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.

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.

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.

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.

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.

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.

Leukocyte reduction's role in the attenuation of infection risks among transfusion recipients.

Despite advances in the screening of donated blood for infectious agents, the risk of transmitting viral, bacterial, and protozoal infections, as well as newly emerging diseases, via transfusion persists. A complementary approach is leukocyte reduction (LR), the removal of leukocytes from donated blood by filtration. Published evidence, establishing the benefit of LR in reducing the risk of febrile nonhemolytic reactions, cytomegalovirus transmission, and human leukocyte antigen alloimmunization has led to its use for some time for the care of immunosuppressed and other individuals considered to be at high risk for such complications. Recent literature suggests that LR may be effective in reducing the risk of transmission of a number of additional transfusion-transmitted infectious agents, including herpesviruses, retroviruses, bacteria, protozoa, and prions. There is also evidence that LR may reduce the risk of transfusion-related immunomodulation, further contributing to protection against infections that would complicate treatment. With the mounting evidence of potential benefit, a number of countries, as well as many hospitals and blood centers in the United States, have adopted a policy of performing LR for all donated blood. Physicians who care for immunosuppressed patients and those who are responsible for institutional infection-control practices should remain informed of the growing body of literature on LR.

An overview of prion biology and the role of blood filtration in reducing the risk of transfusion-transmitted variant Creutzfeldt-Jakob disease.

Prions are infectious proteins believed to be responsible for a variety of progressive and fatal neurodegenerative diseases, collectively referred to as transmissible spongiform encephalopathies (TSE). By 1996, it was recognized that ingestion of beef from cattle afflicted with a TSE known as bovine spongiform encephalopathy, could result in a devastating human TSE known as variant Creutzfeldt-Jakob disease (vCJD). Two recent reports of probable transfusion-transmitted vCJD have raised concerns about the safety of the blood supply. The relatively long asymptomatic latency of vCJD, as well as the lack of sensitive and specific antemortem tests, increase the risk that asymptomatic, infected individuals may become blood donors. To this point, donor deferral has been a strategy used to reduce this risk. Nevertheless, this strategy may be unreliable and, furthermore, may threaten blood availability. Leukoreduction has also been helpful in reducing cell-associated infectious prion, which has been reported to reduce up to 42% of the infectivity in blood. Proprietary prion affinity surface modifications have been developed and applied to filters, which exploit an understanding of the unique chemical characteristics of prion surfaces. These have been successfully adapted to existing high-efficiency blood filter matrices for the reduction of prions present in blood components for transfusion.

GB virus C infection in children with perinatal human immunodeficiency virus infection.

BACKGROUND: GB virus C (GBV-C) infection occurs in 20-40% of human immunodeficiency virus (HIV)-infected adults, and coinfection is associated with improved HIV disease outcome. METHODS: To determine the prevalence of GBV-C infection in children who were perinatally infected with HIV, we conducted a cross-sectional prevalence survey in a cohort of perinatally infected HIV-positive children selected from a large, multicenter observational protocol. A blood specimen was obtained and tested for GBV-C viremia with the use of a qualitative GBV-C RNA assay and screened for past GBV-C infection with enzyme-linked immunosorbent assay to detect antibodies to the GBV-C envelope protein E2 (E2 Ab). RESULTS: The 354 children who participated in the substudy were relatively healthy, with a median CD4 of 784 cells/mm and median HIV-1 viral load of 1055 copies/mL. The prevalence of GBV-C viremia was 20 of 353 or 5.7% (95% confidence interval, 3.5-8.6%), and the prevalence of E2 Ab was 12 of 354 or 3.4% (95% confidence interval, 1.8-5.8%). GBV-C viremic patients were older than patients without past GBV-C infection (median age, 12.8 years versus 10.7 years). Median CD4 lymphocyte counts were highest in subjects without GBV-C infection and lowest in those with E2 Ab. CONCLUSIONS: GBV-C prevalence rates are lower in children with perinatal HIV infection than those reported for HIV-infected adults. With the exception of evidence that GBV-C viremic children had lower rates of Centers for Disease Control and Prevention HIV disease category C disease before GBV-C testing, we did not find evidence of improved HIV disease outcome in coinfected patients, but the number of HIV/GBV-C-coinfected children was small.

Prion biology in transfusion medicine: implications for lab testing.

Although eerily silent for many years after the recognition of scrapie in 1759, TSEs remained present within the genome of some mammals. Not since the mid-1950s when Dr. Carleton Gadjusek visited the Fore Indians of New Guinea to study kuru, however, has there been a more frenetic interest by governmental investigators. Certainly, the U.K. experience has heralded a renewed interest in TSEs due to the notoriety associated with younger subjects succumbing to a variant CJD traced to the ingestion of beef. Human TSEs and the potential for their transmission among and across species of mammals has also captured the attention of many. Yet, to date, there is no reliable antemortem test available to screen for infected animals or humans. Antibody-based assays are difficult to develop because most of them do not have specificity for the pathogenic form of prion protein. Whether or not prion testing efforts will change dramatically depends upon the incidence of disease. Some speculate a reduction in testing, because BSE incidence is waning since the adoption of remedial steps in the U.K. in 1989. Others remind us, however, of the long latency of prion diseases and of the recent observations of two patients who succumbed to vCJD after having received blood products from donors who subsequently died of vCJD. The growing incidence of CWD, combined with the emerging observation that as many as 26% of Alzheimer's patients may have been misdiagnosed--having died instead of prion disease--maintains pressure for legislators to adhere to the precautionary principle and support blood-donor exclusionary criteria, antemortem-test development, and pathogen removal from donated blood. The laboratorian can expect to see new tests for prion disease work their way into clinical-testing practice in the near future. In addition, the adoption of newer filtration technologies holds the promise of improved protection from transfusion-transmitted prion disease.

Enfuvirtide (T-20): a novel human immunodeficiency virus type 1 fusion inhibitor.

The development of highly active antiretroviral therapy has improved life expectancy and reduced progression to acquired immunodeficiency syndrome in human immunodeficiency virus (HIV)-infected patients. However, resistance to currently available classes of antiretroviral drugs has become a problem, limiting the options for patients with advanced disease who have been heavily treated. Enfuvirtide (T-20; ENF), a synthetic peptide, is the first of a new class of antiretrovirals that block entry of virus into host cells. ENF interferes with conformational changes required for membrane fusion and injection of virus into the host cell. Optimal treatment of HIV infection will likely require combinations of drugs that target novel stages of HIV type 1 entry and replication.

Hepatitis C prevalence in children with perinatal human immunodeficiency virus infection enrolled in a long-term follow-up protocol.

OBJECTIVE: To evaluate the prevalence of hepatitis C virus (HCV) infection in children with perinatal human immunodeficiency virus (HIV) infection. DESIGN: Cross-sectional substudy. SETTING: Multicenter study from 41 sites in the United States. PATIENTS: Children with perinatal HIV infection were randomly selected from a large, long-term, follow-up protocol. MAIN OUTCOME MEASURE: Hepatitis C infection was defined as having positive test results on both HCV antibody and HCV RNA assays. RESULTS: Five hundred thirty children enrolled in the substudy; definitive HCV test results were available for 525 children. Eighty-three percent were of a minority race or ethnicity. They were equally distributed by sex, had a median age of 10.7 years, and were relatively healthy, with 75% having CD4+ lymphocyte counts greater than 500 cells/mm3. Eight of 525 children (1.5%; 95% confidence interval [CI], 0.7%-3.0%) infected with HIV were coinfected with HCV. In contrast, the rate of HCV infection in a serosurvey of more than 2700 children aged 6 to 11 years from the National Health and Nutrition Examination Survey was 0.2% (95% CI, 0.04%-0.6%). In our study, there were no differences between children coinfected with HIV and HCV and those without HCV infection in terms of demographic characteristics, CD4+ or CD8+ T-lymphocyte counts, HIV 1 RNA levels, preterm or mode of delivery, or liver disease; however, the number of children coinfected with HIV and HCV was small. CONCLUSION: While HCV prevalence infection rates are low in children with perinatal HIV infection, they are 8 to 10 times higher than reported in HCV serosurveys of children in the United States.

HIV infection and antiphospholipid antibody: literature review and link to the antiphospholipid syndrome.

There is a high incidence of antiphospholipid antibodies, detected by assays for anticardiolipin or lupus-like anticoagulant, in HIV disease. However, a link to the antiphospholipid syndrome, with clinical thrombosis, is tenuous. We report a case of a 25-year-old man with undetermined risk factors for HIV presenting with possible antiphospholipid syndrome manifesting as necrotic skin lesions as the initial clinical presentation for HIV. We also review the literature exploring the association between HIV and antiphospholipid syndrome.

Virologic testing in the management of perinatal HIV exposure.

Over the last several years, virologic assays for the detection and measurement of HIV-1 RNA have become important in the diagnosis and management of perinatal HIV infection. Since AIDS Clinical Trials Group 076, a number of prospective and retrospective analyses have investigated the role of viral load in perinatal transmission. Although no universal virologic threshold for perinatal HIV transmission has been established, much has been learned about the timing of perinatal transmission and the relationship between maternal viral load and disease progression in HIV-infected neonates. Virologic assays have become accepted as standards of care in monitoring viral load during pregnancy, diagnosing neonatal infection, and establishing prognosis and response to therapy in infected infants.

Diagnosis and management of infectious esophagitis associated with human immunodeficiency virus infection.

Esophageal disease is a common complication and cause of morbidity in patients with human immunodeficiency virus (HIV) infection. Opportunistic infections are the leading cause of esophageal complaints and may be a predictor of poor long-term prognosis, presumably as a reflection of severe underlying HIV immunodeficiency. The esophagus may be the site of the first acquired immunodeficiency syndrome (AIDS)-defining opportunistic illness in a large number of patients. Barium esophagography and upper gastrointestinal endoscopy are diagnostic modalities, commonly used to evaluate esophageal complaints in patients with AIDS. Treatment for most etiologies of esophagitis generally has a high degree of success, with a resultant improvement in quality of life. In addition to optimizing antiretroviral therapy, a thorough diagnostic assessment of every HIV-infected patient with esophageal complaints is warranted, followed by timely and appropriate treatment.