Systematic review of the impact of protease-inhibitor-based combination antiretroviral therapy on renal transplant outcomes in recipients living with HIV infection.

Advances in human immunodeficiency virus (HIV) treatment, including combination antiretroviral therapy (cART), have transformed HIV into a chronic condition. Kidney diseases cause morbidity and mortality in patients living with HIV (PLWH), though cART has permitted kidney transplants with acceptable post-transplant graft and patient survival. Risk of allograft rejection remains high, which may be related to interactions between cART, specifically protease inhibitors (PI), and immunosuppressants prescribed post-transplant. This systematic review evaluates renal transplant outcomes in PLWH treated with PI- vs non-PI-based cART. A search strategy was generated with terms related to renal transplant, HIV, and cART and run on PubMed, Embase, Scopus, and Cochrane. Studies were evaluated using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines on Covidence by two reviewers and then evaluated for bias. Of 803 studies, 9 were included. Included papers were prospective or retrospective cohort studies or chart reviews of adult patients. Outcome measures included acute graft rejection, graft survival, and patient survival. One study had significant results demonstrating that PI-based therapy was correlated with increased graft rejection rates. Two studies demonstrated significant graft survival benefit to non-PI-based therapy, while one demonstrated significant benefit to PI-based therapy. Two studies found significant patient survival benefit to non-PI-based therapy. For each outcome measure, remaining data suggested improved outcomes with non-PI-based therapies without achieving statistical significance. The results demonstrate superior outcomes in PLWH taking non-PI-based cART, though the paucity of significant results suggests that PLWH who require PI-based cART for virological control may continue their regimen safely post-kidney transplant.

Impact of Antiretroviral Therapy on Kidney Disease in HIV Infected Individuals - A Qualitative Systematic Review.

Kidney disease is the fourth most common cause of non-AIDS-related mortality in people living with HIV. Combination antiretroviral therapy (cART) remains the cornerstone of treatment. However, little is known about the impact of cART on disease outcomes in patients with HIV-associated nephropathy (HIVAN) and HIV-immune complex kidney disease (HIVICK). This systematic review evaluates the impact of cART on progression to end-stage kidney disease (ESKD) and other outcomes in HIV-infected individuals. We conducted a literature search utilizing PubMed, and Cochrane database and 11 articles met inclusion criteria for analysis of which nine HIVAN studies showed decreased progression to ESKD or death for subjects when treated with cART versus those untreated. However, two studies showed no survival advantage with cART. Three HIVICK studies showed improvement in delaying ESKD in subjects on cART compared to untreated subjects. cART appeared to reduce the risk to ESKD or death in patients with both HIVAN and HIVICK.

Acceptability of HIV testing for adolescents and young adults by delivery model: a systematic review.

HIV infections are prevalent among adolescents and young adults, of whom 44% remain unaware of their diagnosis. HIV screening presents numerous challenges including stigma, fear, and concerns about confidentiality, which may influence young people's acceptance of HIV screening and linkage to care differently from individuals in other age groups. It is imperative to understand which care delivery models are most effective in facilitating these services for youth. This systematic review analyzes the rates of HIV test acceptance and linkage to care by care delivery model for adolescents and young adults. Studies were classified into emergency department (ED), primary care/inpatient setting, community-based program, or sexually transmitted infection clinic models of care. From 6395 studies initially identified, 59 met criteria for inclusion in the final analyses. Rate of test acceptance and linkage to care were stratified by model of care delivery, gender, race, age ranges (13-17, 18-24 years) as well as site (North America vs rest of the world). A significant difference in acceptance of HIV testing was found between care models, with high rates of test acceptance in the ED setting in North America and primary care/hospital setting in the rest of the world. Similarly, linkage to care differed by model of care, with EDs having high rates of linkages to HIV care in North America. Future studies are needed to test mechanisms for optimizing outcomes for each care delivery model in addressing the unique challenges faced by adolescents and young adults.

Predictors of misperceptions, risk perceptions, and personal risk perceptions about COVID-19 by country, education and income.

Government interventions, such as mandating the use of masks and social distancing, play crucial roles in controlling the spread of pandemic infection. Adherence depends on public perceptions about pandemic risk. The goal was to explore the roles of education, income, and country on misperceptions, risk perceptions and personal risk perceptions about COVID-19. Data were extracted from 3 preregistered surveys. Binary logistic regressions were conducted to investigate the roles country, education, and income had on outcome variables. Across the USA, Canada, and UK, individuals in the highest income quartile were significantly less likely to hold misperceptions (OR=0.61, 95% CI 0.45 to 0.83) and to perceive personal risk (OR=0.38, 95% CI 0.20 to 0.75) regarding COVID-19 compared with individuals in the lowest income quartile. When comparing these income quartiles in the USA, the difference in perceived risk was heightened (OR=0.21, 95% CI 0.07 to 0.57). Citizens of the UK were more likely to have risk perceptions compared with citizens of the USA (OR=1.50, 95% CI 1.20 to 1.88). Citizens of Canada were less likely to perceive personal risk compared with US citizens (OR=0.40, 95% CI 0.23 to 0.69). Proper risk perception and understanding of COVID-19 are necessary for adherence to public health initiatives. The lowest income quartile was shown to have more misperceptions and personal risk perceptions across all 3 countries, highlighting the disproportionate impact of COVID-19 in this group. Our findings support the importance of education and income in affecting health perceptions and outcomes. Further research is needed to explore interventions to minimize misperceptions, accurately shape risk perception, and effectively communicate science.

Interventions to improve medication adherence in adolescents with HIV: a systematic review and meta-analysis.

As of 2017, 1.8 million people living with HIV (PLWH) were adolescents between ages 10 and 19, accounting for 5% of all PLWH and 590,000 people between the ages 15 and 24 were newly infected with HIV. Between 2004 and 2011, AIDS-related deaths increased 50% among adolescents, and optimal adolescent adherence to antiretroviral treatment (ART) is estimated at only 62% of adolescents worldwide. While there have been great strides toward achieving the UNAIDS 90-90-90 goals, adolescents remain a group lacking appropriate resources and research to achieve these. This review analyzes current interventions aimed toward increasing adolescent ART adherence. Systematic searches of EMBASE, PubMed and PsycINFO were performed using the keywords 'adolescent HIV medication adherence interventions'. The Gain Score effect size was calculated for studies reporting the Cohen's d and variance to include both prestudy and poststudy values. A random-effects model analyzed intervention significance. Authors were contacted to obtain additional data values and study clarification. Twelve studies met inclusion criteria for meta-analysis. There were no significant differences seen between control and intervention groups in medication adherence (z=-1.4714, p<0.1412), viral load (z=-0.1946, p<0.8547) or CD4+ lymphocyte count (z=0.2650, p<0.7910). There was no significant difference between studies in increasing medication adherence. Results indicate that interventions did not improve medication adherence in adolescents with HIV. However, the paucity of quantitative research available speaks to a need for more quantitative intervention studies and standardization of measures of intervention efficacy.

Systematic review of cognitive behavior therapy to improve mental health of women living with HIV.

Psychological distress is highly prevalent in people living with HIV. Cognitive behavior therapy (CBT) has been associated with improved mental health outcomes in HIV-infected men who have sex with men (MSM); however, little is known of its effect in women living with HIV/AIDS (WLHA). We review current literature on CBT and its effects on depression, anxiety, stress and mental health quality of life (QOL) in WLHA. We undertook a systematic review of the literature indexed in PubMed, Medline, Psychiatry Online and ScienceDirect. Of the 273 relevant studies discovered, 158 contained duplicate data, and 105 studies did not meet the inclusion and exclusion criteria, yielding 10 studies for analysis. Data were independently extracted by each researcher, with differences resolved through discussion and consensus. For WLHA, CBT substantially improved QOL, symptoms of depression and stress, but appeared to have less impact on anxiety. Three of the six studies measuring depression outcomes showed statistically significant decreases in depression. Three of three studies measuring mental health QOL, and three of three studies measuring stress also demonstrated statistically significant improvement. Two of two studies measuring anxiety did not show statistically significant change. CBT is a promising therapy for WLHA. CBT may reduce psychological distress, improving symptoms of depression, stress and QOL. There is a need for additional, better standardized studies that examine CBT for WLHA.

Easing the transition of HIV-infected adolescents to adult care.

The past two decades have witnessed dramatic reductions in HIV-related morbidity and mortality following the introduction of combination antiretroviral therapy (cART) for infants and children. Improved therapeutic outcomes have changed the face of the HIV epidemic and with it the needs of patients and families. Consequently, many perinatally- and behaviorally-infected adolescents are now transitioning to adult care. What follows is a brief review and commentary concerning original research, reviews, and clinical guidelines describing challenges and best practices in facilitating care transitions for HIV-infected youth to adult care. Over 25,000 HIV-infected US youth aged 13-24 years will require transition to adult care within the next decade. Transition planning must address issues of cognitive development and mental health, medication adherence, sexuality, reproductive, and gender identity, socioeconomic and health insurance status, stigma and disclosure, disrupted relationships with pediatric care providers, and communication. Clinical experience with HIV and other chronic illnesses supports a multidisciplinary, developmentally-sensitive approach to meeting the challenges inherent in care transition that begins early and is monitored with regular evaluation and revision. Specific clinical recommendations have been made by the U.S. Department of Health and Human Services and the New York State Department of Health AIDS Institute.

Effect of probiotic bacteria on microbial host defense, growth, and immune function in human immunodeficiency virus type-1 infection.

The hypothesis that probiotic administration protects the gut surface and could delay progression of Human Immunodeficiency Virus type1 (HIV-1) infection to the Acquired Immunodeficiency Syndrome (AIDS) was proposed in 1995. Over the last five years, new studies have clarified the significance of HIV-1 infection of the gut associated lymphoid tissue (GALT) for subsequent alterations in the microflora and breakdown of the gut mucosal barrier leading to pathogenesis and development of AIDS. Current studies show that loss of gut CD4+ Th17 cells, which differentiate in response to normal microflora, occurs early in HIV-1 disease. Microbial translocation and suppression of the T regulatory (Treg) cell response is associated with chronic immune activation and inflammation. Combinations of probiotic bacteria which upregulate Treg activation have shown promise in suppressing pro inflammatory immune response in models of autoimmunity including inflammatory bowel disease and provide a rationale for use of probiotics in HIV-1/AIDS. Disturbance of the microbiota early in HIV-1 infection leads to greater dominance of potential pathogens, reducing levels of bifidobacteria and lactobacillus species and increasing mucosal inflammation. The interaction of chronic or recurrent infections, and immune activation contributes to nutritional deficiencies that have lasting consequences especially in the HIV-1 infected child. While effective anti-retroviral therapy (ART) has enhanced survival, wasting is still an independent predictor of survival and a major presenting symptom. Congenital exposure to HIV-1 is a risk factor for growth delay in both infected and non-infected infants. Nutritional intervention after 6 months of age appears to be largely ineffective. A meta analysis of randomized, controlled clinical trials of infant formulae supplemented with Bifidobacterium lactis showed that weight gain was significantly greater in infants who received B. lactis compared to formula alone. Pilot studies have shown that probiotic bacteria given as a supplement have improved growth and protected against loss of CD4+ T cells. The recognition that normal bacterial flora prime neonatal immune response and that abnormal flora have a profound impact on metabolism has generated insight into potential mechanisms of gut dysfunction in many settings including HIV-1 infection. As discussed here, current and emerging studies support the concept that probiotic bacteria can provide specific benefit in HIV-1 infection. Probiotic bacteria have proven active against bacterial vaginosis in HIV-1 positive women and have enhanced growth in infants with congenital HIV-1 infection. Probiotic bacteria may stabilize CD4+ T cell numbers in HIV-1 infected children and are likely to have protective effects against inflammation and chronic immune activation of the gastrointestinal immune system.

Nontuberculous mycobacterial hypersensitivity pneumonitis related to a home shower: treatment and secondary prevention.

A 57-year-old physician with increasing dyspnoea and hypoxaemia had a high-resolution CT scan of the chest, which disclosed diffuse pulmonary ground glass opacities, more pronounced in the upper lobes with minimal mediastinal lymphadenopathy. Transbronchial biopsy of the right middle and lower lobes was performed, demonstrating varying degrees of well circumscribed organising granulomatous pneumonitis thought to be most consistent with hypersensitivity to nontuberculous mycobacteria. Cultures of water obtained from the patient's home shower were positive for Mycobacterium avium complex. The patient began substituting baths for showers, experiencing some gradual improvement of his symptoms. Subsequently, he installed point-of-use 0.2 micron membrane filters on his shower, and resumed regular showering after installation with continued symptomatic improvement. CT scans at 3 and 18 months revealed improvement and resolution, respectively. Four years later, he continues to shower in filtered home shower water and remains clinically well.

Associations of proinflammatory cytokine levels with lipid profiles, growth, and body composition in HIV-infected children initiating or changing antiretroviral therapy.

OBJECTIVES: To measure proinflammatory cytokines (PIC) in HIV-infected children beginning or changing antiretroviral therapy (ART), evaluating associations with virologic, immunologic, serum lipid, growth, and body composition measures, markers of growth hormone action and glucose metabolism. METHODS: Forty-nine prepubertal HIV-infected children had measurements of viral load (VL), CD4 lymphocyte count and percentage, serum lipids, apolipoprotein AI/B, IGF-1, IGFBP-1, and IGFBP-3, anthropometry, bioelectrical impedance analysis, TNF-α, IL-1 ß, and IL-6 at baseline and 48 weeks of ART. RESULTS: Baseline levels were detectable (>0.1 pg/mL) for IL-1 ß in 28 of 48, and for TNF-α and Il-6 in all 49 children. TNF-α decreased with ART (P < 0.001) and IL-6 demonstrated a similar trend (P = 0.065). Children with 48-week VL <400 copies/mL had greater declines in TNF-α (mean 45%) than subjects with higher VL (5%; P = 0.009). Each 10% improvement in CD4% was associated with 26% lower TNF-α (P = 0.002) and 31% lower IL-6 (P = 0.016). Greater reductions in TNF-α were associated with lower total/HDL cholesterol ratio (P = 0.003) at week 48. CONCLUSIONS: In HIV-infected children initiating or changing ART, PIC were detectable at baseline and decreased over 48 weeks. Better immunologic responses were associated with greater reductions in TNF-α and IL-6. Reductions in TNF-α were associated with improved total/HDL cholesterol ratio.

Preventive efficacy and cost-effectiveness of point-of-use water filtration in a subacute care unit.

Infections with Pseudomonas aeruginosa and other waterborne pathogens (WBPs) are major contributors to serious morbidity and mortality in hospitals. We sought to determine whether point-of-use (POU) water filtration might result in decreased risk of infection in the subacute care unit (SACU) of a 208-bed medical center. Our findings indicate that POU water filtration can significantly and cost-effectively reduce colonization of and infection with WBPs, including ventilator-associated pneumonia, in an SACU.

Insulin-like growth factor-1 and lean body mass in HIV-infected children.

OBJECTIVES: To describe insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-1-binding protein-1 (IGFBP-1) and IGFBP-3 in HIV+ children before and after initiating or changing antiretroviral therapy and to evaluate association of growth and body composition to growth factors at baseline and over time. METHODS: Ninety-seven prepubertal HIV+ children aged 1 month to younger than 13 years were observed over 48 weeks after beginning or changing antiretroviral therapy. Serum IGF-1, IGFBP-1, and IGFBP-3 were measured and compared with age- and sex-specific norms. Anthropometric measures were compared as follows: subjects vs matched children from (a) the National Health and Nutrition Examination Survey to generate z scores and (b) HIV-exposed, uninfected children from Women and Infants Transmission Study; and subjects with normal vs abnormal IGF-1 and IGFBP concentrations at baseline. Anthropometric changes were compared for children whose IGF-1 level normalized vs remaining subjects. Multivariate analysis adjusting for sex, race, and baseline age evaluated associations between anthropometry and IGF-1 and IGFBP concentrations. RESULTS: In multivariate analysis, lower baseline IGF-1 and IGFBP-3 were associated with lower mean weight, height, mid-arm muscle circumference, and mid-thigh circumference z scores. Twenty-four percent of children had a low IGF-1 level at baseline, 50% of whom normalized IGF-1 on study. Children whose IGF-1 normalized had greater increases in mean mid-arm muscle circumference z score (1.00 vs -0.03, P = 0.029), but a trend toward lesser mean height increase (P = 0.082) than remaining subjects. Likewise, in comparison to controls from Women and Infants Transmission Study, mean mid-arm muscle circumference also increased more in children whose IGF-1 normalized (P = 0.024) but mean height changed less (P = 0.003). Fifty-five percent of children had elevated IGFBP-1 at baseline, 69% of whom normalized. CONCLUSIONS: IGF-1 increases and IGFBP-1 decreases in HIV-infected children upon initiation or change in antiretroviral therapy. Improved muscle mass, but not linear growth, is associated with normalized IGF-1 concentration. These findings suggest that IGF-1 may merit evaluation as a potential therapeutic strategy to improve lean body mass in HIV-infected children.

Lipid and glucose alterations in HIV-infected children beginning or changing antiretroviral therapy.

OBJECTIVE: The objective of this study was to describe lipid profiles and glucose homeostasis in HIV-positive children after initiating or changing antiretroviral therapy and their associations with viral, immune, antiretroviral therapy, and growth factor parameters. METHODS: Ninety-seven prepubertal HIV-positive children aged 1 month to <13 years were observed for 48 weeks after beginning or changing antiretroviral therapy. Fasting lipid panels, serum glucose, insulin, insulin-like growth factor-1 and binding proteins-1 and -3, plasma viral load, and CD4% were measured. Each child was matched on age, gender, and race/ethnicity to children from the National Health and Nutrition Examination Survey, used to give z scores for each child's lipid values. Multivariate regression was used to evaluate the association of changes in z scores over 48 weeks with suppression of HIV-1 RNA, change in CD4% and growth factors, and antiretroviral therapy, adjusted for entry z score, CD4%, log(10) HIV-1 RNA, Centers for Disease Control and Prevention category, and total fat and cholesterol dietary intake. RESULTS: Lipid, apolipoprotein, and insulin levels all increased significantly by 48 weeks. Multivariate analysis of changes demonstrated that increased HDL and decreased total-HDL cholesterol ratio were associated with CD4% increase and with insulin-like growth factor-1, which increased to normal (versus remained stable or became low) over 48 weeks. Total cholesterol levels increased among children who achieved HIV-1 RNA of <400 copies per mL. Antiretroviral therapy regimens that included both a protease inhibitor and a non-nucleoside reverse transcriptase inhibitor were associated with greater increases in total-HDL cholesterol ratio than regimens that contained a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor but not both. CONCLUSIONS: In these HIV-positive children with predominantly mild-to-moderate disease, initiation or change in antiretroviral therapy was associated with significant increases in multiple lipid measures and insulin resistance. Favorable lipid changes were associated with CD4% increases, suggesting a protective effect of immune reconstitution on atherosclerosis, and with increased insulin-like growth factor-1 levels, supporting the theory that reduced growth hormone resistance may be a mechanism by which lipid profiles are improved. Finally, antiretroviral therapy regimens that contain both a non-nucleoside reverse transcriptase inhibitor and a protease inhibitor are associated with worse lipid profiles than regimens that contain 1 but not both of these drug classes.