RESUMEN
BACKGROUND: Lenacapavir is a long-acting HIV-1 capsid inhibitor for treatment of HIV-1 infection. We evaluated the efficacy and safety of lenacapavir in combination with an investigator-selected optimized background regimen (OBR) after 104 weeks in adults with multidrug-resistant HIV-1. METHODS: This ongoing, international, Phase 2/3 trial at 42 sites included 72 adults living with multidrug-resistant HIV-1. Following a 2-week oral lenacapavir loading phase, participants received subcutaneous lenacapavir every 26 weeks with an OBR. HIV-1 RNA, CD4 cell counts, and adverse events were assessed over 104 weeks. One participant did not enter the extension phase. RESULTS: At Week 104, 44 of 71 participants (62%, 95% CI 50; 73) had HIV-1 RNA <50 copies/mL via US Food & Drug Administration (FDA) snapshot algorithm. When missing data (including discontinuations) were excluded, 44 of 54 participants (82%) had HIV-1 RNA <50 copies/mL at Week 104, mean CD4 cell count increased by 122 cells/µL (95% CI 80; 165), and the proportion of participants with CD4 cell count <200 cells/µL decreased from 64% (46 of 72) at Baseline to 29% (16 of 55). Fourteen participants had treatment-emergent lenacapavir resistance; seven resuppressed (HIV-1 RNA <50 copies/mL) while maintaining lenacapavir use. There were no Grade 4 or serious treatment-related adverse events. One participant discontinued study drug due to an injection site reaction. CONCLUSIONS: Treatment with subcutaneous lenacapavir in combination with an OBR was well tolerated and resulted in a high rate of virological suppression over 104 weeks. Lenacapavir represents an important treatment option in people with multidrug-resistant HIV-1.
RESUMEN
BACKGROUND: Real-world evidence is an essential component of evidence-based medicine. The aim of the BICSTaR (BICtegravir Single Tablet Regimen) study is to assess effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in antiretroviral treatment-naïve (TN) and treatment-experienced (TE) people with HIV. METHODS: BICSTaR is a prospective, observational cohort study. Participants (≥18 years) are being followed for 24 months. A pooled analysis is presented at 12 months, with the primary endpoint of effectiveness (HIV-1 RNA <50 copies/mL) and secondary endpoints of safety and tolerability (as per protocol). An exploration of patient-reported outcome measures using standardized questionnaires is included. RESULTS: Between June 2018 and May 2021, 1552 people with HIV were enrolled across 12 countries. The analysed population comprised 1509 individuals (279 TN, 1230 TE); most were white (76%), male (84%) and had one or more comorbid conditions (68%). Median age was 47 years. After 12 months of B/F/TAF treatment, HIV-1 RNA was <50 copies/mL in 94% (221/236) of TN participants and 97% (977/1008) of TE participants. Median CD4 cell count increased by 214 cells/µL (p < 0.001) in TN participants and 13 cells/µL (p = 0.014) in TE participants; median CD4/CD8 ratios increased by 0.30 and 0.03, respectively (both p < 0.001). Persistence was high at 12 months (TN, 97%; TE, 95%). No resistance to B/F/TAF emerged. Study drug-related adverse events occurred in 13% of participants through 12 months, leading to B/F/TAF discontinuation in 6%. CONCLUSIONS: The findings of this study provide robust real-world evidence to support the broad use of B/F/TAF in both TN and TE people with HIV.
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Alanina , Amidas , Fármacos Anti-VIH , Infecciones por VIH , Piperazinas , Piridonas , Tenofovir , Humanos , Masculino , Persona de Mediana Edad , Adenina/uso terapéutico , Fármacos Anti-VIH/efectos adversos , Combinación de Medicamentos , Emtricitabina/efectos adversos , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Compuestos Heterocíclicos de 4 o más Anillos/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Estudios Prospectivos , ARN/uso terapéutico , Tenofovir/análogos & derivados , Resultado del Tratamiento , FemeninoRESUMEN
BACKGROUND: Canadian clinical guidelines recommend at least annual and up to quarterly bacterial sexually transmitted infection (STI) testing among sexually active gay, bisexual, and other men who have sex with men (GBM). However, testing rates are suboptimal. Innovative solutions are needed to close the gap because there is currently limited knowledge on how best to approach this issue. OBJECTIVE: Our aim was to build consensus regarding interventions with the greatest potential for improving local STI testing services for GBM communities in Toronto, Ontario, Canada, using a web-based e-Delphi process. METHODS: The e-Delphi method involves using a panel format to conduct successive rounds of prioritization, with feedback between rounds, to determine priorities among groups. We recruited experts separately from the community (GBM who sought or underwent STI testing in the preceding 18 months; conducted between October 2019 and November 2019) and health care providers (those who offered STI testing to GBM in the past 12 months; conducted between February 2020 and May 2020). The experts prioritized 6 to 8 potential interventions on a 7-point Likert scale ranging from definitely not a priority to definitely a priority over 3 survey rounds and ranked their top 3 interventions. Consensus was defined as ≥60% within a ±1 response point. Summaries of responses were provided in successive rounds. We reported the percentage of a priority (encompassing somewhat a priority, a priority, and definitely a priority responses) at the end of the final round of the survey. RESULTS: Of the community experts (CEs), 84% (43/51) completed all rounds; 19% (8/43) were living with HIV; 37% (16/43) were HIV negative and on pre-exposure prophylaxis; and 42% (18/43) were HIV negative and not on pre-exposure prophylaxis. We reached consensus on 6 interventions: client reminders (41/43, 95%), express testing (38/43, 88%), routine testing (36/43, 84%), an online booking app (36/43, 84%), online-based testing (33/43, 77%), and nurse-led testing (31/43, 72%). The CEs favored convenient interventions that also maintain a relationship with their provider. Of the provider experts (PEs), 77% (37/48) completed all rounds; 59% (22/37) were physicians. Consensus was reached on the same 6 interventions (range 25/37, 68%, to 39/39, 100%) but not for provider alerts (7/37, 19%) and provider audit and feedback (6/37, 16%). Express testing, online-based testing, and nurse-led testing were prioritized by >95% (>37/39) of the PEs by the end of round 2 because of streamlined processes and decreased need to see a provider. CONCLUSIONS: Both panels were enthusiastic about innovations that make STI testing more efficient, with express testing rating highly in both the prioritizations and top 3 rankings. However, CEs preferred convenient interventions that involved their provider, whereas PEs favored interventions that prioritized patient independence and reduced patient-provider time. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/13801.
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Infecciones por VIH , Minorías Sexuales y de Género , Enfermedades de Transmisión Sexual , Masculino , Humanos , Técnica Delphi , Homosexualidad Masculina , Personal de Salud , Ontario , Enfermedades de Transmisión Sexual/diagnóstico , Enfermedades de Transmisión Sexual/prevención & controlRESUMEN
BACKGROUND: Rates of bacterial sexually transmitted infections (STIs) continue to rise among gay, bisexual, and other men who have sex with men (GBMSM) globally. Testing and treatment can prevent morbidity and transmission. However, testing rates remain suboptimal. METHODS: In 2018, we conducted an online cross-sectional survey to explore STI testing ordering practices, 14 potential barriers for testing and 11 possible ways to improve testing from the perspective of health care providers in Toronto, Ontario. An estimated 172 providers were invited from primary care and sexual health clinic settings. Providers were eligible to complete the survey if they provided care for ≥1 GBMSM per week and were involved in the decision-making process in providing STI tests. We used descriptive statistics to summarize survey responses. RESULTS: Ninety-five providers (55% response rate) participated, of whom 68% worked in primary care and 32% in sexual health settings. Most (66%) saw ≤10 GBMSM clients per week. In primary care (65%) and sexual health (40%) clinic settings, insufficient consultation time was the most common barrier to STI testing. In primary care, other common barriers included difficulty introducing testing during unrelated consultations (53%), forgetting (47%), and patients being sexually inactive (31%) or declining testing (27%). The following were most likely to improve testing: express/fast-track testing services (89%), provider alerts when patients are due for testing (87%), patient-collected specimens (84%), nurse-led STI testing (79%), and standing orders (79%). CONCLUSIONS: Promising interventions to improve bacterial STI testing included initiatives that simplify and expedite testing and expand testing delivery to other health care professionals.
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Infecciones por VIH , Minorías Sexuales y de Género , Enfermedades de Transmisión Sexual , Estudios Transversales , Personal de Salud , Homosexualidad Masculina , Humanos , Masculino , Ontario , Enfermedades de Transmisión Sexual/diagnóstico , Enfermedades de Transmisión Sexual/epidemiología , Enfermedades de Transmisión Sexual/prevención & controlRESUMEN
BACKGROUND: The resistance profiles for patients on first-line antiretroviral therapy (ART) regimens after viremia have not been well studied in community clinic settings in the modern treatment era. OBJECTIVE: To determine time to viremia and the ART resistance profiles of viremic patients. METHODS: HIV-positive patients aged ≥16 years initiating a three-drug regimen were retrospectively identified from 01/01/06 to 12/31/12. The regimens were a backbone of two nucleoside reverse transcriptase inhibitors (NRTIs) and a third agent: a protease inhibitor (PI), non-nucleoside reverse transcriptase inhibitor (NNRTI), or an integrase inhibitor (II). Time to viremia was compared using a proportional hazards model, adjusting for demographic and clinical factors. Resistance profiles were described in those with baseline and follow-up genotypes. RESULTS: For 653 patients, distribution of third-agent use and viremia was: 244 (37%) on PIs with 80 viremia, 364 (56%) on NNRTIs with 84 viremia, and 45 (7%) on II with 11 viremia. Only for NNRTIs, time to viremia was longer than PIs (p = 0.04) for patients with a CD4 count ≥200 cells/mm(3). Of the 175 with viremia, 143 (82%) had baseline and 37 (21%) had follow-up genotype. Upon viremia, emerging ART resistance was rare. One new NNRTI (Y181C) mutation was identified and three patients taking PI-based regimens developed NRTI mutations (M184 V, M184I, and T215Y). CONCLUSIONS: Time to viremia for NNRTIs was longer than PIs. With viremia, ART resistance rarely developed without PI or II mutations, but with a few NRTI mutations in those taking PI-based regimens, and NNRTI mutations in those taking NNRTI-based regimens.
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Fármacos Anti-VIH/uso terapéutico , Farmacorresistencia Viral , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Viremia , Adulto , Fármacos Anti-VIH/administración & dosificación , Femenino , Infecciones por VIH/sangre , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Carga ViralRESUMEN
The BICSTaR (BICtegravir Single Tablet Regimen) study is investigating the effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in people with human immunodeficiency virus (HIV) treated in routine clinical practice. BICSTaR is an ongoing, prospective, observational cohort study across 14 countries. Treatment-naïve (TN) and treatment-experienced (TE) people with HIV (≥18 years of age) are being followed for 24 months. We present an analysis of the primary endpoint (HIV-1 RNAâ <â 50 copies/mL; missing-equals-excluded [Mâ =â E]) at month 12 in the BICSTaR Canada cohort, including secondary (CD4 count, CD4/CD8 ratio, safety/tolerability) and exploratory (persistence, treatment satisfaction) endpoints. In total, 201 participants were enrolled in the BICSTaR Canada cohort. The analysis population included 170 participants (TN, nâ =â 10; TE, nâ =â 160), with data collected between November 2018 and September 2020. Of the participants, 88% were male, 72% were White, and 90% hadâ ≥â 1 comorbid condition(s). Median (quartile [Q]1-Q3) age was 50 (39-58) years and baseline CD4 count was 391.5 (109.0-581.0) cells/µL in TN participants and 586.0 (400.0-747.0) cells/µL in TE participants. After 12 months of B/F/TAF treatment, HIV-1 RNA wasâ <â 50 copies/mL in 100% (9/9) of TN-active participants and 97% (140/145) of TE-active participants (Mâ =â E analysis). Median (Q1-Q3) CD4 cell count increased byâ +195 (125-307) cells/µL in TN participants and byâ +â 30 (-50 to 123) cells/µL in TE participants. Persistence on B/F/TAF was high through month 12 with 10% (1/10) of TN and 7 % (11/160) of TE participants discontinuing B/F/TAF within 12 months of initiation of treatment. No resistance to B/F/TAF emerged. Study drug-related adverse events occurred in 7% (12/169) of participants, leading to B/F/TAF discontinuation in 4 of 169 participants. Improvements in treatment satisfaction were observed in TE participants. B/F/TAF demonstrated high levels of effectiveness, persistence, and treatment satisfaction, and was well tolerated through month 12 in people with HIV treated in routine clinical practice in Canada.
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Alanina , Amidas , Fármacos Anti-VIH , Infecciones por VIH , VIH-1 , Piperazinas , Piridonas , Tenofovir/análogos & derivados , Masculino , Humanos , Preescolar , Persona de Mediana Edad , Femenino , Infecciones por VIH/tratamiento farmacológico , Emtricitabina/efectos adversos , Estudios Prospectivos , Adenina/uso terapéutico , Resultado del Tratamiento , Canadá , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Fármacos Anti-VIH/efectos adversos , Combinación de Medicamentos , ARNRESUMEN
BACKGROUND: Herpes simplex virus type 2 (HSV-2) reactivations are associated with increased HIV load, but whether HSV-2 coinfection accelerates HIV disease is unclear. We compared rates of CD4 count decline according to HSV-2 status in untreated HIV-infected adults. METHODS: HIV-infected patients with a past period of antiretroviral therapy (ART)-untreated follow-up with initial CD4 count of 400-900 cells/mm(3) and no chronic anti-HSV therapy were included. HSV-2 status was determined by HerpeSelect enzyme-linked immunosorbent assay. Rates of CD4 count change were compared by HSV-2 status using mixed linear regression models, and time to the first of ART initiation or CD4 <350 cells/mm(3) using proportional hazards models. RESULTS: Of 218 patients included, 123 (56.4%) were seropositive for HSV-2 and 161 (73.8%) for HSV-1. In univariate analysis, the difference in the rate of CD4 count change associated with HSV-2 was not statistically significant at +13.6 cells/mm(3)/year (P = .12). Results were similar at -4.5 cells/mm(3)/year (P = .68) after adjustment for sex, HSV type 1, oral and genital herpes symptoms, immigrant status, and the interaction of immigrant status with time. However, HSV-2 seropositivity was associated with a shorter time to the first of ART initiation or CD4 <350 cells/mm(3), with an adjusted hazard ratio of 2.07 (95% confidence interval, 1.28-3.33). CONCLUSIONS: HSV-2 coinfection was not associated with the rate of CD4 count decline during ART-untreated HIV infection, but was associated with an earlier combined endpoint of ART initiation or CD4 <350 cells/mm(3). Attenuating effects of acyclovir on HIV disease progression observed in recent clinical trials may result from direct anti-HIV activity rather than indirect benefits from HSV-2 suppression.
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Linfocitos T CD4-Positivos/inmunología , Coinfección/inmunología , Infecciones por VIH/complicaciones , Infecciones por VIH/inmunología , Herpes Genital/inmunología , Herpesvirus Humano 2/aislamiento & purificación , Adulto , Recuento de Linfocito CD4 , Coinfección/virología , Ensayo de Inmunoadsorción Enzimática , Femenino , Herpes Genital/virología , Humanos , MasculinoRESUMEN
OBJECTIVE: To compare the immunologic effectiveness of raltegravir-maraviroc (R+M+)-based regimens with raltegravir-based regimens that do not include maraviroc (R+M-) in treatment-experienced patients in clinical practice. METHODS: We conducted a retrospective study of treatment-experienced HIV-infected adults receiving either R+M+- or R+M--based therapy. Longitudinal CD4 counts were analyzed using a linear mixed model. RESULTS: One hundred and fifty-six patients were included in the analysis, of whom 32 were receiving R+M+ and 124 R+M-. Mean baseline CD4 counts in patients on R+M+ and R+M- were 463.8 and 442.3 cells/mm(3), respectively (P = .67). In multivariable mixed models, a baseline viral load ≥50 copies/mL was significantly associated with CD4 change during follow-up (P < .0001). No difference between R+M+ and R+M- was observed during follow-up (P = .81). CONCLUSION: CD4 cell recovery was similar among patients receiving either R+M+- or R+M--based therapy during a 24-month period of follow-up.
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Fármacos Anti-VIH/inmunología , Terapia Antirretroviral Altamente Activa , Ciclohexanos/inmunología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Pirrolidinonas/inmunología , Triazoles/inmunología , Fármacos Anti-VIH/uso terapéutico , Recuento de Linfocito CD4 , Ciclohexanos/uso terapéutico , Femenino , Infecciones por VIH/virología , Humanos , Masculino , Maraviroc , Persona de Mediana Edad , Pirrolidinonas/uso terapéutico , Raltegravir Potásico , Estudios Retrospectivos , Triazoles/uso terapéutico , Carga ViralRESUMEN
Because antiretroviral therapy (ART) is allowing people living with human immunodeficiency virus (PLWH) to survive longer, they are developing more age-related comorbidities. We evaluated the effects of age and gender on the burden of age-related comorbidities among PLWH. In this retrospective real-world study, de-identified data were extracted from the medical charts of 2000 HIV-positive adults on ART across 10 sites in Canada. The prevalence of age-related comorbidities was determined in 6 age subgroups (<30, 30-39, 40-49, 50-59, 60-69, and ≥70 years). The effects of gender on these comorbidities were also examined. Risks of cardiovascular disease and chronic kidney disease (CKD) were calculated using the Framingham and D:A:D equations. Most persons were White (68%), male (87%), and virologically suppressed (94%). The mean age was 50.3 years (57% aged ≥50 years), and mean CD4+ T-cell count was 616 cells/mm3. The most common comorbidities were neuropsychiatric symptoms (61%), overweight/obesity (43%), liver disease (37%), and dyslipidemia (37%). The mean number of comorbidities increased across age subgroups (P < .001). Across all age subgroups, the prevalence of hypertension (P = .04), dyslipidemia (P = .04), CKD (P = .03), bone fragility (P = .03), and depression (P = .02) differed between males and females. Both age (P < .001) and gender (P < .001) impacted cardiovascular disease and CKD risk. Age and gender influenced the burden, types, and risks of age-related comorbidities in PLWH in this Canadian cohort. These comorbidities should be diagnosed and treated in routine clinical practice.
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Enfermedades Cardiovasculares , Infecciones por VIH , Insuficiencia Renal Crónica , Adulto , Canadá/epidemiología , Enfermedades Cardiovasculares/epidemiología , Estudios Transversales , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Insuficiencia Renal Crónica/epidemiología , Estudios RetrospectivosRESUMEN
PURPOSE: To evaluate polyalkylamide gel (PAIG) use in treating HIV-associated facial lipoatrophy (FLA) 4 years after its injection in an open-label, randomized controlled trial (RCT). METHODS: Five patients were treated with PAIG in a pilot study, and 31 patients were subsequently enrolled in the RCT of immediate or delayed (12 weeks later) PAIG injections. Endpoints included proportion of participants with complications; changes in FLA severity score (FLSS); and quality of life (QoL), depression, anxiety, and satisfaction scores. Infections were classified as "confirmed" if purulent material was extracted and/or an organism cultured. Infections were classified as "possible" if only clinical signs were present without purulent discharge or microbiologic confirmation. RESULTS: Year 4 results were available for 5 pilot and 27 full-scale study participants. Delayed complications included 5 confirmed infections (15.6%), 3 possible infections (9.4%), nodules (25%), and bleeding (3%). No significant changes were observed between years 2 to 4 in patient-graded FLSS, QoL, depression, and anxiety scores. Whereas 94% of participants were satisfied with their overall treatment, only 69% were satisfied with PAIG treatment specifically. CONCLUSION: Even though PAIG treatment was associated with delayed complications including high rates of infection and nodules, most patients were satisfied with the treatment.
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Resinas Acrílicas/uso terapéutico , Síndrome de Lipodistrofia Asociada a VIH/terapia , Resinas Acrílicas/administración & dosificación , Adulto , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Esquema de Medicación , Cara/patología , Femenino , Geles , Humanos , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Proyectos PilotoRESUMEN
We assessed renal and metabolic changes associated with switching from tenofovir disoproxil fumarate (TDF)- to tenofovir alafenamide (TAF)-containing regimens among patients with HIV at the Maple Leaf Medical Clinic, Toronto, Canada. Using an electronic medical records retrospective chart review from July 2005 to December 2019, 651 patients aged ≥16 years taking TDF-containing regimens for ≥6 months who switched to TAF-containing regimens for ≥6 months were included. Change in estimated glomerular filtration rate (eGFR) was examined at 12-month follow-up. Secondary outcomes included change in urine albumin-to-creatinine ratio, serum phosphate, alkaline phosphatase (ALP), cholesterol markers, HbA1C, and weight. After 12 months, eGFR increased in 63% of the baseline eGFR <60 mL/min/1.73 m2 group (mean change [SD] = +5.1 [10.8], p = 0.002), 52% for the baseline eGFR = 60-90 mL/min/1.73 m2 group (+0.5 [10.4], p = 0.490), and 26% for baseline eGFR >90 mL/min/1.73 m2 group (-7.2 [11.2], p <0.001). The multivariable generalized estimating equations model showed a significant reduction in eGFR after 12 months. Advanced age, HCV coinfection, and being switched to or on integrase inhibitors were significantly associated with reduced eGFR. Among secondary outcomes, ALP significantly decreased, while high-density lipoprotein, low-density lipoprotein, and weight significantly increased. Our findings suggest that TDF-to-TAF switching was beneficial for those with preexisting renal impairment (eGFR <60 mL/min/1.73 m2).
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Fármacos Anti-VIH , Infecciones por VIH , Alanina , Fármacos Anti-VIH/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Humanos , Estudios Retrospectivos , Tenofovir/análogos & derivados , Tenofovir/uso terapéuticoRESUMEN
Men who have sex with men (MSM) are disproportionately affected by anal cancer, predominantly caused by high-risk (HR) human papillomavirus (HPV) infection. Currently, the nonavalent HPV vaccine provides coverage against nine HPV genotypes, including seven HR-HPV genotypes. Here, we characterize anal HR-HPV genotype distribution and associated risk factors in MSM from Toronto, Canada recruited between September 2010 and June 2012. Wilcoxon-Mann-Whitney test was used for continuous variables, Chi-square test was performed for categorical variables, and a multivariable model using logistic regression was created to assess for correlates of anal HR-HPV infection. A total of 442 MSM were recruited, with a median age of 45 (IQR 38-50) and an overall HPV prevalence of 82%. The prevalence of any HR-HPV infection was 65.3% and 50.7% in the HIV-positive and HIV-negative MSM, respectively. No participant tested positive for all genotypes covered by the nonavalent vaccine. HIV status (aOR 1.806; 95% CI 1.159-2.816), smoking (aOR 2.176; 95% CI 1.285-3.685) and the number of lifetime sexual partners (aOR 2.466; 95% CI 1.092-5.567) were independent risk factors for anal HR-HPV infection. Our findings will be useful to inform HPV vaccine rollout and HPV prevention strategies in Canadian MSM.
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Alphapapillomavirus/aislamiento & purificación , Infecciones por Papillomavirus/epidemiología , Adulto , Alphapapillomavirus/genética , Canal Anal/virología , Enfermedades del Ano/virología , Canadá/epidemiología , Genotipo , Homosexualidad Masculina , Humanos , Masculino , Persona de Mediana Edad , Infecciones por Papillomavirus/complicaciones , Factores de Riesgo , Parejas SexualesRESUMEN
Following cardiovascular events (CVE) among people living with HIV (PLWH) is essential. Abacavir (ABC)'s impact on CVE challenges clinicians. We characterized CVE at our HIV clinic associated with ABC versus tenofovir disoproxil fumarate (TDF). This was a retrospective study of PLWH who started combination antiretroviral therapy with no prior CVE. Patients were evaluated as antiretroviral naive or antiretroviral experienced. Regimens included the following: always-ABC, always-TDF, first-ABC-switched-to-TDF, and first-TDF-switched-to-ABC regimens. Frequencies, rates, and Poisson regression were used to analyze CVE (cardiovascular/cerebrovascular) and were stratified with an a priori cutoff of before or after January 1, 2009. 1,440/2,852 patients were antiretroviral naive; 658 on always-ABC regimens, 1,186 on always-TDF regimens, 737 first-ABC-switched-to-TDF regimens, and 271 first-TDF-switched-to-ABC regimens. Seventy seven CVE occurred overall [16 naive vs. 61 experienced (p < .0001)]. Sixty events were cardiovascular and 17 cerebrovascular (p < .0001). Sixty-nine CVE occurred before 2009 and eight after (p < .0001). There were 5.65 CVE-per-1,000-years [95% confidence interval (CI) 3.23-9.87] in the always-ABC, 1.95 CVE-per-1,000-years (95% CI 1.08-3.51) in the always-TDF, 2.01 CVE-per-1,000-years (95% CI 1.14-3.56) in the ABC-switched-to-TDF, and 1.82 CVE-per-1,000-years (95% CI 0.77-4.30) in TDF-switched-to-ABC (p <.01). Multivariable Poisson regression incidence rate ratios (IRRs) revealed that being on ABC-only (IRR 2.89; 95% CI 2.13-3.94), age (IRR 1.06 per year; 95% CI 1.04-1.07), and smoking (IRR for current 2.81; 95% CI 1.97-3.99; IRR for former 2.49; 95% CI 1.72-3.61) increased risk of CVE. Thus, in our clinic, CVE rates were increased in those on ABC and adds to the body of literature suggesting concern.
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Fármacos Anti-VIH , Enfermedades Cardiovasculares , Infecciones por VIH , Fármacos Anti-VIH/efectos adversos , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/epidemiología , Didesoxinucleósidos , Infecciones por VIH/tratamiento farmacológico , Humanos , Estudios Retrospectivos , Tenofovir/efectos adversosRESUMEN
OBJECTIVE: To examine whether persons with asymptomatic neurocognitive impairment (ANI) were more likely to show progression to mild neurocognitive disorder or HIV-associated dementia than those who were neuropsychologically normal (NP-N). DESIGN: Longitudinal observational cohort study. METHODS: Study sample included 720 HIV-1 seropositive persons (317 with ANI and 403 NP-N) receiving care in Toronto, Canada [83% were on antiretroviral treatment; 71% had undetectable (<50 copies/ml) plasma HIVRNA]. Neuropsychological assessments were conducted at 12 months intervals for a median follow-up time of 34 months. Neuropsychological data were corrected for age, education, sex, and race/ethnicity, and corrected for practice effect at follow-ups. Progression to mild neurocognitive disorder and HIV-associated dementia at each time point was determined using the Global Deficit Score and presence of cognitive symptoms. RESULTS: Over the follow-up period, 170 individuals (24%) progressed to symptomatic HIV-associated neurocognitive disorders (HAND). Persons with ANI were more likely to progress to symptomatic HAND than persons with NP-N after adjusting for baseline and time-varying confounders (adjusted hazards ratio: 1.88; 95% confidence interval: 1.37-2.60; Pâ<â0.001). Female sex, depression, and cigarette smoking were associated with higher risk of progression to symptomatic HAND, but traditional HIV markers and antiretroviral treatment were not. CONCLUSION: ANI is associated with a two-fold increased risk of progression to symptomatic HAND in a cohort with universal healthcare access. This represents the largest replication of comparable US results. Reproducibility of these findings indicate that routine monitoring of persons with ANI and exploration of clinical interventions to prevent or delay progression to symptomatic HAND are imperative. SEARCH TERMS: HIV, HAND, HIV-associated dementia, cohort study, replicability, reproducibility.
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Complejo SIDA Demencia , Infecciones por VIH , Complejo SIDA Demencia/diagnóstico , Complejo SIDA Demencia/epidemiología , Canadá , Estudios de Cohortes , Estudios Transversales , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Pruebas Neuropsicológicas , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: In DISCOVER, a multinational, randomised controlled trial, emtricitabine and tenofovir alafenamide compared with emtricitabine and tenofovir disoproxil fumarate showed non-inferior efficacy for HIV prevention and improved bone mineral density and renal safety biomarkers at week 48. We report outcomes analysed after all participants had completed 96 weeks of follow-up. METHODS: This study is an ongoing, randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial done at 94 community, public health, and hospital-associated clinics located in Europe and North America. Adult cisgender men and transgender women who have sex with men, both with a high risk of acquiring HIV as determined by self-reported sexual behaviour or recent sexually transmitted infections, were randomly assigned (1:1) to receive either emtricitabine and tenofovir alafenamide (200/25 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir alafenamide group), or emtricitabine and tenofovir disoproxil fumarate (200/300 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir disoproxil fumarate group). The primary efficacy outcome was incident HIV infection. Incidence of HIV-1 infection per 100 person-years was assessed when the last participant had completed 96 weeks of follow-up. This trial is registered with ClinicalTrials.gov, number NCT02842086. FINDINGS: Between Sept 13, 2016, and June 30, 2017, 5387 participants were randomly assigned to receive emtricitabine and tenofovir alafenamide (n=2694) or emtricitabine and tenofovir disoproxil fumarate (n=2693), contributing 10 081 person-years of follow-up. At 96 weeks of follow-up, there were eight HIV infections in participants who had received emtricitabine and tenofovir alafenamide (0·16 infections per 100 person-years [95% CI 0·07-0·31]) and 15 in participants who had received emtricitabine and tenofovir disoproxil fumarate (0·30 infections per 100 person-years [0·17-0·49]). Emtricitabine and tenofovir alafenamide maintained its non-inferiority to emtricitabine and tenofovir disoproxil fumarate for HIV prevention (IRR 0·54 [95% CI 0·23-1·26]). Approximately 78-82% of participants reported taking study medication more than 95% of the time across all study visits. Rates of sexually transmitted infections remained high and similar across groups (21 cases per 100 person-years for rectal gonorrhoea and 28 cases per 100 person-years for rectal chlamydia). Emtricitabine and tenofovir alafenamide continued to show superiority over emtricitabine and tenofovir disoproxil fumarate in all but one of the six prespecified bone mineral density and renal biomarkers. There was more weight gain among participants who had received emtricitabine and tenofovir alafenamide (median weight gain 1·7 kg vs 0·5 kg, p<0·0001). INTERPRETATION: Emtricitabine and tenofovir alafenamide is safe and effective for longer-term pre-exposure prophylaxis in cisgender men and transgender women who have sex with men. FUNDING: Gilead Sciences.
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Adenina/análogos & derivados , Alanina/uso terapéutico , Fármacos Anti-VIH/uso terapéutico , Emtricitabina/uso terapéutico , Infecciones por VIH/prevención & control , Organofosfonatos/uso terapéutico , Tenofovir/uso terapéutico , Adenina/efectos adversos , Adenina/uso terapéutico , Adulto , Anciano , Alanina/efectos adversos , Fármacos Anti-VIH/efectos adversos , Método Doble Ciego , Quimioterapia Combinada/efectos adversos , Emtricitabina/efectos adversos , Femenino , Estudios de Seguimiento , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , VIH-1/fisiología , Humanos , Masculino , Persona de Mediana Edad , Organofosfonatos/efectos adversos , Profilaxis Pre-Exposición , Tenofovir/efectos adversos , Resultado del Tratamiento , Adulto JovenRESUMEN
The long-term safety and efficacy of products used in the correction of HIV-associated facial lipoatrophy (FLA) are largely unknown. The purpose of this study was to describe the long-term efficacy and safety of polyalkylimide gel (PAIG) in the treatment of HIV-associated FLA. In this open-label, randomized, single-center study, 31 HIV-positive individuals (median age 48 years (interquartile ranges (IQR) 45, 55, 97% male) with FLA were randomized to immediate (week 0 and six) or delayed (week 12 and 18) PAIG injections. Week 96 endpoints included change in FLA severity scores (FLSS) (five-point scale), proportion of patients with adverse events, and changes in quality of life, depression and anxiety using validated surveys. Results at week 96 were available for 28 patients. Adverse events, including swelling, redness, bruising and pain, were mild, and resolved after a median of three days following the injection. At week 96, median changes in physician and patient FLSS scores were -2 (IQR -3, -1; p<0.001 vs. baseline) and -2 (IQR -2, -1; p<0.001 vs. baseline), respectively. Physician and patient FLSS scores were not significantly different between the groups at week 96. Significant improvements in patient's anxiety (p<0.001), depression (p<0.001) and mental health (p=0.01) were observed from baseline to week 96. In conclusion, treatment with PAIG was associated with sustained improvements in both the physical and psychological components of FLA through 96 weeks of follow-up.
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Resinas Acrílicas/administración & dosificación , Fármacos Dermatológicos/administración & dosificación , Síndrome de Lipodistrofia Asociada a VIH/tratamiento farmacológico , Resinas Acrílicas/efectos adversos , Trastornos de Ansiedad/etiología , Trastorno Depresivo/etiología , Cara , Femenino , Geles , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Resultado del TratamientoRESUMEN
Information on the virologic durability of modern antiretroviral regimens is important to clinicians. We aimed to describe virologic durability of first-line integrase strand transfer inhibitor (INSTI)-, nonnucleoside reverse transcriptase inhibitor (NNRTI)-, or protease inhibitor (PI)-based antiretroviral regimens. This was a retrospective study of antiretroviral-naïve patients that initiated first-line antiretroviral regimens with two nucleoside reverse transcriptase inhibitors and an INSTI, NNRTI, or PI between January 2006 and June 2016. The outcome was time to virologic failure, which was assessed by Kaplan-Meier survival analysis and Cox regression models. There were 780 patients (median age = 37 years [interquartile range (IQR) = 30-45], 93.3% male, 56.2% Caucasian, median HIV duration = 1.8 years [IQR = 0.4-5.4], baseline log10 viral load [VL]=4.6 [IQR = 4.1-5.1], and baseline CD4+ cell count = 320 cells/µl [IQR = 217-440]). In total, 189/780 were on a third agent INSTI, 339/780 on a third agent NNRTI, and 252/780 on a third agent PI. Kaplan-Meier survival probability revealed longer time to virologic failure for INSTI, followed by NNRTI then PI (p < 0.001). Multivariable Cox regression revealed that being on an INSTI regimen (aHR = 0.27; 95%CI = 0.18-0.41) or NNRTI regimen (aHR = 0.64; 95%CI = 0.47-0.87) versus PI regimen, frequent VL testing (per year), (aHR = 0.64; 95%CI = 0.47-0.87), and duration of ART (aHR = 0.22; 95%CI = 0.17-0.30) (years) were inversely associated with time to virologic failure, and log10 of baseline VL (aHR = 1.94; 95%CI = 1.58-2.39 per log10) increased risk. Virologic failure was delayed and virologic durability prolonged for INSTI- compared to NNRTI- and PI-based regimens, supporting current antiretroviral therapy guidelines.
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Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Carga Viral/efectos de los fármacos , Adulto , Femenino , Infecciones por VIH/virología , Inhibidores de Integrasa VIH/uso terapéutico , Inhibidores de la Proteasa del VIH/uso terapéutico , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
BACKGROUND: HIV-positive and HIV-negative (gay, bisexual, and other) men who have sex with men (MSM) have experienced a dramatic increase in bacterial sexually transmitted infections (STIs)-syphilis, gonorrhea, and chlamydia. STI testing and treatment mitigate adverse health outcomes and substantially reduce transmission; yet, testing rates remain below recommended levels. Innovation is needed to produce the required increases in testing levels, frequency, and the use of appropriate testing technologies in ways that are engaging, nonstigmatizing, and acceptable to men. OBJECTIVE: The aim of this study is to build consensus with regard to interventions with the greatest potential for improving local STI testing services for MSM communities in Toronto, Canada. METHODS: Following a literature review of evidence regarding the effectiveness of novel testing interventions, and focus groups, and surveys to describe local barriers and facilitators of testing among MSM, we will conduct a Web-based, modified Delphi study (e-Delphi). We will form expert panels of community members and STI test providers. Panelists will rate potential interventions in terms of their priority, using a 7-point Likert scale from definitely not a priority to definitely a priority. They will also rank their preferences by selecting their top 3 preferred interventions. Surveys will be distributed in 3 rounds, with feedback on the distribution of responses from preceding rounds provided in rounds 2 and 3. We will define consensus as having ≥60% (18/30) members indicate a preference within 2 adjacent response points. Qualitative data on disagreements will be obtained using open-ended text responses to explain for ratings and rankings that are different from the majority. RESULTS: On the basis of a literature review and identification of barriers and facilitators to STI testing among community members and test providers in Toronto, we have selected 8 potential interventions for inclusion in the e-Delphi panel surveys. These include 4 interventions that streamline STI testing for asymptomatic individuals, 2 interventions that are targeted at clients and 2 interventions that are targeted at providers. CONCLUSIONS: Findings will provide community direction for informed decision making regarding the implementation of STI testing interventions in this setting. They will characterize the intervention climate for innovation to STI testing services, including perceived needs for changes to test delivery, relative priorities for change, and readiness for implementation. These methods may be transferable to other urban jurisdictions experiencing similar epidemics and for other contexts where stakeholder input is needed to manage sensitive areas of concern. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/13801.
RESUMEN
BACKGROUND: Non-disclosure criminal prosecutions among gay, bisexual and other men who have sex with men (MSM) are increasing, even though transmission risk is low when effective antiretroviral treatment (ART) is used. Reduced HIV testing may reduce the impact of HIV "test and treat" strategies. We aimed to quantify the potential impact of non-disclosure prosecutions on HIV testing and transmission among MSM. METHODS: MSM attending an HIV and primary care clinic in Toronto completed an audio computer-assisted self-interview questionnaire. HIV-negative participants were asked concern over non-disclosure prosecution altered their likelihood of HIV testing. Responses were characterized using cross-tabulations and bivariate logistic regressions. Flow charts modelled how changes in HIV testing behaviour impacted HIV transmission rates controlling for ART use, condom use and HIV status disclosure. RESULTS: 150 HIV-negative MSM were recruited September 2010 to June 2012. 7% (9/124) were less or much less likely to be tested for HIV due to concern over future prosecution. Bivariate regression showed no obvious socio/sexual demographic characteristics associated with decreased willingness of HIV testing to due concern about prosecution. Subsequent models estimated that this 7% reduction in testing could cause an 18.5% increase in community HIV transmission, 73% of which was driven by the failure of HIV-positive but undiagnosed MSM to access care and reduce HIV transmission risk by using ART. CONCLUSIONS: Fear of prosecution over HIV non-disclosure was reported to reduce HIV testing willingness by a minority of HIV-negative MSM in Toronto; however, this reduction has the potential to significantly increase HIV transmission at the community level which has important public health implications.
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Infecciones por VIH/diagnóstico , VIH-1 , Conductas de Riesgo para la Salud , Homosexualidad Masculina , Aplicación de la Ley , Encuestas y Cuestionarios , Adulto , Infecciones por VIH/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Ontario/epidemiología , Estudios Retrospectivos , AutorrevelaciónRESUMEN
Coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide (E/C/F/TAF) has high efficacy and improved renal and bone safety in multiple phase 3 trials; TAF single agent is being studied in 2 phase 3 trials in patients with chronic hepatitis B. We report the results of an open-label, noncomparative switch study evaluating the efficacy and safety of E/C/F/TAF in HIV/hepatitis B virus (HBV)-coinfected adults. At 48 weeks, 91.7% of the 72 participants maintained or achieved virologic suppression (HIV-1 RNA <50 copies/mL; HBV DNA <29 IU/mL). Seroconversion occurred in 2.9% of hepatitis B surface antigen-positive participants and in 3.3% of HBV e antigen-positive participants; 40% of those with abnormal alanine aminotransferase normalized. E/C/F/TAF was associated with improved renal function and reduced bone turnover. These data support the use of E/C/F/TAF in treating HIV/HBV coinfection.