Off-label use of combined antiretroviral therapy, analysis of data collected by the Italian Register for HIV-1 infection in paediatrics in a large cohort of children

Background Early start of highly active antiretroviral therapy (HAART) in perinatally HIV-1 infected children is the optimal strategy to prevent immunological and clinical deterioration. To date, according to EMA, only 35% of antiretroviral drugs are licenced in children < 2 years of age and 60% in those aged 2–12 years, due to the lack of adequate paediatric clinical studies on pharmacokinetics, pharmacodynamics and drug safety in children. Methods An observational retrospective study investigating the rate and the outcomes of off-label prescription of HAART was conducted on 225 perinatally HIV-1 infected children enrolled in the Italian Register for HIV Infection in Children and followed-up from 2001 to 2018. Results 22.2% (50/225) of included children were receiving an off-label HAART regimen at last check. Only 26% (13/50) of off-label children had an undetectable viral load (VL) before the commencing of the regimen and the 52.0% (26/50) had a CD4 + T lymphocyte percentage > 25%. At last check, during the off label regimen, the 80% (40/50) of patients had an undetectable VL, and 90% (45/50) of them displayed CD4 + T lymphocyte percentage > 25%. The most widely used off-label drugs were: dolutegravir/abacavir/lamivudine (16%; 8/50), emtricitbine/tenofovir disoproxil (22%; 11/50), lopinavir/ritonavir (20%; 10/50) and elvitegravir/cobicistat/emtricitabine/ tenofovir alafenamide (10%; 10/50). At logistic regression analysis, detectable VL before starting the current HAART regimen was a risk factor for receiving an off-label therapy (OR: 2.41; 95% CI 1.13–5.19; p = 0.024). Moreover, children < 2 years of age were at increased risk for receiving off-label HAART with respect to older children (OR: 3.24; 95% CI 1063–7.3; p = 0.001). Even if our safety data regarding off-label regimens where poor, no adverse event was reported. Conclusion The prescription of an off-label HAART regimen in perinatally HIV-1 infected children was common, in particular in children with detectable VL despite previous HAART and in younger children, especially those receiving their first regimen. Our data suggest similar proportions of virological and immunological successes at last check among children receiving off-label or on-label HAART. Larger studies are needed to better clarify efficacy and safety of off-label HAART regimens in children, in order to allow the enlargement of on-label prescription in children.

Plitidepsin as a successful rescue treatment for prolonged viral SARS-CoV-2 replication in a patient with previous anti-CD20 monoclonal antibody-mediated B cell depletion and chronic lymphocytic leukemia

Background There is an urgent need for highly efficacious antiviral therapies in immunosuppressed hosts who develop coronavirus disease (COVID-19), with special concern for those affected by hematological malignancies. Case presentation Here, we report the case of a 75-year-old male with chronic lymphocytic leukemia who was deficient in CD19+CD20+ B-lymphocyte populations due to previous treatment with anti-CD20 monoclonal antibodies. The patient presented with severe COVID-19 pneumonia due to prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and was treated with two courses of the antiviral plitidepsin on a compassionate use basis. The patient subsequently achieved an undetectable viral load, and his pneumonia resolved. Conclusions Treatment with plitidepsin was well-tolerated without any further hematological or cardiovascular toxicities. This case further supports plitidepsin as a potential antiviral drug in SARS-CoV-2 patients affected by immune deficiencies and hematological malignancies.

Neutrophil Expression of T and B Immunomodulatory Molecules in HIV Infection

ObjectiveEvaluate the expression of B and T cell immunomodulatory molecules in polymorphonuclear neutrophils (PMN) in HIV-infected patients.MethodsHIV load, bacterial translocation and neutrophils’ expression of T [programmed death ligand, interleukin-10+, arginase 1+] and B [BAFF, APRIL] molecules were analyzed in different cohorts and time points: a control group of 25 healthy individuals and two groups of HIV-infected patients. Group 1 of patients included 35 untreated patients, studied at baseline and after antiretroviral therapy (ART). Group 2 was composed of 25 patients with undetectable viral load after a median of 101 months of ART prior to inclusion in the study.ResultsCompared with the control group, group 1 patients showed increased bacterial translocation and their PMN had a significantly higher expression of T and B-cell immunomodulatory molecules, both at baseline and after 12 months of ART. Group 2 patients showed reduced bacterial translocation levels when compared with group 1 patients after 12 months of treatment. PMN expression of B-cell modulators was similar between group 2 patients and healthy controls, although the expression of T-cell modulators remained increased.ConclusionIn HIV-infected patients, the expression of B-cell stimulatory and T-cell suppressive molecules by neutrophils was increased at baseline and after a limited time of therapy. After a prolonged period of ART, only PMNs expression of T-cell immunosuppressive molecules remained elevated.

SPECTRUM OF DISEASE, MANAGEMENT, EFFICIENCY, CLINICAL PROFILE AND OUTCOMES OF RETROVIRAL DISEASE PATIENTS

HIV is a virus that targets and alters the immune system, increasing the risk and impact of other infections and diseases. Without treatment, the infection might progress to an advanced disease stage called AIDS. A prospective study was conducted for a period of 6 months in a tertiary care hospital with the sample size of 102 patients. A data collection form was taken, which includes the details of demographics date of visit to the hospital, diagnosis, past and current medication history. 102 Inpatients and Outpatients diagnosed with HIV were considered. For the management of HIV, 52 % of 2 NRTI and 1 NNRTI combination and 35 % of 2 NRTI and 1 integrase inhibitor combination were used. The drug usage pattern was found to be tenofovir 74.5 %, lamivudine 83.3 % and Efavirenz 50.9 %. The percentage of subjects with opportunistic infections was 66.6 % and, among these opportunistic infections, tuberculosis was found to be 47.05 %. The viral load after 6 months of ART was found to be undetectable in 95.09 % patients. The levels of CD4 counts were raised after initiation of the ART in 6 months of duration. The death rate was found to be 4.90 %. Due to highly active antiretroviral therapy and effi cient opportunistic infection management, the patients had elevated CD4 levels and undetectable viral load. Hence HAART is highly effi cient in management of HIV which ultimately improves the quality of life of patients.

Attenuated Negative Feedback in Monocyte-Derived Macrophages From Persons Living With HIV: A Role for IKAROS

Persons living with HIV (PLWH) are at higher risk of developing secondary illnesses than their uninfected counterparts, suggestive of a dysfunctional immune system in these individuals. Upon exposure to pathogens, monocytes undergo epigenetic remodeling that results in either a trained or a tolerant phenotype, characterized by hyper-responsiveness or hypo-responsiveness to secondary stimuli, respectively. We utilized CD14+ monocytes from virally suppressed PLWH and healthy controls for in vitro analysis following polarization of these cells toward a pro-inflammatory monocyte-derived macrophage (MDM) phenotype. We found that in PLWH-derived MDMs, pro-inflammatory signals (TNFA, IL6, IL1B, miR-155-5p, and IDO1) dominate over negative feedback signals (NCOR2, GSN, MSC, BIN1, and miR-146a-5p), favoring an abnormally trained phenotype. The mechanism of this reduction in negative feedback involves the attenuated expression of IKZF1, a transcription factor required for de novo synthesis of RELA during LPS-induced inflammatory responses. Furthermore, restoring IKZF1 expression in PLWH-MDMs partially reinstated expression of negative regulators of inflammation and lowered the expression of pro-inflammatory cytokines. Overall, this mechanism may provide a link between dysfunctional immune responses and susceptibility to co-morbidities in PLWH with low or undetectable viral load.

Justified Suspicion: Symptomatic Syphilitic Alopecia in a Patient with Well-Controlled HIV

Background. An estimated 25% of primary and secondary syphilis, a sexually transmitted infection caused by the spirochete bacterium Treponema pallidum, occurs in patients coinfected with human immunodeficiency virus (HIV) (Chesson et al., 2005). This association is especially evident in men who have sex with men (MSM). In HIV-positive patients, primary syphilis infection may progress more rapidly to the tertiary, and most destructive, stage and reinfection can start with the latent or tertiary stage; in such patients, advanced syphilis may arise without clinical warning signs (Kenyan et al., 2018). It is important to note that neurosyphilis can occur during any stage of infection in all patients, regardless of immunocompetence status (CDC, 2021). Case Presentation. A 56-year-old male with a past medical history of well-controlled HIV with a CD4 count of 700 cells/mm3 and an undetectable viral load, psoriasis, and a remote episode of treated syphilis, presented with a two-week history of a diffuse desquamating rash, alopecia, sinusitis, unilateral conjunctivitis, and blurred vision. His last sexual encounter was over ten months ago. The diagnosis of syphilis was confirmed by microhemagglutination assay, and he was treated for presumed neuro-ocular infection with a two-week course of intravenous Penicillin G. Conclusion. Syphilis has acquired a reputation as “the great masquerader” due to its protean manifestations. It may follow an unpredictable course, especially in HIV-positive patients, including those whose treatment has achieved undetectable serology. For example, ocular syphilis may present in an otherwise asymptomatic individual (Rein, 2020) and alopecia may arise as the sole indication of acute syphilitic infection (Doche et al., 2017). Therefore, a high index of suspicion is warranted in order to prevent severe and irreversible complications.

912. Expansion of Hepatitis C Treatment with New Medicaid Subscription Model in Louisiana

Background It is estimated that nearly 80,000 people with hepatitis C are living in Louisiana, many with Medicaid coverage. Previously, only Medicaid patients free from drugs and alcohol with a fibrosis score of F3 or F4 were eligible for treatment, resulting in few patients receiving treatment. Beginning in July 2019, generic sofosbuvir/velpatasvir was made available through the Medicaid program in a subscription model, allowing unlimited hepatitis C treatment in Louisiana’s Medicaid program for 5 years at a set price to the program. This has dramatically expanded access to Hepatitis C treatment for people with Medicaid in Louisiana. Methods Patients with Hepatitis C seen in the Infectious Diseases Center at University Medical Center in New Orleans, in 2020 by the 5 main hepatitis C providers were included. Demographics and laboratory data were collected to determine outcomes. Results Most patients with a hepatitis C (HCV) viral load and insurance data had Medicaid (80%, N=275). Twenty-two (8%) were HIV co-infected. Most were men (75%) and African-American (77%). Among the mono-infected patients with Medicaid and an HCV viral load, 216 (85%) had an undetectable viral load by the beginning of June 2021. Of the remaining 37 patients, 30 patients were prescribed treatment; but did not take it (n=4), didn’t follow-up (n=23), or followed-up but never got labs (n=3). One was treated but had a treatment failure (n=1). Six of the 37 were not prescribed medications due to a short life expectancy or significant drug interactions. The percentage of patients with an undetectable viral load was similar by gender and race, however younger age groups had lower viral suppression. In those aged less than 35, only 47% had an undetectable viral load and among those aged 36 to 44, it was 66%. Using the previous criteria of requiring a fibrosis score of F3 or F4, only 20% (n=44) would have been eligible for medicine to treat hepatitis C. Conclusion The new hepatitis C treatment subscription model with resultant removal of previous barriers has dramatically expanded treatment for people with Medicaid in Louisiana. More than five times the number of Medicaid patients received treatment in 2020 in our academic medical clinic. Disclosures Yussef Bennani, MD, MPH, Gilead Sciences (Scientific Research Study Investigator)ViiV Healthcare (Scientific Research Study Investigator)

Vulnerability of the Brazilian LGBT population in HIV treatment

Introduction: Human immunodeficiency virus (HIV) infection affects the lesbian, gay, bisexual, transvestite, and transsexual (LGBT) population. We aimed to identify the indidual vulnerability profile of the LGBT population ling with H/acquired immunodeficiency syndrome (AIDS) and correlate it with the treatment situation. Methodology: This cross-sectional study included 510 LGBT people living with HIV (PLHIV)/AIDS who attended the Complex of Chronic Communicable Diseases of the municipality of São José do Rio Preto, São Paulo, Brazil, between 2008 and 2015. Results: There was a predominance of indiduals who were white (70.2%), male (98.4%), single (87.1%), aged 25–44 years (70.0%), educated up to high school (47.7%), economically acte (91.2%), under treatment (80.8%), having CD4 > 350 cells/mm3 (77.1%), and having undetectable viral load (53.3%). HIV transmission was mainly sexual (97.0%) and most people used drugs (76.5%). There was a weak correlation between the variables ‘in treatment’ and acte occupation (r = 0.148, p = 0.001), single marital status (r = 0.128, p = 0.004), white race/colour (r = 0.117, p = 0.008), high school education (r = 0.111, p = 0.012), sexual transmission (r = 0.222, p = 0.000), drug use (r = 0.087, p = 0.049), and CD4 > 350 cells/mm3 (r = 0.118, p = 0.008); and strong correlation between the variables ‘in treatment’ and undetectable viral load (r = -0.937, p = 0.113). Conclusions: The characteristics of the indidual vulnerability of LGBT people involve, among other aspects, issues of gender and social exclusion, a situation that is part of the daily life of PLHIV/AIDS in many scenarios and territories. This can be alleviated with a network of social and health support and effecte and efficient, protecte, attitudinal, and behavioural public policies.

Features of application of raltegravir in HIV-infected patients with different somatic pathologies

Purpose of the study. Evaluation of the efficacy, safety and tolerability of raltegravir regimens in HIV-infected patients with concomitant pathology in real clinical practice.Materials and methods. A retrospective analysis was carried out of 277 outpatient records of HIV-infected patients who received raltegravir (RAL) as a third component both in patients without previous experience of antiretroviral therapy (ART) and in patients with experience of treatment with various somatic pathologies. The main criterion for the effectiveness of the scheme was the proportion of patients with undetectable viral load at the start of the analysis. Additional criteria for evaluating the efficacy and safety of the regimen were the dynamics of the number of CD4-lymphocytes, the frequency and nature of undesirable side reactions.Results. On average, patients with no experience of treatment and with experience of treatment received regimens with raltegravir for about 5 years. At the time of the study in 2020, 69.8% of patients on ART for the first time continued to take a regimen containing raltegravir. In this group, the proportion of patients with virological suppression (PCR of HIV RNA less than 50 kopecks / ml) was 97.7%. 75.2% of patients in the second group in 2020 continued to take the RAL regimen. The proportion of patients with virological suppression (VL less than 50 kopecks / ml) in this group was 97.5%. During the treatment, there was no discontinuation of the regimen in both groups due to undesirable side reactions to raltegravir.Conclusion. The results of this study confirm that RAL-based regimens provide a high level of efficacy with a good tolerance and safety profile in routine clinical practice for both naive and experienced patients with various somatic pathologies.

Patterns of changing pregnancy intentions among women living with HIV in Canada

Background Women with an undetectable viral load can become pregnant and have children with no risk of HIV transmission to their sexual partners and low risk of transmission to their infants. Contemporary pregnancy intentions of women living with HIV in Canada are poorly understood, evidenced by high rates of unintended pregnancy and low uptake of contraceptives. Methods We used longitudinal survey data from the Canadian HIV Women’s Sexual and Reproductive Health Cohort Study (CHIWOS) to measure and compare pregnancy intentions (Yes vs No vs Unsure) at baseline, 18-months and 36-months follow-up (from 2013 to 2018) among women living with HIV of reproductive age (16–49 years) and potential. We used Sankey diagrams to depict changes in pregnancy intentions over time and multivariable logistic regression to examine the relationship between pregnancy intention within 2 years and subsequent pregnancy. Results At baseline, 41.9% (119/284) of women intended to become pregnant, 43.3% did not, and 14.8% were unsure. Across 36-months of follow-up, 41.9% (119/284) of women changed their pregnancy intentions, with 25% changing from intending to not intending to become pregnant and 13.1% vice versa. Pregnancy intentions were not strongly associated with subsequent pregnancy between baseline and 18-months (aOR 1.44; 95% CI 0.53, 3.72) or between 18 and 36-months (aOR 2.17; 95% CI 0.92, 5.13). Conclusions Our findings underscore the need for healthcare providers to engage in ongoing discussions with women living with HIV to support their dynamic pregnancy intentions.