Current adherence assessments typically detect missed doses long after they occur. Real-time, wireless monitoring strategies for antiretroviral therapy may provide novel opportunities to proactively prevent virologic rebound and treatment failure. Wisepill, a wireless pill container that transmits a cellular signal when opened, was pilot tested in ten Ugandan individuals for 6 months. Adherence levels measured by Wisepill, unannounced pill counts, and self-report were compared with each other, prior standard electronic monitoring, and HIV RNA. Wisepill data was initially limited by battery life and signal transmission interruptions. Following device improvements, continuous data was achieved with median (interquartile range) adherence levels of 93% (87–97%) by Wisepill, 100% (99–100%) by unannounced pill count, 100% (100–100%) by self-report, and 92% (79–98%) by prior standard electronic monitoring. Four individuals developed transient, low-level viremia. After overcoming technical challenges, real-time adherence monitoring is feasible for resource-limited settings and may detect suboptimal adherence prior to viral rebound.

BackgroundIn healthy, HIV seronegative, CMV seropositive adults, a large proportion of T cells are CMV-specific. High-level CMV-specific T cell responses are associated with accelerated immunologic aging (“immunosenesence”) in the elderly population. The impact of untreated and treated HIV infection on the frequency of these cells remains undefined.Methodology/Principal FindingsWe measured the proportion of CD4+ and CD8+ T cells responding to CMV pp65 and IE proteins was measured using flow cytometry in 685 unique HIV seronegative and seropositive individuals. The proportion of CMV-specific CD8+ T cells was consistently higher in the HIV-seropositive subjects compared to the HIV-seronegative subjects. This HIV effect was observed even in patients who lacked measurable immunodeficiency. Among the HIV-seropositive subjects, CMV-specific CD8+ T cell responses were proportionately lower during recent infection, higher during chronic untreated infection and higher still during long-term antiretroviral treated infection. The CD8+ T cell response to just two CMV proteins (pp65 and IE) was approximately 6% during long-term therapy, which was over twice that seen in HIV-seronegative persons. CMV-specific CD4+ T cell responses followed the same trends, but the magnitude of the effect was smaller.Conclusions/SignificanceLong-term successfully treated HIV infected patients have remarkably high levels of CMV-specific effector cells. These levels are similar to that observed in the elderly, but occur at much younger ages. Future studies should focus on defining the potential role of the CMV-specific inflammatory response in non-AIDS morbidity and mortality, including immunosenescence.

The authors found that Long COVID symptoms in a post-acute cohort were associated with serological evidence suggesting recent EBV reactivation and pre-existing HIV infection when adjusted for participant factors, sample timing, comorbid conditions and prior hospitalization, whereas underlying CMV infection was associated with decreased odds of Long COVID.

David Bangsberg and colleagues explore the challenges and rewards of sharing research findings with participants living with HIV enrolled in observational research in rural sub-Saharan Africa.

Background Incomplete antiretroviral therapy (ART) adherence has been linked to deleterious immunologic, inflammatory, and clinical consequences, even among virally suppressed (<50 copies/mL) persons with HIV (PWH). The impact of improving adherence in the risk of severe non-AIDS events (SNAEs) and death in this population is unknown. Methods We estimated the reduction in the risk of SNAEs or death resulting from an increase in ART adherence by: a) applying existing data on the association between adherence with high residual inflammation/coagulopathy in virally suppressed PWH, and b) using a Cox proportional hazards model derived from changes in plasma interleukin (IL)-6 and d-dimer from three randomized clinical trials. Comparatively, assuming 100% ART adherence in a PWH who achieves viral suppression, we estimated the number of persons in whom a decrease in adherence to <100% would need to be observed for an additional SNAE or death event to occur during 3- and 5-year follow-up. Results Increasing ART adherence to 100% in PWH who are suppressed on ART despite imperfect adherence translated into a 6-37% reduction in the risk of SNAEs or death. Comparatively, based on an anticipated 12% increase in IL-6, 254 and 165 PWH would need to decrease their adherence from 100% to <100% for an additional event to occur over 3- and 5-year follow-up, respectively. Conclusions Modest gains in ART adherence could have clinical benefits beyond virologic suppression. Increasing ART adherence (e.g., via an intervention or switch to long-acting ART) in PWH who remain virally suppressed despite incomplete adherence should be evaluated.