Reducing Unnecessary Respiratory Viral Testing to Promote High-Value Care.

BACKGROUND AND OBJECTIVES: Viral respiratory infections are common in children, and practice guidelines do not recommend routine testing for typical viral illnesses. Despite results often not impacting care, nasopharyngeal swabs for viral testing are frequently performed and are an uncomfortable procedure. The aim of this initiative was to decrease unnecessary respiratory viral testing (RVT) in the emergency department (ED) and the pediatric medicine wards (PMWs) by 50% and 25%, respectively, over 36 months. METHODS: An expert panel reviewed published guidelines and appropriate evidence to formulate an RVT pathway using plan-do-study-act cycles. A multifaceted improvement strategy was developed that included implementing 2 newer, more effective tests when testing was deemed necessary; electronic order modifications with force functions; audit and feedback; and education. By using statistical process control charts, the outcomes analyzed were the percentage of RVT ordered in the ED and the rate of RVT ordered on the PMWs. Balancing measures included return visits leading to admission and inpatient viral nosocomial outbreaks. RESULTS: The RVT rate decreased from a mean of 3.0% to 0.5% of ED visits and from 44.3 to 30.1 per 1000 patient days on the PMWs and was sustained throughout the study. Even when accounting for the new rapid influenza test available in the ED, a 50% decrease in overall ED RVT was still achieved without any significant impact on return visits leading to admission or inpatient nosocomial infections. CONCLUSIONS: Through implementation of a standardized, electronically integrated RVT pathway, a decrease in unnecessary RVT was successfully achieved. Audit and feedback, reminders, and biannual education all supported long-term sustainability of this initiative.

Viral Load of Severe Acute Respiratory Syndrome Coronavirus 2 in Adults During the First and Second Wave of Coronavirus Disease 2019 Pandemic in Houston, Texas: The Potential of the Superspreader.

BACKGROUND: During the coronavirus disease 2019 pandemic, a minority of index cases are associated with a majority of secondary cases suggesting that superspreaders could drive the pandemic. We identified a phenotype in individuals with extremely high viral load who could act as superspreaders. METHODS: Data were analyzed from individuals tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from 18 March through 15 August 2020. Outcomes were compared using contingency table and quantile regression to test the equality of medians between the pandemic waves and by viral load groups. RESULTS: Of the 11 564 samples tested, 1319 (11.4%) were positive for SARS-CoV-2. An increase in weekly median viral load occurred in the second wave of the SARS-CoV2 pandemic. This population was more likely to be women, outpatients, and symptomatic and to have an extremely high or high viral load. In patients with multiple reverse-transcription polymerase chain reaction-positive test results, the durations of viral shedding were comparable between individuals with asymptomatic/mild and mild/moderate illness severity. CONCLUSIONS: We detected a small group of individuals with extremely high SARS-CoV-2 viral loads and mild illness. We believe that these individuals' characteristics could be consistent with the superspreader phenomenon and that greater awareness of the social dynamics of these individuals is needed to understand the spread of SARS-CoV-2.

Association of Adverse Neighborhood Exposures With HIV Viral Load in Pregnant Women at Delivery.

Importance: Racial disparities in maternal morbidity and mortality are in large part driven by poor control of chronic diseases. The association between adverse neighborhood exposures and HIV virologic control has not been well described for women with HIV during pregnancy. Objective: To evaluate the association between adverse neighborhood exposures and HIV viral load at delivery. Design, Setting, and Participants: This population-based cohort study assessed HIV surveillance data for pregnant women with HIV who had live deliveries in Philadelphia from January 1, 2005, through December 31, 2015. Data analyses were completed in August 2020. Exposures: Neighborhood exposures included extreme poverty, educational attainment, crime rates (using separate and composite measures), and social capital categorized above or below the median. Each neighborhood exposure was modeled separately to estimate its association with elevated HIV viral load. Main Outcomes and Measures: The main outcome was elevated HIV viral load of ≥200 copies/mL at delivery. We hypothesized that adverse neighborhood exposures would be associated with higher odds of having an elevated viral load at delivery. Confounders included birth year, age, race/ethnicity, previous birth while living with HIV, and prenatal HIV diagnosis. Prenatal care and substance use were considered potential mediators. We used logistic mixed effects models to estimate the association between neighborhood exposures and elevated viral load, adjusting for confounders in Model 1 and confounders and mediators in Model 2. Results: There were 905 births among 684 women with HIV, most of whom were aged 25 to 34 years (n = 463 [51.2%]) and were Black non-Hispanic (n = 743 [82.1%]). The proportion of women with elevated viral load decreased from 58.2% between 2005 and 2009 to 23.1% between 2010 and 2015. After adjusting for confounders in Model 1, higher neighborhood education was associated with lower odds of having an elevated viral load (adjusted odds ratio [AOR], 0.70; 95% CI, 0.50-0.96). More violent crime (AOR, 1.51; 95% CI, 1.10-2.07), prostitution crime (AOR, 1.46; 95% CI, 1.06-2.00), and a composite measure of crime (AOR, 1.44; 95% CI, 1.05-1.98) were positively associated with having a higher HIV viral load. These associations remained after adjusting for mediators in Model 2. In addition, the AOR for intermediate prenatal care varied between 1.93 (95% CI, 1.28-2.91) and 1.97 (95% CI, 1.31-2.96), whereas the AOR for inadequate prenatal care varied between 3.01 (95% CI, 2.05-4.43) and 3.06 (95% CI, 2.08-4.49) across regression models. Conclusions and Relevance: In this cohort study, adverse neighborhood exposures during pregnancy and poor engagement in prenatal care were associated with poor virologic control at delivery. These findings suggest that interventions targeted at improving maternal health need to take the social environment into consideration.

Natural history of SARS-CoV-2 infection in healthcare workers in Northern Italy.

At present, the time-frame used for the quarantine of individuals with coronavirus disease 2019 (COVID-19) is the entire duration of symptoms plus 14 days after symptom recovery; however, no data have been reported specifically for healthcare workers (HCWs). In the study population of 142 HCWs with COVID-19, the mean time for viral clearance was 31.8 days. Asymptomatic subjects cleared the virus more quickly than symptomatic subjects (22 vs 34.2 days; P<0.0001). The presence of fever at the time of diagnosis was associated with a longer time to viral clearance (relative risk 11.45, 95% confidence interval 8.66-14.25; P<0.0001). These findings may have a significant impact on healthcare strategies for the future management of the COVID-19 pandemic.

Impact of behavioral and medication treatment for alcohol use disorder on changes in HIV-related outcomes among patients with HIV: A longitudinal analysis.

BACKGROUND: For people with HIV (PWH) and alcohol use disorder (AUD) who initiated behavioral treatment (BAUD) we: 1) describe BAUD intensity and medication (MAUD); and 2) examine whether BAUD and MAUD were associated with changes in HIV-related outcomes (CD4 cell count, HIV-1 viral load [VL], VACS Index score 2.0, and antiretroviral [ARV] adherence) from before to one year after treatment initiation. METHODS: We used Veterans Aging Cohort Study (VACS) data to describe BAUD intensity and MAUD (acamprosate, disulfiram, and naltrexone, gabapentin or topiramate). Linear regression models estimated changes in outcomes and included BAUD, MAUD, age and race/ethnicity. RESULTS: We identified 7830 PWH who initiated BAUD from 01/2008-09/2017. Median age was 53, 60% were African-American and 28% white. BAUD intensity groups were: 1) Single Visit - 35%; 2) Minimal - 44% recieved ∼2 visits during first month; 3) Sustained Moderate - 17% recieved ∼8 visits/month initially; and 4) Intensive - 4% started out receiving ∼14-16 visits/month. Only 9% recieved MAUD, the majority of which was gabapentin. Among those with detectable VL: all HIV-related outcomes improved more among those with more intensive BAUD. Among those with undetectable VL: adherence improved more among those with greater BAUD intensity. MAUD was associated with increased CD4 among those with detectable VL and with improved adherence among both groups. CONCLUSION: Of those with >1 BAUD visit, only 21% received at least moderate BAUD and 9% received at least 6 months of MAUD. Increasing AUD treatment intensity may improve HIV-related outcomes, especially among those with detectable VL.

Trends in CD4 and viral load testing 2005 to 2018: multi-cohort study of people living with HIV in Southern Africa.

INTRODUCTION: The World Health Organization (WHO) recommends a CD4 cell count before starting antiretroviral therapy (ART) to detect advanced HIV disease, and routine viral load (VL) testing following ART initiation to detect treatment failure. Donor support for CD4 testing has declined to prioritize access to VL monitoring. We examined trends in CD4 and VL testing among adults (≥15 years of age) starting ART in Southern Africa. METHODS: We analysed data from 14 HIV treatment programmes in Lesotho, Malawi, Mozambique, South Africa, Zambia and Zimbabwe in 2005 to 2018. We examined the frequency of CD4 and VL testing, the percentage of adults with CD4 or VL tests, and among those having a test, the percentage starting ART with advanced HIV disease (CD4 count <200 cells/mm3 ) or failing to suppress viral replication (>1000 HIV-RNA copies/mL) after ART initiation. We used mixed effect logistic regression to assess time trends adjusted for age and sex. RESULTS: Among 502,456 adults, the percentage with CD4 testing at ART initiation decreased from a high of 78.1% in 2008 to a low of 38.0% in 2017; the probability declined by 14% each year (odds ratio (OR) 0.86; 95% CI 0.86 to 0.86). Frequency of CD4 testing also declined. The percentage starting ART with advanced HIV disease declined from 83.3% in 2005 to 23.5% in 2018; each year the probability declined by 20% (OR 0.80; 95% CI 0.80 to 0.81). VL testing after starting ART varied; 61.0% of adults in South Africa and 10.7% in Malawi were tested, but fewer than 2% were tested in the other four countries. The probability of VL testing after ART start increased only modestly each year (OR 1.06; 95% CI 1.05 to 1.06). The percentage with unsuppressed VL was 8.6%. There was no evidence of a decrease in unsuppressed VL over time (OR 1.00; 95% CI 0.99 to 1.01). CONCLUSIONS: CD4 cell counting declined over time, including testing at the start of ART, despite the fact that many patients still initiated ART with advanced HIV disease. Without CD4 testing and expanded VL testing many patients with advanced HIV disease and treatment failure may go undetected, threatening the effectiveness of ART in sub-Saharan Africa.

Characteristics of COVID-19 Clinical Trials in China Based on the Registration Data on ChiCTR and ClinicalTrials.gov.

OBJECTIVE: This study aimed to evaluate the fundamental characteristics of coronavirus disease (COVID-19) clinical trials registered in China. METHODS: COVID-19 clinical trials registered in China were analyzed from databases on ChiCTR and ClinicalTrials.gov. The study designs, samples, primary end points, and intervention measures were evaluated. RESULTS: In total, 262 intervention clinical trials were retrieved on March 10, 2020. Overall, 181 (69.1%) trials involved two groups, 200 (76.3%) trials were randomized parallel trials, 24 (9.2%) trials were double blind, and 60.3% of trials included ≤100 participants. Sixty (22.9%) trials considered symptom improvement as the primary endpoint and 43 (16.4%) trials considered the rate or time at which the subjects became virus-free as the primary endpoint. Of 262 intervention studies, chemical drugs and biological products were studied in 105 (40.1%) intervention studies, of which antiviral drugs accounted for 15.3% and malaria drugs accounted for 8.4% of the studies. Among all trials, 27.9% of the studies used traditional Chinese medicine (TCM), 10.3% used cell therapy, and 5.0% used plasma therapy. CONCLUSION: This study is the first snapshot of the landscape of COVID-19 clinical trials registered in China and provided the basic features of clinical trial designs for the treatment and prevention of COVID-19 to offer useful information to guide future clinical trials on COVID-19 in other countries.

Modelling of viral load dynamics and CD4 cell count progression in an antiretroviral naive cohort: using a joint linear mixed and multistate Markov model.

BACKGROUND: Patients infected with HIV may experience a succession of clinical stages before the disease diagnosis and their health status may be followed-up by tracking disease biomarkers. In this study, we present a joint multistate model for predicting the clinical progression of HIV infection which takes into account the viral load and CD4 count biomarkers. METHODS: The data is from an ongoing prospective cohort study conducted among antiretroviral treatment (ART) naïve HIV-infected women in the province of KwaZulu-Natal, South Africa. We presented a joint model that consists of two related submodels: a Markov multistate model for CD4 cell count transitions and a linear mixed effect model for longitudinal viral load dynamics. RESULTS: Viral load dynamics significantly affect the transition intensities of HIV/AIDS disease progression. The analysis also showed that patients with relatively high educational levels (ß = - 0.004; 95% confidence interval [CI]:-0.207, - 0.064), high RBC indices scores (ß = - 0.01; 95%CI:-0.017, - 0.002) and high physical health scores (ß = - 0.001; 95%CI:-0.026, - 0.003) were significantly were associated with a lower rate of viral load increase over time. Patients with TB co-infection (ß = 0.002; 95%CI:0.001, 0.004), having many sex partners (ß = 0.007; 95%CI:0.003, 0.011), being younger age (ß = 0.008; 95%CI:0.003, 0.012) and high liver abnormality scores (ß = 0.004; 95%CI:0.001, 0.01) were associated with a higher rate of viral load increase over time. Moreover, patients with many sex partners (ß = - 0.61; 95%CI:-0.94, - 0.28) and with a high liver abnormality score (ß = - 0.17; 95%CI:-0.30, - 0.05) showed significantly reduced intensities of immunological recovery transitions. Furthermore, a high weight, high education levels, high QoL scores, high RBC parameters and being of middle age significantly increased the intensities of immunological recovery transitions. CONCLUSION: Overall, from a clinical perspective, QoL measurement items, being of a younger age, clinical attributes, marital status, and educational status are associated with the current state of the patient, and are an important contributing factor to extend survival of the patients and guide clinical interventions. From a methodological perspective, it can be concluded that a joint multistate model approach provides wide-ranging information about the progression and assists to provide specific dynamic predictions and increasingly precise knowledge of diseases.

'Distribution of Hepatitis C Virus genotypes in northern Greece in the last decade: descriptive analysis and clinical correlations'.

Hepatitis C virus (HCV) represents a major public health problem, while the identification of a HCV genotype is clinically very important for therapy prescription. The aim of the present study was to determine the HCV genotype distribution patients from northern Greece with HCV RNA positive viral load and to identify whether there is a shift in this distribution, during 2009-2017. The study was performed on 915 HCV positive patients and according to the results, genotype 3 was the most prevalent genotype (Ν = 395, 43.2%) followed by genotype 1 (Ν = 361, 39.5%). Regarding the gender of the patients, genotype 1 was mostly detected in women. Moreover, genotype 1 was associated with higher viral loads, while genotype 3 was most frequently detected in patients with a history of intravenous drug use. In conclusion, our results show that genotype 3 is the most prevalent genotype in Greece during the last decade as opposed to older epidemiological studies, likely due to intravenous drug use becoming the major source of infection.

The roles of heavy drinking and drug use in engagement in HIV care among hospitalized substance using individuals with poorly controlled HIV infection.

BACKGROUND: Substance use can reduce care engagement for individuals with HIV. However, little is known as to whether heavy drinkers differ from drug users. This study compares heavy drinkers, drug users, and those drinking heavily and using drugs on their HIV care engagement. METHODS: HIV-infected adult inpatients (n = 801; 67% male; 78% Black) from 11 urban hospitals across the United States participated in a multisite clinical trial to improve patient engagement in HIV care and virologic outcomes. All participants drank heavily and/or used drugs, and had poorly controlled HIV. Participants reported care history at baseline. We compared heavy drinkers, drug users, and those both drinking heavily and using drugs (reference group) on their engagement in care. RESULTS: Heavy drinkers reported lowest rates of lifetime HIV care, AOR = 0.59 (95% CI = 0.36, 0.97). Groups did not differ in recent care, prescription of HIV medication, medical mistrust, or patient-provider relationship. Drug users evidenced the best medication adherence, AOR = 2.38 (95% CI = 1.33, 4.23). Exploratory analyses indicated that drinkers had lower initial care engagement, but that it increased more rapidly with duration of known HIV infection, with similar rates of recent care. Drinkers had the lowest CD4 counts (B=-0.28, p < 0.0001), but no difference in viral load. CONCLUSIONS: Heavy drinkers were least likely to have ever been in HIV care. More research is needed to determine why heavy drinkers evidence the lowest initial care engagement and current CD4 counts, and whether drinking intervention early in infection may increase HIV care engagement.

Point-of-Care HIV Viral Load Testing: an Essential Tool for a Sustainable Global HIV/AIDS Response.

The global public health community has set ambitious treatment targets to end the HIV/AIDS pandemic. With the notable absence of a cure, the goal of HIV treatment is to achieve sustained suppression of an HIV viral load, which allows for immunological recovery and reduces the risk of onward HIV transmission. Monitoring HIV viral load in people living with HIV is therefore central to maintaining effective individual antiretroviral therapy as well as monitoring progress toward achieving population targets for viral suppression. The capacity for laboratory-based HIV viral load testing has increased rapidly in low- and middle-income countries, but implementation of universal viral load monitoring is still hindered by several barriers and delays. New devices for point-of-care HIV viral load testing may be used near patients to improve HIV management by reducing the turnaround time for clinical test results. The implementation of near-patient testing using these new and emerging technologies may be an essential tool for ensuring a sustainable response that will ultimately enable an end to the HIV/AIDS pandemic. In this report, we review the current and emerging technology, the evidence for decentralized viral load monitoring by non-laboratory health care workers, and the additional considerations for expanding point-of-care HIV viral load testing.

Trends in HIV care cascade engagement among diagnosed people living with HIV in Ontario, Canada: A retrospective, population-based cohort study.

BACKGROUND: The HIV cascade is an important framework for assessing systems of care, but population-based assessment is lacking for most jurisdictions worldwide. We measured cascade indicators over time in a population-based cohort of diagnosed people living with HIV (PLWH) in Ontario, Canada. METHODS: We created a retrospective cohort of diagnosed PLWH using a centralized laboratory database with HIV diagnostic and viral load (VL) test records linked at the individual-level. Individuals enter the cohort with record of a nominal HIV-positive diagnostic test or VL test, and remain unless administratively lost to follow-up (LTFU, >2 consecutive years with no VL test and no VL test in later years). We calculated the annual percent of diagnosed PLWH (cohort individuals not LTFU) between 2000 and 2015 who were in care (≥1 VL test), on ART (as documented on VL test requisition) or virally suppressed (<200 copies/ml). We also calculated time from diagnosis to linkage to care and viral suppression among individuals newly diagnosed with HIV. Analyses were stratified by sex and age. Upper/lower bounds were calculated using alternative indicator definitions. RESULTS: The number of diagnosed PLWH increased from 8,859 (8,859-11,389) in 2000 to 16,110 (16,110-17,423) in 2015. Over this 16-year period, the percent of diagnosed PLWH who were: in care increased from 81% (63-81%) to 87% (81-87%), on ART increased from 55% (34-60%) to 81% (70-82%) and virally suppressed increased from 41% (23-46%) to 80% (67-81%). Between 2000 and 2014, the percent of newly diagnosed individuals who linked to care within three months of diagnosis or achieved viral suppression within six months of diagnosis increased from 67% to 82% and from 22% to 42%, respectively. Estimates were generally lower for females and younger individuals. DISCUSSION: HIV cascade indicators among diagnosed PLWH in Ontario improved between 2000 and 2015, but gaps still remain-particularly for younger individuals.

Changes in hepatitis B virus surface antibody titer and risk of hepatitis B reactivation in HBsAg-negative/HBcAb-positive patients undergoing biologic therapy for rheumatic diseases: a prospective cohort study.

BACKGROUND: Our aim was to investigate dynamic changes in hepatitis B virus (HBV) surface antibody (HBsAb) titer and the associated risk of HBV reactivation and clinical course in patients with HBV surface antigen negative/core antibody positive (HBsAg-/HBcAb+) serostatus during antirheumatic therapy with biologic agents. METHODS: In a prospective study from January 2013 to June 2017, we monitored the HBV serostatus of HBsAg-/HBcAb+ patients undergoing biologic therapy for rheumatic diseases. From HBsAb titers at baseline and subsequent time points, we calculated the person-years (PY) contributed by patients with different HBsAb levels: < 10 mIU/mL (negative); 10-100 mIU/mL (low); and > 100 mIU/mL (high). We analyzed the incidence of detectable HBV DNA and HBV reactivation in each group, and documented the clinical courses of patients. RESULTS: Among 380 participants, 83 (21.8%) had baseline HBsAb < 10 mIU/mL, 156 (41.1%) HBsAb 10-100 mIU/mL, and 141 (37.1%) HBsAb > 100 mIU/mL. Total PY at study end were 169.3 PY from the HBsAb-negative group, 362.7 PY from the low-titer group, and 285.8 PY from the high-titer group. Seventeen patients had detectable HBV DNA, with respective incidence rates in negative, low- and high-titer groups of 4.7/100 PY, 2.5/100 PY, and 0/100 PY. Two HBsAb-negative patients subsequently developed HBV reactivation, an incidence of 1.2/100 PY. CONCLUSIONS: The risk of HBV reactivation varied with HBsAb titer, which changed during biologic therapy. Neither HBV DNA nor reactivation were detected in patients with HBsAb > 100 mIU/mL, whereas HBV DNA without reactivation occurred periodically in patients with HBsAb 10-100 mIU/mL; HBsAb-negative serostatus was associated with a risk of HBV reactivation.

Over the influence: The HIV care continuum among methamphetamine-using men who have sex with men.

BACKGROUND: HIV-positive persons who use stimulants such as methamphetamine experience greater difficulties in navigating the HIV care continuum. In the era of HIV treatment as prevention (TasP), little is known about the prevalence and correlates of success along the HIV care continuum among people who use stimulants. SETTING: San Francisco, California USA METHODS: Cross-sectional study that enrolled 129 HIV-positive men who have sex with men (MSM) from 2013 through 2017 who had biologically confirmed, recent methamphetamine use. Multivariable logistic regressions were built to identify correlates of success across the HIV care continuum. RESULTS: Although two-thirds (87/129) of participants had undetectable HIV viral load (<40 copies/mL), only one-in-four (32/129) reported taking at least 90% of their antiretroviral therapy (ART). Those who were homeless in the past year (adjusted odds ratio [aOR] = 0.20; 95% CI = 0.06-0.65) had 80% lower odds of being undetectable and adherent to ART. Substance use disorder treatment was associated with 77% lower odds of being engaged in HIV care (aOR = 0.23; 95% CI = 0.06-0.84) but also close to 3-fold greater odds of being adherent to ART (aOR = 2.91; 95% CI = 1.12-7.60). CONCLUSION: Despite the fact that many HIV-positive, methamphetamine-using MSM are able to achieve undetectable viral load in this sample, difficulties with ART adherence threaten to undermine the clinical and public health benefits of TasP. Expanded efforts to boost the effectiveness of TasP in this population should focus on meeting the unique needs of homeless individuals, optimizing ART adherence, and facilitating the integration of HIV care with substance use disorder treatment.

Determinants of viral load rebound on HIV/AIDS patients receiving antiretroviral therapy: results from South Africa.

BACKGROUND: Antiretroviral therapy (ART) has become the standard of care for patients with HIV infection in South Africa and has led to the reduction in AIDS related morbidity and mortality. In developing countries, the nucleosides reverse transcriptase inhibitors (NRTIs) class are widely used because of their low production costs. However patients treated with NRTIs develop varying degree of toxicity after long-term therapy. For this study patients are administered with a triple therapy of two NRTIs and one non-nucleoside reverse transcriptase inhibitor (NNRTI). METHOD: In this study the progression of HIV in vivo is divided into some viral load states and a continuous time-homogeneous model is fitted to assess the effects of covariates namely gender, age, CD4 baseline, viral load baseline, lactic acidosis, peripheral neuropathy, non-adherence and resistance to treatment on transition intensities between the states. Effects of different drug combinations on transition intensities are also assessed. RESULTS: The results show no gender differences on transition intensities. The likelihood ratio test shows that the continuous time Markov model for the effects of the covariates including combination give a significantly better fit to the observed data. From almost all states, rates of viral suppression were higher than rates of viral rebound except for patients in state 2 (viral load between 50 and 10,000 copies/mL) where rates of viral rebound to state 3 (viral load between 10,000 and 100,000 copies/mL) were higher than rates of viral suppression to undetectable levels. For this transition, confidence intervals were very small. This was quite notable for patients who were administered with AZT-3TC-LPV/r and FTC-TDF-EFV. Although patients on d4T-3TC-EFV also had higher rates of viral rebound from state 2 than suppression, the difference was not significant. CONCLUSION: From these findings, we can conclude that administering of any HIV drug regimen is better when based on the viral load level of an HIV+ patient. Before initiation of treatment, patients should be well equipped on how antiretroviral drugs operate including possibilities of toxicity in order to reduce chances of non-adherence to treatment. There should also be a good relationship between patient and health-care-giver to ensure proper adherence to treatment. Uptake of therapy by young patients should be closely monitored by adopting pill counting every time they come for review.

Decreased telomere length in the small airway epithelium suggests accelerated aging in the lungs of persons living with human immunodeficiency virus (HIV).

Human immunodeficiency virus (HIV) infection is associated with an increased risk of chronic obstructive pulmonary disease (COPD) independent of cigarette smoke exposure. Previous studies have demonstrated that decreased peripheral leukocyte telomere length is associated with HIV, suggesting an accelerated aging phenomenon. We demonstrate that this process of telomere shortening also occurs in the lungs, with significant decreases in telomere length observed in small airway epithelial cells collected during bronchoscopy. Molecular evidence of accelerated aging in the small airway epithelium of persons living with HIV may be one clue into the predisposition for chronic lung disease observed in this population.

Discontinuation of Efavirenz in Paediatric Patients: Why do Children Switch?

BACKGROUND: Efavirenz, a non-nucleoside reverse transcriptase inhibitor (NNRTI) is used globally as first-line antiretroviral therapy (ART) in combination with a dual nucleoside backbone in adults and children from 3 years of age. Up to 40% of adults taking efavirenz report central nervous system (CNS) adverse effects, and the rates of discontinuation of efavirenz-based treatment are higher than other first-line regimens. Data on efavirenz discontinuation are more limited for children and adolescents. OBJECTIVE: In this study, we aimed to describe our single-centre paediatric experience of efavirenz. METHODS: Retrospective case-note audit of children and adolescents with perinatally acquired HIV who ever received efavirenz. RESULTS: From 1998 and 2014, 51 children and adolescents aged ≤ 18 years received efavirenz-based treatment. Median age at efavirenz initiation was 9.4 years (interquartile range [IQR] 7-13). More than half (30/51; 59%) subsequently switched off efavirenz-15 (29%) following virological failure with NNRTI-associated resistance mutations, and 16 (30%) after reporting adverse effects. Of those who experienced adverse effects, one-fifth (19.6%) described CNS adverse effects, including sleep disturbance, reduced concentration, headaches, mood change and psychosis. Four children (three males) developed gynaecomastia, two developed hypercholesterolaemia, and one child developed Stevens-Johnson syndrome. Comparison between those reporting side effects and the rest of the cohort showed no difference in age, sex, initial CD4 cell count, viral suppression, length of efavirenz-based treatment, weight, or efavirenz dose per kilogram. Median time to switch was 25 months (IQR 10-71) in those who experienced side effects and 22 months (IQR 12-50) for virological failure. One individual experienced both virological failure and adverse effects. CONCLUSION: Almost two-thirds of this paediatric cohort switched from efavirenz-based treatment to an alternative regimen, due in equal proportions to both virological failure and toxicity. The majority of side effects involved the CNS. First-line regimens with improved tolerability and a higher genetic barrier to resistance should be the preferred option for children.

Routine CD4 monitoring in HIV patients with viral suppression: Is it really necessary? A Portuguese cohort.

PURPOSE: CD4 cell-count has been regarded as the key surrogate marker for prognostic staging and therapeutic monitoring of HIV-infected individuals. Our purpose was to assess the probability of maintaining a CD4 count >200 cells/µL in patients with continuous viral suppression and CD4 cell counts >200 cells/µL. METHODS: Retrospective cohort study of HIV-infected patients, treatment naïve, who started antiretroviral therapy between 2007 and 2011. We estimated the probability of maintaining CD4 counts >200 cells/µL during continuous viral suppression using the Kaplan-Meier method. The hazard ratios of a CD4 count <200 cells/µL were estimated and compared using Cox proportional hazards regression. RESULTS: 401 patients were included: 70.1% men; median age 37 years; 98.8% HIV-1 infected. The median duration of continuous viral suppression with CD4 counts >200 cells/µL was 40.5 months. Ninety-three percent of patients maintained CD4 counts ≥200 cells/µL during the period of continuous viral suppression. Compared with those with an initial CD4 count ≥350 cells/µL, patients with initial CD4 count <300 cells/µL had a significantly higher risk of a CD4 count <200 cells/µL. Patients with viral suppression and CD4 counts ≥350 cells/µL had a 97.1% probability of maintaining CD4 cell counts ≥200 cells/µL for 48 months. CONCLUSIONS: The probability of a CD4 count <200 cells/µL in an HIV-infected patient with viral suppression and CD4 ≥350 cells/µL was very low. These data suggests less frequent monitoring of CD4 counts in these patients.