Aim Viral blips that occur among virally suppressed HIV-positive patients suggest immune activation and inflammation and associated with slower CD4 count and CD4/CD8 ratio normalisation. With the advances in HIV treatment, lifestyle and comorbidities begin to be a concern despite successful antiretroviral therapy. We reported a study incorporating the effect of CD4 and CD4/CD8 ratio normalisation on viral blips in joint disease progression (DP) and time-to-event (TTE) model. Methods A total of 152 HIV-positive patients receiving efavirenz therapy were recruited. Joint DP and TTE models on viral blip were developed for CD4 and CD4/CD8 ratio separately. Risk factors, such as smoking status, pack-year and comorbidity scores, were included in the analysis. Results Gompertz model best described the CD4 and CD4/CD8 ratio DP models, while viral blips data were fitted with the Cox proportional hazard model. History of opportunistic infections and changing of antiretroviral regimen significantly affect the baseline CD4 and CD4/CD8 ratio. Comorbidity score was significant in both CD4 (asymptote CD4) and CD4/CD8 ratio DP model (recovery rate). Increase in cumulative pack-year resulted in lower CD4/CD8 ratio recovery rate (β -0.02, 95%CI: -0.03 to -0.01; p<0.001). Active smokers with slow CD4 or CD4/CD8 ratio normalisation associated with more viral blips. Conclusion CD4 and CD4/CD8 ratio are significant risk factors of viral blips and potential markers of non-AIDS related morbidities in virally suppressed patients. Early identification of high-risk group with repeated viral load testing, lifestyle modification and comorbidities management should be emphasised in the HIV treatment long-term care plan.

The link between COPD and osteoporosis is unclear and yet to be understood. This study aimed at detecting the prevalence and investigate the predictors for low bone mineral density among COPD patients and tested a new risk assessment tool for the early screening of osteoporosis among COPD patients.This study is a longitudinal observational study conducted from June-2019 until December-2020 at a tertiary care setting in Penang, Malaysia. Follow-ups were arranged every six months. During the study, patients’ BMD was checked every visit, and the subjects’ pulmonary parameters were recorded, including; mMRC dyspnea scores, CAT scores, spirometry results, exacerbations history, and SpO2%. Furthermore, a novel risk assessment tool was validated in this study, and logistic regression was conducted to find low BMD predictors among COPD patients. Based on T-score, more than 50% of subjects were osteoporotic based. The overall mean±SD for patients’ age was 65.4±10.04. The overall mean±SD for patients’ BMI was 23.32±5.43. Both FEV1% predicted, and FEV/FVC was significantly lower among osteoporotic subjects, and lower mMRC stages were observed among non-osteoporotic patients. For the novel risk assessment tool, a cutoff point of 34 made the optimum balance between sensitivity and specificity (0.867 and 0.087, respectively) with an AUC of 0.934. Furthermore, severe COPD patients were four times at higher risk of getting osteoporosis, FEV% predicted, and FEV/FVC was inversely related to the risk of osteoporosis. Patients with severe dyspnea had twice the risk of getting osteoporosis.Osteoporosis was prevalent among COPD patients. For a screening tool, the risk assessment tool showed good sensitivity and precision in detecting osteoporotic subjects among COPD patients. Severe COPD patients were significantly at higher risk of getting osteoporosis.

Aim: Efavirenz is still widely used as the preferred first-line antiretroviral agent in the middle- and low- income countries, including Malaysia. The efavirenz population pharmacokinetic profile among HIV-positive smokers is still unknown. We aimed to assess the association of smoking with efavirenz and the differences in HIV clinical outcomes. Methods: A total of 154 stable HIV-positive patients on efavirenz in northern Malaysia were recruited with a sparse sampling for this multicentre prospective cohort study. The association between smoking and efavirenz pharmacokinetic parameters was determined using the non-linear mixed-effect model (NONMEM). A mixture model of clearance was adopted to describe the metaboliser status because genetic data is unavailable. The effect of smoking on HIV clinical markers (CD4, CD4 / CD8 ratio and viral blips) for at least two years after the antiretroviral initiation was also investigated. Results: Our data were best fitted with a one-compartment mixture model with first-order absorption without lag time. Smoking significantly associated with higher clearance (CL/F) (β = 1.39; 95% confidence interval (CI): 1.07 to 1.91), while weight affected both CL/F and volume (V/F). From the mixture model, 20% of patients were in the slow clearance group, which mimic the genotype distribution of slow metaboliser. An efavirenz dose reduction is not recommended for smokers ≥60kg with normal metabolism rate. Smoking significantly associated with slower normalisation of CD4 and CD4 / CD8 ratio. Conclusion: HIV-positive smokers presented with significantly higher efavirenz clearance and unfavourable clinical outcomes. Close monitoring of adherence and clinical response among smokers is warranted.