The use of highly active antiretroviral therapy (HAART) has extremely enhanced the clinical outcome of HIV disease with a decrease in mortality and morbidity. However, the inclusion of protease inhibitors (PIs) and nucleoside reverse transcriptase inhibitors (tNRTIs) has strongly been linked to the development of metabolic abnormalities and lipodystrophy. Lipodystrophy is defined by the loss of peripheral subcutaneous fat and central adiposity, mainly in the abdomen, breast and dorsocervical region. These disorders are reported to be cosmetically distressing and socially stigmatizing to many patients leading to decreased adherence to antiretroviral therapy. Metabolic syndrome precedes lipodystrophy leading to increased risk of diabetes and cardiovascular diseases. With a shifted trajectory of HIV/AIDS morbidity from immunodeficiency and opportunistic infections to metabolic complications, clinical management of these patients has therefore become more complex. Currently there are no evidence-based standard guidelines for the management of HIV-associated lipodystrophy. Several pharmacological interventions such as using anti-diabetic, anti-dyslipidemic drugs or hormone replacement therapy have been tried to effectively improve metabolic syndrome and lipodystrophy but have been hampered by low efficacy, drug interactions, or unwanted side-effects. Non-pharmacological interventions including surgical manipulations, dietary and lifestyle modifications have also been tried with limited success. This review focuses on the proposed mechanisms involved in the development of metabolic syndrome and lipodystrophy, and highlights suggested potential therapeutic interventions to prevent lipodystrophy associated with HAART.
BackgroundInsulin resistance, glucose intolerance and overt diabetes are known metabolic complications associated with chronic use of HIV-Protease Inhibitors. Naringin is a grapefruit-derived flavonoid with anti-diabetic, anti-dyslipidemia, anti-inflammatory and anti-oxidant activities.ObjectivesThe study investigated the protective effects of naringin on glucose intolerance and impaired insulin secretion and signaling in vivo.MethodsMale Wistar rats were divided into six groups (n = 6) and were daily orally treated with distilled water {3.0 ml/kg body weight (BW)}, atazanavir (133 mg/kg BW), saquinavir (333 mg/kg BW) with or without naringin (50 mg/kg BW), respectively for 56 days. Body weights and water consumption were recorded daily. Glucose tolerance tests were carried out on day 55 of the treatment and thereafter, the rats were sacrificed by halothane overdose.ResultsAtazanavir (ATV)- or saquinavir (SQV)-treated rats exhibited significant weight loss, polydipsia, elevated Fasting blood glucose (FBG), reduced Fasting Plasma Insulin (FPI) and expression of phosphorylated, Insulin Receptor Substrate-1 (IRS-1) and Akt proteins, hepatic and pancreatic glucokinase levels, and also increasing pancreatic caspase-3 and -9 as well as UCP2 protein expressions compared to controls, respectively. These effects were completely reversed by naringin treatment.ConclusionNaringin prevents PI-induced glucose intolerance and impairment of insulin signaling and as nutritional supplement it could therefore alleviate metabolic complications associated with antiretroviral therapy.
Background Adverse drug reactions (ADRs) remain a global public health concern. Pharmacovigilance practises are essential in ensuring patients safety and post drug marketing surveillance. This study aimed to describe practices, perceptions and barriers towards ADR reporting practices amongst People Living with HIV/AIDS (PLWHA), who are on Highly Active Anti-Retroviral Therapy (HAART) and their doctors. Methods The study took place at 3 public sector hospitals. The first phase of the study was a quantitative cross-sectional study using a closed ended questionnaire that was given to PLWHA. Phase two was a retrospective analysis of these patients’ medical files, whilst phase 3 included a descriptive statistics to determine the frequencies and percentages for variables such as ADR reporting practices by doctors. Results Spontaneous reporting, was evident with 202 patients (48%) indicating that they reported experiencing ADRs to their doctors. Ten doctors (77%) indicated that they received PV training. Eight (62%) doctors indicated that the completed ADR reporting forms were submitted to the pharmacy manager in the hospital for forwarding to the regulatory authority, with 2 (15%) indicating that they submitted directly to the South African Health Products Regulatory Authority. Four (31%) doctors stated that the system of reporting ADRs is ineffective with the majority of the doctors 12 (92%) responding that the reporting of ADRs is very important/critical. A barrier cited by 4 patients (0.9%) for non-reporting of their ADRs was transport cost. Whilst doctors' barriers included reporting being time consuming (31%), and a lack of availability of reporting forms (31%). Conclusion Patients and doctors are reporting ADRs but more education and easier reporting process should be available to strengthen the knowledge and reporting of ADRs. Doctors agree that it is critical to report ADRs. Electronic reporting should be encouraged to lessen the time it takes to report ADRs.
Introduction even though Highly Active Antiretroviral Therapy (HAART) is effective in managing Human Immuno-deficiency Virus (HIV) infection, it is not without its adverse drug effects (ADE) and or adverse drug reactions (ADRs). The study of ADRs associated with HAART in hospitals and clinics is crucial in gauging the burden of the severity of morbidity and mortality in such facilities, hence the reporting of such ADRs is important. Methods the study was divided into 2 phases: the 1 st phase entailed collecting data from HIV infected patients using a questionnaire on ADR experienced, whilst the 2 nd phase was a retrospective analysis of respective patients´ medical files to record if an ADR was experienced. Three antiretroviral clinics linked to public sector facilities in EThekwini Metro, Kwa-Zulu Natal were the study sites. Results seventy-two percent of patients reported at least one ADR after HAART initiation. Skin rash (11%) was the most commonly stated ADR by patients, whilst anemia (29%) and cardiovascular disease (23%) were the most commonly recorded ADRs on the patients´ medical files. Of those patients who reported ADRs, 57% were on the first line regimen consisting of Tenofovir, Emtricitabine and Efavirenz. Thirty-six patients reported that they were admitted to hospitals due to ADRs, however none resulted in death. These ADRs were experienced by patients on different regimens, with 10 admissions from the same regimen. Conclusion adverse drug reactions were experienced by South African patients, however the reporting of ADRs by patients were inconsistent with what was recorded on their medical files.
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