• HIV
• antiretroviral therapy
• hepatic metabolism
• latest-generation ARV therapies
• liver function
• liver metabolic health
• old-generation ARV therapies

• HIV-1 infection
• antiretroviral therapy
• liver damage

• clinical treatment
• coinfection
• hepatitis B virus
• human immunodeficiency virus
• liver disease

This study applied a structural equation modeling (SEM) to evaluate the role of substance use (alcohol, smoking, and trado-medicine use) to changes in the liver enzymes (AST, ALT, and ALP) levels in HIV-infected adult patients on a highly active antiretroviral treatment (HAART) for not <1 year. The study was a cross-sectional, part of a randomized comparative trial (Ref: UPH/CEREMAD/REC/19), involving 129 (46 males and 83 females) HIV-infected adult patients. Liver enzyme levels were determined from analyzed blood samples using the Clinical Chemistry Analyser (VS10) manufactured by Vitro Scient, while the study determined substance use using a reliable (Cronbach alpha = 0.805) rapid-exploratory survey questionnaire. Liver enzyme values were further categorized into: normal or abnormal using normal reference ranges (ALT = 7–55 U/L, AST = 8–48 U/L, and ALP = 40–129 U/L). STATGRAPHICS V16.1.11 (StatPoint Tech., Inc.) and SPSS (IBM® Amos V21.0.0, USA) were used to analyze the data. Among the HIV-HAART patients, 27.9% were alcohol users, 20.9% smokers, and 20.1% trado-medicine users. In addition, ALP (71.3%) abnormality was higher than ALT (34.9%) and AST (28.7%). The result from the SEM provided only a partial support for our hypotheses of direct substance use effects on the liver enzyme levels and abnormalities; with a direct association of alcohol with an elevated AST (b = 0.170, p = 0.05) and smoking with a higher AST (b = 0.484, p < 0.01) and ALT (b = 0.423, p < 0.01) values. Trado-medicine use was not directly associated with enzyme elevation and abnormality. In conclusion, ALP abnormality was the most common, and there is a close association between an elevated ALT and AST, with or without an elevated ALP. The study found that HIV-HAART patients who drink or smoke will have at least one or more abnormal transaminases. The possible explanation to the increased risk among HIV-HAART patients could be associated with the metabolic pressures and supra-additive effects on the livers.

• HIV
• hepatotoxicity
• liver enzyme elevation
• real-world

Hepatotoxicity is one of the risk factors associated with treatment non-adherence, which is the main risk factor for drug resistance. Therefore, this study aimed to determine the incidence and risk factors of hepatotoxicity during highly active antiretroviral therapy (HAART) among people living with HIV in Ethiopia.

A prospective cohort study was conducted between April 2007 and January 2011 at Saint Peter Specialized Hospital, Akaki and Kality Health Centers, Addis Ababa, Ethiopia. A total of 316 HIV-infected adult individuals (70 participants were HIV and TB co-infected and 246 were infected with HIV alone) were included in this study. The study participants were followed for a total of 18 months with or without HAART. Socio-demographic data were collected using a structured questionnaire, and venous blood samples were collected for laboratory tests. Logistic regression and Poisson regression were used to determine the independent effect of each variable on hepatotoxicity at baseline and end of follow-up.

Of 316 HIV-infected people, 72 (22.8%) participants had an elevated ALT/AST which was 100% mild-to moderate hepatotoxicity at baseline. Baseline CD4 T-cell count (p = 0.027) and HIV co-infection with TB (p < 0.001) were independently associated with hepatotoxicity at baseline. The overall incidence rate of hepatotoxicity in participants on HAART (21.8 per 100 person-years) was lower than participants who were HAART naïve (33.3 per 100 person-years) (p = 0.009).

High incidence of mild-to-moderate hepatotoxicity and low severe hepatotoxicity were observed in HIV-infected individuals who were on HAART or were HAART naïve. HAART may minimize the occurrence of hepatotoxicity. Although HAART could minimize hepatotoxicity among HIV-infected people, to manage mild and moderate hepatotoxicity liver function test monitoring is required.

• HAART
• hepatotoxicity

The available data concerning hepatitis B virus (HBV) infection in Uganda are limited, particularly in the case of people living with HIV/AIDS (PLWH). HBV is not routinely tested when starting antiretroviral therapy (ART). We aimed to determine the prevalence, the correlates of the risk of HBV infection, and the association with outcomes of ART among PLWH attending a busy HIV clinic in a referral hospital in Northern Uganda.

From April to June 2016, a random sample of 1000 PLWH attending the outpatients’ clinic of St. Mary’s Hospital, Gulu, Uganda were systematically selected to undergo a rapid hepatitis B surface antigen (HBsAg) test after administering a questionnaire in this cross-sectional study. HIV care parameters were obtained from client files. Multivariate logistic regression and general linear model were used for the analysis.

950 of the 985 evaluable patients (77% females; mean age 42.8 years) were receiving ART. The overall prevalence of HBsAg was 7.9% (95% confidence interval [CI] 6.2–9.6%), and was significantly lower among the females (6.8% vs 11.7%; p = 0.020). The factors independently associated with higher HBV infection were having lived in an internally displaced persons’ camp (adjusted odds ratio [aOR] 1.76, 95% CI 1.03–2.98; p = 0.036) and having shared housing with HBV-infected people during childhood (aOR 3.30, 95% CI 1.49–7.32; p = 0.003). CD4+ T cell counts were significantly lower in HBV patients (p = 0.025), and co-infection was associated with a poorer CD4+ T cell response to ART (AOR 0.88; 95% CI 0.79–0.98; p = 0.030).

The observed prevalence of HBV among the PLWH may be underestimated or a signal of HBV decline in the region. The factors favouring horizontal HBV transmission identified suggest extending HBV screening and vaccine prophylaxis among PLWH.

• Adult
• Coinfection/complications
• Cross-Sectional Studies
• Female
• HIV Infections/complications
• Hepatitis B/complications
• Hepatitis B/epidemiology
• Humans
• Male
• Middle Aged
• Prevalence
• Uganda/epidemiology

Highly active antiretroviral therapy (HAART) has reduced HIV-related morbidity and mortality at all stages of infection and reduced transmission of HIV. Currently, the immediate start of HAART is recommended for all HIV patients, regardless of the CD4 count. There are several concerns, however, about starting treatment in critically ill patients. Unpredictable absorption of medication by the gastrointestinal tract, drug toxicity, drug interactions, limited reserve to tolerate the dysfunction of other organs resulting from hypersensitivity to drugs or immune reconstitution syndrome, and the possibility that subtherapeutic levels of drug may lead to viral resistance are the main concerns. The objective of our study was to compare the early onset (up to 5 days) with late onset (after discharge from the ICU) of HAART in HIV-infected patients admitted to the ICU.

This was a randomized, open-label clinical trial enrolling HIV-infected patients admitted to the ICU of a public hospital in southern Brazil. Patients randomized to the intervention group had to start treatment with HAART within 5 days of ICU admission. For patients in the control group, treatment should begin after discharge from the ICU. The patients were followed up to determine mortality in the ICU, in the hospital and at 6 months. The primary outcome was hospital mortality. The secondary outcome was mortality at 6 months.

The calculated sample size was 344 patients. Unfortunately, we decided to discontinue the study due to a progressively slower recruitment rate. A total of 115 patients were randomized. The majority of admissions were for AIDS-defining illnesses and low CD4. The main cause of admission was respiratory failure. Regarding the early and late study groups, there was no difference in hospital (66.7% and 63.8%, p = 0.75) or 6-month (68.4% and 79.2%, p = 0.20) mortality. After multivariate analysis, the only independent predictors of in-hospital mortality were shock and dialysis during the ICU stay. For the mortality outcome at 6 months, the independent variables were shock and dialysis during the ICU stay and tuberculosis at ICU admission.

Although the early termination of the study precludes definitive conclusions being made, early HAART administration for HIV-infected patients admitted to the ICU compared to late administration did not show benefit in hospital mortality or 6-month mortality.

ClinicalTrials.gov, NCT01455688. Registered 20 October 2011, https://clinicaltrials.gov/show/NCT01455688

• AIDS-Related Opportunistic Infections/etiology
• AIDS-Related Opportunistic Infections/prevention & control
• Adult
• Anti-HIV Agents/administration & dosage
• Anti-HIV Agents/adverse effects
• Anti-HIV Agents/pharmacokinetics
• Anti-HIV Agents/therapeutic use
• Antiretroviral Therapy, Highly Active/adverse effects
• Brazil
• CD4 Lymphocyte Count
• Critical Care/methods
• Critical Illness
• Drug Administration Schedule
• Female
• HIV Infections/drug therapy
• Hospital Mortality
• Hospitals, Public
• Humans
• Immune Reconstitution Inflammatory Syndrome/etiology
• Immune Reconstitution Inflammatory Syndrome/prevention & control
• Intensive Care Units
• Length of Stay/statistics & numerical data
• Male
• Middle Aged
• Respiration, Artificial
• Respiratory Insufficiency/etiology
• Respiratory Insufficiency/therapy

• antiretroviral therapy
• diagnosis
• drug-induced liver injury
• human immunodeficiency virus
• mechanisms

• Animals
• Anti-HIV Agents/administration & dosage
• Anti-HIV Agents/adverse effects
• Biomarkers/metabolism
• Chemical and Drug Induced Liver Injury/diagnosis
• Chemical and Drug Induced Liver Injury/etiology
• Chemical and Drug Induced Liver Injury/physiopathology
• HIV Infections/drug therapy
• Humans

• South African Agency for Science and Technology Advancement
• South African Medical Research Council

• HIV–TB integration
• South Africa
• antiretroviral treatment
• liver injury
• tuberculosis treatment

• Adult
• Aged
• Anti-HIV Agents/therapeutic use
• CD4 Lymphocyte Count
• Chemical and Drug Induced Liver Injury/epidemiology
• Chemical and Drug Induced Liver Injury/etiology
• Coinfection/drug therapy
• HIV Infections/complications
• HIV Infections/drug therapy
• Humans
• Tuberculosis/complications
• Tuberculosis/drug therapy
• Tuberculosis/epidemiology

• D43 TW000231 FIC NIH HHS
• UM1 AI069469 NIAID NIH HHS
• PEPFAR
• U.S. President’s Emergency Plan for AIDS Relief
• National Institutes of Health
• Columbia University–South Africa Fogarty AIDS International Training and Research Program

• Fibrosis
• Hepatitis B virus
• Hepatitis C virus
• Human immunodeficiency virus
• Stiffness
• Treatment

• Antiviral Agents/therapeutic use
• Coinfection/drug therapy
• Coinfection/epidemiology
• Coinfection/pathology
• Coinfection/virology
• Comorbidity
• Disease Progression
• Drug Therapy, Combination
• HIV/immunology
• HIV Infections/drug therapy
• HIV Infections/epidemiology
• HIV Infections/pathology
• HIV Infections/virology
• Hepacivirus/immunology
• Hepatitis B/drug therapy
• Hepatitis B/epidemiology
• Hepatitis B/pathology
• Hepatitis B/virology
• Hepatitis B virus/immunology
• Hepatitis C/drug therapy
• Hepatitis C/epidemiology
• Hepatitis C/pathology
• Hepatitis C/virology
• Humans
• Liver/pathology
• Liver/virology

• K01 AA026864 NIAAA NIH HHS
• R24 OD018546 NIH HHS

• AIDS
• Acquired Immune Deficiency Syndrome
• Hepatitis B
• Human Immunodeficiency Virus

• Antiviral Agents/therapeutic use
• Coinfection/diagnosis
• Coinfection/drug therapy
• Coinfection/immunology
• HIV
• HIV Infections/diagnosis
• HIV Infections/drug therapy
• HIV Infections/immunology
• Hepatitis B Surface Antigens/immunology
• Hepatitis B e Antigens/immunology
• Hepatitis B virus/immunology
• Hepatitis B, Chronic/diagnosis
• Hepatitis B, Chronic/drug therapy
• Hepatitis B, Chronic/immunology
• Humans
• Immune Reconstitution Inflammatory Syndrome/diagnosis
• Immune Reconstitution Inflammatory Syndrome/drug therapy
• Immune Reconstitution Inflammatory Syndrome/immunology
• Male
• Middle Aged
• Seroconversion

• Alcohol
• Antiretroviral therapy
• Apoptosis
• Fibrosis
• Immunodeficiency virus
• Inflammation
• Liver cells

• Alcohol Drinking/adverse effects
• Anti-HIV Agents/adverse effects
• Anti-HIV Agents/therapeutic use
• Chemical and Drug Induced Liver Injury/epidemiology
• Chemical and Drug Induced Liver Injury/etiology
• Chemical and Drug Induced Liver Injury/pathology
• Coinfection/epidemiology
• Coinfection/virology
• Disease Progression
• HIV/drug effects
• HIV/isolation & purification
• HIV/pathogenicity
• HIV Infections/drug therapy
• HIV Infections/epidemiology
• HIV Infections/virology
• Hepacivirus/isolation & purification
• Hepacivirus/pathogenicity
• Hepatitis B/epidemiology
• Hepatitis B/pathology
• Hepatitis B/virology
• Hepatitis B virus/pathogenicity
• Hepatitis C/epidemiology
• Hepatitis C/pathology
• Hepatitis C/virology
• Hepatocytes/drug effects
• Hepatocytes/pathology
• Hepatocytes/virology
• Humans
• Incidence
• Liver/cytology
• Liver/drug effects
• Liver/pathology
• Liver/virology
• Liver Cirrhosis/epidemiology
• Liver Cirrhosis/pathology
• Liver Cirrhosis/virology

• K01 AA026864 NIAAA NIH HHS
• R24 OD018546 NIH HHS

• Antiretroviral therapy
• HIV/HBV coinfection
• Hepatocytes
• Liver enzyme elevation

• Antiretroviral Therapy, Highly Active
• Critical Illness
• HIV Infections/drug therapy
• Humans

• HIV
• drug-induced liver injury
• hepatic decompensation
• hepatitis C
• hepatotoxicity
• mitochondrial toxicity
• pharmacoepidemiology

• Chemical and Drug Induced Liver Injury, Chronic/complications
• Chemical and Drug Induced Liver Injury, Chronic/etiology
• Coinfection/drug therapy
• Female
• HIV Infections/drug therapy
• Hepatitis C, Chronic/drug therapy
• Humans
• Incidence
• Liver/drug effects
• Liver Cirrhosis/complications
• Liver Failure/epidemiology
• Liver Failure/etiology
• Male
• Middle Aged
• Mitochondria/drug effects
• Proportional Hazards Models
• Retrospective Studies
• Reverse Transcriptase Inhibitors/adverse effects

• K01 AI070001 NIAID NIH HHS
• UL1 TR001863 NCATS NIH HHS
• R01 HS018372 AHRQ HHS
• U01 AA020790 NIAAA NIH HHS
• U01 AA013566 NIAAA NIH HHS
• T32 DK060455 NIDDK NIH HHS
• R01 CA206465 NCI NIH HHS
• U24 AA020794 NIAAA NIH HHS

Liver enzyme abnormalities are common in HIV patients, and the prevalence varies across the nations. In Nepal, however, prevalence of liver enzyme disorder and the spectrum of these populations are lacking.

The present study sheds light on prevalence and clinical spectrum of liver disease in Nepalese HIV-sero-positive patients.

This cross-sectional study was conducted at OPD/ART, Clinic of Bir Hospital, NAMS. One hundred and forty-four HIV positive patients were enrolled consecutively and their clinical profiles of liver injury were investigated.

Of 144 recruited patients, liver enzyme injury was observed in 82 (56.9%). Majority 61 (42.4%) of these cases had hepatocellular type of liver injury. Opportunistic infections were reported in 18 cases, with 9 (6.2%) TB and 8 (5.6%) HCV. Test for significance of liver injury confirmed the absence of any tendency towards an association with coinfection, CD4 cells, ART regimen, and alcohol consumption (P > 0.05). However, gender significantly linked with liver injury as well as the pattern of liver injury (P < 0.05).

The study revealed high rate of liver injury in a substantial proportion of HIV individuals, stressing that a regular clinic follow-up is necessary for the HIV individuals who are undergoing ART.

• HIV
• acute care
• antiretrovirals
• hospitalization

• Adult
• Alanine Transaminase/blood
• Anti-HIV Agents/adverse effects
• Anti-HIV Agents/therapeutic use
• Aspartate Aminotransferases/blood
• CD4 Lymphocyte Count
• Chemical and Drug Induced Liver Injury/enzymology
• Chemical and Drug Induced Liver Injury/epidemiology
• Chemical and Drug Induced Liver Injury/etiology
• Disease Management
• Drug Eruptions/epidemiology
• Drug Eruptions/etiology
• Drug Therapy, Combination
• Female
• HIV Infections/drug therapy
• Humans
• Incidence
• Male
• Middle Aged
• Nucleosides/adverse effects
• Nucleosides/therapeutic use
• RNA, Viral/blood
• Retrospective Studies
• Reverse Transcriptase Inhibitors/adverse effects
• Reverse Transcriptase Inhibitors/therapeutic use
• Risk Factors
• Severity of Illness Index
• Taiwan/epidemiology
• Viral Load
• Viremia/drug therapy
• Young Adult

• the Centers for Disease Control, Taiwan

• Acute liver failure
• Alcohol
• Cirrhosis
• Drug-induced liver injury
• Liver toxicity
• Smoking

• Acetaminophen/administration & dosage
• Acetaminophen/adverse effects
• Alcohol Drinking/adverse effects
• Antitubercular Agents/administration & dosage
• Antitubercular Agents/adverse effects
• Chemical and Drug Induced Liver Injury/epidemiology
• Chemical and Drug Induced Liver Injury/etiology
• Environmental Exposure/adverse effects
• Female
• Humans
• Liver/drug effects
• Liver Cirrhosis/epidemiology
• Liver Cirrhosis/etiology
• Liver Cirrhosis/pathology
• Liver Function Tests
• Male
• Prognosis
• Risk Assessment
• Smoking/adverse effects
• Smoking/epidemiology

• T32 DK007769 NIDDK NIH HHS

The emergence of highly active antiretroviral therapy (HAART) has dramatically improved quality of life in prolonging survival of human immunodeficiency virus (HIV)-infected patients on treatment in developed as well as developing countries. However, the main shortcoming of HAART in long-term use is its potential to cause liver and kidney derangements that may be life threatening. The drugs are actively accumulated in the proximal renal tubule resulting in functional disturbance with mitochondrial injury being one of the most important targets recognized. Therefore, the aim of this study was to assess the adverse effects of HAART on kidney and liver functions among HIV-infected patients presenting to the University of Gondar Hospital, Ethiopia.

An institution-based retrospective study was conducted from 2010 to 2015 on a subset of HIV-infected patients. Data were collected from the registration book of the University of Gondar Hospital antiretroviral clinic laboratory after checking the completeness of age, gender, creatinine, blood urea nitrogen, and alanine aminotransferase level. Data were entered and analyzed using SPSS version 20. Descriptive statistics, chi-square test, one-way analysis of variance, and logistic regression were done to determine associations. A P-value <0.05 was considered statistically significant.

A total of 275 study subjects were included in the study. Of these, 62.2% were females, and the overall prevalence of chronic kidney disease (CKD) before and after treatment was 3.6% and 11.7%, respectively. A majority of the CKD patients were in stage 3 for patients after treatment. The overall prevalence of hepatotoxicity was 6.5% and 16.7% before and after treatment, respectively. A majority of the patients developed Grade 2 hepatotoxicity 66.7% and 65.2% before and after treatment, respectively. Binary and multiple logistic regression analysis indicated that the female gender was a risk factor for CKD.

The prevalence of nephrotoxicity and hepatotoxicity were high among patients who took HAART. Stage 3 nephrotoxicity and Grade 2 hepatotoxicity had the highest incidences of the total toxicities, and the female gender was a risk factor for nephrotoxicity. Further prospective studies are recommended to determine the effect of HAART and contributing factors.

• CKD
• Ethiopa
• Gondar
• HAART
• hepatotoxicity
• nephrotoxicity

HIV infection aggravates the progression of liver damage in HCV-coinfected patients, with the underlying pathogenesis being multifactorial. Although high level of oxidative stress has been observed frequently in patients infected with HIV or HCV, the status of oxidative stress in HIV/HCV coinfection and its contribution to HCV liver damage have not been determined. This study involved 363 HBsAg-negative, anti-HCV-positive former blood donors recruited from a village in central China in July 2005; of these, 140 were positive for HIV. Of these 363 subjects, 282 were successfully followed up through July 2009. HIV/HCV-coinfected subjects had higher rates of end-stage liver disease-related death than those monoinfected with HCV. Liver ultrasound manifestations were poor in HIV-positive than in HIV-negative individuals, in both chronic HCV carriers and those with resolved HCV. Serum concentrations of total glutathione (tGSH), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), GSSG, and reduced GSH were higher in HIV-positive than HIV-negative subjects. GSSG concentrations were higher in HIV-infected subjects with abnormal ALT/AST levels than in those with normal ALT/AST levels and were associated with poorer liver ultrasound manifestations. These finding indicated that HIV infection accelerated HCV-associated liver damage in HIV/HCV-coinfected individuals. Increased oxidative stress, induced primarily by HIV coinfection, may contribute to aggravated liver damage.

As the roll-out of antiretroviral therapy continues to drive downwards morbidity and mortality in people living with HIV/AIDS (PLWHAs), organ toxicities (especially the liver) are frequently becoming a major concern for researchers, scientists and healthcare planners.

This study was conducted to investigate the possible protective effect of Hypoxis hemerocallidea (AP) against highly active antiretroviral therapy (HAART)-induced hepatotoxicity. A total of 63 pathogen-free adult male Sprague-Dawley rats were divided into 9 groups and treated according to protocols.

While no mortality was reported, animals treated with adjuvant HAART and AP recorded least% body weight gain. Significant derangements in serum lipid profiles were exacerbated by treatment of with AP as LDL (increased p < 0.03), triglycerides (increased p < 0.03) with no change in total cholesterol levels. Adjuvant AP with HAART caused reduction in LDL (p < 0.05 and 0.03), increased HDL (p < 0.05) and TG (p < 0.05 and 0.001 for AP₁₀₀ and AP₂₀₀ doses respectively). Markers of liver injury assayed showed significant increase (p < 0.003, 0.001) in AST in AP alone as well as HAART+ vitamins C and E groups respectively. Adjuvant HAART and AP and vitamins C and E also caused significant declines in ALT and ALP levels. Serum GGT was not markedly altered. Disturbances in histopathology ranged from severe hepatocellular distortions, necrosis and massive fibrosis following co-treatment of HAART with vitamins C and E as well as HAART alone. These results warrant caution on the adjuvant use of AP with HAART by PLWHAs as implications for hepatocellular injuries are suspect with untoward cardiometabolic changes.

• Biochemistry
• Cytotoxicity
• HAART
• Lipid profile
• Liver morphology
• Stains

In human immunodeficiency virus–hepatitis C-coinfected, both protease inhibitor- and nonnucleoside reverse transcriptase inhibitor-based regimens were associated with progression of liver fibrosis over time when paired with a backbone of abacavir/lamivudine but not tenofovir/emtricitabine.

Background. Liver diseases progress faster in human immunodeficiency virus (HIV)–hepatitis C virus (HCV)-coinfected persons than HIV-monoinfected persons. The aim of this study was to compare rates of liver fibrosis progression (measured by the aspartate-to-platelet ratio index [APRI]) among HIV-HCV–coinfected users of modern protease inhibitor (PI)- and nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens with a backbone of tenofovir/emtricitabine (TDF/FTC) or abacavir/lamivudine (ABC/3TC).

Methods. Data from a Canadian multicenter cohort study were analyzed, including 315 HCV polymerase chain reaction–positive persons who initiated antiretroviral therapy with a PI or NNRTI and a backbone containing either TDF/FTC or ABC/3TC. Multivariate linear regression analyses with generalized estimating equations were performed after propensity score matching to balance covariates across classes of anchor agent.

Results. A backbone of TDF/FTC was received by 67% of PI users and 69% of NNRTI users. Both PI and NNRTI use was associated with increases in APRI over time when paired with a backbone of ABC/3TC: 16% per 5 years (95% confidence interval [CI], 4%, 29%) and 11% per 5 years (95% CI, 2%, 20%), respectively. With TDF/FTC use, no clear association was found among PI users (8% per 5 years, 95% CI, −3%, 19%) or NNRTI users (3% per 5 years, 95% CI, −7%, 12%).

Conclusions. Liver fibrosis progression was more influenced by the backbone than by the class of anchor agent in HIV-HCV–coinfected persons. Only ABC/3TC-containing regimens were associated with an increase of APRI score over time, regardless of the class of anchor agent used.

• APRI
• HIV
• combination antiretroviral therapy
• hepatitis C
• liver fibrosis

Highly active antiretroviral therapy (HAART) is effective and well tolerated, but hepatotoxicity is relatively common. Different non-invasive methods are available for detecting liver fibrosis in patients with chronic liver disease.

Patients who were HIV positive and who had given their informed consent were included in this cross-sectional study. Transient elastography [FibroScan^® (FS); Echosens], serum hyaluronic acid (HA), Hepascore (HS), Fibrosis-4 (FIB-4), and aspartate aminotransferase to platelet ratio index (APRI) were used to detect liver fibrosis in the patients. The agreement between FS and the other methods was evaluated. To observe the hepatotoxicity of HAART, patients with chronic viral hepatitis B or C were excluded by detection of hepatitis B surface antigens and hepatitis C virus antibodies. Patients with chronic alcohol intake were excluded by measuring carbohydrate-deficient transferrin (CDT). FS correlation with the duration of therapy with protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI) was evaluated.

Overall, 203 patients were included in the study. The agreement between the different tests ranged from 64% to 77%: FS vs. HA, 72%; FS vs. APRI, 74%; FS vs. HS, 77%; and FS vs. FIB-4, 64%. After excluding patients with chronic hepatitis B or C and elevated CDT, 153 patients remained for studying the hepatotoxicity of HAART. A significant correlation of FS with the duration of medication intake was observed for PIs (P = 0.026; r = 0.18). NRTI and NNRTI therapy duration did not correlate with FS.

The agreement between FS and other tests ranged from 64% to 77%. A significant correlation was found between liver stiffness and the duration of therapy with PIs, which underlines the known hepatotoxicity of this substance group.

Heinz-Ansmann Foundation.

The online version of this article (doi:10.1007/s40121-015-0073-y) contains supplementary material, which is available to authorized users.

• FibroScan®
• HIV
• Hepatotoxicity
• Highly active antiretroviral therapy (HAART)
• Liver
• Transient elastography

• Ansmann Foundation for AIDS-research

• Coinfection
• DAA
• HIV
• Hepatitis B virus
• Hepatitis C virus

• Adult
• Alanine Transaminase/blood
• Alkaline Phosphatase/blood
• Alkynes
• Antiretroviral Therapy, Highly Active/adverse effects
• Aspartate Aminotransferases/blood
• Benzoxazines
• CD4 Lymphocyte Count
• Chemical and Drug Induced Liver Injury
• Cholinesterases/blood
• Cohort Studies
• Cyclopropanes
• Female
• HIV Infections/blood
• HIV Infections/drug therapy
• HIV Infections/virology
• HIV-1/genetics
• HIV-1/growth & development
• Humans
• Liver Diseases/blood
• Liver Diseases/enzymology
• Male
• Nevirapine/adverse effects
• Nevirapine/therapeutic use
• Oxazines/adverse effects
• Oxazines/therapeutic use
• Prospective Studies
• RNA, Viral/blood
• Reverse Transcriptase Inhibitors/adverse effects
• Reverse Transcriptase Inhibitors/therapeutic use
• Serum Albumin/metabolism
• gamma-Glutamyltransferase/blood

• Antiviral Agents/administration & dosage
• HIV Infections/complications
• Hepatitis C, Chronic/complications
• Hepatitis C, Chronic/therapy
• Humans
• Interferon alpha-2
• Interferon-alpha/administration & dosage
• Liver Transplantation
• Recombinant Proteins
• Ribavirin/administration & dosage

• Adenine/adverse effects
• Adenine/analogs & derivatives
• Adenine/therapeutic use
• Anti-HIV Agents/adverse effects
• Antiretroviral Therapy, Highly Active
• Antiviral Agents/therapeutic use
• Female
• HIV
• HIV Infections/complications
• HIV Infections/drug therapy
• Hepacivirus/genetics
• Hepatitis C/complications
• Hepatitis C/drug therapy
• Humans
• Interferon alpha-2
• Interferon-alpha/therapeutic use
• Kidney/drug effects
• Liver/drug effects
• Male
• Organophosphonates/adverse effects
• Organophosphonates/therapeutic use
• Polyethylene Glycols/therapeutic use
• RNA, Viral/blood
• Recombinant Proteins
• Ribavirin/therapeutic use
• Tenofovir

• Drug-induced liver injury
• Fatty liver
• Hepatitis
• Highly active antiretroviral therapy
• Metabolic syndrome
• Nonalcoholic fatty liver disease
• Nonalcoholic steatohepatitis
• Opportunistic infections

The antiretroviral therapy (ART) program of Cameroon recommends routine laboratory monitoring of haematological toxicity if a regimen contains zidovudine (AZT) and of hepatotoxicity for NVP-containing regimens on the 15^th day after ART initiation. This study aimed to assess the relevance of this repeated laboratory measurements considered to be precocious, inaccessible and unavailable in a resource limited setting.

A retrospective cohort of HIV-infected patients of age 15 years and above enrolled for first line ART at The Regional Hospital of Nkongsamba in Cameroon. We monitored liver transaminases and blood cell indices after two weeks of ART initiation for any significant change from baseline. Factors associated with abnormal changes were examined using a multivariable logistic regression model with random effects.

Enrolled were 154 patients of whom 105 (68.2%) were females. The mean ALAT (alanine aminotransferase) level at baseline was 17.87 ± 20.48 U/L increasing to 19.25 ± 12.01 U/L at two weeks of follow-up (p = 0.53) while the mean ASAT (aspartate aminotransferase) level increased from 17.32 ± 11.87 U/L at baseline to 21.02 ± 14.12 U/L at two weeks of follow-up (p = 0.02). We observed a drop in the mean haemoglobin concentration from 10.86 ± 2.63 g/dL at baseline to 10.36 ± 1.92 g/dL at the second week of follow-up (p = 0.02). The prevalence of elevated liver enzymes and anaemia after two weeks of treatment were 7.5% and 39.2% respectively. Stavudine containing regimens were most likely to induce hepatotoxicity [adjusted Odd Ratio (aOR) = 36.52, 95% CI: 1.44-924.38, p=0.029]. Baseline anaemia (aOR=60.08, 95% CI: 13.36-270.20, p < 0.0001) and body weight ≥ 60kg (aOR=0.28, 95% CI: 0.09-0.83, p = 0.02) were associated with anaemia at follow-up.

There was no significant rise in the mean level of transaminases and thus scheduling their routine monitoring at the end of the second week could be skipped. Conversely, the drop in mean haemoglobin level had little clinical importance but the high prevalence of anaemia after a fortnight on treatment suggests a targeted instead of a routine monitoring; focusing on the high risk population with baseline anaemia and low body weight.

The online version of this article (doi:10.1186/1471-2334-14-519) contains supplementary material, which is available to authorized users.

• Coinfection
• Liver Fibrosis
• Transient Elastometry

• Antiretroviral therapy
• Clinical outcomes
• HIV
• Hepatitis B
• Lamivudine

• Adult
• Animals
• Anti-Retroviral Agents/chemistry
• Anti-Retroviral Agents/pharmacology
• Anti-Retroviral Agents/therapeutic use
• HIV Infections/drug therapy
• HIV Infections/metabolism
• Humans
• Lopinavir
• Pyrimidinones/chemistry
• Pyrimidinones/pharmacology
• Pyrimidinones/therapeutic use

Despite the major advances in the management of HIV infection, HIV-infected patients still have greater morbidity and mortality than the general population. Serious non-AIDS events (SNAEs), including non-AIDS malignancies, cardiovascular events, renal and hepatic disease, bone disorders and neurocognitive impairment, have become the major causes of morbidity and mortality in the antiretroviral therapy (ART) era. SNAEs occur at the rate of 1 to 2 per 100 person-years of follow-up. The pathogenesis of SNAEs is multifactorial and includes the direct effect of HIV and associated immunodeficiency, underlying co-infections and co-morbidities, immune activation with associated inflammation and coagulopathy as well as ART toxicities. A number of novel strategies such as ART intensification, treatment of co-infection, the use of anti-inflammatory drugs and agents that reduce microbial translocation are currently being examined for their potential effects in reducing immune activation and SNAEs. However, currently, initiation of ART before advanced immunodeficiency, smoking cessation, optimisation of cardiovascular risk factors and treatment of HCV infection are most strongly linked with reduced risk of SNAEs or mortality. Clinicians should therefore focus their attention on addressing these issues prior to the availability of further data.