YouTube video by SMILE Band

YouTube video by SMILE Band

YouTube video by IAS-USA

Tuberculosis-preventive treatment (TPT) is recommended for those at risk of tuberculosis, but despite encouraging trial data, evidence of its effectiveness from routine settings with diverse TPT regimens is limited. We describe routine TPT implementation outcomes in people living with human immunodeficiency virus (HIV; PLWH) to identify bottlenecks and opportunities for improvement along the cascade of care.MethodsFrom 2021–2023, we conducted a 24-month prospective cohort study of PLWH facilities in Ethiopia, South Africa and Zimbabwe. Sociodemographic and clinical data were collected at enrollment. During follow-up, we collected TPT initiation, TPT-related adverse effects, and completion data. A subgroup was allocated digital boxes as a proxy measure for assessing treatment completion. Tuberculosis diagnoses were confirmed from clinic records or symptom agnostic sputum testing using Xpert MTB/RIF assay and mycobacteria growth indicator tube (MGIT) culture at 12- and 24 months after enrollment.ResultsWe enrolled 2095 participants, mostly female (n = 1489 [71.1%]), with a median age of 42 years (interquartile range, 35–50 years). Approximately 60% (n = 1312) were considered eligible for TPT, and 1110 (84.6%) initiated TPT within 60 days of antiretroviral therapy initiation or refill during follow-up (rifapentine and isoniazid [3HP] in 625 and 6 or 12 months of isoniazid [6H/12H] in 487). TPT was completed in 55.4% (406 of 733). Mild symptoms compatible with TPT adverse effects were commonly reported in 3HP versus 6H/12H (190 [31.0%] vs 51 [11.0%], respectively; P < .001]. The tuberculosis incidence rate was 1.27/100 person-years (95% confidence interval, .95–1.69) during study follow-up in a mostly long-term antiretroviral therapy population and was lower for PLWH who completed TPT (adjusted incidence rate ratio, 0.39 [.20–.78]; P = .01).ConclusionsThere were losses along the cascade, particularly at completion. In programmatic settings, we observed more potential mild symptoms from 3HP compared to 6H/12H use. Interventions to support TPT completion are needed.

Patients with chronic non-HIV immunosuppression demonstrated persistent antigenuria and cleared antigen more slowly compared to immunocompetent patients and immune reconstituted PLWH. Given the association of antigen persistence with immune status, its clinical significance in non-HIV immunocompromi …

Previous studies examining Histoplasma antigen trends are largely in people living with HIV (PLWH) before the antiretroviral therapy era, with limited generalizability to modern cohorts of histoplasmosis.MethodsWe conducted a single-center, retrospective study of adult patients diagnosed with histoplasmosis by positive antigen testing and undergoing treatment between 2007 to 2021. Mean rates of antigen clearance were estimated using a linear mixed effects model. Time to H. capsulatum antigen negativity was calculated using competing risk analysis. Per-patient, mean antigen levels were compared at time of diagnosis and subsequent 6mo intervals.Results83 patients met inclusion criteria: 25 transplant, 21 immunocompetent, 16 biologic therapy, 11 PLWH, and 10 with other immunocompromise (OI). The transplant (-0.07), biologic (-0.07), and OI groups (-0.05) cleared antigenuria significantly slower than PLWH (-0.21) and the immunocompetent group (-0.16). Median time to antigen negativity in the presence of competing risk of death was transplant: 20.3 months (95% CI: 11.6, 69.3), biologic: 14.6 months (9.0, 42.6), OI: 13.2 months (2.0, 82.5), PLWH: 12.9 months (1.9, 19.2), and immunocompetent: 6.8 months (2.8, 13.0). At one year, antigen positivity was more common in immunocompromised than immunocompetent patients (22/40, 55% vs. 3/16, 19%; p = 0.02) and among the immunocompromised groups only transplant, biologic, and OI patients had positivity at two years.ConclusionsPatients with chronic non-HIV immunosuppression demonstrated persistent antigenuria and cleared antigen more slowly compared to immunocompetent patients and immune reconstituted PLWH. Given the association of antigen persistence with immune status, its clinical significance in non-HIV immunocompromised populations requires evaluation.

Eradicating latent HIV reservoirs remains a global health priority as it would liberate millions of people living with HIV (PLWH) from the economic and physiological burdens of lifelong antiretroviral therapy (ART). By utilizing a primary human cell model that resembles in vivo conditions across diverse viral strains, we identified that simply preventing CD16 receptor shedding from natural killer (NK) cells is insufficient to improve HIV-1 clearance. Instead, we demonstrated that enhancing the binding of antibodies to the CD16 receptor enables NK cells to overcome viral immune evasion and the loss of CD16 expression. This allows for potent elimination of infected cells through antibody-dependent cellular cytotoxicity (ADCC). These findings provide a clear strategy for designing more effective “kill” components in future therapeutic strategies.

Despite demonstrated virological efficacy, real-world evidence on the long-term effectiveness of dolutegravir plus lamivudine (DTG/3TC) in people living with HIV (PLWH) remains limited; this study assessed effectiveness, examining immunological response, resistance and safety.MethodsCARAVEL was a French, prospective, noninterventional, single-arm, multicenter, 3-year cohort study in treatment-naive PLWH (TN-PLWH) and pretreated PLWH (PT-PLWH) receiving DTG/3TC for the first time.ResultsForty-nine centers enrolled 304 participants: 56 TN-PLWH and 248 PT-PLWH. Effectiveness was evaluable in 49 (87%) TN-PLWH and 234 (94%) PT-PLWH. Initial virological suppression was attained for 44 (89.8%) TN-PLWH after 6 months of initiating DTG/3TC, with a median time to virological suppression of 1.1 months (IQR 1.0 to 2.1), and no virological failure during the follow-up. After switching, 220 (94%) PT-PLWH maintained virological suppression. During the follow-up, 14 PT-PLWH did not maintain virological suppression: 5 due to intermittent viraemia, and 9 due to virological failure (VF). Among the 9 participants with VF, a genotypic resistance test was available for 3 participants of whom 1 developed 3TC resistance [M184V] in the context of nonadherence. DTG/3TC was discontinued in 63 participants, mainly at their request (N = 40, 64.5%), as well as tolerability and VF. The average change in body weight over the follow-up was +2.0 (±6.0) (P = .13) kg in TN-PLWH and −0.2 (±6.5) (P = .78) kg in PT-PLWH, among participants with available data (N = 156).ConclusionsThese real-world data demonstrated high virological success and good safety after up to 3 years on DTG/3TC in both TN-PLWH and PT-PLWH populations.

The US Food and Drug Administration (FDA) approval of gene therapies for sickle cell disease (SCD) marks a paradigm shift. Patients living with HIV (PLWH) and SCD were excluded from the pivotal SCD gene therapy clinical trials.1,2 The FDA labels for exagamglogene autotemcel (Casgevy) and lovotibeglogene autotemcel (Lyfgenia) specify no contraindication, but the prescribing information for lovotibeglogene autotemcel and exagamglogene autotemcel states that there are no data for their use in HIV-positive patients and such patients will not be accepted for these treatments. Medicaid and other third-party payers closely mirror clinical trial eligibility criteria and exclude PLWH, a group who face significantly increased risks of both SCD and HIV complications.3 Get Access

A health crisis in Florida looms for PLWH

“I’ve never seen anything like it in my 40 years of doing international research. It’s unethical, it’s dangerous and it’s reckless.”

Oral antiretrovirals provide life-saving treatments for millions of people living with HIV (PLWH) and can prevent new infections via pre-exposure prophylaxis (PrEP)1-5. However, some heavily treatment...