genotype distribution by cervical disease grade in WHIV in this region; and further expanded globally for comparison across regions.A systematic review of the literature from June 2016 to January 2020 revealed 15 studies reporting HPV genotype distribution by cervical disease state (normal, low-grade disease, high-grade disease, and invasive cervical cancer) across different global regions.Across all studies, there were 6,928 WHIV from 4 global regions, 3,952 of whom were HPV-positive. Three studies from LAC were reviewed, with one providing enough detail to describe HPV genotypes by cervical disease grade and identified type 31 and 35 in high-grade cervical lesions. Of the studies included, 4 from Africa and Europe/North America each, and 1 from Asia included data that were able to be summarized.Latin America, a region which experiences high rates of HPV, HIV, and cervical disease, had few published studies reporting HPV genotypes by cervical disease grade, with one reporting individual HPV genotype and specific cervical disease grade. Identifying HPV types associated with CIN2+ in WHIV in this region has the potential to improve screening and treatment for cervical cancer prevention and should be the focus of future research.

4.
J Acquir Immune Defic Syndr ; 87(3): 978-984, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34110312

RESUMO

BACKGROUND: Women living with HIV (WLWH) experience high rates of anal cancer. Screening using anal cytology, high-resolution anoscopy (HRA) with biopsies, can histologically diagnose anal cancer precursors called high-grade squamous intraepithelial lesions (HSIL). The low specificity of screening using anal cytology results in HRA referral for many WLWH without HSIL. Screening using high-risk human papillomavirus (HR-HPV) may improve specificity. METHODS: Two hundred seven WLWH (63% non-Hispanic black) were screened for anal histologic HSIL (hHSIL) using cytology, HRA-guided biopsies, and Xpert HPV. Xpert performance for predicting anal hHSIL was compared with that of cytology. Usng Xpert 5 HPV genotypic results and accompanying cycle thresholds, receiver operator characteristic curve and recursive partitioning analyses were used to create predictive models for hHSIL. RESULTS: The performance of Xpert to predict hHSIL was not different from that of cytology with a sensitivity (Sn) of 89% and specificity (Sp) of 49%. Interpretation of Xpert was modified using genotypic results and receiver operator characteristic curve analysis, which produced a screen with an Sn and Sp of 75% and 84% for hHSIL, respectively. Another reinterpretation of Xpert was created using recursive partitioning and cycle thresholds, which predicted hHSIL with an Sn and Sp of 75% and 86%, respectively. The detection of HPV-16 was highly predictive of hHSIL in all analyses. These modified screening tests would reduce HRA referral in this population by almost half compared with anal cytology. CONCLUSIONS: Xpert HPV is an alternative to anal cytology to screen for anal HSIL and can be optimized to reduce the number of unnecessary HRAs performed in WLWH.


Assuntos
Infecções por HIV/complicações , HIV-1 , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Lesões Intraepiteliais Escamosas/virologia , Adulto , Canal Anal/patologia , Feminino , Humanos , Lesões Intraepiteliais Escamosas/diagnóstico
5.
AIDS ; 35(10): 1585-1595, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33831911

RESUMO

OBJECTIVE: The objective of this study was to compare HIV-negative cisgender women (CGW) with MSM for mucosal tissue differences in pharmacokinetics, HIV infectivity and cell phenotype. DESIGN: A substudy of HPTN 069/ACTG A5305, 48-week study of three oral candidate preexposure prophylaxis regimens: maraviroc, maraviroc/emtricitabine and maraviroc/tenofovir disoproxil fumarate (TDF) compared with a TDF/emtricitabine control group. METHODS: Plasma, peripheral blood mononuclear cells and cervical and colorectal tissue biopsies were collected at Baseline (no drug), Week 24 and 48 (on drug), and Week 49 (1-week postdrug). Drug concentrations were assessed in all matrices. HIV infectivity was assessed using tissue biopsy 'explants' challenged with HIV ex vivo followed by HIV p24 measurement. Flow cytometry evaluated colorectal cell phenotype. RESULTS: Thirty-seven CGW and 54 MSM participated. CGW's colorectal explant p24 was higher than MSM before (0.31 log10, P = 0.046), during (1.01-1.19 log10, P = 0.016) and one week after (0.61 log10, P = 0.011) study drug dosing. Pooling regimens, cervical explant p24 did not differ among visits. CGW had higher plasma maraviroc and colorectal tissue tenofovir diphosphate and lower colorectal tissue emtricitabine (all P < 0.005) compared with MSM. Each study drug's cervical tissue concentrations were more than 10-fold below paired colorectal concentrations (P < 0.001). Cell phenotype sex differences included 4% higher CD38+/CD8+ cells at baseline and 3-7% higher CD69+/CD8+ cells throughout Weeks 24-49 in CGW compared with MSM (P < 0.05). CONCLUSION: Colorectal explants in CGW demonstrated greater HIV infectivity than MSM with and without study drugs. Small differences in adherence, drug concentration and colorectal tissue flow cytometry cannot fully explain this difference.


Assuntos
Fármacos Anti-HIV , Neoplasias Colorretais , Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Emtricitabina , Feminino , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Humanos , Leucócitos Mononucleares , Masculino
7.
Cancer Cytopathol ; 127(6): 407-413, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31145557

RESUMO

BACKGROUND: The incidence of squamous cell carcinoma of the anal canal has been increasing in high-risk populations. To the authors' knowledge, there is no international consensus regarding screening for squamous cell carcinoma of the anal canal, but screening is commonly comprised of a Papanicolaou (Pap) test in combination with digital anorectal examination followed by high-resolution anoscopy if necessary. The current study focused on individuals living with HIV and particularly on women living with HIV. METHODS: In this 5-year retrospective study, the authors identified 5982 Pap tests, 1848 of which had follow-up biopsy within 6 months. The rate of atypical squamous cells of undetermined significance was 42%, and approximately 38.1% of cases with this interpretation were diagnosed as high-grade squamous intraepithelial lesions on follow-up biopsy. In addition, 82 women with anal cytology had long-term follow-up (>10 years) available. RESULTS: The authors investigated a relationship between cervicovaginal human papillomavirus (HPV) results, cervical pathology, CD4 T-cell count, and CD4/8 ratio with the anal cytology interpretation. A statistical correlation was noted between the CD4 count and the CD4/8 ratio and the presence of anal dysplasia. Nearly one-half of the women without cervicovaginal HPV positivity presented with anal dysplasia. CONCLUSIONS: The results of the current study demonstrated that, among women living with HIV, screening for anal dysplasia should not be eschewed, regardless of lower genital tract pathology and/or HPV status. To the authors' knowledge, the current study is the largest reported retrospective anal cytology cohort in individuals living with HIV.


Assuntos
Canal Anal/patologia , Neoplasias do Ânus/diagnóstico , Infecções por HIV/complicações , Infecções por Papillomavirus/diagnóstico , Lesões Pré-Cancerosas/diagnóstico , Canal Anal/citologia , Canal Anal/diagnóstico por imagem , Neoplasias do Ânus/imunologia , Neoplasias do Ânus/patologia , Neoplasias do Ânus/virologia , Células Escamosas Atípicas do Colo do Útero/patologia , Consenso , Exame Retal Digital , Feminino , Seguimentos , Infecções por HIV/imunologia , Humanos , Masculino , Programas de Rastreamento/normas , Pessoa de Meia-Idade , Teste de Papanicolaou/normas , Papillomaviridae/imunologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Guias de Prática Clínica como Assunto , Lesões Pré-Cancerosas/imunologia , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/virologia , Proctoscopia/normas , Estudos Retrospectivos , Fatores Sexuais
8.
Top Antivir Med ; 27(1): 50-68, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31137003

RESUMO

The 2019 Conference on Retroviruses and Opportunistic Infections included many exciting advances in antiretroviral therapy (ART). Investigators presented a case report of a second patient possibly cured of HIV through an allogeneic hematopoietic stem cell transplant from a CC chemokine receptor 5-delta 32 donor. Two clinical trials of long-acting injectable cabotegravir and rilpivirine showed promising safety, efficacy, and tolerability as maintenance ART. Test-and-treat and rapid-ART-start strategies show promise in advancing progress toward the HIV care cascade 90-90-90 Joint United Nations Programme on HIV/AIDS/World Health Organization targets. However, late diagnosis and mortality after ART initiation remain high, even in the context of HIV service scale-up, and mortality from unintentional opioid overdose in people living with HIV in the United States is on the rise. In vitro studies were presented that identified and evaluated the effect of resistance-associated mutations on ART susceptibility and elucidated mechanisms of resistance. Epidemiologic data were reported on the prevalence, impact, regional variation, and changes over time of resistance-associated mutations. Decreasing regional and national rates of resistance may be a benefit of increasing use of integrase strand transfer inhibitors (InSTIs). New findings were presented on maternal and fetal health outcomes in women of reproductive potential, drug-drug interactions between hormonal contraception and ART, and further exploration of the association between InSTIs and birth defects.


Assuntos
Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Infecções por HIV/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Antirretrovirais/farmacocinética , Continuidade da Assistência ao Paciente , Anticoncepcionais Orais Hormonais/farmacocinética , Anticoncepcionais Orais Hormonais/farmacologia , Gerenciamento Clínico , Interações Medicamentosas , Farmacorresistência Viral , HIV/efeitos dos fármacos , HIV/genética , Infecções por HIV/diagnóstico , Humanos , Mutação , Resultado do Tratamento , Estados Unidos
9.
Vaccine ; 37(18): 2502-2510, 2019 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-30940485

RESUMO

Duration and functional aspects of the oral and systemic antibody responses following HPV vaccination in HIV-negative (HIV-) and HIV-positive (HIV+) men are not well characterized. Oral and systemic HPV-16 and HPV-18-specific antibody levels were evaluated over 18-months of follow-up, in HIV+ and HIV- men. Sera and oral gargles from 147 HIV- men, ages 27-45 and 75 HIV+ men, ages 22-61, who received 3-doses of quadrivalent HPV vaccine were tested for HPV-16 and HPV-18 antibodies at Day 1, Month 7 (1 month post-dose 3), and Month 18 (12 months post-dose 3) and HPV avidity (Day 1, and Month 7) using L1-VLP ELISA. All individuals seroconverted, regardless of HIV-status, following 3-doses of vaccine for HPV-16 and HPV-18. Serum HPV-16 and HPV-18 antibody geometric mean levels were >2-fold lower in HIV+ compared to HIV- men at Month 7 (HPV-16: 808.5 versus 2119.8 EU/mL, and HPV-18: 285.8 versus 611.6 EU/mL, p < 0.001) but not significantly different at Month 18 (HPV-16: 281.8 versus 359.7 EU/mL, p = 0.145, and HPV-18: 120.2 versus 93.4 EU/mL, p = 0.372). Post-vaccination, only oral HPV-16 antibody levels at Month 7 were significantly different between HIV+ and HIV- men (127.7 versus 177.1 EU/mg of IgG, p = 0.008). Among baseline HPV-seronegative men, circulating levels of HPV-16 and HPV-18 antibodies were up to >3 fold lower in HIV+ men, at Months 7 and 18. In contrast, levels of HPV-16 and HPV-18 antibodies after vaccination were not inferior in baseline HPV-seropositive, HIV+ men. HPV-16 and HPV-18 avidity was lower among HIV+ compared to HIV- men at Month 7 (HPV-16: 1.95 M versus 2.12 M, p = 0.027; HPV-18: 1.50 M versus 1.72 M, p < 0.001). Although differences in peak antibody levels were observed between HIV+ and HIV- men following 3 doses of vaccine, plateau antibody levels were overall comparable, and avidity was relatively high for both groups. These data indicate that the vaccine induced antibody affinity maturation in both HIV+ and HIV- men and will likely result in long-term protective immune responses.


Assuntos
Alphapapillomavirus/imunologia , Anticorpos Antivirais/sangue , Infecções por HIV/complicações , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/imunologia , Boca/imunologia , Infecções por Papillomavirus/prevenção & controle , Adulto , Anticorpos Neutralizantes/sangue , Afinidade de Anticorpos , Infecções por HIV/epidemiologia , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/administração & dosagem , Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/imunologia , Vacinação , Adulto Jovem
10.
Qual Life Res ; 28(5): 1265-1269, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30617704

RESUMO

PURPOSE: The Anal Cancer HSIL Outcomes Research (ANCHOR) trial aims to determine whether treating precancerous anal high-grade squamous intraepithelial lesions (HSIL), versus active surveillance, is effective in reducing anal cancer incidence in HIV-infected individuals. We evaluated the reliability (i.e., internal consistency, test-retest) and between-group stability of a 25-item ANCHOR Health-Related Symptom Index (A-HRSI). METHODS: ANCHOR participants at least 1-month post-randomization to treatment or active surveillance completed the A-HRSI via telephone. Participants were contacted 7-10 days later to complete the A-HRSI and a participant global impression of change (PGIC) item. RESULTS: Participants (n = 100) were enrolled (mean age = 51.4, 79% cisgender-male, 73% African American, 9% Hispanic) from five ANCHOR sites. Cronbach's α was good for the physical symptoms (0.82) domain and fair for the physical impacts (0.79) and psychological symptoms (0.73) domains. Intraclass correlation coefficients were good for each of respective domains (i.e., 0.80, 0.85, and 0.82). There were no significant differences in PGIC between the treatment (n = 56) and active surveillance (n = 44) groups (F(1,98) = 2.03, p = 0.16). CONCLUSIONS: The A-HRSI is able to reliably assess participant-reported symptoms and impacts of anal HSIL across a 7-10 days of timeframe. Future work will involve the establishment of construct and discriminant validity prior to inclusion in the full ANCHOR trial.


Assuntos
Neoplasias do Ânus/prevenção & controle , Qualidade de Vida/psicologia , Autorrelato , Lesões Intraepiteliais Escamosas Cervicais/psicologia , Lesões Intraepiteliais Escamosas Cervicais/terapia , Conduta Expectante/métodos , Síndrome de Imunodeficiência Adquirida/complicações , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Lesões Intraepiteliais Escamosas Cervicais/patologia , Inquéritos e Questionários , Resultado do Tratamento
11.
PLoS One ; 13(12): e0206577, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30586364

RESUMO

INTRODUCTION: Tenofovir (TDF)-containing PrEP is effective for HIV prevention, but its effect on health-related quality of life (QOL) is unknown. Using data from HPTN 069/ACTG A5305, a randomized study of potential PrEP regimens comparing maraviroc alone, or together with TDF or emtricitabine (FTC), to TDF + FTC (control), we evaluated the impact of these regimens on QOL in at-risk HIV-uninfected U.S. women and men. METHODS: QOL was measured at baseline (before starting medications) and every 8 weeks through week 48 using the EQ-5D-3L. Responses were converted to a scale from 0.0 (death) to 1.0 (perfect health), using published valuation weights. Mean scores were compared between groups at each time point using nonparametric testing. Multivariable linear regression was used to adjust for potential confounders. RESULTS: We analyzed 186 women (median age 35 years, 65% black, 17% Hispanic) and 405 men (median age 30 years, 28% black, 22% Hispanic), including 9 transgender participants analyzed based on sex-at-birth. Mean baseline QOL was 0.91 for women and 0.95 for men. There were minimal changes in mean QOL over time for any regimen (women: p = 0.29; men: p = 0.14). There were no significant differences between participants who continued the regimen compared to participants who discontinued early (women: p = 0.61; men: p = 0.1). Mean QOL did not differ significantly by regimen at any time point, both unadjusted and after adjustment for age, race/ethnicity, adherence, and use of alcohol, marijuana, opiates, and other substances. CONCLUSIONS: QOL in at-risk individuals starting candidate PrEP regimens in a clinical trial is similar to the general population and maintained over time. This finding did not vary among regimens or when adjusted for demographics, adherence, and substance use. Our findings are the first to show that starting a candidate PrEP regimen in at-risk HIV-uninfected U.S. women and men was not associated with significant changes in QOL. TRIAL REGISTRATION: Clinicaltrials.gov NCT01505114.


Assuntos
Emtricitabina/administração & dosagem , Infecções por HIV/prevenção & controle , HIV-1 , Maraviroc/administração & dosagem , Qualidade de Vida , Tenofovir/administração & dosagem , Adolescente , Adulto , Idoso , Feminino , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia
12.
Top Antivir Med ; 26(3): 85-88, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30384331

RESUMO

Human papillomavirus (HPV)-related cancers, including anal cancer and oropharyngeal cancer, occur more frequently in individuals living with HIV infection than in the general population. Strategies for prevention among individuals with HIV infection include HPV vaccination, anal cancer screening programs, and early initiation of antiretroviral therapy (ART). HPV vaccination is not yet optimally used; a stronger and more persistent effort is needed to increase vaccination rates. Although anal cancer screening is not recommended by all authorities, there is a least some evidence that screening and treatment of anal high-grade squamous intraepithelial lesions may prevent progression to cancer. However, more definitive evidence is needed. Early initiation of ART reduces the risk of infection-related cancers, with some evidence of benefit in preventing HPV-associated cancer in individuals with HIV infection. This article summarizes a presentation by Timothy J. Wilkin, MD, MPH, at the IAS-USA continuing education program held in Los Angeles, California in April 2018.


Assuntos
Neoplasias do Ânus/epidemiologia , Neoplasias do Ânus/patologia , Infecções por HIV/complicações , Neoplasias Orofaríngeas/epidemiologia , Neoplasias Orofaríngeas/patologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Antirretrovirais/uso terapêutico , Neoplasias do Ânus/prevenção & controle , Detecção Precoce de Câncer , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Neoplasias Orofaríngeas/prevenção & controle , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Lesões Intraepiteliais Escamosas Cervicais/diagnóstico , Lesões Intraepiteliais Escamosas Cervicais/epidemiologia , Lesões Intraepiteliais Escamosas Cervicais/patologia , Lesões Intraepiteliais Escamosas Cervicais/terapia
13.
Value Health ; 21(8): 984-992, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30098677

RESUMO

BACKGROUND: Anal cancer, caused by oncogenic types of human papillomavirus, is a growing problem in the United States. A key focus of anal cancer prevention has been screening for and treating precancerous high-grade squamous intraepithelial anal lesions (HSILs). OBJECTIVES: To develop a health-related symptom index for HSIL using qualitative techniques because anal HSIL and its treatment may have a negative impact on health-related quality of life (HRQOL), and no HRQOL measure specific to this condition and treatment currently exists. METHODS: Expert consultation was used to guide one-on-one concept elicitation interviews with participants to identify HRQOL aspects they attribute to their anal HSIL and its treatment. This resulted in a draft instrument, which was administered to an independent participant sample, where cognitive interview techniques assessed comprehension. RESULTS: Eighteen anal HSIL-related concepts were identified by the expert panel. Across the 41 concept elicitation interviews, 23 items representing physical symptoms, physical impacts, and psychological symptoms were identified to comprise the initial measure, which was then evaluated during three rounds of cognitive interviews (n = 45). Several questionnaire aspects were refined on the basis of participant input, with three additional items added per expert/participant recommendation. One item was removed because of poor comprehension, resulting in a 25-item measure. CONCLUSIONS: Using state-of-the-art qualitative methodology, we have established the content validity of this new instrument, the ANCHOR Anal HSIL Health-Related Symptom Index. Quantitative validation efforts are currently underway. The participant-driven process of developing this tool will facilitate a participant-centered evaluation of the impact on morbidity for treatment of anal HSIL or observation without treatment.


Assuntos
Neoplasias do Ânus/complicações , Psicometria/normas , Qualidade de Vida/psicologia , Lesões Intraepiteliais Escamosas Cervicais/psicologia , Adulto , Neoplasias do Ânus/psicologia , Feminino , Infecções por HIV/complicações , Infecções por HIV/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria/instrumentação , Psicometria/métodos , Lesões Intraepiteliais Escamosas Cervicais/complicações , Inquéritos e Questionários
14.
Top Antivir Med ; 26(1): 40-53, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29727296

RESUMO

The 2018 Conference on Retroviruses and Opportunistic Infections (CROI) showcased exciting data on new investigational agents including MK-8591 and tri-specific antibody targeting 3 highly conserved epitopes on HIV-1 in a single antibody. Clinical trials of initial antiretroviral therapy (ART) and switch studies involving bictegravir/emtricitabine/tenofovir alafenamide were presented. Intensification of initial ART with integrase strand transfer inhibitors did not increase the risk of immune reconstitution inflammatory syndrome. Pharmacokinetic issues were discussed, including the substantial drug-drug interactions between efavirenz-based ART and hormonal contraception delivered via a vaginal ring. Studies on pre-ART drug resistance and emergence of drug resistance after initial and second-line ART in different settings and populations were highlighted. Novel technologies to identify drug resistance included a free, cloud-based web service for HIV genotyping analysis and a promising technology for point-of-care drug resistance mutations testing. New strategies to improve the HIV care continuum included home-based testing with initiation of same-day ART and stratified care with specialized clinics to serve those disengaged in care, but the data on financial incentives were not encouraging. Several studies provided insights into the impact of early ART on decreasing the size of the HIV reservoir in HIV-infected infants. Pertinent conference findings relating to women's health issues included similar clinical outcomes between breastfeeding and formula feeding HIV-infected women, the problem of viral rebound and ART nonadherence in pregnancy and postpartum.


Assuntos
Adenina/análogos & derivados , Antirretrovirais/uso terapêutico , Congressos como Assunto/tendências , Emtricitabina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Tenofovir/uso terapêutico , Adenina/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Desoxiadenosinas/uso terapêutico , Quimioterapia Combinada , HIV-1/genética , Humanos , Carga Viral
15.
Clin Infect Dis ; 67(9): 1339-1346, 2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-29659751

RESUMO

Background: Adults living with human immunodeficiency virus (HIV) are at increased risk for anal and oropharyngeal cancer caused by human papillomavirus (HPV). The efficacy of HPV vaccines in this population is unknown. Methods: In this phase 3, double-blind, randomized, controlled trial, we assigned HIV-infected adults aged ≥27 years to the quadrivalent HPV (types 6, 11, 16, 18) vaccine or placebo (1:1) stratified by sex and presence of anal high-grade squamous intraepithelial lesions on biopsy (bHSIL). The primary endpoint was vaccine efficacy against incident persistent anal infection with quadrivalent vaccine types or single detection at the final visit that were not present at baseline. Secondary endpoints included vaccine efficacy for anal bHSIL after week 52, persistent oral HPV infection. Results: A total of 575 participants were randomized. The Data and Safety Monitoring Board stopped the study early due to futility. Vaccine efficacy was 22% (95.1% confidence interval [CI], -31%, 53%) for prevention of persistent anal infection or single detection at the final visit, 0% (95% CI -44%, 31%) for improving bHSIL outcomes and 88% (95.1% CI 2%, 98%) for preventing persistent oral HPV infection, but was 32% (95.1% CI -80%, 74%) for 6-month persistent oral HPV infection or single detection at the final visit. Conclusions: These results do not support HPV vaccination of HIV-infected adults aged ≥27 years to prevent new anal HPV infections or to improve anal HSIL outcomes. However, our data suggest a role for prevention of oral HPV infections, but this finding should be confirmed in future studies. Clinical Trials Registration: NCT01461096.


Assuntos
Neoplasias do Ânus/prevenção & controle , Infecções por HIV/microbiologia , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/uso terapêutico , Neoplasias Orofaríngeas/prevenção & controle , Infecções por Papillomavirus/prevenção & controle , Adulto , Canal Anal/patologia , Canal Anal/virologia , Neoplasias do Ânus/virologia , Brasil , Método Duplo-Cego , Término Precoce de Ensaios Clínicos , Feminino , Infecções por HIV/complicações , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/imunologia , Humanos , Masculino , Futilidade Médica , Pessoa de Meia-Idade , Boca/virologia , Neoplasias Orofaríngeas/virologia , Papillomaviridae/imunologia , Infecções por Papillomavirus/diagnóstico , Potência de Vacina
16.
Ann Intern Med ; 167(6): 384-393, 2017 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-28828489

RESUMO

Background: Maraviroc (MVC) is a candidate drug for HIV preexposure prophylaxis (PrEP). Objective: To assess the safety and tolerability of MVC-containing PrEP over 48 weeks in U.S. women at risk for HIV infection. Design: Phase 2 randomized, controlled, double-blinded study of 4 antiretroviral regimens used as PrEP. (ClinicalTrials.gov: NCT01505114). Setting: 12 clinical research sites of the HIV Prevention Trials Network and AIDS Clinical Trials Group. Participants: HIV-uninfected women reporting condomless vaginal or anal intercourse with at least 1 man with HIV infection or unknown serostatus within 90 days. Intervention: MVC only, MVC-emtricitabine (FTC), MVC-tenofovir disoproxil fumarate (TDF), and TDF-FTC (control). Measurements: At each visit, clinical and laboratory (including HIV) assessments were done. Primary outcomes were grade 3 and 4 adverse events and time to permanent discontinuation of the study regimen. All randomly assigned participants were analyzed according to their original assignment. Results: Among 188 participants, 85% completed follow-up, 11% withdrew early, and 4% were lost to follow-up; 19% discontinued their regimen prematurely. The number discontinuing and the time to discontinuation did not differ among regimens. Grade 3 or 4 adverse events occurred in 5 (MVC), 13 (MVC-FTC), 9 (MVC-TDF), and 8 (TDF-FTC) participants; rates did not differ among regimens. One death (by suicide) occurred in the MVC-TDF group but was judged not to be related to study drugs. Of available plasma samples at week 48 (n = 126), 60% showed detectable drug concentrations. No new HIV infections occurred. Limitations: Participants were not necessarily at high risk for HIV infection. The regimen comprised 3 pills taken daily. The study was not powered for efficacy. Conclusion: Maraviroc-containing PrEP regimens were safe and well-tolerated compared with TDF-FTC in U.S. women. No new HIV infections occurred, although whether this was due to study drugs or low risk in the population is uncertain. Maraviroc-containing PrEP for women may warrant further study. Primary Funding Source: National Institutes of Health.


Assuntos
Cicloexanos/efeitos adversos , Cicloexanos/uso terapêutico , Inibidores da Fusão de HIV/efeitos adversos , Inibidores da Fusão de HIV/uso terapêutico , Infecções por HIV/prevenção & controle , Profilaxia Pré-Exposição , Triazóis/efeitos adversos , Triazóis/uso terapêutico , Adolescente , Adulto , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Maraviroc , Pessoa de Meia-Idade , Pacientes Desistentes do Tratamento , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
17.
Top Antivir Med ; 25(2): 51-67, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28598790

RESUMO

The 2017 Conference on Retroviruses and Opportunistic Infections (CROI) featured exciting preclinical data on investigational antiretroviral agents with good in vitro efficacy and long half-lives. Investigational medications, including bictegravir, demonstrated excellent efficacy and tolerability, as did dual-agent therapy with dolutegravir paired with rilpivirine or with lamivudine. Dolutegravir monotherapy proved inadvisable due to virologic failure and resistance. The gap between high- and low-income settings along the HIV care continuum is narrowing, with Zimbabwe, Malawi, and Zambia approaching the 90-90-90 targets established by the joint United Nations Programme on HIV/AIDS (UNAIDS), whereas communities in the Southern United States are falling behind. Innovative strategies to improve outcomes include 2-way text messaging, home-based HIV testing, peer navigation, and New York City's realignment of services into comprehensive sexual health programs. A high prevalence of resistance was documented in low- and middle-income settings and policy considerations were modeled to address increasing resistance rates. Novel resistance mutations to integrase strand transfer inhibitors and nucleoside analogue reserve transcriptase inhibitors were identified, but the clinical implications are unclear and require further investigation. Several studies provided insights on dosing and safety of antiretroviral therapy to prevent mother-to-child transmission through pharmacokinetic analysis. A special session devoted to Zika virus included a study of its effects on the central nervous system and a promising animal study of a Zika vaccine.


Assuntos
Antirretrovirais/uso terapêutico , Fármacos Anti-HIV , Infecções por HIV , Humanos , Lamivudina , Cidade de Nova Iorque , Zika virus , Infecção por Zika virus
18.
J Acquir Immune Defic Syndr ; 75(3): e59-e64, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28141783

RESUMO

BACKGROUND: Anal cancer is a relatively common cancer among HIV-infected populations. There are limited data on the prevalence of anal high-risk human papillomavirus (HR-HPV) infection and anal dysplasia in HIV-infected women from resource-constrained settings. METHODS: A cross-sectional study of HIV-infected women aged 25-65 years recruited from an HIV clinic in Johannesburg, South Africa. Cervical and anal swabs were taken for conventional cytology and HR-HPV testing. Women with abnormal anal cytology and 20% of women with negative cytology were seen for high-resolution anoscopy with biopsy of visible lesions. RESULTS: Two hundred women were enrolled. Anal HR-HPV was found in 43%. The anal cytology results were negative in 51 (26%); 97 (49%) had low-grade squamous intraepithelial lesions (SIL), 32 (16%) had atypical squamous cells of unknown significance, and 19 (9.5%) had high-grade SIL or atypical squamous cells suggestive of high-grade SIL. On high-resolution anoscopy, 71 (36%) had atypia or low-grade SIL on anal histology and 17 (8.5%) had high-grade SIL. Overall, 31 (17.5%) had high-grade SIL present on anal cytology or histology. Abnormal cervical cytology was found in 70% and cervical HR-HPV in 41%. CONCLUSIONS: We found a significant burden of anal HR-HPV infection, abnormal anal cytology, and high-grade SIL in our cohort. This is the first study of the prevalence of anal dysplasia in HIV-infected women from sub-Saharan Africa. Additional studies are needed to define the epidemiology of these conditions, as well as the incidence of anal cancer, in this population.


Assuntos
Canal Anal/patologia , Doenças do Ânus/epidemiologia , Doenças do Ânus/patologia , Infecções por HIV/epidemiologia , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/patologia , Lesões Pré-Cancerosas/epidemiologia , Adulto , Canal Anal/virologia , Doenças do Ânus/virologia , Biópsia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Estudos Transversais , Citodiagnóstico , Feminino , Infecções por HIV/patologia , Humanos , Infecções por Papillomavirus/diagnóstico , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/virologia , Prevalência , Proctoscopia , África do Sul/epidemiologia
19.
J Infect Dis ; 215(2): 238-246, 2017 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-27811319

RESUMO

Background: Maraviroc (MVC) is a candidate for human immunodeficiency virus (HIV) pre-exposure prophylaxis. Methods: Phase 2 48-week safety/tolerability study was conducted, comparing 4 regimens: MVC alone, MVC plus emtricitabine (FTC), MVC plus tenofovir disoproxil fumarate (TDF), and TDF plus FTC. Eligible participants were HIV-uninfected men and transgender women reporting condomless anal intercourse with ≥1 HIV-infected or unknown-serostatus man within 90 days. At each visit, assessments, laboratory testing, and counseling were done. Analyses were intention to treat. Results: Among 406 participants, 84% completed follow-up, 7% stopped early, and 9% were lost to follow-up; 9% discontinued their regimen early. The number discontinuing and the time to discontinuation did not differ among study regimens (P = .60). Rates of grade 3-4 adverse events did not differ among regimens (P = .37). In a randomly selected subset, 77% demonstrated detectable drug concentrations at week 48. Five participants acquired HIV infection (4 MVC alone, 1 MVC + TDF; overall annualized incidence, 1.4% [95% confidence interval, .5%-3.3%], without differences by regimen; P = .32); 2 had undetectable drug concentrations at every visit, 2 had low concentrations at the seroconversion visit, and 1 had variable concentrations. Conclusions: MVC-containing regimens were safe and well tolerated compared with TDF + FTC; this study was not powered for efficacy. Among those acquiring HIV infection, drug concentrations were absent, low, or variable. MVC-containing regimens may warrant further study for pre-exposure prophylaxis. Clinical Trials Registration: NCT01505114.


Assuntos
Antagonistas dos Receptores CCR5/administração & dosagem , Antagonistas dos Receptores CCR5/efeitos adversos , Cicloexanos/administração & dosagem , Cicloexanos/efeitos adversos , Transmissão de Doença Infecciosa/prevenção & controle , Infecções por HIV/prevenção & controle , Profilaxia Pré-Exposição/métodos , Triazóis/administração & dosagem , Triazóis/efeitos adversos , Adolescente , Adulto , Idoso , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Método Duplo-Cego , Homossexualidade Masculina , Humanos , Masculino , Maraviroc , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
20.
PLoS One ; 11(8): e0160341, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27500639

RESUMO

Little is known about the humoral immune response against DNA prime-recombinant adenovirus 5 (rAd5) boost HIV vaccine among HIV-infected patients on long-term suppressive antiretroviral therapy (ART). Previous studies emphasized cellular immune responses; however, current research suggests both cellular and humoral responses are likely required for a successful therapeutic vaccine. Thus, we aimed to understand antibody response and function induced by vaccination of ART-treated HIV-1-infected patients with immune recovery. All subjects participated in EraMune 02, an open-label randomized clinical trial of ART intensification followed by a six plasmid DNA prime (envA, envB, envC, gagB, polB, nefB) and rAd5 boost HIV vaccine with matching inserts. Antibody binding levels were determined with a recently developed microarray approach. We also analyzed neutralization efficiency and antibody-dependent cellular cytotoxicity (ADCC). We found that the DNA prime-rAd5 boost vaccine induced a significant cross-clade HIV-specific antibody response, which correlated with antibody neutralization efficiency. However, despite the increase in antibody binding levels, the vaccine did not significantly stimulate neutralization or ADCC responses. This finding was also reflected by a lack of change in total CD4+ cell associated HIV DNA in those who received the vaccine. Our results have important implications for further therapeutic vaccine design and administration, especially in HIV-1 infected patients, as boosting of preexisting antibody responses are unlikely to lead to clearance of latent proviruses in the HIV reservoir.


Assuntos
Vacinas contra a AIDS/imunologia , Adenoviridae/genética , Anticorpos Anti-HIV/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Imunização Secundária/métodos , Vacinas de DNA/imunologia , Vacinas contra a AIDS/administração & dosagem , Adenoviridae/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Linfócitos T CD4-Positivos , Feminino , Anticorpos Anti-HIV/sangue , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/genética , Proteínas do Vírus da Imunodeficiência Humana/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Vacinas de DNA/administração & dosagem
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