ABSTRACT
BACKGROUND AND AIMS: Following antiretroviral therapy (ART) initiation, HIV-associated immune reconstitution inflammatory syndrome (IRIS), indicated by an array of opportunistic infections, may occur, presenting as either paradoxical, a worsening of a previously treated infection, or unmasking, a flare-up of an underlying, previously undiagnosed infection. The impact of ART as the backbone of HIV treatment and prevention has prolonged the survival of people living with HIV. In pregnancy, benefits have been shown by slowing HIV progression and preventing perinatal transmission; however, there have been risks of adverse reactions with ART, including immune responses to both the fetus and mother. This study sought to estimate the incidence of HIV-IRIS cumulatively and by type either paradoxical or unmasking IRIS, determine the baseline maternal and HIV clinical markers as predictors of, and analyze the log-rank test for survival time to IRIS outcome assessed by relying on an increase in CD4 count and/or a rapid decrease in viral load. METHODS: An active records study was conducted between June 2019 and March 2020 among ART-naïve pregnant women attending the antenatal care units (ANCu) at the Kenyatta National and Mbagathi Hospitals, Nairobi, Kenya. Participants were aged between 20 and 49 years and had a confirmed HIV-positive test. To ascertain a true case of IRIS, the diagnosis was adjudicated for accuracy and consistency by an independent review committee. Plasma HIV viral load, CD4 counts, and routine laboratory evaluations (hemoglobin, white blood cell count (WBC)) were performed by each hospital's clinical laboratory. The IRIS incidence was assessed using the International Network for Studies Against HIV-Associated IRIS (INSHI) during the first three months after ART initiation. Multivariate Cox regression with IRIS as the outcome, using the SPSSSurvival package, examined the relationship between baseline maternal characteristics and HIV clinical markers before ART initiation and IRIS, and finally, decision-tree analysis for predicting IRIS was performed. RESULTS: From a pool of 532 ART-naïve pregnant women, 133 (25%) developed IRIS, and 97 (72.9%) were in the unmasking category. The accumulated risk of experiencing IRIS symptoms increased from week two (hazard ratio (HR)=0.0287) to week 12 (HR=3.6158). Participants with a maternal BMI (MBMI) of 25-29.9 kg/m2 at baseline were at a higher risk of unmasking IRIS (HR=2.478; P=0.010). The WHO-HIV clinical stages 1 and 2 skewed towards paradoxical IRIS (regression coefficients =-0.111 and -0.276 (P<0.05)), while stage 4 skewed towards unmasking IRIS (regression coefficient=0.047, HR=1.048, P=0.941). A CD4 count > 500 cells/mm^3 skewed towards unmasking IRIS (regression coefficient=0.192, HR=1.211, P=0.416), while RNA-HIV viral loads >50 copies/ml towards paradoxical IRIS (regression coefficient=-0.199, HR=0.820, P=0.360. On decision tree analysis, 85% (P=0.001) of ART-naïve pregnant women with a baseline CD4 count below 500 copies/mm^3 presented with unmasking IRIS. CONCLUSION: For ART-naïve pregnant women, unmasking IRIS is the most common type, and an MBMI of 25-29.9 kg/m2, advanced HIV infection, a CD4 count <500 cells/mm^3, and a higher parity at baseline may be clinically useful predictors. The higher proportion of ART-naïve pregnant women experiencing unmasking as compared to paradoxical IRIS supports the need for earlier assessment based on potential predictors.
ABSTRACT
The built environment encompasses buildings we live in; the distribution systems that provide us with water and electricity; and the roads, bridges, and transportation systems we use to get from place to place. It provides safety, health, and well-being and meaning to its dwellers, as a place to work, live, learn, play, and thrive. Poor-quality housing affects dwellers' health through toxins such as radon and lead, mold, cold indoor temperatures, and overcrowding. Physicians' practices should investigate their patients' diagnoses such as stress, depression, asthma, adverse childhood experiences, and anxiety, as potentially housing-related and make ameliorating recommendations or referrals.
Subject(s)
Housing , Social Determinants of Health , Humans , Built Environment , AnxietyABSTRACT
The aim of this review was to evaluate the risk of COVID-19 cytokine release syndrome (CRS) with HIV infection and meta-regress for indicator covariates. Electronic databases, including Google Scholar, Cochrane Library, Web of Sciences (WOS), EMBASE, Medline/PubMed, COVID-19 Research Database, and Scopus, were systematically searched till February 30, 2022. All human studies were included, irrespective of publication date or region. Eleven studies, with a total of 2,005,274 detailing cytokine release syndrome defined by specific parameters, were included. To pool the estimate, a random-effects model with risk ratio (RR) as the effect measure was used. Moreover, publication bias and sensitivity analysis were evaluated followed by meta-regression analysis to account for any possible covariates. This systematic review, meta-analysis, and meta-regression trial was registered (CRD42021264761) on the PROSPERO register. HIV infection showed an increased risk for COVID-19 cytokine release syndrome (RR= 1.48, 95% CI (1.16, 1.88) (P=0.002)) with substantial heterogeneity (I2 > 80%) and a 4.6% cumulative incidence. The true effects size in 95% of all the comparable populations (prediction interval) fell between 0.67 to 3.29. HIV infection further showed an increased risk for intensive care unit (ICU) admission ((P<0.0001) (I² = 0%)] and mechanical ventilation (MV) ((P=0.04) (I² = 0%)) as the key indicators of cytokine release syndrome. Meta-regression analysis demonstrated that COVID-19 cytokine release syndrome was influenced by the year a study was published (R² = 0.55) and the region from where the study was conducted (R² = 0.11). On meta-regression analysis, the combined impact of all covariates in the model explained at least some of the variance in effect size (Q = 16.21, df = 6, P= 0.0127), and the proportion of variance explained by covariates on comparing the model with and without the covariates was 73 % and highly significant (Tau² = 0.1100, Tau = 0.3317, I² = 86.5%, Q = .99, df = 10, P<0.0001) (R² = 0.73). Our updated meta-analysis indicated that HIV infection was significantly associated with an increased risk for COVID-19 cytokine release syndrome, which, in addition, might be moderated by the year a study was published and the region in which the study was conducted. Further, the risk for intensive care unit (ICU) admission and mechanical ventilation (MV) were identified as the key indicators of cytokine release syndrome. We believe the updated data anchoring cytokine release syndrome will contribute to more substantiation of the findings reported by similar earlier studies.
