Use Of Highly Active Antiretroviral Therapy Research Articles

HAART in hand: The change in Kaposi's sarcoma presentation in KwaZulu-Natal, South Africa.

HIV/AIDS-related Kaposi's sarcoma (HIV-KS) is a public health problem in South Africa (SA). It is AIDS defining. There have been no studies evaluating its prevalence since the national roll-out of highly active antiretroviral therapy (HAART). To evaluate the effect of HAART on the disease profile of HIV-KS in KwaZulu-Natal Province (KZN), SA. Charts of patients with histologically confirmed HIV-KS were reviewed at an oncology clinic in KZN. The significance of associations of HAART with age, gender, CD4 count, urban/rural residence, fungating lesions, ulceration and lymphoedema, and treatment delay, was determined by t-tests for normally distributed continuous variables and χ2 tests for categorical variables. Logistic regression models were used to analyse the association of HAART with CD4 count. Of 198 patients, 194 were documented as HIV-positive; 168 (86.6%) were on HAART at the time of their KS diagnosis. The mean CD4 count of 266 cells/μL was higher than that in previous studies at this site. The mean age at presentation was 36.6 (standard deviation 10.1) years. Females presented at a younger mean age than males (p<0.001). The mean age of females on HAART was 34.7 years and that of males 39.0 years (p=0.003). HAART-naive patients were three times more likely than those receiving HAART (15.4% v. 4.8%) to have visceral involvement (p=0.03). HAART use has resulted in outcome improvement. Mean age at presentation has increased in the group as a whole and for females in particular. The trend in mean CD4 counts has shown positive growth. Females no longer shoulder a disproportionate burden of disease.

Drug-Drug Interactions Based on Pharmacogenetic Profile between Highly Active Antiretroviral Therapy and Antiblastic Chemotherapy in Cancer Patients with HIV Infection.

The introduction of Highly Active Antiretroviral Therapy (HAART) into clinical practice has dramatically changed the natural approach of HIV-related cancers. Several studies have shown that intensive antiblastic chemotherapy (AC) is feasible in HIV-infected patients with cancer, and that the outcome is similar to that of HIV-negative patients receiving the same AC regimens. However, the concomitant use of HAART and AC can result in drug accumulation or possible toxicity with consequent decreased efficacy of one or both classes of drugs. In fact, many AC agents are preferentially metabolized by CYP450 and drug–drug interactions (DDIs) with HAART are common. Therefore, it is important that HIV patients with cancer in HAART receiving AC treatment at the same time receive an individualized cancer management plan based on their liver and renal functions, their level of bone marrow suppression, their mitochondrial dysfunction, and their genotype profile. The rationale of this review is to summarize the existing data on the impact of HAART on the clinical management of cancer patients with HIV/AIDS and DDIs between antiretrovirals and AC. In addition, in order to maximize the efficacy of antiblastic therapy and minimize the risk of drug–drug interaction, a useful list of pharmacogenomic markers is provided.

Nitric oxide levels in HIV-infected, untreated patients and HIV-infected patients receiving antiretroviral therapy.

The role of nitric oxide (NO) in HIV infection is ambiguous; controversy exists around whether the levels of serum NO are increased or decreased in HIV-infected patients. Thus, it is necessary to reassess NO levels in HIV-infected patients. The aim of this study was to investigate the nitrite/nitrate metabolite (NOx) levels in HIV-infected untreated patients and in HIV-infected patients receiving highly active antiretroviral therapy (HAART), compared with HIV-uninfected individuals (control group). The HIV-infected patients enrolled in this study had been receiving HAART for at least 6 months (HIV-treated) or had not received HAART for at least 6 months (HIV-untreated group). New recommendations encourage initiating treatment in HIV-infected adults at a CD4 cell count of 500 cells/mm(3) or less. We also investigated whether levels of NOx were associated with immunophenotypic characteristic of HIV-infected patients. Our results showed a statistically significant increase in NOx levels in the HIV-untreated group (164.0 ± 166.6 μmol/L), compared with both the control (98.9 ± 59.4 μmol/L) and HIV-treated group (71.7 ± 53.3 μmol/L). Multiple regression analysis showed that the differences in NOx level were independent of gender, liver enzyme level, lipid measurement, and hematological parameters. In addition, a lower CD4/CD8 ratio was associated with higher NOx levels in HIV-infected patients. The results further revealed that NOx levels were increased in HIV infection, and that derangement of immune system function was associated with increased NO levels. The levels of NOx were found to decline with the use of HAART, which may contribute to cardiovascular disease in HIV-infected patients.

Prevalence and correlates of probable common mental disorders in a population with high prevalence of HIV in Zimbabwe.

BackgroundIn 2014 close to 10 million people living with HIV (PLWH) in sub-Saharan Africa were on highly active anti-retroviral therapy (HAART). The incidence of non-communicable diseases has increased markedly in PLWH as mortality is reduced due to use of HAART. Common mental disorders (CMD) are highly prevalent in PLWH. We aimed to determine factors associated with probable CMD and depression, assessed by 2 locally validated screening tools in a population with high prevalence of HIV in Harare, Zimbabwe.MethodsWe carried out a cross-sectional survey of a systematic random sample of patients utilizing the largest primary health care facility in Harare. Adults aged ≥18 years attending over a 2-week period were eligible, excluding those who were critically ill or unable to give written informed consent. Two locally validated screening tools the Shona symptom questionnaire (SSQ-14) and the Patient Health Questionnaire (PHQ-9) were administered by trained research assistants to identify probable CMD and depression.ResultsOf the 264 participants, 165 (62.5 %) were PLWH, and 92 % of these were on HAART. The prevalence of probable CMD (SSQ14 > = 9) and depression (PHQ9 > = 11) were higher among people living with HIV than among those without HIV (67.9 and 68.5 % vs 51.4 and 47.2 % respectively). Multivariable analysis showed female gender and recent negative life events to be associated with probable CMD and depression among PLWH (gender: OR = 2.32 95 % CI:1.07–5.05; negative life events: OR = 4.14; 95 % CI 1.17–14.49) and with depression (gender: OR = 1.84 95 % CI:0.85–4.02; negative life events: OR = 4.93.; 95 % CI 1.31–18.50)ConclusionElevated scores on self-report measures for CMD and depression are highly prevalent in this high HIV prevalence population. There is need to integrate packages of care for CMD and depression in existing primary health care programs for HIV/AIDS.

Appropriate adherence to antiretroviral therapy in the Alto Paranaiba, Minas Gerais, Brazil

OBJECTIVE: This study aimed to assess the adherence to antiretroviral treatment of HIV-infected patients at the Centro de Referencia Viva Vida in Patos de Minas, Minas Gerais, Brazil. METHODS: As a descriptive and quantitative retrospective cross-sectional study, we enlisted HIV-infected patients, over 18 years old, users of highly active antiretroviral therapy (HAART) from June 2011 to July 2012. Data on withdrawal of medication and viral load were collected from the drug logistics management information system and from the medical records, respectively. Sociodemographic and data regarding HAART use were collected manually, using appropriate forms. The CEAT-HIV questionnaire was filled out by140 patients who were using HAART. For data analysis, we used ANOVA and Kruskal-Wallis Rank Sum tests, complemented with Dunn's test, when necessary. P < 0.05 was adopted as the limit for significance. RESULTS: The age group 18-30 years presented lower adherence compared with the group aged over 60 years (p = 0.047). Regarding the HAART usage time, there was no difference between groups (p = 0.515). For the number of pills taken per day, there was greater adherence for patients taking up to 4 pills compared to those taking 5-10 pills daily (p = 0.037). Concerning adherence measured by the CEAT-HIV questionnaire, there was strict/rigorous adherence in 57.8% of patients, with 21.4% of the patients classified as having adequate adherence, according to the data on dispensation of medicines. CONCLUSION: Patients participating in HAART and taking up to 4 pills had good adherence to treatment.

Highly active antiretroviral therapy reduces pulmonary IL-8 in HIV-positive women smokers.

Increased levels of the proinflammatory cytokine IL-8 are detected in the sputum of patients with chronic obstructive pulmonary disease (COPD) and during the pathological pulmonary manifestations of HIV infection : To explore a potential interrelationship between smoking, highly active antiretroviral therapy (HAART) and HIV immune status, we collected sputum samples, along with complete pulmonary function tests from groups of HIV-infected women smokers who were either on or off HAART. Analysis of the patient's sputum for cell count along with quantitative measures of IL-8 was performed and correlated with concurrent assessment of pulmonary function test (PFT). We found that HIV-positive smokers had decreased measurements on PFT of the diffusing capacity of the lung for carbon monoxide (D(LCO)) compared to standard reference values that did not differ with HAART usage. HAART, when controlled for CD4, showed a suppressive effect on the levels of pro inflammatory cytokine IL-8 in sputum. We conclude that in the era of HAART, HIV along with concurrent tobacco smoking is associated with declines in PFT in HIV-infected women. The use of HAART in patients appears to mitigate the increases in IL-8 levels in relation to immune status based on CD4 count.

Risk Factors of Cardiovascular Diseases in HIV/AIDS Patients on HAART.

Background : The introduction and widespread use of combination antiretroviral therapy referred to as highly active antiretroviral therapy (HAART) in the mid 1990’s, has led HIV-infected individuals to experience a dramatic decline in immunodeficiency-related events and death. There is growing concern on metabolic complications associated with HIV and HAART which may increase cardiovascular risk and disease. The aim of this study was to investigate the cardiovascular risk profile of HIV/AIDS patients receiving HAART and those not receiving HAART at HIV/AIDS treatment centres in the South West Region of Cameroon.Methods : Consenting participants, who had been receiving HAART, were compared with HAART naive participants. A questionnaire was administered; anthropometric and blood pressure measurements were recorded under standard conditions. Blood samples were obtained for the determination of plasma glucose and lipid levels.Results : Two hundred and fifteen participants were recruited, 160 (74.4%) were on HAART and 55 (25.6%) were HAART naive. Among the individual lipid abnormalities, increased total cholesterol was the most prevalent (40.0%). Participants on HAART were significantly about 8 times at risk of developing hypercholesterolemia when compared to the HAART inexperienced group (OR 8.17; 95% CI: 3.31-20.14; p<0.001). Hypertension had a prevalence of 25.6% (95% CI: 15.3%-35.9%) and was about 2 times significantly higher in the HAART treated than the HAART untreated group (p=0.033). The prevalence of low HDL-c was significantly higher in males (24.1%) compared to females (11.2%) (p=0.0196). Many females (27.3%) were obese compared to males (7.4%) (p=0.0043). HAART use and treatment duration of more than five years were significantly associated with higher prevalence of CVD risk factors.Conclusion : HAART treatment was associated with significantly higher prevalence of hypercholesterolemia, increased LDL-c and hypertension, hence the risk of cardiovascular diseases.

Vertical transmission rate of human immunodeficiency virus amid formula-fed infants in a resource-constrained tertiary hospital in Jos, Nigeria

Background: Human Immunodeficiency Virus (HIV) can be transmitted from infected mother to her baby. Objective: To assess transmission rate of HIV from seropositive mothers on highly active anti-retroviral therapy (HAART) to their formula-fed babies. Method: A cross-sectional study of 65 paired mothers on HAART and their formula-fed babies was carried out. Polymerase chain reaction-deoxyribonucleic acid (PCR-DNA) of the babies was done at six weeks of age. Epi info was used to analyse data. Results: Mean age of mothers was 30.26 ± 0.5 years. About 73.8% of the paired mothers were diagnosed with HIV before their current pregnancies and 69.2% initiated HAART before their current pregnancies. Duration of HAART use was between three months and two years. Modes of deliveries were caesarean section (15.4%) and vaginal route (84.6%). Only one (1.5%) of the babies was positive to PCR-DNA test at six weeks of age. There was no statistically significant association between the baby’s PCR-DNA at six weeks of age and the mode of delivery (OR-0.0047, CI-95%, Fisher Exact=0.8461) as well as between the time of initiation of HAART by the paired mothers and the paired baby’s PCR-DNA results (RR-0.9778, CI-95%, Fisher Exact=0.6923). Conclusions: Overall mother to child transmission (MTCT) rate in this study was 1.5%. Use of HAART for more than three months, irrespective of delivery route, is capable of significantly reducing MTCT of HIV even in resource-constrained settings. Sri Lanka Journal of Child Health, 2015; 44(3): 153-157

Incidence Rate and Risk Factors for Contralateral Eye Involvement among Patients with AIDS and Cytomegalovirus Retinitis Treated with Local Therapy

Purpose: To calculate the incidence of, and to identify the risk factors for developing contralateral eye involvement among patients with AIDS and unilateral cytomegalovirus retinitis (CMV retinitis), who were treated, in the era of highly-active antiretroviral therapy (HAART), with repetitive intravitreal ganciclovir injections.Materials and Methods: The clinical records of 119 patients were included. The main outcome measurement was the occurrence of contralateral eye involvement.Results: Over a mean follow-up period of 1.6 years, the overall incidence rate of contralateral involvement was 0.17/person-year. The cumulative incidence of contralateral involvement at 6 months and 1 year was 23.8% and 28.4%, respectively. Receiving HAART at the visit before the event was associated with a decreased risk of developing contralateral retinitis (hazard ratio [HR] = 0.26, P = 0.002).Conclusions: The use of HAART, associated with subsequent immune recovery, significantly reduced the incidence of contralateral eye involvement by approximately 75% among patients in our setting.

Effect of mother to child transmission intervention strategies and clinical, hematological, immunological characteristics in children born to HIV-1 infected mothers in India

We evaluated the effect of interventions for preventing mother to child transmission (MTCT) of human immunod- eficiency virus type 1 (HIV-1) infection and studied the effect of highly active antiretroviral therapy (HAART) on clinical, hematological and immunological characteristics in a cohort of HIV-1 seropositive infants. We included 399 HIV exposed infants from July 2002 to October 2008. Of these, 49 infants received MTCT prophylaxis (intervention group); while 350 infants were born to mothers received no prophylactic measures and comprised the non-intervention group. DNA polymerase chain reaction was done to confirm the HIV status before 18 months and enzyme-linked immunosorbent assay (ELISA) beyond 18 months of age. Children found to be HIV-1 positive were started on anti retroviral treatment (ART) as per guidelines, and followed up after 10 months interval. Hemoglobin levels and CD4 counts were also recorded at each visit. A significant difference was observed in MTCT rates between intervention and non-intervention groups (P = 0.001). Antiretroviral therapy was started for 23 of the 94 HIV-1 infected children after recording baseline clinical, hematological and immunological parameters. Hemoglobin levels increased significantly after initiation of HAART (pre vs. months post zidovudine: P = 0.002). The CD4 counts, CD4% and CD4/CD8 ratio improved significantly post therapy in all children. (P = 0.0001, P = 0.0001, and P = 0.0001 respectively). Identification of maternal HIV infection at an early stage is important to maximize option and allow optimal timing of therapeutic strategies to prevent MTCT of HIV-1 infection. The early use of HAART improves clinical, hematological and immunological characteristics, delays the progression of disease and improves survival in HIV-1-infected children.

Oral innate immunity in HIV infection in HAART era.

Oral innate immunity, an important component in host defense and immune surveillance in the oral cavity, plays a crucial role in the regulation of oral health. As part of the innate immune system, epithelial cells lining oral mucosal surfaces not only provide a physical barrier but also produce different antimicrobial peptides, including human β-defensins (hBDs), secretory leukocyte protease inhibitor (SLPI), and various cytokines. These innate immune mediators help in maintaining oral homeostasis. When they are impaired either by local or systemic causes, various oral infections and malignancies may be developed. Human immunodeficiency virus (HIV) infection and other co-infections appear to have both direct and indirect effects on systemic and local innate immunity leading to the development of oral opportunistic infections and malignancies. Highly active antiretroviral therapy (HAART), the standard treatment of HIV infection, contributed to a global reduction of HIV-associated oral lesions. However, prolonged use of HAART may lead to adverse effects on the oral innate immunity resulting in the relapse of oral lesions. This review article focused on the roles of oral innate immunity in HIV infection in HAART era. The following five key questions were addressed: (i) What are the roles of oral innate immunity in health and disease?, (ii) What are the effects of HIV infection on oral innate immunity?, (iii) What are the roles of oral innate immunity against other co-infections?, (iv) What are the effects of HAART on oral innate immunity?, and (v) Is oral innate immunity enhanced by HAART?

Herb–drug interaction between an anti-HIV Chinese herbal SH formula and atazanavir in vitro and in vivo

Ethnopharmacological relevanceWith the prevalent use of highly active antiretroviral therapy (HAART) for AIDS patients since 1996, the mortality of HIV/AIDS patients has been remarkably decreased. With long-term use of HAART, drug resistance and side effects of antiretrovirals have been frequently reported, which not only reduce the efficacy, but also decreases the tolerance of patients. Traditional herbal medicine has become more popular among HIV/AIDS patients as adjuvant therapy to reduce these adverse effects of HAART. SH formula is a Chinese herbal formula consisting of five traditional Chinese herbs including Morus alba L., Glycyrrhiza glabra L., Artemisia capillaris Thumb., Astragalus membranaceus Bge., and Carthamus tinctorius L. SH formula is clinically used for HIV treatment in Thailand. However, the possible pharmacokinetic interactions between these Chinese herbs and antiretroviral drugs have not been well documented. The aim of this study was to investigate the potential herb-drug interaction between SH herbal Chinese formula and the antiretroviral drug atazanavir (ATV). Materials and methodsThe combination effect of SH formula and ATV on HIV protease was studied in HIV-1 protease inhibition assay in vitro. The inhibition of SH formula on rat CYP3A2 was assessed by detecting the formation of 1′–OH midazolam from midazolam in rat liver microsomes in vitro. The in vivo pharmacokinetic interaction between SH formula and ATV was investigated by measuring time-dependent plasma concentrations of ATV in male Sprague–Dawley rats with liquid chromatography–mass spectrometry. ResultsThrough the in vitro HIV-1 protease inhibition assay, combination of SH formula (41.7–166.7μg/ml) and ATV (16.7–33.3ng/ml) showed additive inhibition on HIV-1 protease activity than SH formula or ATV used alone. In vitro incubation assay indicated that SH formula showed a weak inhibition (IC50=231.2µg/ml; Ki=98.2µg/ml) on CYP3A2 activity in rat liver microsomes. In vivo pharmacokinetic study demonstrated that SH formula did not affect the metabolism of ATV in rats. ConclusionsOur study demonstrated for the first time that there is no metabolism-based herb-drug interaction between SH formula and ATV in rats, but this combination enhances the inhibition potentials against HIV protease activity. This observation may support the combinational use of anti-HIV treatment in human.

Prevalence of and Risk Factors for Lipoatrophy in Patients with HIV Infection in Nigeria.

Background. Although the association between lipoatrophy and highly active antiretroviral therapy (HAART) is well known, other nondrug factors may be associated with lipoatrophy in people living with HIV/AIDS (PLWHA). There are no reports of lipoatrophy from Nigeria, a country with the second largest number of PLWHA. We aimed to determine the prevalence, characteristics, and factors associated with lipoatrophy in a cohort of patients attending the HIV clinic in Lagos University Teaching Hospital, Nigeria. Methods. Two hundred and eighty-eight patients with HIV infection were recruited for the study. The study protocol involved administration of a questionnaire, targeted physical examination (including anthropometric indices and skin fold thickness), and bioelectrical impedance analysis measurements. Lipoatrophy was defined clinically. Results. Lipoatrophy was present in 75 (26.0%) persons. It was associated with lower body circumferences, skin fold thicknesses, and lower % body fat with preservation of skeletal muscle mass (all P < 0.05). Male gender and HAART use were the factors associated with lipoatrophy on multivariate analysis (P < 0.05). Conclusion. Lipoatrophy is frequently encountered in patients with HIV infection in Nigeria, with HAART use conferring an added factor in its development. There is need for more physician and patient awareness of this condition.

Assessment of Metabolic syndrome among adult human immunodeficiency virus/acquired immunodeficiency syndrome patients in a tertiary health facility in Southeast Nigeria

Context: Metabolic syndrome (MS) on the background of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome has not been reported from Southeast Nigeria. Aims: We sought to determine the prevalence of MS among HIV-infected Nigerians seen at the Federal Medical Centre, Umuahia, its correlation with highly active antiretroviral therapy (HAART) and other demographics. A total of 105 HAART-treated and 60 HAART-naοve patients were reviewed. Settings and Design: This study was cross-sectional, and the data were prospectively collected. Methodology: They were matched for sex and age. Anthropometric data including current weight and height, waist circumference, blood pressure, as well as blood lipids and fasting glucose were measured. MS was determined using National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III criteria. Statistical Analysis Used: SPSS version 17.0 (Chicago IL, USA) was used for data collection and analysis. Results: There was 24.3% overall prevalence of MS in the study population, 28.8% in HAART-treated, and 25% in HAART-naive patients (P = 0.554). The prevalence of MS components was as follows: hypertension (49.7%), impaired fasting glucose (9.62%), hypertriglyceridemia (32.0%), low high-density lipoprotein-cholesterol (44.2%), and central obesity (22.1%). Correlation of MS with female gender was highly significant (r = −0.306, P = 0.002). Conclusions: MS was not significantly associated with the use of HAART in our patients but correlated with female gender.

Impact of antiretroviral therapy on lipid metabolism of human immunodeficiency virus-infected patients: Old and new drugs.

For human immunodeficiency virus (HIV)-infected patients, the 1990s were marked by the introduction of highly active antiretroviral therapy (HAART) representing a new perspective of life for these patients. The use of HAART was shown to effectively suppress the replication of HIV-1 and dramatically reduce mortality and morbidity, which led to a better and longer quality of life for HIV-1-infected patients. Apart from the substantial benefits that result from the use of various HAART regimens, laboratory and clinical experience has shown that HAART can induce severe and considerable adverse effects related to metabolic complications of lipid metabolism, characterized by signs of lipodystrophy, insulin resistance, central adiposity, dyslipidemia, increased risk of cardiovascular disease and even an increased risk of atherosclerosis. New drugs are being studied, new therapeutic strategies are being implemented, and the use of statins, fibrates, and inhibitors of intestinal cholesterol absorption have been effective alternatives. Changes in diet and lifestyle have also shown satisfactory results.

Individualization of antiretroviral therapy--pharmacogenomic aspect.

Combination therapy with three drug regimens for human immunodeficiency virus (HIV) infection significantly suppresses the viral replication. However, this therapeutic impact is restricted by adverse drug events and response in terms of short and long term efficacy. There are multiple factors involved in different responses to antiretrovirals (ARVs) such as age, body weight, disease status, diet and heredity. Pharmacogenomics deals with individual genetic make-up and its role in drug efficacy and toxicity. In depth genetic research has provided evidence to predict the risk of developing certain toxicities for which personalized screening and surveillance protocols may be developed to prevent side effects. Here we describe the use of pharmacogenomics for optimal use of HAART (highly active antiretroviral therapy).

Long-term effect of Haart on biochemical profiles of HIV/AIDS patients in a tertiary health facility in Benin city, Nigeria

Purpose: To assess the long-term effect of highly active antiretroviral therapy (HAART) on biochemical parameters of HIV-infected patients in University of Benin Teaching Hospital (UBTH), Benin City, Nigeria.Methods: HIV/AIDS patients on HAART for 2 - 8 years (297), those who were not on HAART (112, positive control), and healthy subjects (103, negative control) were recruited in the Infectious Diseases Clinic (IDC) of UBTH. Their sera were assayed for biochemical parameters. WHOQoL bref instrument was used to assess patients’ Quality of life (QoL).Results: Patients who have been on HAART had significantly elevated ALT and AST levels (p &lt; 0.001) but mild liver toxicity. QoL of these patients was not significantly different from that of the healthy controls. The levels of Na+ (133.4 ± 5.2 mmol/l), K+ (3.6 ± 0.4 mmol/l) and Cl- (101.3 ± 4.0 mmol/l) were significantly lower in patients on HAART than those of the positive (137.5 ± 5.1, 3.9 ± 0.5, 104.3 ± 5.7 mmol/l respectively, p &lt; 0.001). Also, levels of creatinine (0.8 ± 0.2 mg/dl), TBil (0.5 ± 0.2 mg/dl), and CB (0.3 ± 0.5 mg/dl) were significantly higher in patients on HAART than those of either the positive (0.7 ± 0.3, 0.4 ± 0.2, 0.2 ± 0.1 mg/dl) or negative (0.7 ± 0.3, 0.3 ± 0.1, 0.2 ± 0.1 mg/dl) controls respectively (p &lt; 0.001).Conclusion: Treatment with HAART for 2 - 8 years may not produce severe hepatotoxicity in HIV/AIDS patient though mild liver toxicity should be expected. The patients’ QoL was not negatively affected by the use of HAART for 2 - 8 years.Keywords: Biochemical parameters, HIV/AIDS, Long-term HAART, Quality of life (QoL).

Role of Oxidative Stress in HIV-1-Associated Neurocognitive Disorder and Protection by Gene Delivery of Antioxidant Enzymes.

HIV encephalopathy covers a range of HIV-1-related brain dysfunction. In the Central Nervous System (CNS), it is largely impervious to Highly Active AntiRetroviral Therapy (HAART). As survival with chronic HIV-1 infection improves, the number of people harboring the virus in their CNS increases. Neurodegenerative and neuroinflammatory changes may continue despite the use of HAART. Neurons themselves are rarely infected by HIV-1, but HIV-1 infects resident microglia, periventricular macrophages, leading to increased production of cytokines and to release of HIV-1 proteins, the most likely neurotoxins, among which are the envelope glycoprotein gp120 and HIV-1 trans-acting protein Tat. Gp120 and Tat induce oxidative stress in the brain, leading to neuronal apoptosis/death. We review here the role of oxidative stress in animal models of HIV-1 Associated Neurocognitive Disorder (HAND) and in patients with HAND. Different therapeutic approaches, including clinical trials, have been used to mitigate oxidative stress in HAND. We used SV40 vectors for gene delivery of antioxidant enzymes, Cu/Zn superoxide dismutase (SOD1), or glutathione peroxidase (GPx1) into the rat caudate putamen (CP). Intracerebral injection of SV (SOD1) or SV (GPx1) protects neurons from apoptosis caused by subsequent inoculation of gp120 and Tat at the same location. Vector administration into the lateral ventricle or cisterna magna protects from intra-CP gp120-induced neurotoxicity comparably to intra-CP vector administration. These models should provide a better understanding of the pathogenesis of HIV-1 in the brain as well as offer new therapeutic avenues.

Highly active antiretroviral therapy-related hepatotoxicity in human immunodeficiency virus and hepatitis C virus co-infected patients with advanced liver fibrosis in Taiwan.

The prevalence of patients co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is higher in Taiwan than in Western countries. This study aimed to analyze the frequency and risk factors for highly active antiretroviral therapy (HAART)-related liver toxicity in patients co-infected with HIV and HCV with advanced liver fibrosis in Taiwan. This retrospective cohort study included 228 HAART-experienced and HAART-naïve patients who were co-infected with HIV and HCV from January 2013 to December 2013 in Taiwan. Transaminase elevation (TE) was defined by grades. Fibrosis 4 score and aspartate-to-platelet ratio index were used to evaluate liver fibrosis. Cox proportional hazard regression model was used to analyze the risk factors for time to TE events. A total of 228 patients were included. Only two episodes (1.28%) of high-grade TE were observed. The overall prevalence rate of TE was 16%, and the incidence was 1.38 cases/100 patient-months. Two predictive factors of TE were the initiation of HAART during the study period and CD4 cell count less than 350cells/mm(3). Subgroup analysis showed that HAART improved liver fibrosis status in patients who had advanced liver fibrosis at baseline (p=0.033). The frequency of HAART-related TE in HIV and HCV co-infected patients in Taiwan was much lower than that observed in previous studies. Pre-existing advanced liver fibrosis had no influence on the frequency of TE. The use of HAART showed benefits on liver fibrosis progression in patients with underlying advanced liver fibrosis.

Assessing the impact of HAART on the incidence of defining and non-defining AIDS cancers among patients with HIV/AIDS: a systematic review.

After highly active antiretroviral therapy (HAART) became widespread, several studies demonstrated changes in the incidence of defining and non-defining AIDS cancers among HIV/AIDS patients. We conducted a systematic review of observational studies evaluating the incidence of malignancies before and after the introduction of HAART in people with HIV/AIDS. Eligible studies were searched up to December 2012 in the following databases: Pubmed, Embase, Scielo, Cancerlit and Google Scholar. In this study, we determined the cancer risk ratio by comparing the pre- and post-HAART eras. Twenty-one relevant articles were found, involving more than 600,000 people with HIV/AIDS and 10,891 new cases of cancers. The risk for the development of an AIDS-defining cancer decreased after the introduction of HAART: Kaposi's sarcoma (RR=0.30, 95% CI: 0.28-0.33) and non-Hodgkin's lymphoma (RR=0.52, 95% CI: 0.48-0.56), in contrast to invasive cervical cancer (RR=1.46, 95% CI: 1.09-1.94). Among the non-AIDS-defining cancers, the overall risk increased after the introduction of HAART (RR=2.00, 95% CI: 1.79-2.23). The incidence of AIDS-defining cancers decreased and the incidence of non-AIDS-defining cancers increased after the early use of HAART, probably due to better control of viral replication, increased immunity and increased survival provided by new drugs.