Although human immunodeficiency virus (HIV) coinfection is the most important risk factor for a poor antituberculosis (anti-TB) treatment response, its effect on the pharmacokinetics of the first-line drugs in children is understudied. This study examined the pharmacokinetics of the four first-line anti-TB drugs in children with TB with and without HIV coinfection. Ghanaian children with TB on isoniazid, rifampin, pyrazinamide, and ethambutol for at least 4 weeks had blood samples collected predose and at 1, 2, 4, and 8 hours postdose. Drug concentrations were determined by validated liquid chromatography-mass spectrometry methods and pharmacokinetic parameters calculated using noncompartmental analysis. The area under the concentration-time curve from 0 to 8 h (AUC 0 -8 ), maximum concentration (C max ), and apparent oral clearance divided by bioavailability (CL/F) for each drug were compared between children with and without HIV coinfection. Of 113 participants, 59 (52.2%) had HIV coinfection. The baseline characteristics were similar except that the coinfected patients were more likely to have lower weight-for-age and height-for-age Z scores (P Ͻ 0.05). Rifampin, pyrazinamide, and ethambutol median body weight-normalized CL/F values were significantly higher, whereas the plasma AUC 0 -8 values were lower, in the coinfected children than in those with TB alone. In the multivariate analysis, drug dose and HIV coinfection jointly influenced the apparent oral clearance and AUC 0 -8 for rifampin, pyrazinamide, and ethambutol. Isoniazid pharmacokinetics were not different by HIV coinfection status. HIV coinfection was associated with lower plasma exposure of three of the four first-line anti-TB drugs in children. Whether TB/HIV-coinfected children need higher dosages of rifampin, pyrazinamide, and ethambutol requires further investigation. (This study has been registered at ClinicalTrials.gov under identifier NCT01687504.)

Introduction Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) has infected >6 million people worldwide since December 2019. Global reports of HIV/SARS‐CoV‐2 coinfection are limited. To better understand the impact of the coronavirus disease 2019 (COVID‐19) pandemic on persons with HIV and improve their care, we present an outpatient and inpatient clinical experience of HIV/SARS‐CoV‐2 coinfection from Rhode Island, US. Methods We describe outpatient and inpatient preparedness for the COVID‐19 pandemic, and present a case series of all known patients with HIV/SARS‐CoV‐2 coinfection at The Miriam Hospital and Rhode Island Hospital, and The Miriam Hospital Infectious Diseases and Immunology Center, in Providence, Rhode Island, US. Results and discussion The Infectious Diseases and Immunology Center rapidly prepared for outpatient and inpatient care of persons with HIV and SARS‐CoV‐2. Between 30 March and 20 May 2020, 27 patients with HIV were diagnosed with SARS‐CoV‐2. Twenty were male, six female and one transgender female; average age was 49 years; 13/27 were Hispanic and 6/27 were African American. All had HIV viral load <200 copies/mL and were on antiretroviral therapy with CD4 count range 87 to 1441 cells/µL. Twenty‐six of the 27 had common COVID‐19 symptoms for one to twenty‐eight days and most had other co‐morbidities and/or risk factors. Nine of the 27 were hospitalized for one to thirteen days; of those, three lived in a nursing home, six received remdesivir through a clinical trial or emergency use authorization and tolerated it well; eight recovered and one died. Overall, 17% of known Center people had HIV/SARS‐CoV‐2 coinfection, whereas the comparable state‐wide prevalence was 9%. Conclusions We highlight challenges of outpatient and inpatient HIV care in the setting of the COVID‐19 pandemic and present the largest detailed case series to date from the United States on HIV/SARS‐CoV‐2 coinfection, adding to limited global reports. The aggregated clinical findings suggest that the clinical presentation and outcomes of COVID‐19 appear consistent with those without HIV. Whether SARS‐CoV‐2 infection is more frequent among persons with HIV remains to be determined. More data are needed as we develop our understanding of how HIV and antiretroviral therapy are affected by or have an impact on this pandemic.

There is a high burden of underlying substance use and mental illness in HIV-infected populations. HIV-care settings provide an important opportunity to assess substance and mental health needs among HIV-positive patients and to provide or make referrals for appropriate treatment services. In 2003, with funding from the Center for Substance Abuse Treatment (CSAT), we developed a model of integrated substance-use counselling and referral for treatment within a primary care HIV-care setting at The Miriam Hospital in Providence, Rhode Island. The project uses a multidisciplinary approach to provide linkage to treatment services for substance use and mental illness as well as to help participants with social service needs, such as housing and medical coverage, to ensure continuity of care and optimal HIV treatment adherence. Twelve percent of the 965 HIV-infected patients in care at our center have been enrolled in the project. Of these, all have a current substance-use disorder and 79.3% have been diagnosed with a mental illness. In addition, most participants are hepatitis C-positive (HCV) (65.5%). The majority of participants are on antiretroviral therapy (76.7%). Participants have been referred for the following treatment modalities: intensive outpatient services, methadone, buprenorphine, outpatient services and residential as well as individual and group counselling. Our model has been successful in assessing the substance-use and mental health needs of HIV-infected individuals with numerous co-morbidities and referring them for ancillary medical and social services.