Low bone mineral density (BMD) is prevalent in human immunodeficiency virus (HIV)-infected subjects. Initiation of antiretroviral therapy is associated with a 2%–6% decrease in BMD over the first 2 ...years, a decrease that is similar in magnitude to that sustained during the first 2 years of menopause. Recent studies have also described increased fracture rates in the HIV-infected population. The causes of low BMD in individuals with HIV infection appear to be multifactorial and likely represent a complex interaction between HIV infection, traditional osteoporosis risk factors, and antiretroviral-related factors. In this review, we make the point that HIV infection should be considered as a risk factor for bone disease. We recommend screening patients with fragility fractures, all HIV-infected post-menopausal women, and all HIV-infected men ⩾50 years of age. We also discuss the importance of considering secondary causes of osteoporosis. Finally, we discuss treatment of the more severe cases of bone disease, while outlining the caveats and gaps in our knowledge.
Obesity rates are increasing among HIV-infected individuals, but risk factors for obesity development on ART remain unclear.
In a cohort of HIV-infected adults in Rio de Janeiro, Brazil, we aimed to ...determine obesity rates before and after ART initiation and to analyse risk factors for obesity on ART.
We retrospectively analysed data from individuals initiating ART between 2000 and 2015. BMI was calculated at baseline (time of ART initiation). Participants who were non-obese at baseline and had ≥90 days of ART exposure were followed until the development of obesity or the end of follow-up. Obesity incidence rates were estimated using Poisson regression models and risk factors were assessed using Cox regression models.
Of participants analysed at baseline (n = 1794), 61.3% were male, 48.3% were white and 7.9% were obese. Among participants followed longitudinally (n = 1567), 66.2% primarily used an NNRTI, 32.9% a PI and 0.9% an integrase strand transfer inhibitor (INSTI); 18.3% developed obesity and obesity incidence was 37.4 per 1000 person-years. In multivariable analysis, the greatest risk factor for developing obesity was the use of an INSTI as the primary ART core drug (adjusted HR 7.12, P < 0.0001); other risk factors included younger age, female sex, higher baseline BMI, lower baseline CD4+ T lymphocyte count, higher baseline HIV-1 RNA, hypertension and diabetes mellitus.
Obesity following ART initiation is frequent among HIV-infected adults. Key risk factors include female sex, HIV disease severity and INSTI use. Further research regarding the association between INSTIs and the development of obesity is needed.
We aimed to evaluate the relationship between food intake of lipids with nonalcoholic fatty liver disease (NAFLD) and/or liver fibrosis in people living with HIV/AIDS (PLWHA). In this cross-sectional ...study, transient elastography was used to detect the presence of NAFLD and/or liver fibrosis. The dietary intake of fats and fatty acids (FA) were assessed by two 24 h dietary recalls (24-HDR) (n = 451). Multivariate logistic regression models were performed. Participants with higher intake of total fat were associated with higher odds for NAFLD compared to those with lower consumption adjusted odds ratio (aOR) = 1.91 (95% confidence interval (95% CI) 1.06–3.44). Furthermore, participants with intermediate intake of n6-PUFA (n6-poly-unsaturated FA) and lauric FA had lower odds for NAFLD, respectively aOR = 0.54 (95% CI 0.3–0.98) and aOR = 0.42 (95% CI 0.22–0.78). Additionally, a higher intake of myristoleic FA (fourth quartile) was a significant protective factor for NAFLD aOR = 0.56 (95% CI 0.32–0.99). Participants with higher intake of lauric FA 0.38 (95% CI 0.18–0.80), myristic FA 0.38 (0.17–0.89), palmitoleic FA 0.40 (0.19–0.82) and oleic FA 0.35 (0.16–0.79) had positively less odds of having liver fibrosis. On the other hand, higher intake of n-6 PUFA was significantly associated with fibrosis aOR = 2.45 (95% CI 1.12–5.32). Dietary assessment of total fat and FA should be incorporated into HIV care as a tool for preventing NAFLD and fibrosis in PLWHA.
Global mortality from AIDS-related diseases has been declining since 2005, resulting primarily from the widespread use and early initiation of combination antiretroviral therapy. Despite the ...significant improvements, high rates of early mortality, usually defined as that occurring within the 1st year of entry to care, have been observed, especially in resource-limited settings. This analysis draws upon data from an observational cohort of people with HIV (PWH) followed at a reference center for HIV/AIDS care and research in the city of Rio de Janeiro, Brazil, to identify the pattern and factors associated with early mortality.
The study population includes PWH aged 18 or older followed at the National Institute of Infectious Diseases Evandro Chagas who were enrolled between 2004 and 2015. The primary outcome was early mortality, defined as deaths occurring within 1 year of inclusion in the cohort, considering two follow-up periods: 0 to 90 days (very early mortality) and 91 to 365 days (early mortality). Cox proportional hazards models were used to identify the variables associated with the hazard of very early and early mortality.
Overall, 3879 participants contributed with 3616.4 person-years of follow-up. Of 220 deaths, 132 happened in the first 90 days and 88 between 91 and 365 days. Very early mortality rate ratios (MRR) show no statistically significant temporal differences between the periods 2004-2006 to 2013-2015. In contrast, for early mortality, a statistically significant decreasing trend was observed: mortality rates in the periods 2004-2006 (MR = 5.5; 95% CI 3.9-7.8) and 2007-2009 (MR = 3.9; 95% CI 2.7-5.7) were approximately four and three-fold higher when compared to 2013-2015 (MR = 1.4; 95% CI 0.7-2.7). Low CD4 count and prior AIDS-defining illness were strongly associated with higher hazard ratios of death, especially when considering very early mortality.
The present study shows an excess of mortality in the 1st year of follow-up with no changes in the mortality rates within 90 days among PWH from Rio de Janeiro. We note the significant impact of initiating treatment with immunosuppression, as evidenced by the increased risk of death among those with low CD4 cell count and with AIDS-defining illnesses.
Daily adherence to antiretroviral therapy (ART) increases the length and quality of life of people living with HIV (PLHIV). We explored whether socioeconomic status directly impacts ART adherence and ...whether part of the effect is mediated by pathways through alcohol misuse or food insecurity. A cross-sectional study was conducted in Rio de Janeiro/Brazil (November/2019 to March/2020) with PLHIV aged ≥ 18 years. Validated instruments were used to measure alcohol use, food insecurity, and ART adherence. Using structural equation modeling we assessed the direct and indirect effects of variables on ART adherence. Participants reported significant challenges: hunger: 12%, alcohol use: 64%, and missing ART doses: 24%. Results showed that lower socioeconomic status increased poor adherence and that this effect was mediated through higher food insecurity. Alcohol misuse also increased poor adherence through a strong direct effect. Providing socio-economic support coupled with interventions to mitigate alcohol’s harmful impact can aid HIV care.
Data on the acceptability and usability of hepatitis C virus self-testing (HCVST) remain scarce. We estimated the pooled rates of acceptability/feasibility and re-reading/re-testing agreement of ...HCVST using oral fluid tests (PROSPERO-CRD42022349874). We searched online databases for studies that evaluated acceptability, usability and inter-reader/operator variability for HCVST using oral fluid tests. Pooled estimates of feasibility, agreement and post-testing perspectives were analysed. Sensitivity analyses were performed in men who have sex with men (MSM) and people who inject drugs (PWID). Heterogeneity was assessed using the I
statistics. A total of six studies comprising 870 participants were identified: USA (n = 95 with liver disease), Kenya (n = 150 PWID), Egypt (n = 116 from the general population), Vietnam (n = 104 MSM and n = 105 PWID), China (n = 100 MSM) and Georgia (n = 100 MSM and n = 100 PWID). All studies used OraQuick® HCV Rapid Antibody Test. The pooled overall estimates for correct sample collection and for people who performed HCVST without needing assistance in any step (95% confidence interval CI) were 87.2% 76.0-95.3 (n = 755; I
= 93.7%) and 62.6% 37.2-84.8 (n = 755; I
= 98.0%), respectively. The pooled estimate of agreement for re-reading was 95.0% 95% CI 91.5-97.6 (n = 831; I
= 74.0%) and for re-testing was 94.4% 90.3-97.5 (n = 726; I
= 77.1%). The pooled estimate of those who would recommend HCVST was 94.4% 84.7-99.6 (n = 625; I
= 93.7%). Pooled estimates (95% CI) of correct sample collection (72.8% 63.3-81.5 vs. 90.8% 85.9-94.8) and performance of HCVST without needing assistance (44.1% 14.1-76.7 vs. 78.1% 53.4-95.3) was lower in PWID compared to MSM. In summary, HCV testing with oral fluid HCVST was feasible and well-accepted. Oral fluid HCVST should be considered in key populations for uptake HCV testing.
Abstract
Background
Protease inhibitor-based antiretroviral therapy may be used in resource-limited settings in persons with human immunodeficiency virus and tuberculosis (HIV-TB). Data on safety, ...pharmacokinetics/pharmacodynamics (PK/PD), and HIV-TB outcomes for lopinavir/ritonavir (LPV/r) used with rifampin (RIF) or rifabutin (RBT) are limited.
Methods
We randomized adults with HIV-TB from July 2013 to February 2016 to arm A, LPV/r 400 mg/100 mg twice daily + RBT 150 mg/day; arm B, LPV/r 800 mg/200 mg twice daily + RIF 600 mg/day; or arm C, LPV/r 400 mg/100 mg twice daily + raltegravir (RAL) 400 mg twice daily + RBT 150 mg/day. All received two nucleoside reverse transcriptase inhibitors and other TB drugs. PK visits occurred on day 12 ± 2. Within-arm HIV-TB outcomes were summarized using proportions and 95% CIs; PK were compared using Wilcoxon tests.
Results
Among 71 participants, 52% were women; 72% Black; 46% Hispanic; median age, 37 years; median CD4+ count, 130 cells/mm3; median HIV-1 RNA, 4.6 log10 copies/mL; 46% had confirmed TB. LPV concentrations were similar across arms. Pooled LPV AUC12 (157 203 hours × ng/mL) and Ctrough (9876 ng/mL) were similar to historical controls; RBT AUC24 (7374 hours × ng/mL) and Ctrough (208 ng/mL) were higher, although 3 participants in arm C had RBT Cmax <250 ng/mL. Proportions with week 48 HIV-1 RNA <400 copies/mL were 58%, 67%, and 61%, respectively, in arms A, B, and C.
Conclusions
Double-dose LPV/r+RIF and LPV/r+RBT 150mg/day had acceptable safety, PK and TB outcomes; HIV suppression was suboptimal but unrelated to PK. Faster RBT clearance and low Cmax in 3 participants on RBT+RAL requires further study.
Double-dose lopinavir/ritonavir plus rifampin and standard-dose lopinavir/ritonavir plus 150mg rifabutin were associated with acceptable tuberculosis outcomes, safety, tolerability, and pharmacokinetic profiles in persons with both human immunodeficiency virus and tuberculosis.
To determine the performance of the baseline monocyte to lymphocyte ratio (MLR), baseline anemia severity and combination of these biomarkers, to predict tuberculosis (TB) incidence in people with ...HIV (PWH) after antiretroviral therapy (ART) initiation.
Multicenter, retrospective cohort study.
We utilized the data from study A5175 (Prospective Evaluation of Antiretroviral Therapy in Resource-limited Settings: PEARLS). We assessed the utility of MLR, anemia severity and in combination, for predicting TB in the first year after ART. Cox regression was used to assess associations of MLR and anemia with incident TB. Harrell's C index was used to describe single model discrimination.
A total of 1455 participants with a median age of 34 interquartile range (IQR) 29, 41 were included. Fifty-four participants were diagnosed with TB. The hazard ratio (HR) for incident TB was 1.77 95% confidence interval (CI) 1.01-3.07; P = 0.04 for those with MLR ≥0.23. The HR for mild/mod anemia was 3.35 (95% CI 1.78-6.29; P < 0.001) and 18.16 (95% CI 5.17-63.77; P < 0.001) for severe anemia. After combining parameters, there were increases in adjusted HR (aHR) for MLR ≥0.23 to 1.83 (95% CI 1.05-3.18), and degrees of anemia to 3.38 (95% CI 1.80-6.35) for mild/mod anemia and 19.09 (95% CI 5.43-67.12) for severe anemia.
MLR and hemoglobin levels which are available in routine HIV care can be used at ART initiation for identifying patients at high risk of developing TB disease to guide diagnostic and management decisions.
To compare the efficacy of generic direct-acting agents and brand-name medicines for treating hepatitis C virus (HCV) infection by conducting a systematic review and meta-analysis.
We searched online ...databases for studies that reported sustained virological responses 12 weeks after the end of HCV treatment with generic direct-acting agents. We derived pooled proportions of treated patients with a sustained virological response from intention-to-treat and per-protocol analyses. In addition, we calculated the pooled relative risk (RR) of a sustained virological response brand-name versus generic direct-acting agents using a random-effects model (DerSimonian-Laird) from the data available. Between-study heterogeneity was assessed using the
statistic.
We identified 19 studies involving a total of 57 433 individuals from eight territories or regions. The pooled overall proportions of patients with a sustained virological response were 98% (95% confidence interval, CI: 97-99; 18 studies;
= 94.1%) in per-protocol analyses and 96% (95% CI: 93-98; 8 studies;
= 68.1%) in intention-to-treat analyses. The likelihood of a sustained virological response with brand-name medicines was similar to that with generic direct-acting agents (RR: 1.00; 95% CI: 0.98-1.02;
= 0.0%). The likelihood of a sustained virological response was significantly higher in patients without than with cirrhosis (RR:1.03; 95% CI: 1.01-1.06; 7 studies) but was not significantly affected by either previous treatment (3 studies) or human immunodeficiency virus coinfection (3 studies).
Generic direct-acting agents are highly effective for treating hepatitis C. Generic agents should be considered in resource-constrained settings for decreasing the burden of liver disease in HCV-infected patients.
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