To examine syphilis serology after treatment in people living with HIV. No unanimous guidelines exist in the era of increasing coinfection.
Retrospective review using a tertiary care clinic in ...Toronto from 2000 to 2017.
The 2015 Centers for Diseases Control and Prevention syphilis guidelines were used to define an adequate serologic response. Cumulative distribution estimates and proportional hazards models accounting for interval censoring estimated the time to serologic response and seroreversion. Multistate models were used to investigate extended periods of serofast serology.
A total of 171 patients with syphilis met our inclusion criteria (16 primary, 53 secondary, 26 early latent, 46 late latent, 30 neurosyphilis). Serologic response was achieved by 12 months for 65 (94%) patients and by 12-18 months for four (6%) patients with primary/secondary syphilis. For latent and neurosyphilis, 94 (92%) achieved serologic response by 24 months and one (1%) at 24.1 months. 84 (49%) patients achieved seroreversion with a median (95% confidence interval) time of 2 (1.44, 2.68) years. Latent syphilis was associated with a lower likelihood of achieving serologic response hazard ratio (HR) = 0.52, P = 0.05 and seroreversion (HR = 0.27, P < 0.001) compared with primary/secondary syphilis. The probability of moving from a new infection state to a serofast state within 1 year was high (0.65) but the 1-year probability of transitioning from a serofast state to seroreversion was low (0.27).
The majority of people living with HIV infected with syphilis will achieve an adequate serologic response as per the Centers for Diseases Control and Prevention guidelines. Seroreversion was observed in about half but can take years to occur.
Dolutegravir is the newest integrase strand transfer inhibitor to be approved for the treatment of human immunodeficiency virus (HIV) infection. Dolutegravir is equivalent or superior to existing ...treatment regimens in both treatment-naïve and treatment-experienced patients including those with previous raltegravir or elvitegravir failure. The consistent efficacy coupled with excellent tolerability and infrequent drug-drug interactions makes the co-formulation of dolutegravir with two nucleotide reverse-transcriptase inhibitors an attractive treatment option. This review summarizes the pharmacokinetics, adverse event profile, and efficacy of dolutegravir in the treatment of HIV.
Dolutegravir (S/GSK1349572), a once-daily, unboosted integrase inhibitor, was recently approved in the United States for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in ...combination with other antiretroviral agents. Dolutegravir, in combination with abacavir-lamivudine, may provide a simplified regimen.
We conducted a randomized, double-blind, phase 3 study involving adult participants who had not received previous therapy for HIV-1 infection and who had an HIV-1 RNA level of 1000 copies per milliliter or more. Participants were randomly assigned to dolutegravir at a dose of 50 mg plus abacavir-lamivudine once daily (DTG-ABC-3TC group) or combination therapy with efavirenz-tenofovir disoproxil fumarate (DF)-emtricitabine once daily (EFV-TDF-FTC group). The primary end point was the proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter at week 48. Secondary end points included the time to viral suppression, the change from baseline in CD4+ T-cell count, safety, and viral resistance.
A total of 833 participants received at least one dose of study drug. At week 48, the proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter was significantly higher in the DTG-ABC-3TC group than in the EFV-TDF-FTC group (88% vs. 81%, P=0.003), thus meeting the criterion for superiority. The DTG-ABC-3TC group had a shorter median time to viral suppression than did the EFV-TDF-FTC group (28 vs. 84 days, P<0.001), as well as greater increases in CD4+ T-cell count (267 vs. 208 per cubic millimeter, P<0.001). The proportion of participants who discontinued therapy owing to adverse events was lower in the DTG-ABC-3TC group than in the EFV-TDF-FTC group (2% vs. 10%); rash and neuropsychiatric events (including abnormal dreams, anxiety, dizziness, and somnolence) were significantly more common in the EFV-TDF-FTC group, whereas insomnia was reported more frequently in the DTG-ABC-3TC group. No participants in the DTG-ABC-3TC group had detectable antiviral resistance; one tenofovir DF-associated mutation and four efavirenz-associated mutations were detected in participants with virologic failure in the EFV-TDF-FTC group.
Dolutegravir plus abacavir-lamivudine had a better safety profile and was more effective through 48 weeks than the regimen with efavirenz-tenofovir DF-emtricitabine. (Funded by ViiV Healthcare; SINGLE ClinicalTrials.gov number, NCT01263015 .).
Serious non-AIDS disease events (SNAE) are experienced disproportionately by immunologic non-responders (INRs), HIV-infected individuals who do not restore CD4 T cells in blood despite effective ...viral suppression. We aimed to characterize the inflammatory biomarker profile of the INR phenotype. Blinded cross-sectional cohort study comparing markers of immune activation and gut homing between INR and non-INR individuals. HIV-positive participants had HIV RNA suppression on antiretroviral therapy and were categorized as either INR (N = 36) or Clinical Responders ("CR"; CD4>350/mm.sup.3 ; N = 47). 18 HIV-negative comparator individuals were included. Cellular markers were assessed by flow cytometry, with soluble markers assessed by ELISA and LC/MS-MS. Multivariable linear regression models estimated the association between INR phenotype and markers, adjusting for age, sex, duration of ART, and recent infection/vaccination. INR participants demonstrated a reduced CD4/CD8 ratio (p<0.001), 35% more CD8 activation (p = 0.02), 36% greater alpha4beta7+ CD4 T cells (p<0.01), 54% more HLA-DR+ CD4 T cells (p<0.001), and 20% higher plasma VCAM (p<0.01) compared to CRs. The INR phenotype was not associated with levels of Kyn/Trp, CRP, TNF, IFNgamma, IL-8, IL-6, sCD14, D-Dimer, I-FABP, MCP-1, ICAM or CD8%HLA-DR+. Peripheral CD4 non-recovery during long-term treated HIV infection is characterized by elevated CD8 activation and CD4 gut homing. Gut-focused interventions may be warranted in the INR context, and CD8 activation may serve as a surrogate endpoint for clinical interventions.
The Rotterdam Healthy Aging Score (HAS) is a validated multidimensional index constructed from five health domains. We describe the HAS distribution in a cohort of HIV-positive adults and correlate ...it with health outcomes.
A cross-sectional pilot study of 101 adults aged at least 40 years, on suppressive antiretroviral therapy attending a tertiary HIV clinic in Toronto, Canada.
Participants completed questionnaires to calculate their HAS (range 0-14). Demographics, HAS and sub-scores were compared by age and sex. The HAS was compared with results of the Fried Frailty Score, Short Performance Physical Battery score (SPPB) and measures of health utilization. Kruskal--Wallis Rank-Sum and Fisher's exact tests were used for all comparisons.
Median (IQR) age was 56 (50--62), 81 (80%) men and 50 (50%) born in Canada. Median (IQR) CD4 cell count was 574 (417--794) cells/μl. Median (IQR) HAS was 12 (10--13) with 39 (39%) achieving a score more than 12 (considered healthy aging). Younger participants experienced more depression, whereas women had greater pain. The HAS score correlated with the Fried Frailty Score (P = 0.008) and trended with the SPPB Score (P = 0.077). Those with the poorest HAS scores were more likely to have been hospitalized in the preceding 6 months (P = 0.034).
The HAS ranged from 5 to 14 in this cohort of older HIV adults with 39% attaining scores in the 'healthy' range. The HAS correlated with measures of physical performance and health utilization. Further validation of an objective outcome in HIV-positive patients will facilitate evaluation of interventional studies to improve healthy aging.
Although micronutrient and antioxidant supplementation are widely used by persons with human immunodeficiency virus (HIV), a therapeutic role beyond recommended daily allowances (RDA) remains ...unproven. An oral high-dose micronutrient and antioxidant supplement (Treatment) was compared to an RDA supplement (Control) for time to progressive immunodeficiency or initiation of antiretroviral therapy (ART) in people living with HIV (PLWH). This study was a randomized, double-blind, placebo-controlled multicenter clinical trial. PLWH were recruited from Canadian HIV Trials Network sites, and followed quarterly for two years. Eligible participants were asymptomatic, antiretroviral treatment (ART)-naïve, HIV-seropositive adults with a CD4 T lymphocyte count (CD4 count) between 375-750 cells/muL. Participants were randomly allocated 1:1 to receive Treatment or Control supplements. The primary outcome was a composite of time-to-first of confirmed CD4 count below 350 cells/muL, initiation of ART, AIDS-defining illness or death. Primary analysis was by intention-to-treat. Secondary outcomes included CD4 count trajectory from baseline to ART initiation or two years. A Data and Safety Monitoring Board reviewed the study for safety, recruitment and protocol adherence every six months. Of 171 enrolled participants: 66 (38.6%) experienced a primary outcome: 27 reached a CD4 count below 350 cells/muL, and 57 started ART. There was no significant difference in time-to-first outcome between groups (Hazard Ratio = 1.05; 95%CI: 0.65, 1.70), or in time to any component outcome. Using intent-to-treat censoring, mean annualized rates of CD4 count decline were -42.703 cells/muL and -79.763 cells/muL for Treatment and Control groups, with no statistical difference in the mean change between groups (-37.06 cells/muL/52 weeks, 95%CI: (-93.59, 19.47); p = 0.1993). Accrual was stopped at 171 of the 212 intended participants after an interim analysis for futility, although participant follow-up was completed. In ART-naïve PLWH, high-dose antioxidant, micronutrient supplementation compared to RDA supplementation had no significant effect on disease progression or ART initiation.
Objectives
This review aimed to map the current state of knowledge regarding the implementation considerations of existing geriatric‐HIV models of care, to identify areas of further research and to ...inform the implementation of future geriatric‐HIV interventions that support older adults living with HIV.
Methods
We conducted a scoping review that was methodologically informed by the Arskey and O’Malley's 5 step framework and theoretically informed by the Consolidated Framework for Implementation Research (CFIR). A systematic search of six databases was conducted for peer‐reviewed literature. The grey literature was also searched. Article screening was performed in duplicate. Data was extracted for the purpose of this secondary analysis using a data extraction template informed by the CFIR. Data was inductively and deductively analyzed.
Results
In total, 11 articles met the inclusion criteria. The models of care described varied in terms of their location and setting, the number and type of care providers involved, the mechanism of patient referral, the type of assessments and interventions performed and the methods of longitudinal patient follow‐up. Four key categories emerged to describe factors that influenced their implementation: care provider buy‐in, patient engagement, mechanisms of communication and collaboration, and available resources.
Conclusions
The findings from this scoping review provide an initial understanding of the key factors to consider when implementing geriatric‐HIV models of care. We recommend health system planners consider mechanisms of communication and collaboration, opportunities for care provider buy‐in, patient engagement and available resources. Future research should explore implementation in more diverse settings to understand the nuances that influence implementation and care delivery.
Since May, 2022, a large global outbreak of human mpox (formerly known as monkeypox) has predominantly affected men who have sex with men. The strain responsible, Clade IIb, has mutated substantially ...from precursors originating from the 2017–18 outbreak in Nigeria. Immunity to smallpox, another orthopoxvirus, via previous infection or vaccination provides lifelong immunity. However, since the 2022 mpox outbreak, recent clusters were described in individuals with presumed immunity through recent infection or vaccination. We aim to describe the epidemiological and clinical characteristics of mpox in individuals with past infection or vaccination to improve the understanding of this disease in the setting of previous immunity.
In this global case series, international collaborators from nine countries provided data on individuals with PCR-confirmed mpox after documented previous infection or vaccination between May 11, 2022, and June 30, 2023. We excluded cases that could not confirm vaccination status or cases with partial immunisation or any doses received before the current multi-national mpox outbreak (cutoff date May 1, 2022). Data were collected via a case report spreadsheet that reported on dates of infection and vaccination, route of immunisation, demographic characteristics, clinical findings, HIV status, concomitant sexually transmitted infections, and markers of disease severity (mpox severity score system). We describe case epidemiology, clinical course, and mpox severity scores; all analyses were descriptive.
We report mpox infections in 37 gay and bisexual men who have sex with men: seven individuals had mpox reinfections, 29 individuals had mpox infections that occurred after two appropriately spaced Modified Vaccinia Ankara-Bavarian Nordic vaccine courses, and one individual had an infection that met the criteria for both reinfection and infection after vaccination. The median age of individuals was 36 years (IQR 30–45; range 21–58). Those with natural immunity after initial infection had a shorter disease course with less mucosal disease upon reinfection than with their initial infection. Infections post-vaccination were characterised by few lesions, little mucosal disease, and minimal analgesia requirements; two people received oral tecovirimat. Overall, there were no deaths, no bacterial superinfections, and all individuals were managed in the ambulatory clinic with one hospital admission for a necrotising neck lesion.
The epidemiology of people with mpox reinfection or infection post-vaccination was similar to other published cohorts during the 2022 outbreak—predominantly young, sexually active gay and bisexual men who have sex with men. Clinical features and outcomes of repeat infection and infection after vaccination appear to be less clinically severe than those described in 2022 case literature. Specifically, compared with the 2022 case series, these individuals in the present study had fewer confluent lesions, less mucosal involvement, reduced analgesia requirement, and fewer admissions. Natural immunity and vaccine-induced immunity are not fully protective against mpox infection. However, in this small series both disease duration and severity appear to be reduced.
None.
Background. Protease inhibitor (PI)-based combination antiretroviral therapy (cART) is administered during pregnancy to prevent perinatal human immunodeficiency virus (HIV) transmission. However, PI ...use has been associated with adverse birth outcomes, including preterm delivery and small-for-gestational-age (SGA) births. The mechanisms underlying these outcomes are unknown. We hypothesized that Pis contribute to these adverse events by altering progesterone levels. Methods. PI effects on trophoblast progesterone production were assessed in vitro. A mouse pregnancy model was used to assess the impact of PI-based cART on pregnancy outcomes and progesterone levels in vivo. Progesterone levels were assessed in plasma specimens from 27 HIV-infected and 17 HIV-uninfected pregnant women. Results. PIs (ritonavir, lopinavir, and atazanavir) but not nucleoside reverse transcriptase inhibitors (NRTIs) or nonnucleoside reverse transcriptase inhibitors reduced trophoblast progesterone production in vitro. In pregnant mice, Pi-based cART but not dual-NRTI therapy was associated with significantly lower progesterone levels that directly correlated with fetal weight. Progesterone supplementation resulted in a significant improvement in fetal weight. We observed lower progesterone levels and smaller infants in HIV-infected women receiving Pi-based cART, compared with the control group. In HIV-infected women, progesterone levels correlated significantly with birth weight percentile. Conclusions. Our data suggest that PI use in pregnancy may lead to lower progesterone levels that could contribute to adverse birth outcomes.
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