HIV Viral Control Research Articles

Association between HIV and cytomegalovirus and neurocognitive outcomes among children with HIV.

Children with HIV may experience adverse neurocognitive outcomes despite antiretroviral therapy (ART). Cytomegalovirus (CMV) is common in children with HIV. Among children on ART, we examined the influences of early HIV viral load (VL) and CMV DNA on neurocognition. We determined the association between pre-ART VL, cumulative VL, and CMV viremia and neurocognition using data from a cohort study. Children who initiated ART before 12 months of age were enrolled from 2007-2010 in Nairobi, Kenya. Blood was collected at enrollment and every 6 months thereafter. Four neurocognitive assessments with 12 domains were conducted when children were a median age of 7 years. Primary outcomes included cognitive ability, executive function, attention, and motor. Generalized linear models were used to determine associations between HIV VL (pre-ART and cumulative; N = 38) and peak CMV DNA (by 24 months of age; N = 20) and neurocognitive outcomes. In adjusted models, higher peak CMV viremia by 24 months of age was associated with lower cognitive ability and motor z-scores. Higher pre-ART HIV VL was associated with lower executive function z-scores. Among secondary outcomes, higher pre-ART VL was associated with lower mean nonverbal and metacognition z-scores. Higher pre-ART VL and CMV DNA in infancy were associated with lower executive function, nonverbal and metacognition scores and cognitive ability scores in childhood, respectively. These findings suggest long-term benefits of early HIV viral suppression and CMV control on neurocognition.

Pregnancy Management in HIV Viral Controllers: Twenty Years of Experience.

(1) Background: The evidence base for the management of spontaneous viral controllers in pregnancy is lacking. We describe the management outcomes of pregnancies in a series of UK women with spontaneous HIV viral control (<100 copies/mL 2 occasions before or after pregnancy off ART). (2) Methods: A multi-centre, retrospective case series (1999-2021) comparing pre- and post-2012 when guidelines departed from zidovudine-monotherapy (ZDVm) as a first-line option. Demographic, virologic, obstetric and neonatal information were anonymised, collated and analysed in SPSS. (3) Results: A total of 49 live births were recorded in 29 women, 35 pre-2012 and 14 post. HIV infection was more commonly diagnosed in first reported pregnancy pre-2012 (15/35) compared to post (2/14), p = 0.10. Pre-2012 pregnancies were predominantly managed with ZDVm (28/35) with pre-labour caesarean section (PLCS) (24/35). Post-2012 4/14 received ZDVm and 10/14 triple ART, p = 0.002. Post-2012 mode of delivery was varied (5 vaginal, 6 PLCS and 3 emergency CS). No intrapartum ZDV infusions were given post-2012 compared to 11/35 deliveries pre-2012. During pregnancy, HIV was detected (> 50 copies/mL) in 14/49 pregnancies (29%) (median 92, range 51-6084). Neonatal ZDV post-exposure prophylaxis was recorded for 45/49 infants. No transmissions were reported. (4) Conclusion: UK practice has been influenced by the change in guidelines, but this has had little impact on CS rates.

Factors associated with HIV viral load control in the early postpartum period – a Canadian prospective cohort study

ABSTRACT Despite success in managing HIV during pregnancy, challenges remain around sustained adherence with antiretroviral therapy (ART), and the suboptimal viral load (VL) suppression during the postpartum period. The objective of this study was to compare VL levels at delivery and during the postpartum period and assess factors associated with lack of viral suppression during the postpartum period in Canada. We combined data from two Canadian prospective cohorts, which included 286 HIV-positive women (352 pregnancies) who delivered between 2012 and 2020. Delivery VL, postpartum VL, and potential factors associated with an undetectable VL (<50 copies/mL), 2–18 weeks after delivery were assessed. To account for the correlation between multiple pregnancies from the same woman, generalized estimating equations were used to assess bivariate associations. Ninety-nine per cent of pregnant women were on ART during pregnancy compared to 93% during the postpartum period. Of those with available VL results (n = 214 pregnancies), 94% of women achieved an undetectable VL at delivery compared to 87% during the postpartum period. The postpartum period is a challenging time for ART use and VL control. Qualitative studies are needed to better understand these challenges and guide us in designing adequate interventions.

Advancements in Cell-Based Therapies for HIV Cure.

The treatment of human immunodeficiency virus (HIV-1) has evolved since the establishment of combination antiretroviral therapy (ART) in the 1990s, providing HIV-infected individuals with approaches that suppress viral replication, prevent acquired immunodeficiency syndrome (AIDS) throughout their lifetime with continuous therapy, and halt HIV transmission. However, despite the success of these regimens, the global HIV epidemic persists, prompting a comprehensive exploration of potential strategies for an HIV cure. Here, we offer a consolidated overview of cell-based therapies for HIV-1, focusing on CAR-T cell approaches, gene editing, and immune modulation. Persistent challenges, including CAR-T cell susceptibility to HIV infection, stability, and viral reservoir control, underscore the need for continued research. This review synthesizes current knowledge, highlighting the potential of cellular therapies to address persistent challenges in the pursuit of an HIV cure.

The clinical impact of rifampicin-based anti-TB therapy and tenofovir alafenamide-containing ARV regimen drug Interaction in people living with HIV: Case series report

BackgroundPeople living with HIV (PLWH) are prone to developing tuberculosis (TB). Since tenofovir alafenamide (TAF) is the recommended tenofovir (TFV) prodrug and rifampicin is a key component of TB therapy, thus complicating HIV and TB coinfection management. However, there is little data regarding the impact of this drug-drug Interaction in PLWH, which makes health care providers reluctant to prescribe them together. MethodsThis was an observational, retrospective case series carried out at King Faisal Specialist Hospital & Research Center (KFSH&RC), Jeddah, Saudi Arabia. PLWH (≥18 years old) who received the TAF-containing ARV regimen and rifampicin-based anti-TB therapy together for ≥ 4 weeks were included. The objective of this study was to report the clinical impact of this drug-drug interaction (rifampicin + TAF-containing antiretroviral (ARV) regimen) on HIV viral load control in PLWH. ResultsA total of 7 PLWH who met the inclusion criteria, 5 (71 %) out of 7, were males. All patients received dolutegravir 50 mg twice daily (DTG) plus the combination of TAF 25 mg and emtricitabine 200 mg (FTC) once daily as their ARV regimen. Four patients had suppressed viral load levels at baseline, which was maintained throughout TB treatment. Three patients had unsuppressed viral load levels at baseline and attained viral load suppression throughout the TB treatment course ConclusionOverall, the TAF-containing ARV regimen maintained it's efficacy in presence of rifampicin.

Caecum OX40+CD4 T-cell subset associates with mucosal damage and key markers of disease in treated HIV-infection

BackgroundBlood OX40-expressing CD4 T-cells from antiretroviral (ART)-treated people living with HIV (PWH) were found to be enriched for clonally-expanded HIV sequences, hence contributing to the HIV reservoir. OX40-OX40L is also a checkpoint regulator of inflammation in multiple diseases. We explored gut mucosal OX40+CD4+ T-cells and their potential significance in HIV disease. MethodsBiopsies of caecum and terminal-ileum of ART-treated PWH (n = 32) were obtained and mucosal damage and HIV reservoir were assessed. Mucosal OX40+ and Ki67+ CD4 T-cell subsets, as well as several tissue T-cell subsets modulating mucosal integrity and homeostasis (Th17, Th22, Treg, Tc17, Tc22, IL17+TCRγδ, IL22+TCRγδ) were quantified. Inflammatory-related markers, T-cell activation and thymic output were also determined in blood samples. Correlations were explored using Spearman rank test and corrected for multiple comparisons by Benjamini-Hochberg. ResultsCompared to healthy controls, a high frequency of mucosal, mainly caecum, CD4 T-cells were OX40+ in PWH. Such frequency strongly correlated with nadir CD4 (r = −0.836; p < 0.0001), CD4/CD8 ratio (r = −0.630; p = 0.002), caecum mucosal damage (r = 0.606; p = 0.008), caecum Th22 (r = −0.635; p = 0.002), caecum Th17 (r = 0.474; p = 0.03) and thymic output (r = −0.686; p < 0.001). It also correlated with Neutrophil-to-Lymphocyte Ratio and blood CD4 T-cell activation and tended to with mucosal HIV reservoir. ConclusionHigh frequencies of caecum OX40+CD4 T-cells are found in people with HIV (PWH) and successful viral control. Interestingly, this cellular subset reflects key markers of disease and peripheral T-cell activation, as well as HIV-driven mucosal damage. OX40+CD4 T-cells deserve further investigation since they could expand because of T-cell homeostatic proliferation and relate to the Th22/Th17 gut mucosal ratio.

Impact of sub-optimal HIV viral control on activated T-cells: an earnest sub study.

HIV viral load (VL) monitoring is generally conducted 6-12 monthly in low- and middle-income countries, risking relatively prolonged periods of poor viral control. We explored the effects of different levels of loss of viral control on immune reconstitution and activation. : 208 participants starting Protease Inhibitor (PI)-based second-line therapy in the EARNEST trial (ISRCTN37737787) in Uganda and Zimbabwe were enrolled and CD38+/HLA-DR+ immunophenotyping performed (CD8-FITC/CD38-PE/CD3-PerCP/HLA-DR-APC; centrally gated) in real-time at 0, 12, 48, 96 and 144 weeks from randomisation. Viral Load (Viral load (VL) was assayed retrospectively on samples collected every 12-16 weeks and classified as (1) continuous suppression (<40 copies/ml throughout); (2) suppression with transient blips; (3) low-level rebound (two or more consecutive VL >40, <5000 copies/ml); (4) high-level rebound/non-response (two or more consecutive VL >5000 copies/ml). Immunophenotype reconstitution varied between that defined by numbers of cells and that defined by cell percentages. Furthermore, VL dynamics were associated with substantial differences in expression of CD4+ and CD8+ cell activation markers, with only individuals with high-level rebound/non-response (>5000 copies/ml) experiencing significantly greater activation and impaired reconstitution. There was little difference between participants who suppressed consistently and who exhibited transient blips or even low-level rebound by 144 weeks (p > 0.2 vs suppressed consistently). Detectable viral load below the threshold at which WHO guidelines recommend that treatment can be maintained without switching (1000 copies/ml) appear to have at most, small effects on reconstitution and activation, for patients taking a PI-based second-line regimen.

HIV-serodifferent couples' perspectives and practices regarding HIV prevention strategies: A mixed methods study.

A substantial proportion of heterosexually acquired HIV infections in the U.S. occur between partners in primary relationships characterized by mixed HIV status. The U.S. Centers for Disease Control and Prevention have issued guidelines prioritizing HIV-serodifferent couples for primary HIV prevention, including treatment-as-prevention and pre-exposure prophylaxis (PrEP). Yet, very little research has been conducted to understand the perspectives and practices of HIV-serodifferent couples regarding HIV prevention strategies in the U.S. To help fill this gap, we conducted a mixed methods study with 27 mostly Black/African American and Latinx HIV-serodifferent heterosexual couples residing in New York City to explore their knowledge, attitudes, practices, and perspectives regarding combination HIV prevention, including condoms, PrEP and viral control. All couples expressed the desire to maintain viral suppression in the HIV-positive partner, which was not always achieved. There was considerable heterogeneity in the use of HIV prevention methods by couples; and several patterns emerged that were largely driven by gender and relationship dynamics. Female partners, in particular, expressed high levels of anxiety around transmission of HIV and thus desired multiple methods of protection. Healthcare providers should consider couples' psychosocial well-being, relationship quality, and other motivational factors when helping to tailor HIV preventative care for mixed-status couples.

Age group differences in substance use, social support, and physical and mental health concerns among people living with HIV two years after receiving primary care-based alcohol treatment

Objectives: People living with HIV (PWH) have seen reduction in HIV-associated morbidity and increase in near-normal life expectancy, yet unhealthy alcohol use poses substantial risks to older as well as younger adults. Further research regarding age-associated physical and mental health concerns among PWH who drink alcohol is needed to inform services, given the expanding age range of patients in care. Methods: We compared age group differences (18–34, 35–44, 45–54, ≥55 years old) in two-year patient-reported outcomes and HIV viral control among PWH enrolled in a primary care-based behavioral alcohol intervention trial; with 90% follow up from baseline. Results: Of 553 PWH, 50 (9%) were 18–34, 85 (15%) were 35–44, 197 (36%) were 45–54, and 221 (40%) were ≥55 years old. Most were men (97%) and White (64%). At two years, PWH ≥55 reported less substance use in the prior 30 days, fewer social contacts, and more pain; younger PWH had lower antiretroviral therapy (ART) adherence. In adjusted analyses, PWH ages 18–34 had higher odds of unhealthy alcohol use, tobacco, cannabis, or other substances compared to those ≥55; with higher odds of anxiety among PWH 35–44 compared with those ≥55; and physical quality of life was worse among those ≥55 compared with younger groups. Conclusions: While older PWH report less substance use than younger PWH and have better ART adherence post-treatment, they are more likely to experience limited social support and worse physical quality of life. Findings can inform interventions to address varying needs of PWH across the lifespan.

Self-Reported Cannabis Use and HIV Viral Control among Patients with HIV Engaged in Care: Results from a National Cohort Study.

Background: The association between cannabis use and HIV-1 RNA (viral load) among people with HIV (PWH) engaged in care is unclear. Methods: We used data collected from 2002 to 2018 on PWH receiving antiretroviral therapy (ART) enrolled in the Veterans Aging Cohort Study. Generalized estimating equations were used to estimate associations between self-reported past-year cannabis use and detectable viral load (≥500 copies/mL), with and without adjustment for demographics, other substance use, and adherence. Results: Among 2515 participants, 97% were male, 66% were Black, the mean age was 50 years, and 33% had detectable HIV viral load at the first study visit. In unadjusted analyses, PWH with any past-year cannabis use had 21% higher odds of a detectable viral load than those with no past-year use (OR = 1.21; 95% CI, 1.07–1.37). However, there was no significant association between cannabis use and viral load after adjustment. Conclusions: Among PWH engaged in care and receiving ART, cannabis use is associated with decreased adherence in unadjusted analyses but does not appear to directly impact viral control. Future studies are needed to understand other potential risks and benefits of cannabis use among PWH.

322. Prolonged Amenorrhea Is Associated with Decreased Hip Bone Mineral Density in Women Living with HIV

BackgroundWomen living with HIV (WLWH) have higher rates of long-term amenorrhea (no flow for ≥12 months) than HIV-negative women. However, little is known about the consequences of amenorrhea for WLWH. Both amenorrhea and HIV are associated with lower areal bone mineral density (BMD); though the combined effect of both on BMD remains unclear. In this cross-sectional study we investigated whether prolonged amenorrhea adversely affects BMD among WLWH.MethodsWe investigated BMD (using a Hologic bone densitometer) and prolonged amenorrhea among WLWH and HIV-negative control women of similar socioeconomic backgrounds aged 19–68 in the CARMA cohort. Participants were stratified by HIV status and history of prolonged secondary amenorrhea defined as a self-reported absence of menses for at least one year in the past or present, occurring at age <45 years and not due to surgery, breastfeeding, pregnancy or hormonal contraception. Hip and spine Z-scores (age- and race- standardized BMD values) were compared between groups using linear models, followed by multivariable analysis of BMD-related factors.ResultsWLWH (N = 129) had significantly lower hip (mean±SD −0.4 ± 0.9 vs. 0.3 ± 1.1; P < 0.001) and spine (−0.5 ± 1.3 vs. 0.2 ± 1.3; P = 0.001) Z-scores vs. controls (N = 129). Multivariable linear regression found prolonged amenorrhea was independently related to lower hip (P = 0.01), but not spine (P = 0.94) BMD. Within WLWH, the effect of amenorrhea was also additive to that of HIV, with hip Z-scores of -0.8±0.9for those with amenorrhea vs. -0.3±0.8for those normally cycling (P = 0.01). Amongst WLWH, those with prolonged amenorrhea had higher rates of illicit substance use, smoking, chronic opioid therapy, hepatitis C viral infection, and poorer HIV viral control than those with normal menstruation.ConclusionThese data suggest that WLWH having prolonged amenorrhea of ≥1 year’s duration are at increased risk for hip bone loss, a finding influenced by comorbid, HIV-associated conditions. Screening WLWH for menstrual history will allow early discovery of osteoporosis risk, and stimulate preventative measures to mitigate bone loss.Disclosures All authors: No reported disclosures.

Implementing electronic substance use disorder and depression and anxiety screening and behavioral interventions in primary care clinics serving people with HIV: Protocol for the Promoting Access to Care Engagement (PACE) trial

BackgroundSubstance use disorders (SUDs) and psychiatric disorders are common among people with HIV (PWH) and lead to poor outcomes. Yet these conditions often go unrecognized and untreated in primary care. MethodsThe Promoting Access to Care Engagement (PACE) trial currently in process examines the impact of self-administered electronic screening for SUD risk, depression and anxiety in three large Kaiser Permanente Northern California primary care clinics serving over 5000 PWH. Screening uses validated measures (Tobacco, Alcohol, Prescription medication, and other Substance use [TAPS]; and the Adult Outcomes Questionnaire [AOQ], which includes the Patient Health Questionnaire [PHQ-9] and Generalized Anxiety Disorder [GAD-2]) delivered via three modalities (secure messaging, tablets in waiting rooms, and desktop computers in exam rooms). Results are integrated automatically into the electronic health record. Based on screening results and physician referrals, behavioral health specialists embedded in primary care initiate motivational interviewing- and cognitive behavioral therapy-based brief treatment and link patients to addiction and psychiatry clinics as needed. Analyses examine implementation (screening and treatment rates) and effectiveness (SUD, depression and anxiety symptoms; HIV viral control) outcomes using a stepped-wedge design, with a 12-month intervention phase implemented sequentially in the clinics, and a 24-month usual care period prior to implementation in each clinic functioning as sequential observational phases for comparison. We also evaluate screening and treatment costs and implementation barriers and facilitators. DiscussionThe study examines innovative, technology-facilitated strategies for improving assessment and treatment in primary care. Results may help to inform substance use, mental health, and HIV services. Trial registrationNCT03217058

Immune Complex Vaccination.

Antibody/antigen binding results in immune complexes (IC) that have a variety of regulatory functions. One important feature is the enhanced host immune activation against antigen contained in the complex. ICs play important roles at several critical steps that lead to B and T cell activation, including antigen targeting/retention, facilitated antigen uptake, antigen presenting cell activation and proper balancing of positive and negative stimulatory signals. In both poultry industry and clinical health care, ICs have been used as preventive and therapeutic vaccines. With our deepening understanding of antibody biology, particularly in light of new revelations of regulatory functions of Fc receptors, mechanistically more precise engineering has spearheaded tailored use of this tool for infection control and cancer therapy. IC-based treatment and prophylaxis have been tested to different extents in HBV, HIV and influenza viral infection control and are actively examined as an alternative treatment for several forms of tumor. As a part of this book series, this chapter aims to discuss the mechanistic aspects of IC signaling and their impact on immune cells. We give samples how this old technology has been used by practitioners over the last several decades and suggest potential paths for future development of IC-based immune therapy.

Fc-gamma receptor IIA and IIIA variants in two African cohorts: Lack of consistent impact on heterosexual HIV acquisition, viral control, and disease progression

Human Fc-gamma receptors (FcγRs) FcγRIIA and FcγRIIIA contain amino acid variants with both high and low affinities for IgG that modulate antibody-mediated effector functions. Recent HIV vaccine trials suggested that these FcγR variants can influence susceptibility to HIV infection, which prompted us to fully assess the role of FcγR variants on HIV acquisition, viral control, and disease progression in two longitudinal heterosexual transmission cohorts with HIV subtypes A and C as the major circulating viruses. For 836 participants, molecular genotyping resolved genetic variations encoding the FcγRIIA (131 H/R) and FcγRIIIA (158 V/F) single nucleotide polymorphisms. Kaplan-Meier curves, Cox proportional hazards models, and linear regression models did not reveal any clear or consistent FcγR association with time to HIV acquisition, viral load in early infection, or extent of CD4 + T-cell decline over time after infection. Overall, previous epidemiological findings on FcγR variants and vaccine efficacy are not readily applicable to heterosexual HIV transmission.

Viral control in chronic HIV-1 subtype C infection is associated with enrichment of p24 IgG1 with Fc effector activity.

Postinfection HIV viral control and immune correlates analysis of the RV144 vaccine trial indicate a potentially critical role for Fc receptor-mediated antibody functions. However, the influence of functional antibodies in clade C infection is largely unknown. Plasma samples from 361 chronic subtype C-infected, antiretroviral therapy-naive participants were tested for their HIV-specific isotype and subclass distributions, along with their Fc receptor-mediated functional potential. Total IgG, IgG subclasses and IgA binding to p24 clade B/C and gp120 consensus C proteins were assayed by multiplex. Antibody-dependent uptake of antigen-coated beads and Fc receptor-mediated natural killer cell degranulation were evaluated as surrogates for antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC), respectively. p24 IgG1 was the only subclass associated with viral control (P = 0.01), with higher p24-specific ADCP and ADCC responses detected in individuals with high p24 IgG1. Although p24 IgG1 levels were enriched in patients with elevated Gag-specific T-cell responses, these levels remained an independent predictor of low-viral loads (P = 0.04) and high CD4+ cell counts (P = 0.004) after adjusting for Gag-specific T-cell responses and for protective HLA class I alleles. p24 IgG1 levels independently predict viral control in HIV-1 clade C infection. Whether these responses contribute to direct antiviral control via the recruited killing of infected cells via the innate immune system or simply mark a qualitatively superior immune response to HIV, is uncertain, but highlights the role of p24-specific antibodies in control of clade C HIV-1 infection.

Healthcare Empowerment and HIV Viral Control: Mediating Roles of Adherence and Retention in Care

This study assessed longitudinal relationships between patient healthcare empowerment, engagement in care, and viral control in the Women's Interagency HIV Study, a prospective cohort study of U.S. women living with HIV. From April 2014 to March 2016, four consecutive 6-month visits were analyzed among 973 women to assess the impact of Time 1 healthcare empowerment variables (Tolerance for Uncertainty and the state of Informed Collaboration Committed Engagement) on Time 2 reports of ≥95% HIV medication adherence and not missing an HIV primary care appointment since last visit; and on HIV RNA viral control across Times 3 and 4, controlling for illicit drug use, heavy drinking, depression symptoms, age, and income. Data were analyzed in 2017. Adherence of ≥95% was reported by 83% of women, 90% reported not missing an appointment since the last study visit, and 80% were categorized as having viral control. Logistic regression analyses revealed a significant association between the Informed Collaboration Committed Engagement subscale and viral control, controlling for model covariates (AOR=1.08, p=0.04), but not for the Tolerance for Uncertainty subscale and viral control (AOR=0.99, p=0.68). In separate mediation analyses, the indirect effect of Informed Collaboration Committed Engagement on viral control through adherence (β=0.04, SE=0.02, 95% CI=0.02, 0.08), and the indirect effect of Informed Collaboration Committed Engagement on viral control through retention (β=0.01, SE=0.008, 95% CI=0.001, 0.030) were significant. Mediation analyses with Tolerance for Uncertainty as the predictor did not yield significant indirect effects. The Informed Collaboration Committed Engagement healthcare empowerment component is a promising pathway through which to promote engagement in care among women living with HIV.

Association between depressive symptoms, CD4 count and HIV viral suppression among HIV-HCV co-infected people

ABSTRACTDepressive symptoms are associated with poor HIV viral control and immune recovery among people living with HIV. However, no prior studies assessed this association exclusively among people co-infected with HIV-hepatitis C virus (HCV). While people with HIV only and those with HIV-HCV co-infection share many characteristics, co-infected people may become more susceptible to the effects of depressive symptoms on health outcomes. We assessed this association exclusively among people co-infected with HIV-HCV in Canada using data from the Food Security & HIV-HCV Sub-Study (FS Sub-Study) of the Canadian Co-Infection Cohort (CCC). Stabilized inverse probability weighted marginal structural model was used to account for potential time-varying confounders. A total of 725 participants were enrolled between 2012 and 2015. At baseline, 52% of participants reported depressive symptoms, 75% had undetectable HIV viral load, and median CD4 count was 466 (IQR 300–665). People experiencing depressive symptoms had 1.32 times (95% CI: 1.07, 1.63) the risk of having detectable HIV viral load, but had comparable CD4 count to people who did not experience depressive symptoms (fold change of CD4 = 0.96, 95% CI: 0.91, 1.03). Presence of depressive symptoms is a risk factor for incomplete short-term HIV viral suppression among people co-infected with HIV-HCV. Therefore, depressive symptoms screening and related counseling may improve HIV related health outcomes and reduce HIV transmission.

Risk factors for oropharynx cancer in a cohort of HIV-infected veterans

ObjectiveTo evaluate HIV-related and other clinical risk factors associated with oropharynx cancer (OPSCC) in HIV-infected U.S. Veterans. MethodsRetrospective cohort study utilizing Veterans Affairs HIV Clinical Case Registry (CCR) data from 1985 to 2010. Outcome was incident OPSCC as indicated by 1 inpatient or 2 outpatient ICD-9 codes. Cox proportional hazard models were used to determine hazard ratios (HR) and 95% confidence intervals (CI) for each risk factor on the time to OPSCC diagnosis. ResultsA total of 40,996 HIV-infected male veterans were included in the cohort with 97 cases of OPSCC. The age adjusted incidence rate was 23.2/100,000 [95% CI 17.8–29.2]. Age>50 (aHR=3.8, 95% CI 1.9–7.8), recent CD4<200 (aHR=3.8, 95% CI 2.0–7.3), and undetectable HIV viral loads 40–79% of the time (aHR=1.8, 95% CI 1.1–3.0) were associated with an increased risk of OPSCC. Era of HIV diagnosis, utilization of cART, nadir CD4 count, race, smoking history, and previous risk of HPV disease, including condyloma or invasive squamous cell carcinoma of the anus (SCCA) were not associated with increased risk of OPSCC. ConclusionPatients who were older at beginning of follow up, had lower CD4 counts around the time of OPSCC diagnosis, and moderate HIV viral control during follow-up had an increased risk of OPSCC. Other HPV-related diseases such as SCCA and condyloma did not increase the risk for OPSCC.

Implementation and Operational Research: Affordable Care Act Implementation in a California Health Care System Leads to Growth in HIV-Positive Patient Enrollment and Changes in Patient Characteristics.

This study examined implementation of the Affordable Care Act (ACA) in relation to HIV-positive patient enrollment in an integrated health care system; as well as changes in new enrollee characteristics, benefit structure, and health care utilization after key ACA provisions went into effect in 2014. This mixed-methods study was set in Kaiser Permanente Northern California (KPNC). Qualitative interviews with 29 KPNC leaders explored planning for ACA implementation. Quantitative analyses compared newly enrolled HIV-positive patients in KPNC between January and December 2012 ("pre-ACA," N = 661) with newly enrolled HIV-positive patients between January and December 2014 ("post-ACA," N = 880) on demographics; medical, psychiatric, and substance use disorder diagnoses; HIV clinical indicators; and type of health care utilization. Interviews found that ACA preparation focused on enrollment growth, staffing, competition among health plans, concern about cost sharing, and HIV pre-exposure prophylaxis (PrEP) services. Quantitative analyses found that post-ACA HIV-positive patient enrollment grew. New enrollees in 2014 were more likely than 2012 enrollees to be enrolled in high-deductible plans (P < 0.01) or through Medicaid (P < 0.01), and marginally more likely to have better HIV viral control (P < 0.10). They also were more likely to be diagnosed with asthma (P < 0.01) or substance use disorders (P < 0.05) and to have used primary care health services in the 6 months postenrollment (P < 0.05) than the pre-ACA cohort. As anticipated by KPNC interviewees, ACA implementation was followed by HIV-positive patient enrollment growth and changing benefit structures and patient characteristics. Although HIV viral control improved, comorbid diagnosis findings reinforced the importance of coordinated health care.

Immunoregulatory functions of immune complexes in vaccine and therapy.

Clinical and experimental preparations of IgG/soluble antigen complexes, as well as those formed following antibody therapy in vivo, are multifaceted immune regulators. These immune complexes (ICs) have been tested in humans and animal models, mostly in forms of experimental or clinical vaccination, for at least a century. With intensified research on Fcγ receptor‐mediated immune modulation, as well as with immune complex‐directed antigen processing, presentation, and inflammatory responses, there are renewed interests of using ICs in vaccines and immunotherapies. Currently, IC‐based immune therapy has been broadly experimented in HBV and HIV viral infection control and antitumor treatments. However, mechanistic insights of IC‐based treatments are relatively recent subjects of study; strong efforts are needed to establish links to connect laboratory findings with clinical practices. This review covers the history, mechanisms, and in vivo outcomes of this safe and effective therapeutic tool, with a clear aim to bridge laboratory findings with evolving clinical applications.