Antiretroviral Therapy In HIV-positive Patients Research Articles

Association of Substance Use with Immunological Response to Antiretroviral Therapy in HIV-Positive Patients from Southwest Ethiopia: A Prospective Observational Study.

Use of psychoactive substances by HIV-positive patients in the course of antiretroviral drug treatment has become a public health problem globally. Substance use (alcohol, nicotine, and khat) during the course of treatment results in interactions with drugs that lead to undesired treatment outcomes. This condition is understudied, and the consequences of substance use among patients on antiretroviral treatment are not well explored. A prospective observational study was conducted among people on antiretroviral therapy (ART) at Jimma University Medical Center in southwest Ethiopia from April 20 to November 27, 2019. Data were collected using the World Health Organization's alcohol, smoking, and substance involvement screening test among adults who have followed antiretroviral therapy for a minimum of 6 months. Logistic regression analysis was done to identify factors associated with immunological response. The inadequate immunological response was defined as patients who were unable to achieve or maintain a CD4 cell count of >350 cells/mm³ after the 6-months of follow-up. Of the 332 patients enrolled, a majority (64.2%) of the respondents were females. The mean (±SD) age of the patients was 38.5 ± 9.5 years. The proportion of participants with a high level of health risk due to alcohol use was 8.4%, while 63.8% of them were non-alcohol users with no health risk. In multivariable logistic regression analysis, moderate and high levels of health risks from alcohol use were significantly associated with increased odds of inadequate immunological response (AOR: 2.9; 95% CI, 1.1-7.4) and (AOR: 4.3; 95% CI, 1.2-14.8), respectively, but the level of health risk from khat and cigarette use showed no association with inadequate immunological response in this study. Moderate and high levels of health risk from alcohol use were independently associated with inadequate immunological response. People living with HIV/AIDS should regularly be screened for and be educated about substance use and its potential negative impact on CD4 cell recovery.

Phone Calls to Retain Research Participants and Determinants of Reachability in an African Setting: Observational Study.

BackgroundLong-term retention of research participants in studies is challenging. In research in sub-Saharan Africa, phone calls are the most frequently used method to distantly engage with participants.ObjectiveWe aimed to get insight into the effectiveness of phone calls to retain contact with participants and evaluated determinants of reachability.MethodsA cross-sectional study was performed using the databases of two randomized controlled trials investigating different kinds of antiretroviral therapy in HIV-positive patients. One trial finished in 2018 (study 1), and the other finished in 2015 (study 2). A random sample size of 200 participants per study was obtained. There were up to 3 phone numbers available per participant collected during the studies. Participants received a maximum of 3 phone calls on every available number on different days and at different times. Voicemails were left, and emails sent wherever possible. We documented how many calls were answered, who answered, as well as after how many attempts participants were reached. To further increase our understanding of reachability, we conducted a short questionnaire assessing factors contributing to reachability. The study was approved by the Research Ethics Committee of the University of Witwatersrand, Johannesburg, South Africa (reference number M1811107).ResultsIn our sample size of n=200 per study, study 1, with a median time of 11 months since the last visit at the research site, had a response rate of 70.5% (141/200) participants while study 2, with a median duration of 55 months since the last visit, had a response rate of 50.0% (100/200; P<.001). In study 1, 61.5% (123/200) of calls were answered directly by the participant while this was 36.0% (72/200) in study 2 (P=.003). The likelihood of reaching a participant decreased with time (odds ratio [OR] 0.73, 95% CI 0.63 to 0.84) for every year since the last face-to-face visit. Having more phone numbers per participant increased reachability (OR 2.32, 95% CI 1.24 to 4.36 for 2 phone numbers and OR 3.03, 95% CI 1.48 to 6.22 for 3 phone numbers compared with 1 number). A total of 141 of 241 reached participants responded to the questionnaire. Of the 93 participants who had changed phone numbers, 5% (50/93) had changed numbers because their phone was stolen. The most preferred method of being contacted was direct calling (128/141) with participants naming this method followed by WhatsApp (69/141).ConclusionsTime since last visit and the number of phone numbers listed were the only determinants of reachability. Longer follow-up time is accompanied with a decrease in reachability by phone while more listed phone numbers increases the likelihood that someone can be reached.Trial RegistrationClinicalTrials.gov NCT02671383; https://clinicaltrials.gov/ct2/show/NCT02671383 and ClinicalTrials.gov NCT02670772; https://clinicaltrials.gov/ct2/show/NCT02670772

Data Mining Technology Enabled Anti Retroviral Therapy (ART) for HIV Positive Patients in Gondar University Hospital, Ethiopia.

It is of interest to discuss the feasibility for data mining technology enabled antiretroviral therapy (ART) for HIV positive patients at the University of Gondar Specialized Teaching Hospital, Ethiopia. The Knowledge Discovery in Databases (KDD), which is in an iterative process where evaluation measures enhanced, is used to prepare the data set for ART in HIV positive patients. A decision tree J48 model that is the implementation of algorithm ID3 (Iterative Dichotomiser 3) developed by the WEKA project team is used in this study. The J48 model was built with pruned and without pruned parameters by selecting two different test modes for 10-fold cross validation with percentage split. Results using J48 pruned decision tree with 10-fold cross validation produces 80.5% prediction precision for ART starter prognosis enabled treatment in clinical settings.

A Prospective Study on Impact of Early Initiation of Antiretroviral Therapy in Human Immunodeficiency Virus-Positive Adults on Immunological Status and Adverse Events.

Introduction:Antiretroviral therapy (ART) is a lifelong commitment for human immunodeficiency virus infection (HIV)-positive patients. The patients may develop early adverse drug reactions (ADRs) during the first 3 months of treatment, especially when they have advanced HIV disease with low CD4 counts.Materials and Methods:The present study was a prospective observational study that took place from January 2017 to July 2017 at ART center, Government Medical College, Amritsar, Punjab, India. The primary objective of the study was to evaluate ADRs to ART and immunological status in HIV-positive patients. The patients received ART regimens as per the National AIDS Control Organization guidelines. The sample included both ART-naïve and ART-experienced HIV-positive patients. The causality of reported ADRs assessed according to the World Health Organization guidelines. The study was conducted after taking approval from the Institutional Ethics Committee, Government Medical College, Amritsar, and informed consent from the patients. Data were analyzed statistically using Chi-square test, and P < 0.05 was considered statistically significant.Results:Out of total 350 patients screened during study period, 84 patients reported with confirmed ADRs. The most widely used treatment regimen was tenofovir + lamivudine + efavirenz (59.52%). Central nervous system (19.05%)-, renal (14.29%)-, and immune reconstitution inflammatory syndrome (14.29%)-related ADRs were mostly reported. The causality assessment revealed insignificant P value (Chi-square = 8.656 and P = 0.07), with 19.05% probable and 80.95% possible ADRs.Conclusions:The CD4 count <200/μl at the initiation of ART and treatment duration <1 year proved to be predictors for ADRs. Early initiation of ART in HIV-positive patients can improve immunological status and decrease in the incidence of ADRs.

Impact of co-infection by hepatitis C virus on immunological and virological response to antiretroviral therapy in HIV-positive patients.

We assessed the effect of co-infection by hepatitis C virus (HCV) on immunological and virological response at 48 weeks from initiation of antiretroviral therapy (ART).We included patients from the Cohort of Spanish HIV Research Network (CoRIS) starting ART between January 2004 and November 2014, had at least 1 CD4 T-cell count and viral load measurements both in the previous 6 months and at 48 (±12) weeks from ART initiation, and HCV serology before ART initiation. We used linear regression for mean differences in CD4 T-cell count increase from ART initiation and logistic regression to estimate odds ratios for virological response.Of 12,239 patients by November 30, 2015, 5070 met inclusion criteria: 4382 (86.4%) HIV mono-infected and 688 (13.6%) HIV/HCV co-infected. Co-infected patients were more likely to have acquired HIV through injecting drugs use (57.4% vs. 1.1%), to be women, older, and Spanish, have a lower educational level, and having started ART with lower CD4 counts and acquired immunodeficiency syndrome. CD4 T-cell count increase at 48 weeks was 229.7 cell/μL in HIV-monoinfected and 161.9 cell/μL in HIV/HCV-coinfected patients. The percentages of patients achieving a virological response at 48 weeks were 87.0% and 78.3% in mono and coinfected patients, respectively. Multivariable analyses showed that at 48 weeks, coinfected patients increased 44.5 (95% confidence interval [CI]: 24.8–64.3) cells/μL less than monoinfected and had lower probability of virological response (odds ratio: 0.62; 95% CI: 0.44–0.88).HIV/HCV-coinfected patients have lower immunological and virological responses at 48 weeks from ART initiation than monoinfected patients.

Differences in response to antiretroviral therapy in HIV-positive patients being treated for tuberculosis in Eastern Europe, Western Europe and Latin America

BackgroundEfavirenz-based antiretroviral therapy (ART) regimens are preferred for treatment of adult HIV-positive patients co-infected with tuberculosis (HIV/TB). Few studies have compared outcomes among HIV/TB patients treated with efavirenz or non-efavirenz containing regimens.MethodsHIV-positive patients aged ≥16 years with a diagnosis of tuberculosis recruited to the TB:HIV study between Jan 1, 2011, and Dec 31, 2013 in 19 countries in Eastern Europe (EE), Western Europe (WE), and Latin America (LA) who received ART concomitantly with TB treatment were included. Patients either received efavirenz-containing ART starting between 15 days prior to, during, or within 90 days after starting tuberculosis treatment, (efavirenz group), or other ART regimens (non-efavirenz group). Patients who started ART more than 90 days after initiation of TB treatment, or who experienced ART interruption of more than 15 days during TB treatment were excluded. We describe rates and factors associated with death, virological suppression, and loss to follow up at 12 months using univariate, multivariate Cox, and marginal structural models to compare the two groups of patients.ResultsOf 965 patients (647 receiving efavirenz-containing ART, and 318 a non-efavirenz regimen) 50% were from EE, 28% from WE, and 22% from LA. Among those not receiving efavirenz-containing ART, regimens mainly contained a ritonavir-boosted protease inhibitor (57%), or raltegravir (22%). At 12 months 1.4% of patients in WE had died, compared to 20% in EE: rates of virological suppression ranged from 21% in EE to 61% in WE. After adjusting for potential confounders, rates of death (adjusted Hazard Ratio; aHR, 95%CI: 1.13, 0.72–1.78), virological suppression (aHR, 95%CI: 0.97, 0.76–1.22), and loss to follow up (aHR, 95%CI: 1.17, 0.81–1.67), were similar in patients treated with efavirenz and non-efavirenz containing ART regimens.ConclusionIn this large, prospective cohort, the response to ART varied significantly across geographical regions, whereas the ART regimen (efavirenz or non-efavirenz containing) did not impact on the proportion of patients who were virologically-suppressed, lost to follow up or dead at 12 months.

Telmisartan reverses antiretroviral-induced adipocyte toxicity and insulin resistance in vitro.

Background:Antiretroviral therapy in HIV-positive patients leads to insulin resistance which is central to the pathogenesis of various metabolic abnormalities and cardiovascular disease seen in this patient group. We have investigated the dose–response relationship of telmisartan, an antihypertensive, on adipocytes in vitro in order to determine whether it may have metabolic beneficial effects.Methods:Using in vitro chronic toxicity models (3T3-F442A murine and primary human adipocytes), we evaluated the effects of different concentrations of telmisartan on adipocyte differentiation and adipogenic gene expression using lipid accumulation assays and real-time polymerase chain reaction, respectively. Adipokine secretion and expression of insulin signalling mediators were evaluated using enzyme-linked immunosorbent assays.Results:Telmisartan partially reversed the deleterious effects of antiretrovirals on adipocyte lipid accumulation, expression of adipogenic regulators (peroxisome proliferator receptor-gamma and lipin 1), adipokine secretion and expression of the insulin signalling mediator pAktSer473. The metabolic effects of telmisartan followed a non-monotonic response with the maximal effect observed at 5 µM in the primary human adipocyte model.Conclusion:Telmisartan has beneficial metabolic effects in adipocytes in vitro, but its potential to reduce antiretroviral-induced cardiometabolic disease in HIV-infected individuals needs to be evaluated in a well-designed adequately powered clinical trial.

Antiretroviral adherence and virological outcomes in HIV-positive patients in Ugu district, KwaZulu-Natal province

Adherence to antiretroviral therapy is crucial to ensure viral suppression. In the scientific community it is widely accepted that an adherence level of at least 90% is necessary to achieve viral suppression. This study uses pharmacy refill records to describe antiretroviral adherence in HIV-positive patients in Ugu District, KwaZulu-Natal, South Africa and to describe pharmacy refill records as reliable monitoring method of antiretroviral therapy. In total, 61 patients’ records were reviewed. Overall, 50 (82%) of the patients achieved an optimum adherence level of at least 90%, whereas 19 (38%) of these patients did not show any related viral suppression. A statistically significant relationship between adherence and viral suppression was not demonstrated. Therefore, pharmacy refill records cannot be recommended as an alternative method of monitoring response to antiretroviral therapy, but laboratory tests including CD4 cell count and or viral load must be combined with the pharmacy refill method for monitoring of antiretroviral therapy in HIV-positive patients.

Raltegravir Plus Nevirapine as Maintenance Antiretroviral Therapy in HIV-Positive Patients: Safety, Efficacy and Pharmacokinetics.

Tolerability, long-term toxicities and selection of resistant variants limit the use and efficacy of antiretroviral drugs in HIV-positive patients. Novel combinations are needed for mantaining long-term control of HIV replication; nevertheless scarse data are available on protease inhibitor-free dual antiretroviral therapies. A multi-centric retrospective study was conducted including HIV-1-positive patients on raltegravir/nevirapine dual regimens. Plasma concentrations were measured as therapeutic drug monitoring while a subset of patients underwent intensive 12-hour pharmacokinetic evaluation. A total of 77 patients switching from successful regimens (76.6% male, median age 52 years) was included; 10 patients on raltegravir plus nevirapine once-daily while 67 subjects on twice-daily schedule. After a median follow-up of 32 months 69 patients (89.6%) were still successfully on treatment. Three patients discontinued for side effects (skin rash or hepatoxicity). Virological failure was observed in five patients (6.5%, 3 on once-daily schedule): in 4 patients (80%) resistance-associated mutations were observed (4 reverse transcriptase, 2 integrase). Triglycerides decreased in patients switching with lipid abnormalities (n=52) and estimated creatinine clearance increased in those with less than 60 ml/min (n=13). Median trough raltegravir and nevirapine concentrations were 83 ng/ml (32-227) and 5460 ng/ml (4037-7221); intensive 12-hours pharmacokinetic parameters (n=7) were similar to published data. Dual therapy with raltegravir/nevirapine in selected patients was highly effective over a 32-month follow up: virological failure was infrequent (6.5%), most common with once-daily schedule (60%) and often associated with the selection of resistance-associated mutations (80%). Twice-daily raltegravir plus nevirapine deserves further clinical evaluation as an NRTI- and PI-sparing strategy in selected patients.

Adherence to Antiretroviral Therapy in HIV-Positive Patients in Ethiopia: Review

Background: Highly active antiretroviral therapy (HAART) offered HIV-positive individuals tremendous lifesustaining benefits. The benefits are sustainable only through optimal adherence. This systematic review was conducted to synthesize the available studies in order to determine average adherence, identify variables associated with adherence and shed light on the design and improvement of adherence studies and interventions. Method: Studies were selected from electronic databases (Pubmed, Hinari, Google scholar) using HAART or Highly active antiretroviral therapy and adherence [Ethiopia] as search terms. Each study was summarized by using format containing: characteristics of the study, sample size, study design and measures of adherence, factors associated with adherence, reasons for missing dose. Result: A total of 17 studies: 16 cross-sectional and 1 prospective study reporting adherence to HAART in Ethiopian HIV-positive patients were identified in our search items. Almost all of adherence to HAART studies conducted in Ethiopia used cross-sectional study design with self-report as adherence measurement. Though from the lowest evidence design the adherence rate in Ethiopia were higher than many developed countries report. Social support is major positive predictor of adherence to HAART while depression and substance abuse were negative predictors’. Conclusion: We demonstrated a better self-reported adherence to HAART in Ethiopian HIV-positive patients. However rate and determinants of HAART in Ethiopian HIV-positive patients are poorly defined. The type of study design used and the use of self-report (subjective measure) in adherence assessment made adherence to HAART unexplored in Ethiopia. Further studies should be conducted using prospective cohort and interventional study design using varying methods of adherence measurement.

The association of pharmacy drug-delivery services with adherence in an urban HIV population†

Abstract Objective The aim of this study was to examine the effect of drug-distribution methods on antiretroviral medication adherence in HIV-positive patients. Methods This was a longitudinal, retrospective study of an independent retail pharmacy providing complementary delivery services. Patients of 18 years of age or older receiving antiretroviral therapy were evaluated from 1 January to 30 June 2004. Patients were included if they had a minimum of one prescription claim for any antiretroviral medication during the study period and received state medication assistance. Using data obtained from computerized pharmacy records a medication possession ratio was calculated to assess adherence measured by pharmacy refill history over 6 months. To assess the consistency of adherence over time a modified medication possession ratio, termed the compliance/non-compliance index (CNI) at each refill, was developed and compared between each group. Key findings Of the 181 patients included in the study, those who had medications delivered had significantly better adherence (90.3% compared with 82.6%, P = 0.001) and CNI value (73.5% compared with 57.9%, P = 0.001) in comparison with those who picked up their medications. After controlling for age, gender, drug class, insurance type and time and distance from the pharmacy, use of medication-delivery services was significantly associated with adherence (P &amp;lt; 0.0001) and CNI score (P = 0.012). Conclusion Complementary medication-delivery services by pharmacies significantly increased adherence at each refill for antiretroviral therapy in HIV-positive patients. Further research is needed on how medication-distribution strategies can be implemented universally and the economic impact on cost of care to increase medication adherence in this high-risk population.

The prognostic value of baseline CD4+ cell count beyond 6 months of antiretroviral therapy in HIV-positive patients in a resource-limited setting

The risk of death is highest in the first few months after initiation of antiretroviral therapy (ART). We examined whether initial CD4 cell count maintains a strong prognostic value among patients with at least 6 months follow-up after the initiation of ART. Observational study of HIV patients in Uganda aged 14 years or older enrolled in 10 clinics across Uganda. Baseline CD4 cell count of patients with more than 6 months of follow-up were stratified into categories (<50, 50-99, 100-149, 150-249, >250 cells/μl). A Kaplan-Meier survival analysis and Cox proportional hazards regression was used to model the associations between baseline CD4 cell count and mortality. Of 22 315 patients, 20 730 (92.8%) had more than 6 months of follow-up. Six hundred and eleven (2.9%) patients died during follow-up and 737 (3.6%) were lost to follow-up. Relative to a baseline CD4 cell counts of less than 50 cells/μl, the adjusted hazard ratios for death were 0.83 [95% confidence interval (CI) 0.67-1.02], 0.71 (95% CI 0.57-0.88), 0.52 (95% CI 0.42-0.64), and 0.55 (95% CI 0.42-0.70) favouring those with baseline CD4 cell counts of 50-99, 100-149, 150-249, and at least 250 cells/μl, respectively. Differing ages and male sex increased the likelihood of mortality. Among patients with more than 6 months of follow-up after initiation of ART, baseline CD4 cell count at initiation still has important prognostic value. This suggests that active engagement and earlier treatment initiation is important for long-term survival.

Assessment of hematological adverse drug reactions to antiretroviral therapy in HIV positive patients at Kasturba Hospital Manipal

Background HIV-infected patients have a higher risk of developing hematological adverse drug reactions (ADRs) than the general population and have a significant impact on patients’ current and future care options. The study was to determine the causality, the incidence rate, severity pattern of occurrence of hematological ADRs associated with highly active antiretroviral therapy in HIV positive patients. Methods Prospective observational study conducted at medicine department, Kasturba Hospital over a period of 6 months. Enrolled HIV positive patients were intensively monitored for hematological ADRs associated with fixed dose of highly active antiretroviral therapy. Causality of adverse drug reactions was assessed by using WHO probability scale and also with Naranjo’s algorithm. Results Monitoring of 70 HIV positive patients (58 males and 12 females) with fixed dose drug combinations of antiretroviral therapy by active pharmacovigilance identified 47.3% cases of anemia, 15.7% cases of leucopenia, 21% cases of pancytopenia, 5.2% of eosinophilia, 10.5% cases of bicytopenia. The incidence rate of hematological adverse drug reactions was 37.9% and most of the reported ADR’s were definitely predictable and preventable. Fifty percent of these ADR’s were lead to hospitalization and seventy percent of these ADR’s were of moderate in severity. Hematological ADRs were highest with Zidovudine + Lamivudine + Nevirapine (68.4%) and Zidovudine + Lamivudine + Efavirenz (31.57%) combinations. Conclusion With the increasing access to use of highly active antiretroviral in India, clinician must focus for routine monitoring of hematological investigations for early detection and prevention of adverse effects associated with highly active antiretroviral therapy. Author details 1Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal – 576 104, Karnataka, India. 2Department of Medicine, Kasturba Medical College, Manipal University, Manipal – 576 104, Karnataka, India.

The association between depression and adherence to antiretroviral therapy in HIV-positive patients, KwaZulu-Natal, South Africa

AbstractBackground: Depressive disorders are associated with poorer health outcomes in people living with human immunodeficiency virus infection and acquired immunodeficiency syndrome (PLHIV) and have been shown to contribute to non-adherence to antiretroviral therapy (ART) in Western contexts. Limited data from developing countries are available. The aim of this study was to explore whether there was an association between depressive symptoms and adherence to ART among PLHIV in KwaZulu-Natal, South Africa.Method: A cross-sectional analytical study was undertaken in a population of HIV-positive patients accessing ART at a government funded, semi-urban clinic in the eThekwini Municipal District, KwaZulu-Natal, South Africa. The tools used to measure depressive symptoms and adherence were the Centre for Epidemiology Studies Depression Scale (CES-D) and clinic-based pill counts, respectively. Socio-demographic and clinical data were collected during interviews and from patient records.Results: Sixty-two per ...

Comparación de los hallazgos clínicos y de supervivencia entre pacientes VIH positivos y VIH negativos con criptococosis meníngea en un hospital de tercer nivel

Introduction: an increased incidence of cryptococcosis has been documented in Colombia, as well as a high prevalence of Cryptococcus gattii in Cucuta. Objective: to analyze patients with cryptococcal meningitis treated at a tertiary care hospital in Cucuta, Colombia, according to the HIV carrier status. Materials and methods: we performed a retrospective review of medical records in which we evaluated the clinical characteristics and outcomes of patients diagnosed with cryptococcal meningitis during the study period of 15 years (1996-2010). Results: we analyzed 90 cases, 63 (70%) HIV positive and 27 (30%) HIV negative. Most HIV-positive patients were young adults (81.0% versus 25.9% of HIV negative patients, p = <0.001). There was a high prevalence of children among HIV-negative patients (29.6 versus 0%, p = <0.001). The male: female ratio was higher in HIV positive patients (3.8 versus 2.4, p = 0.001). No risk factor was found in 88.9% of HIV negative patients. Among the HIV-positive patients, mos of them (76.2%) were not receiving antiretroviral therapy, very few (7.9%) were taking prophylaxis with fuconazole and 68.8% had <100 CD4 + cells. Intracranial hypertension without hydrocephalus (83.3 versus 48.0%, p = 0.009), visual changes (48.1 versus 20.6%, p = 0.02) and extraneural cryptococcosis (22.2 versus 6, 4%, p = 0.06) were more frequent in HIV-negative patients. HIV-negative patients had higher numbers of leukocytes (124.2 /ml versus 43.0 /ml, p = 0.002) and protein (113.6 versus 89.7 mg/dL, p <0.001) in the CSF. C. neoformans var. grubii was isolated more frequently in HIV-positive patients (100 versus 40%, p <0.001) and C. gattii was predominant in HIV-negative (60% versus 0%, p <0.001). CT skull was more frequently abnormal in HIV-positive patients (73.3 versus 22.7%, p <0.001). Most patients in both groups received amphotericin B as primary therapy (96.8% of HIV positive versus 85.2% of HIV negative). The hospital mortality was higher in HIV positive patients (49.2 versus 16.0%, p = 0.004). HIV infection, altered state of consciousness, lack of antiretroviral therapy in HIV-positive patients, seizures and low CSF cellularity were factors of poor prognosis. Neurological sequelae were common in both groups of patients (40.6% vs 32.0%) without significant difference. The probability of survival was significantly higher in HIV-negative patients (82% vs 46%, p = 0.0066). (Acta Med Colomb 2012; 37: 49-61) Conclusions: cryptococcosis has a high morbidity and mortality, especially in HIV positive patients. The prevalence of Cryptococcus gattii in the HIV negative population and in children is very high.

Potential Benefits of Carnitine in HIV-Positive Patients

Carnitine is a nonessential amino acid that has a central role in lipid peroxidation and mitochondrial metabolism. Carnitine deficiency is rare in adult human subjects who have a normal diet and no underlying chronic diseases. Studies have shown that HIV-infected patients are at increased risk of carnitine deficiency due to decreased intake, increased metabolism, gastrointestinal problems, HIV infection itself, concomitant infections, underlying disease, concomitant drugs and antiretroviral therapy. Decreased serum and muscle carnitine content was reported following antiretroviral therapy in HIV-positive patients. The beneficial effects of carnitine on the human immune system, such as prevention of CD4 cell apoptosis, was reported in these patients. Additionally, polyneuropathy, myopathy, lactic acidosis, dyslipidemia and lipodystrophy are complications of antiretroviral therapy that have been proposed to potentially be related to carnitine deficiency and mitochondrial dysfunction. Carnitine may have a significant role in improving some aspects of mitochondrial toxicity induced by an antiretroviral regimen, such as lipodystrophy. Also, there are nearly sufficient data to support the beneficial effects of carnitine in improving the symptoms of lactic acidosis following antiretroviral therapy. According to available data, it is concluded that carnitine may have beneficial effects in the treatment of antiretroviral-induced neuropathy. Most of the evidence supports carnitine supplementation as a treatment strategy rather than prophylaxis for antiretroviralinduced complications. Several studies have shown the prevalence of carnitine deficiency and its role in different aspects of infection and antiretroviral-induced complications in HIV-positive patients, but the probable beneficial effects of carnitine supplementation are not clear in this population. In this review, we have collected and categorized available evidence regarding the potential benefits of carnitine supplementation in HIV-infected individuals.

Comparison Between Lipofilling and a Nonabsorbable Filler for Facial Wasting Rehabilitation in HIV-Positive Patients

Several treatments have been described for facial wasting rehabilitation in HIV-positive patients. In this article, we compare lipofilling and a nonabsorbable filler for facial wasting rehabilitation induced by antiretroviral therapy in HIV-positive patients. This study was conducted as a clinical prospective study. Twenty-three HIV-positive patients affected by facial wasting were treated for facial rehabilitation, between January 2007 and December 2008, at the Head and Neck Department of the II University of Naples. They were divided into 2 groups; the first group was treated with lipofilling (group A), and the second one with the injection of a nonabsorbable filler, Aquamid reconstruction (Contura International A/S, Soeborg, Denmark) (group B).All the patients were HIV-positive, they had been receiving antiretroviral therapy for several years (1.8-6.7 years, 3.2 years on average) and showed clinical signs of facial lipoatrophy. Group A was composed of 14 patients (9 men, 5 women; mean age, 43.7 years), all presenting facial wasting and lipohypertrophied areas of the body. Group B was composed of 9 male patients, 7 presenting only facial wasting, and 2 presenting lipohypertrophied areas of the body (mean age, 44.8 years). Clinical efficacy was assessed independently by the investigator and the patient, 3 months, 6 months, and 1 year after baseline. The main assessment was made by the investigator using the Global Aesthetic Improvement Scale (GAIS) 1 year after baseline; secondary assessment using the GAIS was made by the investigator and the patient 6 months after baseline. There were no major complications. No infections or other complications were observed. According to GAIS ratings, group A (lipofilling) obtained significantly higher ratings than did group B (nonabsorbable filler) after baseline (P < 0.05). We can treat HIV-related lipodistrophy more extensively with lipofilling because, after harvesting the fat graft, other body contouring procedures also can be performed; there is a better aesthetic outcome in facial rehabilitation performed with lipofilling, probably due to the possibility to fill deeper than with nonabsorbable fillers.

HIV/AIDS affects blood and blood product use at Groote Schuur Hospital, Cape Town.

Use of blood and blood products in the medical wards at Groote Schuur Hospital, Cape Town, has increased substantially and significantly increased expenditure. It was suspected that the increased burden of HIV/AIDS could be a contributing factor. Doctors voluntarily completed a structured questionnaire when blood or blood products were utilised over a 3-month period in 2009. Statistical analysis was performed using Microsoft Excel, SPSS and STATISTICA. Of 67 patients analysed, 46 (68.6%) were female, mean age 36.7 (standard deviation (SD) 8.7) years; 21 (31.3%) were male, mean age 39.3 (SD 13.5) years; and 41 (61.2%) were HIV positive, of whom 17 (41.5%) were on antiretroviral therapy (ART). HIV-infected patients were on average 10 years younger than HIV-uninfected patients (p=0.012). Anaemia was the cytopenia necessitating transfusion in 68.7% of cases, but its causes differed between HIV-infected and uninfected patients. The median CD4 count was 203 cells/ml (range 24 - 540) for HIV-infected patients on ART and 74 cells/ml (range 2 - 276) for those not on ART (p=0.012). The mean numbers of packed red cell and fresh-frozen plasma units transfused in the HIV-infected not on ART, HIV-infected on ART and HIV-uninfected groups were 3.3, 2.0 and 1.5 (p=0.013) and 13.5, 2.7 and 1.0 (p.<0.001), respectively. ART in HIV-positive patients markedly decreased transfusion requirements (p<0.001). There was one minor transfusion reaction. HIV/AIDS is a significant factor contributing to the increased use of blood and blood products in the medical wards at Groote Schuur Hospital. Being on ART appeared to reduce the requirement for blood and blood products.

Metabolic changes associated with antiretroviral therapy in HIV-positive patients

OBJECTIVE: To evaluate metabolic changes associated with highly active antiretroviral therapy (HAART) in HIV-positive patients, and to identify risk factors associated. METHODS: Retrospective study that included 110 HIV-positive patients who where on HAART in the city of Porto Alegre (Southern Brazil) between January 2003 and March 2004. Data on demographic variables, cigarette smoking, diabetes mellitus, cholesterol and triglyceride levels, stage of HIV infection, antiretroviral therapy and HCV coinfection were collected. General linear models procedure for repeated measures was used to test the interaction between HAART and HCV coinfection or protease inhibitor treatment. RESULTS: Total cholesterol, triglycerides, and glucose levels significantly increased after receiving HAART (p&lt;0.001 for all variables), but no interaction with protease inhibitors was seen for total cholesterol, glucose and triglyceride levels (interaction treatment*protease inhibitors p=0.741, p=0.784, and p=0.081, respectively). An association between total cholesterol levels and HCV coinfection was found both at baseline and follow-up (effect of HCV coinfection, p=0.011). Glucose levels were increased by HAART (treatment effect, p=0.036), but the effect was associated to HCV coinfection (treatment*HCV effect, p=0.018). Gender, smoking habit, intravenous drug use and age were not significantly associated with cholesterol, triglyceride and glucose changes. CONCLUSIONS: HCV-infected patients at baseline were significantly less likely to develop hypercholesterolemia. The results provide further evidence of the role of HAART for the development of metabolic disturbances.

Roles and Mechanisms of Human Immunodeficiency Virus Protease Inhibitor Ritonavir and Other Anti-Human Immunodeficiency Virus Drugs in Endothelial Dysfunction of Porcine Pulmonary Arteries and Human Pulmonary Artery Endothelial Cells

The objective of this study was to determine the effects of highly active antiretroviral therapy (HAART) drugs on pulmonary endothelial function. Porcine pulmonary arteries or human pulmonary arterial endothelial cells (HPAECs) were incubated with eight HAART drugs [ritonavir, indinavir, lopinavir, zidovudine (AZT), abacavir, stavudine, didanosine (ddI), and lamivudine] individually or in combination [three HAART drugs (3-plex; indinavir, stavudine, and ddI)] at their clinical plasma concentrations for 24 hours. Endothelium-dependent vasorelaxation in response to bradykinin was reduced significantly by the ritonavir in a concentration-dependent manner. Five other HAART drugs (indinavir, lamivudine, abacavir, AZT, and ddI) and the 3-plex significantly also impaired endothelium-dependent vasorelaxation in response to bradykinin. Five HAART drugs (ritonavir, indinavir, lamivudine, abacavir, and AZT) significantly decreased endothelial nitric oxide synthase (eNOS) expression and increased superoxide anion levels in both vessels and HPAECs. Furthermore, both ritonavir and AZT substantially activated ERK2 in HPAECs. Additionally, the antioxidants ginsenoside Rb1 and ginkgolide A effectively reversed HAART drug-induced vasomotor dysfunction and eNOS down-regulation. Inhibition of ERK1/2 also partially blocked ritonavir- and AZT-induced down-regulation of eNOS and vasomotor dysfunction. Thus, HAART drugs significantly impair endothelial functions of porcine pulmonary arteries and HPAECs, which may be mediated by eNOS down-regulation, oxidative stress, and ERK1/2 activation. These findings suggest that HAART drugs may contribute to the high incidence of pulmonary artery hypertension in human immunodeficiency virus-infected patients.