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People living with HIV (PLWH) experience chronic pain that may impact function. Gaps in knowledge exist for factors that impact pain and pain medication use in older (age 50+) PLWH. Data for this study were obtained from the Aging with Dignity, Health, Optimism and Community (ADHOC) cohort, an observational study of older PLWH from 10 clinics across the United States. Participants self-reported socioeconomic, psychosocial, and health factors via an online questionnaire. Of 1,051 participants, 66% reported pain. In a multivariable regression model, multimorbidity and tobacco use were associated with a greater likelihood of experiencing pain, whereas being male, black, and having higher cognitive function were associated with a lower likelihood of experiencing pain. Of the 696 participants who reported pain, 46% reported using pain medication. In a multivariable regression model, pain medication use was associated with multimorbidity and with lower income. Recognition of the factors associated with pain and pain medication use in this vulnerable population may lead to strategies that mitigate negative health outcomes.

ObjectivesCytomegalovirus (CMV)-specific T-cell effectors (CMV-Teff) protect against CMV end-organ disease (EOD). In HIV-infected individuals, their numbers and function vary with CD4 cell numbers and HIV load. The role of regulatory T cells (Treg) in CMV-EOD has not been extensively studied. We investigated the contribution of Treg and Teff toward CMV-EOD in HIV-infected individuals independently of CD4 cell numbers and HIV load and controlling for CMV reactivations.DesignWe matched 43 CMV-EOD cases to 93 controls without CMV-EOD, but with similar CD4 cell numbers and HIV plasma RNA. CMV reactivation was investigated by blood DNA polymerase chain reaction over 32 weeks preceding the CMV-EOD in cases and preceding the matching point in controls.MethodsCMV-Teff and Treg were characterized by the expression of interferon-γ (IFN-γ), interleukin 2, tumor necrosis factor α (TNFα), MIP1β, granzyme B (GrB), CD107a, TNFα, FOXP3, and CD25.ResultsSixty-five percent cases and 20% controls had CMV reactivations. In multivariate analyses that controlled for CMV reactivations, none of the CMV-Teff subsets correlated with protection, but high CMV-GrB enzyme-linked immunosorbent spot responses and CMV-specific CD4FOXP3+%, CD4TNFα+%, and CD8CD107a% were significant predictors of CMV-EOD.ConclusionsBecause both FOXP3 and GrB have been previously associated with Treg activity, we conclude that CMV-Treg may play an important role in the development of CMV-EOD in advanced HIV disease. We were not able to identify a CMV-Teff subset that could be used as a surrogate of protection against CMV-EOD in this highly immunocompromised population.

Determining the phenotypic impacts of reverse transcriptase (RT) mutations on individual nucleoside RT inhibitors (NRTIs) has remained a statistical challenge because clinical NRTI-resistant HIV-1 isolates usually contain multiple mutations, often in complex patterns, complicating the task of determining the relative contribution of each mutation to HIV drug resistance. Furthermore, the NRTIs have highly variable dynamic susceptibility ranges, making it difficult to determine the relative effect of an RT mutation on susceptibility to different NRTIs. In this study, we analyzed 1,273 genotyped HIV-1 isolates for which phenotypic results were obtained using the PhenoSense assay (Monogram, South San Francisco, CA). We used a parsimonious feature selection algorithm, LASSO, to assess the possible contributions of 177 mutations that occurred in 10 or more isolates in our data set. We then used least-squares regression to quantify the impact of each LASSO-selected mutation on each NRTI. Our study provides a comprehensive view of the most common NRTI resistance mutations. Because our results were standardized, the study provides the first analysis that quantifies the relative phenotypic effects of NRTI resistance mutations on each of the NRTIs. In addition, the study contains new findings on the relative impacts of thymidine analog mutations (TAMs) on susceptibility to abacavir and tenofovir; the impacts of several known but incompletely characterized mutations, including E40F, V75T, Y115F, and K219R; and a tentative role in reduced NRTI susceptibility for K64H, a novel NRTI resistance mutation.

BackgroundWhether HIV viremia, particularly at low levels is associated with inflammation, increased coagulation, and all-cause mortality is unclear.MethodsThe associations of HIV RNA level with C-reactive protein (CRP), fibrinogen, interleukin (IL)-6 and mortality were evaluated in 1116 HIV-infected participants from the Study of Fat Redistribution and Metabolic Change in HIV infection. HIV RNA level was categorized as undetectable (i.e., "target not detected"), 1-19, 20-399, 400-9999, and ≥ 10,000 copies/ml. Covariates included demographics, lifestyle, adipose tissue, and HIV-related factors.ResultsHIV RNA level had little association with CRP. Categories of HIV RNA below 10,000 copies/ml had similar levels of IL-6 compared with an undetectable HIV RNA level, while HIV RNA ≥ 10,000 copies/ml was associated with 89% higher IL-6 (p

Background Previously reported post hoc multivariable analyses exploring predictors of confirmed virologic failure (CVF) with cabotegravir + rilpivirine long-acting (CAB + RPV LA) were expanded to include data beyond week 48, additional covariates, and additional participants. Methods Pooled data from 1651 participants were used to explore dosing regimen (every 4 or every 8 weeks), demographic, viral, and pharmacokinetic covariates as potential predictors of CVF. Prior dosing regimen experience was accounted for using 2 populations. Two models were conducted in each population—baseline factor analyses exploring factors known at baseline and multivariable analyses exploring baseline factors plus postbaseline model-predicted CAB/RPV trough concentrations (4 and 44 weeks postinjection). Retained factors were evaluated to understand their contribution to CVF (alone or in combination). Results Overall, 1.4% (n = 23/1651) of participants had CVF through 152 weeks. The presence of RPV resistance-associated mutations, human immunodeficiency virus-1 subtype A6/A1, and body mass index ≥30 kg/m2 were associated with an increased risk of CVF (P <.05 adjusted incidence rate ratio), with participants with ≥2 of these baseline factors having a higher risk of CVF. Lower model-predicted CAB/RPV troughs were additional factors retained for multivariable analyses. Conclusions The presence of ≥2 baseline factors (RPV resistance-associated mutations, A6/A1 subtype, and/or body mass index ≥30 kg/m2) was associated with increased CVF risk, consistent with prior analyses. Inclusion of initial model-predicted CAB/RPV trough concentrations (≤first quartile) did not improve the prediction of CVF beyond the presence of a combination of ≥2 baseline factors, reinforcing the clinical utility of the baseline factors in the appropriate use of CAB + RPV LA. [ABSTRACT FROM AUTHOR]

Many men age 50+ with HIV (MWH age 50+) are sexually active. However, little is known about the relationship between the number of sexual partners and patient-reported outcomes in this population. To help address this need, analyses were performed on data from the Aging with Dignity, Health, Optimism and Community cohort, an observational study of adults age 50+ with HIV. Of 876 MWH age 50+, 26.8% had 0 sexual partners in the past year, 27.9% had 1, 21.5% had 2–5, and 23.9% had >5. Men with one partner were significantly less lonely and less depressed than any other group (p < .01 for pairwise comparisons). Men with zero partners were more depressed than any other group. Linear regression controlling for race and relationship status showed men with one partner had lower levels of loneliness than any other group. They also had lower levels of depression than men with zero or more than than five sexual partners, although depression levels were not significantly different for men with one or with two to five partners. Linear regression also showed that men in relationships were less lonely and less depressed than men who were not in relationships, after controlling for race and number of sexual partners. Better understanding of the roles that number of sex partners and relationships play in the mental health of MWH age 50+ may help ameliorate the burden of loneliness and depression in this vulnerable population. ClinicalTrials.gov (Identifier: NCT04311554). [ABSTRACT FROM AUTHOR]

Background: GEMINI-1 and GEMINI-2 (ClinicalTrials.gov, NCT02831673 and NCT02831764, respectively) are double-blind, multicenter, phase III studies that demonstrated the non-inferiority of once-daily dolutegravir + lamivudine to dolutegravir + tenofovir disoproxil fumarate/emtricitabine in achieving HIV-1 RNA <50 copies/mL at 48, 96, and 144 weeks in treatment-naive adults with HIV-1 infection. Objective: We present a post hoc analysis of the impact of treatment adherence on Week 48 virologic response. Methods: Adherence was estimated using pill counts and categorized as ≥90% vs <90%. Unadjusted treatment differences with exact 95% CIs were derived for the proportion of participants with HIV-1 RNA <50 copies/mL within each adherence category, using Snapshot algorithm and last available on-treatment viral load through Week 48. Results: In each treatment group, 5% of participants had <90% adherence (dolutegravir + lamivudine group, 35/716; dolutegravir + tenofovir disoproxil fumarate/emtricitabine group, 34/717). The proportion of participants with HIV-1 RNA <50 copies/mL (Snapshot) at Week 48 in the <90% adherence group was 69% in the dolutegravir + lamivudine group and 65% in the dolutegravir + tenofovir disoproxil fumarate/emtricitabine group (analysis by last on-treatment viral load: 91% and 85%, respectively). Corresponding proportions in the ≥90% adherence group were 93% and 96% (analysis by last on-treatment viral load: 97% and 99%, respectively). Conclusions: Decreased adherence resulted in lower Week 48 virologic efficacy outcomes that were comparable between treatment groups. These results indicate that the robust antiviral activity and regimen forgiveness of dolutegravir + lamivudine is similar to dolutegravir-containing 3-drug regimens (see graphical abstract). [ABSTRACT FROM AUTHOR]