ABSTRACTWith early and effective antiretroviral therapy leading to improved life expectancy in people with HIV (PWH), PWH aged 50 or older face concerns and issues related to aging. Providers at the University of Colorado identified a need to assess the healthcare needs of PWH aged 50 and older at the UCHealth Infectious Diseases/Travel (TEAM) Clinic in Aurora, Colorado. A survey was developed to illuminate participants' general rating of their health, factors that made it challenging to get the healthcare needed prior to COVID-19 and during COVID-19, and types of healthcare appointments and providers that would make a difference in healthcare experience. Descriptive statistics and brief thematic analysis of open-ended questions found that most participants rated their current health as very good or good. Participants noted that connecting to resources and appointment scheduling were the top challenges prior to the COVID-19 pandemic, and during the COVID-19 pandemic, participants described challenges with resource connection, communication with providers, and wait times. To reduce these barriers, telehealth video appointments, healthcare visits with a provider who specializes in aging, and healthcare visits with providers who specialize in aging if co-located in the HIV clinic were recognized as beneficial resources from the perspectives of participants.

Humanization of mice with functional T cells currently relies on co-implantation of hematopoietic stem cells from fetal liver and autologous fetal thymic tissue (so-called BLT mouse model). Here, we show that NOD/SCID/IL2rγnull mice humanized with cord blood- derived CD34+ cells and implanted with allogeneic pediatric thymic tissues excised during cardiac surgeries (CCST) represent an alternative to BLT mice. CCST mice displayed a strong immune reconstitution, with functional T cells originating from CD34+ progenitor cells. They were equally susceptible to mucosal or intraperitoneal HIV infection and had significantly higher HIV-specific T cell responses. Antiretroviral therapy (ART) robustly suppressed viremia and reduced the frequencies of cells carrying integrated HIV DNA. As in BLT mice, we observed a complete viral rebound following ART interruption, suggesting the presence of HIV reservoirs. In conclusion, CCST mice represent a practical alternative to BLT mice, broadening the use of humanized mice for research.

Functional MRI studies have demonstrated that HIV-infection affects the fronto-striatal network. It has not been examined what impact efavirenz, an antiretroviral drug notorious for its neurocognitive effects, has on the reward system: a key subcomponent involved in depressive and apathy symptoms. Therefore, this study aims to investigate the effect of efavirenz on reward processing using a monetary incentive delay task. In this multicenter randomized controlled trial, asymptomatic adult participants stable on emtricitabine/tenofovirdisoproxil/efavirenz (FTC/TDF/EFV) were randomly assigned in a 2:1 ratio to switch to emtricitabine/tenofovirdisoproxil/rilpivirine (FTC/TDF/RPV) (n=30) or continue taking FTC/TDF/EFV (n=13). At baseline and twelve weeks after therapy switch, both groups performed a monetary incentive delay task. Behavior and functional brain activity related to reward anticipation and reward outcome were assessed with blood oxygen level dependent functional MRI. Both groups were matched for age, education-level and time since HIV-diagnosis and on EFV. At the behavioral level, both groups had faster response times and better response accuracy during rewarding versus non-rewarding trials, with no improvement resulting from switching FTC/TDF/EFV to FTC/TDF/RPV. No significant change in activation related to reward anticipation in the ventral striatum was found after switching therapy. Both groups had significantly higher activation levels over time, consistent with a potential learning effect. Similar activity related to reward outcome in the orbitofrontal cortex was found. Discontinuing FTC/TDF/EFV was not found to improve activity related to reward anticipation in asymptomatic people living with HIV, with similar cortical functioning during reward outcome processing. It is therefore likely that EFV does not affect motivational control. Further research is needed to determine whether EFV affects motivational control in HIV populations with different characteristics.

Aim: To investigate Prussian blue nanoparticles (PBNPs) coated with the synthetic analog of dsRNA polyinosinic-polycytidylic acid (polyIC) for their ability to function as HIV latency reversing agents. Methods: A layer-by-layer method was used to synthesize polyIC-coated PBNPs (polyIC-PBNPs). PolyIC-PBNPs were stable and monodisperse, maintained the native absorbance properties of both polyIC and PBNPs and were obtained with high nanoparticle collection yield and polyIC attachment efficiencies. Results: PolyIC-PBNPs were more effective in reactivating latent HIV than free polyIC in a cell model of HIV latency. Furthermore, polyIC-PBNPs were more effective in promoting immune activation than free polyIC in CD4 and CD8 T cells. Conclusion: PBNPs function as efficient carriers of nucleic acids to directly reverse HIV latency and enhance immune activation.

Studies have reported significant immediate impacts of the COVID-19 pandemic on the social relationships and healthcare of people living with HIV. This study followed a closed cohort of young people living with HIV over the first year of the COVID-19 pandemic. Participants were men and women (N = 140) age 36 and younger who were living with HIV and had demonstrated suboptimal adherence to antiretroviral therapy (ART), unsuppressed HIV viral load, or active substance use in a run-in study. Results confirmed that participants continued to experience significant disruptions to their social relationships and healthcare over the course of the first year of the COVID-19 pandemic. There was evidence for sustained impacts on transportation, housing stability, and food security during the first year of COVID-19. Multivariable models showed that greater pre-COVID-19 social support predicted greater ART adherence and greater HIV suppression (lower viral load) over the first year of the COVID-19 pandemic. Efforts to plan and prepare people living with HIV for future social crises, including future pandemics, should emphasize building and sustaining social support.

The majority of pediatric human immunodeficiency virus (HIV) infections are the result of vertical transmissions that occur during pregnancy, childbirth, and breastfeeding. The treatment of all pregnant persons living with HIV remains a global health initiative. Early and consistent use of antiretroviral therapy throughout pregnancy and childbirth drastically reduces the risk of perinatal transmission of HIV, resulting in fewer children living with the disease worldwide. Given that the maternal HIV viral load is the strongest predictor of perinatal transmission, suppressive antiretroviral treatment during pregnancy is the principal means to eliminate transmission of HIV from mother to child. With the use of combined antiretroviral therapy, typically with dual-nucleoside reverse transcriptase inhibitors plus an integrase strand transfer inhibitor or a ritonavir-boosted protease inhibitor, HIV-infected mothers can now achieve virologic suppression to undetectable levels and yield a perinatal transmission rate of less than 2%. Important considerations of HIV treatment in pregnancy include the safety and efficacy of antiretroviral drugs, altered pregnancy-related pharmacokinetics, potential for birth defects or adverse neonatal outcomes, and individualized delivery planning based on maternal viral load. This practical review article summarizes the options, considerations, and recommendations for antiretroviral treatment in pregnancy to reduce perinatal HIV transmission and optimize health outcomes for mothers and infants worldwide.

We investigated associations between (1) housing status (four categories measuring housing stability) and outcomes along the HIV care continuum (not currently on antiretroviral therapy [ART]; sub-optimal ART adherence [< 95% in the last 3-4 weeks]; unsuppressed viral load [> 200 copies/ml], median CD4 < 200 in the last six months), and (2) housing status and unmet primary, dental and mental health care needs in the last six months among WLWH. Housing status was defined according to the Canadian Definition of Homelessness and had four categories: unsheltered (i.e., living in ≥ 1 unsheltered location [e.g., street, abandoned buildings]), unstable (i.e., living in ≥ 1 unstable location [e.g., shelter, couch surfing]), supportive housing (i.e., only living in supportive housing), and stable housing (i.e., only living in one's own housing; reference). At baseline, in the last six months, 47.3% of participants reported unstable housing, followed by 24.4% unsheltered housing, 16.4% stable housing, and 11.9% supportive housing. Overall, 19.1% of the full sample (N = 336, 2010-2019) reported not currently on ART; among participants on ART, 28.0% reported sub-optimal ART adherence. Overall, 32.1% had recent unsuppressed viral load. Among a subsample (n = 318, 2014-2019), 15.7% reported unmet primary care needs, 26.1% unmet dental care needs, and 16.4% unmet mental health care needs. In adjusted models, being unsheltered (vs. stable housing) was associated with not currently on ART, unsuppressed viral load, and unmet primary and dental care needs. Housing and health services need to be developed with and for WLWH to address structural inequities and fulfill basic rights to housing and health.

Kaposi sarcoma-associated herpesvirus (KSHV) causes Kaposi sarcoma (KS). The risk of KS is amplified in HIV-immunosuppressed individuals and antiretroviral therapy (ART) reduces KS incidence. Reliable data on the relationship between these factors are lacking in Africa. We used questionnaires and serum from 7,886 black South Africans (18-74 years) with incident cancer, recruited between 1995 and 2016. ART rollout started in 2004. We measured associations between KS, HIV-1 and KSHV before and after ART rollout. We measured seropositivity to HIV-1, KSHV latency-associated nuclear antigen (LANA) and glycoprotein (K8.1) and calculated case-control-adjusted odds ratios (ORadj) and 95% Confidence Intervals (CI) in relation to KS and KSHV infection, before (1995-2004), early (2005-2009) and late (2010-2016) ART rollout periods. KSHV seropositivity among 1,237 KS cases was 98%. Among 6,649 controls, KSHV seropositivity was higher in males (ORadj =1.4 [95%CI1.23-1.52]), in persons with HIV, (ORadj =4.2 [95%CI3.74-4.73]) and lower in high school leavers (ORadj =0.7 [95%CI0.59-0.83]). KSHV seropositivity declined over the three ART rollout periods (37%, 28%, 28% Ptrend <0.001) coinciding with increases in high school leavers over the same periods (46%, 58% and 67%, Ptrend <0.001). HIV-1 seroprevalence increased from 10% in the pre-ART period to 22% in the late ART period (Ptrend <0.001). Compared to HIV-1 and KSHV seronegatives, KSHV seropositives yielded an OR for KS of 26 (95%CI11-62) in HIV-1 seronegative participants and an OR of 2501 (95%CI1083-5776) in HIV-1 seropositive participants. HIV-1 increases the risk of KS in those infected with KSHV by 100-fold. Declines in KSHV seroprevalence coincide with ART rollout and with improvements in educational standards and general hygiene.