Pilot comparison of clinical effects and compliance with commonly prescribed antihypertensive drugs in HIV hypertensive patients at University Teaching Hospital

Pilot comparison of clinical effects and compliance with commonly prescribed antihypertensive drugs in HIV hypertensive patients at UTH. By Dr Takondwa Ngulube Chidumayo HIV infection and hypertension disproportionately affect sub-Saharan Africa including Zambia. The challenges of effectively treating patients with these co-morbidities include pill burden, drug interactions that may influence the efficacy and side effect profile of antihypertensive and antiretroviral therapies. This study determined the association between clinical effects regarding blood pressure control, side effect profile and compliance with the commonly used antihypertensive drugs classes in Zambia. The study was a prospective cohort analysis of randomly selected hypertensive people living with HIV (PLWHIV) on commonly used antihypertensive drug classes. Antihypertensive drug efficacy was assessed using sitting clinic and 24-hour ambulatory blood pressure monitoring (ABPM) for participants on antihypertensive drugs for at least six weeks. The validated anti-retroviral therapy (ART) clinic follow-up questionnaire and ‘WHO questionnaire for hypertension in a rapidly ageing population’ gathered quantitative data on management, treatment, patient knowledge and complications of HIV and hypertension during the 8 -week period at Adult Infectious Disease Centre (AIDC). To determine the most effective, safest antihypertensive therapies acceptable to this population. Participants on CCB (140.4/98.8 mmHg) and CCB with Enalapril (147.9/92.7 mmHg) had higher median daytime blood pressure than Moduretic (136.8/84.2 mmHg, p=0.186 and 0.168 respectively) and Moduretic with Enalapril (140.5/84 mmHg, p= 0.003). The attributable risk for good daytime systolic and diastolic BP control was at least 20 % and 32 % for Moduretic and Enalapril (50 % and 67 %, p=0.046 and 0.0143 respectively) and Moduretic (50 % and 62%, p=0.691 and 0.425 respectively). The circadian systolic and diastolic BP decrease was less than 10 % for Moduretic and Enalapril (8.25 % and 10.25 %, p=0.005 and 0.003, respectively). The difference in the median clinic systolic and diastolic BP (170/106 mmHg) was greater than 22.62 mmHg and 11.20 mm Hg than daytime ABPM (142/95.5 mmHg, p = 0.0001 and 0.001 respectively). Moduretic had the highest side effect proportion (62.5 %), mainly related to hypokalemia in patients on Tenofovir (p=0.25). The highest occurrence of non-compliance was in CCBs with Enalapril (50 %) and CCBs (40 %) with p= 0.048. CCBs with Enalapril (100 %) and Moduretic with Enalapril (100 %) had the highest proportion of awareness of the importance of compliance and BP control (p=0.02). This finding mitigated the effects of increased antihypertensive pill burden which did not affect compliance, especially in the latter group. The study supported the alternative hypothesis. Moduretic with Enalapril had the highest ration of BP, with fewer side effects and better compliance. The use of Nifedipine ® in PLWHIV on NNRTIs should be carefully monitored as combinations with and Enalapril alone is less efficacious in hypertensive PLWHIV of African origin. Antihypertensive drug compliance improved by patient knowledge of hypertension treatment rather than reduced pill burden. A more rigorous study iv long-term with larger samples sizes is required to determine the BP control rates using more diverse combinations of antihypertensive drugs, Nifedipine XR formulations, hypertension in PLWHIV

A 12 week longitudinal study of microbial translocation and systemic inflammation in undernourished HIV-infected Zambians initiating antiretroviral therapy.

BACKGROUND: Undernourished, HIV-infected adults in sub-Saharan Africa have high levels of systemic inflammation, which is a risk factor for mortality and other adverse health outcomes. We hypothesized that microbial translocation, due to the deleterious effects of HIV and poor nutrition on intestinal defenses and mucosal integrity, contributes to heightened systemic inflammation in this population, and reductions in inflammation on antiretroviral therapy (ART) accompany reductions in translocation. METHODS: HIV-infected, Zambian adults with a body mass index <18.5 kg/m2 were recruited for a pilot study to assess the relationships between microbial translocation and systemic inflammation over the first 12 weeks of ART. To assess microbial translocation we measured serum lipopolysaccharide binding protein (LBP), endotoxin core IgG and IgM, and soluble CD14, and to assess intestinal permeability we measured the urinary excretion of an oral lactulose dose normalized to urinary creatinine (Lac/Cr ratio). Linear mixed models were used to assess within-patient changes in these markers relative to serum C-reactive protein (CRP), tumor necrosis factor-α receptor 1 (TNF-α R1), and soluble CD163 over 12 weeks, in addition to relationships between variables independent of time point and adjusted for age, sex, and CD4+ count. RESULTS: Thirty-three participants had data from recruitment and at 12 weeks: 55% were male, median age was 36 years, and median baseline CD4+ count was 224 cells/μl. Over the first 12 weeks of ART, there were significant decreases in serum levels of LBP (median change -8.7 μg/ml, p = 0.01), TNF-α receptor 1 (-0.31 ng/ml, p < 0.01), and CRP (-3.5 mg/l, p = 0.02). The change in soluble CD14 level over 12 weeks was positively associated with the change in CRP (p < 0.01) and soluble CD163 (p < 0.01). Pooling data at baseline and 12 weeks, serum LBP was positively associated with CRP (p = 0.01), while endotoxin core IgM was inversely associated with CRP (p = 0.01) and TNF-α receptor 1 (p = 0.04). The Lac/Cr ratio was not associated with any serum biomarkers. CONCLUSIONS: In undernourished HIV-infected adults in Zambia, biomarkers of increased microbial translocation are associated with high levels of systemic inflammation before and after initiation of ART, suggesting that impaired gut immune defenses contribute to innate immune activation in this population