Allison Agwu’s research while affiliated with Johns Hopkins Medicine and other places

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Publications (50)


Pharmacokinetics and Safety of Bictegravir in Pregnant and Postpartum Persons With HIV and Their Infants
  • Article

November 2024

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18 Reads

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Mauricio Pinilla

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Flynn McMorrow

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[...]

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Jeremiah D. Momper

Background Limited data exist on bictegravir pharmacokinetics in pregnancy among persons with HIV (PWH) and infant washout. Setting Nonrandomized, open-label, multi-center phase-IV prospective study of bictegravir pharmacokinetics and safety in pregnant PWH and their infants. Methods Steady-state 24-hour pharmacokinetic sampling of oral bictegravir 50 mg once daily (a component of fixed-dose combination bictegravir/emtricitabine/tenofovir alafenamide) during the 2 nd and 3 rd trimesters and postpartum was performed. Cord blood and infant washout samples were collected. Total and free bictegravir concentrations were measured by validated LC-MS/MS methods. Within-participant geometric mean ratios (GMR) with 90% confidence intervals (CI) were calculated to compare pharmacokinetics between 2 nd and 3 rd trimester versus postpartum. Infant HIV testing results were obtained. Results Twenty-seven maternal-infant pairs enrolled. Bictegravir AUC 0-24 was 46% lower in the 2 nd trimester (n = 12; P = 0.002; GMR 0.54; 90% CI: 0.43-0.69) and 52% lower in the 3 rd trimester (n=24; P < 0.0001; GMR 0.48; 90% CI: 0.43-0.55), compared to postpartum. C 24 concentrations were above the estimated bictegravir protein-adjusted EC 95 of 0.162 µg/mL. The median ratio of cord-to-maternal blood concentration was 1.38 (n=17; quartiles: 1.17, 1.63). Median T 1/2 for infant bictegravir washout was 33.2 hours (quartiles: 25.7, 45.9) with a Cmax of 2.06 µg/mL (quartiles: 1.37, 2.72). 88-92% of participants maintained suppression <40 copies/mL throughout pregnancy and postpartum. All available infant HIV testing results were negative. The safety profile for pregnant PWH and infants was acceptable. Conclusions Bictegravir exposure was lower during pregnancy compared to postpartum, yet C 24 concentrations were greater than the bictegravir protein-adjusted EC 95 .


Barriers and facilitators to equitable implementation of long-acting ART for adolescents and youth with HIV in low- and middle-income settings

October 2024

Pan African Medical Journal

Recent approvals of long-acting (LA) antiretroviral treatment (ART) support an innovative alternative to daily oral pills that can improve adherence and treatment outcomes among adolescents and youth (AY) with HIV. We solicited stakeholder feedback on the implementation of LA ART for AY in low-and middle-income countries (LMICs) through a consensus-building forum at the 2022 International Workshop on HIV and Adolescence. We used the nominal group technique to generate, record, discuss, vote on, and rank perceived barriers and facilitators to implementing LA ART for AY. All in-person attendees were invited to participate and were assigned to six groups, each representing an intentional mix of AY, clinicians, researchers, program implementers, and policymakers. We collected self-reported de-identified demographics and group rankings of barriers and facilitators. Responses were coded and categorized using the social-ecological model’s five levels of influence. One hundred and thirty-seven (137) Workshop delegates (67.9% male, 27.7% female; 0.7% non-binary, and 46.7% less than 35 years old) participated in the group discussions. A large proportion of participants (51.9%) reported working in public health/program implementation. Most participants (88.4%) were from and/or worked in the African region. We identified 55 barriers and 48 facilitators of LA ART implementation and ranked them in social-ecological categories of public policy, community, institutional/organizational, interpersonal, and individual levels. The highest number of ranked barriers was at the institutional/organizational level. The themes of “equitable access” and “choices of ART” were cross-cutting across individual and interpersonal levels. Other cross-cutting themes were the “cost of LA ART” and the ”need for funding and sustainability of LA ART programs”. Proposed facilitators addressed identified barriers at each social-ecological level of influence and emphasized peer engagement. Our nominal groups identified key barriers and proposed facilitators at five different social-ecological levels, which can inform implementation science-guided design and equitable implementation of youth-centered LA ART in LMICs and globally.


Primary Care Guidance for Providers Who Care for Persons With Human Immunodeficiency Virus: 2024 Update by the HIV Medicine Association of the Infectious Diseases Society of America

October 2024

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25 Reads

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6 Citations

Clinical Infectious Diseases

Advances in antiretroviral therapy (ART) have made it possible for persons with human immunodeficiency virus (HIV) to live a lifespan approaching that of people without HIV, without progressing to AIDS or transmitting HIV to sexual partners or infants. There is, therefore, increasing emphasis on maintaining health throughout the lifespan. To receive optimal medical care and achieve desired outcomes, persons with HIV must be consistently engaged in care and able to access uninterrupted treatment, including ART. Comprehensive evidence-based HIV primary care guidance is, therefore, more important than ever. Creating a patient-centered, stigma-free care environment is essential for care engagement. Barriers to care must be decreased at the societal, health system, clinic, and individual levels. As the population ages and noncommunicable diseases arise, providing comprehensive health care for persons with HIV becomes increasingly complex, including management of multiple comorbidities and the associated challenges of polypharmacy, while also attending to HIV-specific health concerns. Clinicians must address issues specific to preventive health, including cancer screening, providing recommended vaccinations, as well as promoting sexual health, including sexually transmitted infection diagnosis, treatment, and prevention. Clinicians also must address issues for specific populations, including persons of childbearing potential, including during preconception and pregnancy; children; adolescents; and transgender and gender-diverse individuals. This guidance from an expert panel of the HIV Medicine Association of the Infectious Diseases Society of America updates the previous 2020 HIV Primary Care Guidance.


Increase in Cases of Perinatal HIV Transmission in Maryland in 2022

October 2024

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3 Reads

Pediatrics

The perinatal transmission of HIV is preventable through a regimen that includes testing of all pregnant individuals, antiretroviral treatment (ART) for the pregnant individual, prophylactic or preventative ART for the infant, and cesarean section delivery for mothers with HIV viremia at the time of delivery. Under this protocol, the United States has seen a significant decline in the perinatal transmission of HIV and achieved a perinatal HIV transmission rate of 0.9% in 2019. However, despite this progress nationally and after zero transmissions in 2021, Maryland recorded 6 cases of perinatal HIV diagnoses in 2022. Each of the 3 major referral centers for pediatric HIV patients in Maryland reported 2 new cases in 2022. A root cause analysis of the cases identified risk factors including delayed entry into perinatal and HIV care, premature birth, maternal adherence challenges in the setting of substance use and other adverse social determinants of health, and failure to diagnose maternal HIV infection in a timely way. All patients were successfully linked to care and initiated on ART. Multiple factors contributed to the 2022 increase in cases of perinatal HIV in Maryland. To achieve and then sustain the elimination of perinatal HIV transmission, the constancy of systems that eliminate barriers for all pregnant people to access testing, prevention, and treatment is critical.


Adolescents and young adults with HIV and unsuppressed viral load: where do we go from here?

July 2024

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60 Reads

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3 Citations

Current Opinion in HIV and AIDS

Purpose of review Adolescents and youth living with HIV (AYLHIV) have worse outcomes at all stages of the care cascade when compared with adults, yet adolescents and youth with unsuppressed viral load are typically excluded from phase 3 studies of novel HIV therapeutic agents and emerging strategies. Long-acting agents have the potential to radically change outcomes for young people struggling with adherence to daily oral HIV medications. Recent findings 1.5 million children aged less than 15 years live with HIV and more than 100 000 acquire HIV perinatally every year. Adolescents and youth aged 10–24 years comprise ∼40% of global incident HIV infections. Rates of viral suppression among AYLHIV vary markedly from 44 to 88%, resulting in morbidity and risks of transmission to partners and infants. Virological failure is mostly due to poor adherence, and AYLHIV express high levels of interest and acceptability of alternatives to oral daily medications, such as long-acting antiretroviral formulations. Emerging data regarding their use in populations with unsuppressed viral load are encouraging. Summary AYLHIV, including populations without virologic suppression, must be prioritized for the programmatic implementation and research of long-acting HIV drugs and other therapeutic strategies to prevent morbidity and mortality and to ultimately end the HIV epidemic.


Strategic use of salvage long-acting antiretrovirals in the setting of resistance

July 2024

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1 Read

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1 Citation

American journal of health-system pharmacy: AJHP: official journal of the American Society of Health-System Pharmacists

Disclaimer In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose Long-acting cabotegravir/rilpivirine (LA-CAB/RPV) was approved for use in virally suppressed patients with human immunodeficiency virus (HIV) in January 2021. While this was a paradigm shift for many patients living with HIV, as LA-CAB/RPV was the first injectable complete regimen for the treatment of HIV, several patient populations, including those lacking virologic suppression, have not been able to easily access this advance in science and care. Summary In this article, we provide an update on 2 patients from our previous report and describe one further patient who experienced treatment failure following initiation of LA-CAB/RPV. Additionally, we review reports published to date of the clinical outcomes of patients with viremia who have accessed LA-CAB/RPV in the setting of baseline resistance-associated mutations (RAMs) to either component and any resulting RAMs at virologic failure. On the basis of this evidence, we recommend that hybrid or all-injectable regimens be considered for patients who have struggled with adherence to oral antiretroviral therapy or have partial or full resistance to one component of LA-CAB/RPV. Conclusion The case series reported here adds to literature supporting the notion that LA-CAB/RPV can be successfully used in patients who are viremic.


Pharmacokinetics and Safety of Remdesivir in Pregnant and Non-Pregnant Women with COVID-19: Results from IMPAACT 2032

June 2024

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15 Reads

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1 Citation

The Journal of Infectious Diseases

Background Pregnant people with coronavirus disease 2019 (COVID-19) experience higher risk for severe disease and adverse pregnancy outcomes, but no pharmacokinetic (PK) data exist to support dosing of COVID-19 therapeutics during pregnancy. We report PK and safety data for intravenous remdesivir in pregnancy. Methods IMPAACT 2032 was a phase 4 prospective, open-label, nonrandomized opportunistic study of hospitalized pregnant and nonpregnant women receiving intravenous remdesivir as part of clinical care. Intensive PK sampling was performed on infusion days 3, 4, or 5 with collection of plasma and peripheral blood mononuclear cells (PBMCs). Safety data were recorded from first infusion through 4 weeks after last infusion and at delivery. Geometric mean ratios (GMR) (90% confidence intervals [CI]) of PK parameters between pregnant and nonpregnant women were calculated. Results Fifty-three participants initiated remdesivir (25 pregnant; median gestational age, 27.6 weeks; interquartile range, 24.9–31.0 weeks). Plasma exposures of remdesivir, its 2 major metabolites (GS-704277 and GS-441524), and the free remdesivir fraction were similar between pregnant and nonpregnant participants. Concentrations of the active triphosphate (GS-443902) in PBMCs increased 2.04-fold (90% CI, 1.35–3.03) with each additional infusion in nonpregnant versus pregnant participants. Three adverse events in nonpregnant participants were related to treatment (1 grade 3; 2 grade 2 resulting in treatment discontinuation). There were no treatment-related adverse pregnancy outcomes or congenital anomalies detected. Conclusions Plasma remdesivir PK parameters were comparable between pregnant and nonpregnant women, and no safety concerns were identified based on our limited data. These findings suggest no dose adjustments are indicated for intravenous remdesivir during pregnancy. Clinical Trials Registration NCT04582266.


Fig. 1. Detection of HIV in blood and cerebrospinal fluid. (a) Percentage of participants with detectable HIV-RNA in plasma and CSF and HIV-DNA in PBMCs and CSF cells. 95% confidence intervals are provided where possible. Ã Per study design no participants had HIV-RNA in peripheral blood > 20 copies/ml. (b) HIVgag (red) and pol (blue) DNA copies/million cells for each participant. Open symbols reflect results below the LLD. CSF cell count is indicated above each participant, ordered based on the quantity of gag detected in PBMCs. (c) The quantity of HIVgag (left) and pol (right) DNA in PBMCs grouped based on whether HIV-DNA was detected (filled symbol) or not detected (open symbols) for both gag and pol in CSF cells; box shows 25th percentile, median and 75th percentile. The two undetectable HIV-DNA measurements in PBMCs are plotted at the LLD.
Fig. 2. Biomarkers of inflammation and neuronal injury. Concentrations of biomarkers in plasma and CSF from each participant are shown as separate triangles. Filled or open triangles reflect participants with or without HIV-DNA detected in CSF cells, respectively. Five values of NF-L in plasma <LLQ were plotted at the LLQ of 2.74 pg/ml. Only a single value was >LLQ for TNFa in CSF and only three values were >LLQ for sICAM-5 in plasma so these data are not presented. sICAM-5 was not detected in CSF from any participant.
Fig. 3. Antiretroviral drug levels. Concentrations of dolutegravir (DTG), emtricitabine (FTC), and tenofovir (TFV) in hair follicles. Sample size indicates the number of participants taking each drug. Filled or open symbols reflect participants with or without HIV-DNA detected in CSF cells, respectively. For one participant without HIV-DNA detected in CSF cells, both TFV and FTC hair concentrations were below the LLQ and values were plotted at the quantification limit.
Fig. 4. Neurocognitive assessments. Composite scores are on the left side, individual component scores are on the right side, grouped by fluid and crystallized subsets (n ¼ 18). Ã Auditory verbal learning scores were not normalized. Filled or open symbols reflect participants with or without HIV-DNA detected in CSF cells, respectively. For two participants, high Crystallized Composite and Oral Reading Cognition scores and for one participant a high Auditory Verbal Learning score were considered outliers and excluded per team decision.
Prevalence of detectable HIV-DNA and -RNA in cerebrospinal fluid of youth with perinatal HIV and impaired cognition on antiretroviral therapy
  • Article
  • Full-text available

May 2024

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39 Reads

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1 Citation

AIDS (London, England)

Objective Central nervous system (CNS) HIV infection can impact cognition and may be an obstacle to cure in adolescents and young adults with perinatal HIV (AYAPHIV). IMPAACT2015 enrolled AYAPHIV on suppressive antiretroviral therapy (ART) with cognitive impairment to detect and quantify HIV in blood and cerebrospinal fluid (CSF). Design IMPAACT2015 was a U.S.-based multi-site, exploratory, observational study. Methods Cognitive impairment was defined as NIH Toolbox Fluid Cognition Composite score (FCCS) > 1 standard deviation below age-adjusted normative group mean. Cell-free HIV-RNA and cell-associated HIV pol/gag -DNA and 10 biomarkers of inflammation/neuronal injury were measured in paired CSF and blood. ART exposure concentrations were quantified in hair. Results Among 24 participants, 20 had successful CSF collection and 18 also met viral suppression criteria. 9/18 (50%) were female sex-at-birth, 14/18 (78%) were Black. Median (range) age was 20 years (13–27), time on ART 18.3 years (8.0–25.5), and FCCS 68 (53–80). HIV-DNA was detected in PBMCs from all participants. In CSF, 2/18 (11%, 95% CI: 1.4–34.7%) participants had detectable cell-free HIV-RNA, while HIV gag or pol -DNA was detectable in 13/18 (72%, 95% CI: 47–90%). Detectable HIV-DNA in CSF was associated with male sex-at-birth (p = 0.051), lower CD4 count at enrollment (p = 0.016), and higher PBMC HIV pol -DNA copies (p = 0.058). Hair antiretroviral concentrations and biomarkers were not associated with CSF HIV-DNA detection. Conclusions We found a high proportion of AYAPHIV with neurocognitive impairment had CSF cells harboring HIV-DNA during long-term virologic suppression. This evidence of persistent HIV-DNA in CSF suggests that the CNS should be considered in treatment and cure studies.

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2 × 2 Matrix of Provider Prediction and Viral Load Test Results.
Accuracy of Provider Predictions of Viral Suppression Among Adolescents and Young Adults With HIV in an HIV Clinical Program

May 2024

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18 Reads

Journal of the International Association of Providers of AIDS Care

Plain Language Summary Accuracy of Provider Predictions of Viral Suppression among Adolescents and Young Adults with HIV in an HIV Clinical Program Providers caring for adolescents and young adults with HIV (AYA-HIV) mostly base their adherence counseling during clinical encounters on clinical judgment and expectations of patients' medication adherence. Currently, no data exist on provider predictions of viral suppression for AYA-HIV. We aimed to assess the accuracy of provider predictions of patients' viral suppression compared to viral load results. Providers caring for AYA-HIV were asked to predict the likelihood of viral suppression of patients before a clinical encounter with reasons for their predictions. Provider predictions were compared to actual viral load measurements of patients. Patient data were abstracted from electronic health records. The final analysis included nine providers, 28 patients, and 34 observations of paired provider predictions and viral load results. Provider prediction accuracy of viral suppression was low (59%, Cohen's Kappa=0.16). Provider predictions of lack of viral suppression were based on non-adherence to medications, new patient status, or structural vulnerabilities (e.g., unstable housing). Anticipated viral suppression was based on medication adherence, history of viral suppression, and presence of family or other social forms of support. Providers have difficulty predicting viral suppression among AYA-HIV and may base counseling on incorrect assumptions. Rapid point-of-care viral load testing may provide opportunities to improve counseling.



Citations (22)


... In this context, it is also possible that HIV infection during seroconversion may act as a decompensating mechanism in patients with previously undiagnosed AHPs [85]. Previous case reports have correlated the onset of symptoms or clinical signs of AHPs and other forms of porphyria after exposure to different components of highly active antiretroviral therapy (HAART), such as indinavir [87], efavirenz [88,89], nevirapine [90], and tenofovir [86]. It should also be noted that the need for prophylactic therapies to specific polytherapy for various opportunistic infections (e.g., tuberculosis, systemic fungal infections, Pneumocystis jirovecii pneumonia, shingles by Varicella-zoster virus) is a factor requiring greater caution in the treatment of patients with AHPs and HIV/AIDS infection. ...

Reference:

Practical Recommendations in the Treatment of Acute and Chronic Life-Threatening Infectious Diseases in Patients with Acute Hepatic Porphyria
Primary Care Guidance for Providers Who Care for Persons With Human Immunodeficiency Virus: 2024 Update by the HIV Medicine Association of the Infectious Diseases Society of America
  • Citing Article
  • October 2024

Clinical Infectious Diseases

... This long-acting (LA) INSTI/nucleoside reverse transcriptase inhibitor injectable combination given intramuscularly every 1 or 2 months is licensed for adults and adolescents aged ≥12 years and weighing ≥35 kg who are virologically suppressed [43][44][45]. This approval is based on excellent safety and efficacy outcomes in phase III adult trials [46][47][48], and the phase I/II MOCHA trial in adolescents aged 12 to <18 years [49,50]. LATA, a phase III RCT of individuals aged 12-19 years with virological suppression in Africa switching to cabotegravir/rilpivirine (CAB/RPV) versus continuing standard of care, [51] has recently completed recruitment. ...

Safety and pharmacokinetics of oral and long-acting injectable cabotegravir or long-acting injectable rilpivirine in virologically suppressed adolescents with HIV (IMPAACT 2017/MOCHA): a phase 1/2, multicentre, open-label, non-comparative, dose-finding study
  • Citing Article
  • April 2024

The Lancet HIV

... 34 This journey, marked by the development of antiretroviral therapy (ART) and the introduction of long-acting injectable therapies, underscores significant advancements that have improved treatment adherence and quality of life, particularly in resource-limited regions like sub-Saharan Africa. 35 Publications are more than repositories of information; they drive medical progress. 36 Physician-scientists who publish contribute to advancing medical knowledge and improving patient care by educating peers, influencing public health policies, and shaping clinical guidelines. ...

Acceptability and tolerability of long-acting injectable cabotegravir or rilpivirine in the first cohort of virologically suppressed adolescents living with HIV (IMPAACT 2017/MOCHA): a secondary analysis of a phase 1/2, multicentre, open-label, non-comparative dose-finding study
  • Citing Article
  • April 2024

The Lancet HIV

... Despite the international scientific community showing a growing interest in supporting shared decision-making for infant feeding choices [2,3], in Italy the available guidelines for the management of pregnancy in women with HIV recommend against breastfeeding and suggest the administration of zidovudine to the newborn for 4-6 weeks [4]. As discussed in the article, even in Italy there are some cases of breastfeeding in spite of these national guidelines. ...

In Support of Breast/Chest Feeding by People with HIV in High-Income Settings
  • Citing Article
  • January 2024

Clinical Infectious Diseases

... NGT is a structured method used to facilitate group decision-making and prioritize ideas [21]. This technique has been widely utilized in designing HIV prevention interventions [22][23][24][25]. The process involved two steps. ...

Barriers and Facilitators to Equitable Implementation of Long-Acting ART for Adolescents and Youth with HIV in Low- and Middle-Income Settings

... Por otro lado, en las investigaciones encontradas sobre las conductas sexuales de riesgo resalta el estudio realizado por Trent et al. (2023) quienes encontraron que no existe relación entre los riesgos percibidos y el comportamiento sexual durante la pandemia de COVID-19, ya que la preocupación sobre la exposición al coronavirus no afectó la participación en las relaciones sexuales. En el estudio de Amare et al. (2019) se encontró que la prevalencia de padecer enfermedades de transmisión sexual en estudiantes de colegio y universidad es similar, y que los hombres son más propensos a participar en prácticas sexuales de riesgo que las mujeres. ...

Understanding Perceived Risks and Sexual Behavior Among Adolescents and Young Adults During the COVID-19 Pandemic
  • Citing Article
  • January 2023

Journal of Adolescent Health

... Remdesivir was approved by the Food and Drug Administration (FDA) on October 22, 2020 and by the European Medicines Agency (EMA) on July 3, 2020 for the treatment of SARS-CoV-2 [4,5,7]. The first therapeutic indications were established for patients 12 years of age or older and weighing at least 40 kg. ...

P168 Remdesivir in the treatment of children 28 days to < 18 years of age hospitalised with COVID-19 in the CARAVAN study
  • Citing Conference Paper
  • November 2022

Thorax

... This, together with the well-established HIV epidemic, means that an increasing number of South Africans have to manage more than one chronic condition, or stated differently, are living with multimorbidity [7]. It is further argued that aging with HIV could lead to increases in HIV comorbidities and multimorbidity in younger adults, including adolescents, as long-term consequences of being on ART [8]. ...

Preventing and diagnosing HIV-related comorbidities in adolescents
  • Citing Article
  • October 2022

Topics in Antiviral Medicine

... Our results are in agreement with Fitzgerald and colleagues (51) who found that immune activation decreased in pediatric HIV-infected children after ART initiation. Weinberg and colleagues also found that several markers including IFN-, IL-6, TNF-, sCD163, CRP, sCD14 and MCP-1 decreased after virologic control (52). Others found that ALWH on stable ART showed evidence of altered gut permeability and fungal translocation (53) and increased monocyte and T cell activation and higher sCD14 (54). ...

Coordination of inflammatory responses in children with perinatally-acquired HIV infection
  • Citing Article
  • April 2022

AIDS (London, England)

... Youth with HIV (YWH) have high rates of comorbid depression (Benton et al., 2019;Brown et al., 2021), with some reports as high as 37% (Lynn et al., 2019). Treating depressive symptoms is critical, as depression can interfere with HIV treatment including lower rates of medication adherence and poorer health outcomes (Brown et al., 2015). ...

Site-Randomized Controlled Trial of a Combined Cognitive Behavioral Therapy and a Medication Management Algorithm for Treatment of Depression Among Youth Living With HIV in the United States
  • Citing Article
  • August 2021

JAIDS Journal of Acquired Immune Deficiency Syndromes