SOURCES OF DATA: Recent published literature.
AREAS OF AGREEMENT: Corticosteroids and immunomodulators that antagonize the interleukin-6 (IL-6) receptor have been shown to play a critical role in modulating inflammation and improving clinical outcomes in hospitalized patients. Inhaled budesonide reduces the time to recovery in older patients with mild-to-moderate COVID-19 managed in the community.
AREAS OF CONTROVERSY: The clinical benefit of remdesivir remains controversial with conflicting evidence from different trials. Remdesivir led to a reduction in time to clinical recovery in the ACTT-1 trial. However, the World Health Organization SOLIDARITY and DISCOVERY trial did not find a significant benefit on 28-day mortality and clinical recovery.
GROWING POINTS: Other treatments currently being investigated include antidiabetic drug empagliflozin, antimalarial drug artesunate, tyrosine kinase inhibitor imatinib, immunomodulatory drug infliximab, antiviral drug favipiravir, antiparasitic drug ivermectin and antidepressant drug fluvoxamine.
AREAS TIMELY FOR DEVELOPING RESEARCH: The timing of therapeutic interventions based on postulated mechanisms of action and the selection of clinically meaningful primary end points remain important considerations in the design and implementation of COVID-19 therapeutic trials.
METHODS: From 2010 to 2014, men with HIV (N = 212) and opioid dependence before incarceration were enrolled in MMT within 6 months of release from Malaysia's largest prison and followed for 12-months post-release. As a prospective trial, allocation to MMT was at random and later by preference design (predictive nonetheless). MMT dosing was individually targeted to minimally achieve 80 mg/day. Time-to-event analyses were conducted to model linkage to MMT after release.
FINDINGS: Of the 212 participants allocated to MMT, 98 (46 %) were prescribed higher dosages (≥80 mg/day) before release. Linkage to MMT after release occurred in 77 (36 %) participants and significantly higher for those prescribed higher dosages (46% vs 28 %; p = 0.011). Factors associated with higher MMT dosages were being married, on antiretroviral therapy, longer incarceration periods, having higher levels of depression, and methadone preference compared to randomization. After controlling for other variables, being prescribed higher methadone dosage (aHR: 2.53, 95 %CI: 1.42-4.49) was the only independent predictor of linkage to methadone after release.
INTERPRETATION: Higher doses of methadone prescribed before release increased the likelihood of linkage to MMT after release. Methadone dosing should be introduced into international guidelines for treatment of opioid use disorder in prisons and further post-release benefits should be explored.
FUNDING: National Institute of Drug Abuse (NIDA).
METHODS: Thirty HIV-infected prisoners meeting DSM-IV pre-incarceration criteria for opioid dependence were enrolled in a prison-based, pre-release MMT program in Klang Valley, Malaysia; 3 died before release from prison leaving 27 evaluable participants. Beginning 4 months before release, standardized methadone initiation and dose escalation procedures began with 5mg daily for the first week and 5mg/daily increases weekly until 80 mg/day or craving was satisfied. Participants were followed for 12 months post-release at a MMT clinic within 25 kilometers of the prison. Kaplan-Meier survival analysis was used to evaluate the impact of methadone dose on post-release retention in treatment.
FINDINGS: Methadone dose ≥80 mg/day at the time of release was significantly associated with retention in treatment. After 12 months of release, only 21.4% of participants on <80 mg were retained at 12 months compared to 61.5% of those on ≥80 mg (Log Rank χ(2)=(1,26) 7.6, p<0.01).
CONCLUSIONS: Higher doses of MMT at time of release are associated with greater retention on MMT after release to the community. Important attention should be given to monitoring and optimizing MMT doses to address cravings and side effects prior to community re-entry from prisons.
METHODS: Prospective study of predominantly white HIV-infected participants receiving suppressive ART for at least 12 months. We analysed the CD14 SNPs C-260T and the TLR4 SNPs A+896G, C+1196T. We also determined the levels of LPS and soluble CD14 in plasma samples collected pre-ART and post-ART initiation. CD4 T-cell recovery was assessed by linear mixed models.
RESULTS: Following ART, individuals with a TT genotype compared with a CT or CC genotype for CD14 C-260T SNP showed higher levels of soluble CD14 (P = 0.008 and 0.003, respectively). The CC genotype for the CD14 C-260T SNP, compared with CT or TT, and the TLR4 SNP (AC/GT), compared with the homozygous genotype (AA/CC), were both independently associated with enhanced long-term CD4 T-cell recovery (>3 months; P
METHODS: Samples were subjected to microscopy examination and serological test (only for Strongyloides). Speciation for parasites on microscopy-positive samples and seropositive samples for Strongyloides were further determined via polymerase chain reaction. SPSS was used for statistical analysis.
RESULTS: A total of 294 stool and blood samples each were successfully collected, involving 131 HIV positive and 163 HIV negative adult male inmates whose age ranged from 21 to 69-years-old. Overall prevalence showed 26.5% was positive for various IPIs. The IPIs detected included Blastocystis sp., Strongyloides stercoralis, Entamoeba spp., Cryptosporidium spp., Giardia spp., and Trichuris trichiura. Comparatively, the rate of IPIs was slightly higher among the HIV positive inmates (27.5%) than HIV negative inmates (25.8%). Interestingly, seropositivity for S. stercoralis was more predominant in HIV negative inmates (10.4%) compared to HIV-infected inmates (6.9%), however these findings were not statistically significant. Polymerase chain reaction (PCR) confirmed the presence of Blastocystis, Strongyloides, Entamoeba histolytica and E. dispar.
CONCLUSIONS: These data will enable the health care providers and prison management staff to understand the trend and epidemiological situations in HIV/parasitic co-infections in a prison. This information will further assist in providing evidence-based guidance to improve prevention, control and management strategies of IPIs co-infections among both HIV positive and HIV negative inmates in a prison environment.