Comparative evaluation of the applicability of fixed-dose combined drugs in HIV therapy / Avaliação comparativa da aplicabilidade de drogas combinadas em dose fixa na terapia do HIV

The principal global pandemic is Acquired Immunodeficiency Syndrome (AIDS), the early diagnosis and the premature treatment is the main current strategies in combating the development and spread of the disease. Antiretroviral therapy is effective and safe, what is sought nowadays is compliance and convenience for the patient. Different countries adopt different combinations of antiretroviral drugs when using the fixed-dose combination (FDC). The study design was a meta-analysis with clinical trials, patients experienced and naïve of treatment. The Pubmed, Scopus, Embase, Web of Science and Cochrane databases were searched for studies reporting AIDS treatment. The primary outcome was viral load and another outcome is adverse events. The results of the main analysis included 5224 patients. Since there was significant heterogeneity between studies, random effects were selected, and they showed an event rate of 0.67 (95%CI from 0.57 to 0.77). The exploratory analysis showed the general drug effects are not consistently significant along time, and treatments of longer times are more efficient. Specifically, the random analyses of 6 months and 1 year did not show significant drug effects on viral load, while a significant effect of 71% (95% CI from 0.61 to 0.80) in a very heterogeneous analyses (I296%). First, d4T-3TC-NVP showed a mean rate of only 21% efficacy and the second, EFV-TDF-FTC did not reach statistical significance (p=0.07). This meta-analysis shows that fixed-dose combination therapy is tolerability, safety and effective, occurred viral load suppression between patients on FDC.

Is Dosing of Ethambutol as Part of a Fixed-Dose Combination Product Optimal for Mechanically Ventilated ICU Patients with Tuberculosis? A Population Pharmacokinetic Study

Background: Tuberculosis (TB) patients admitted to intensive care units (ICU) have high mortality rates. It is uncertain whether the pharmacokinetics of first-line TB drugs in ICU patients are different from outpatients. This study aims to compare the pharmacokinetics of oral ethambutol in TB patients in ICU versus TB outpatients and to determine whether contemporary dosing regimens achieve therapeutic exposures. Methods: A prospective population pharmacokinetic study of ethambutol was performed in Amazonas State, Brazil. Probability of target attainment was determined using AUC/MIC > 11.9 and Cmax/MIC > 0.48 values. Optimized dosing regimens were simulated at steady state. Results: Ten ICU patients and 20 outpatients were recruited. Ethambutol pharmacokinetics were best described using a two-compartment model with first-order oral absorption. Neither ICU patients nor outpatients consistently achieved optimal ethambutol exposures. The absorption rate for ethambutol was 2-times higher in ICU patients (p < 0.05). Mean bioavailability for ICU patients was >5-times higher than outpatients (p < 0.0001). Clearance and volume of distribution were 93% (p < 0.0001) and 53% (p = 0.002) lower in ICU patients, respectively. Conclusions: ICU patients displayed significantly different pharmacokinetics for an oral fixed-dose combination administration of ethambutol compared to outpatients, and neither patient group consistently achieved pre-defined therapeutic exposures.

Outcome of Fixed Dose Combination of Tenofovir, Lamivudine and Dolutegravir in Rural HIV Care Facility in Nigeria

Background: Antiretroviral therapy (ART) has significantly increased the lifespan of people living with HIV. Currently, fixed dosed combination therapy (Tenofovir, Lamivudine, and Dolutegravir) is being introduced in most countries in the Sub- Saharan Africa. There is need for a clinical and immunological assessment of HIV patients transitioned to this new therapy over a period of 2 years. Objectives: To determine the proportion of patients whose viral load was suppressed to <20 copies/ml following two years therapy with Dolutegravir-based fixed-dose combination therapy. Methods: This retrospective cohort study was carried out in a Comprehensive Healthcare Centre (CHC), a facility affiliated with Nnamdi Azikiwe University Teaching Hospital Nigeria. The primary outcome measure was the proportion of patients whose viral load was suppressed to <20 copies/ml. The plasma viral load (HIV-RNA) assay was done using real time PCR and CD4+ T- lymphocyte (CD4+) counts were estimated using Flow Cytometry. The exclusion criteria were patients who has invalid data base and patients with comorbidities associated with HIV. Results: A total of 537 HIV1 sero-positive patients were enrolled for ART care over a period of 2 years (2017-2018). Females in the age group (41-50 years) constituted the bulk (36.9%) of the patients whilst the least (5.3%) were males in the age group (8 to 30 years). The mean CD4 count of patients was 847.35cells/mm3. More females (45.9%) had CD4+counts over 500cells/mm3 whilst the percentage of males with CD4+ cell counts over 500cells/mm3 was 43.8%. Majority, 405 constituting 75.4% of the patients have suppressed viral load (<20 copies/ml) signifying that the centre is achieving success with respect to service delivery and ART. Patients with unsuppressed viral loads were more among Females with CD4+ counts in the range of 200-499 cells/mm3and this may be as a result of other associated factors which will be elucidated in future studies. Conclusion: Dolutegravir-based fixed-dose combination therapy suppressed viral load to <20 copies/ml in more than 75% of patients receiving the therapy. Enhanced adherence and effective doctor-patient relationship could be associated with the viral suppression observed in this study. Key words: Immunology, virology, HIV Outcome, Dolutegravir-based combination therapy, anti retroviral therapy.