Effect of Two Forms of Tenofovir on Duodenal Enterocytes - a Hypothesis for Different Effect of TDF and TAF on Body Weight and Plasma Lipids.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) compared to tenofovir alafenamide (TAF) leads to lower body weight and plasma lipids by an unknown mechanism. We hypothesize that TDF, when absorbed, may damage enterocytes of the proximal duodenum, leading to reduced absorption of nutrients. METHODS: People living with HIV, without significant gastrointestinal symptoms, receiving TDF (n=12) or TAF (n=12) containing regimen underwent esophagogastroduodenoscopies with duodenal biopsies. Plasma/serum concentrations of nutrients absorbed from proximal duodenum and serum intestinal fatty-acid-binding protein (I-FABP), a marker of enterocyte damage, were measured. COX/SDH histochemical staining and electron microscopy (EM) were conducted to evaluate mitochondria. RESULTS: Five patients in TDF (celiac disease (excluded from further analyses), helicobacter gastritis, and three esophagitis) and two in TAF group (two esophagitis) had a pathological finding in esophagogastroduodenoscopy. Villi were flatter (337 (59) vs. 397 (42) µm, p=0.016), crypts non-significantly deeper (200 (46) vs. 176 (27) µm, p=0.2), and villus to crypt ratio lower (1.5 (0.42) vs. 2.5 (0.51), p=0.009) in TDF vs. TAF group. I-FABP concentration was higher in TDF vs. TAF group (3.0 (1.07) vs. 1.8 (0.53) ng/ml, p=0.003). TDF group had numerically but not statistically significantly lower concentrations of folate, vitamins A, B1, D, and E. COX/SDH staining showed signs of mitochondrial damage in 10 participants in TDF and 11 in TAF group. EM studies showed similar mitochondrial damage in both groups. CONCLUSIONS: Duodenal villous alterations may explain TDF-associated decrease in body weight and plasma lipids. Larger studies are needed to evaluate concentrations of nutrients absorbed from duodenum among TDF users.

A qualitative study to identify thematic areas for HIV related patient-reported outcome measures (PROM) and patient-reported experience measures (PREM).

BACKGROUND: The use of patient-reported outcome measures (PROM) and patient-reported experience measures (PREM) provide health providers with valuable feedback on how to improve clinical care and patient outcomes. This paper describes a qualitative study that was conducted to learn about factors influencing the well-being of people living with HIV (PLHIV) in Finland. The findings will be used to develop themes for HIV-specific PROM and PREM questions. METHODS: PROMs and PREMs were developed by the Finnish Institute for Health (THL) as a part of a project to develop a national quality-of-care registry for HIV. The study aimed to identify issues and concerns among people living with HIV (PLHIV) that influence their well-being (PROMs) and their experiences in the healthcare system (PREMs). The data were collected through face-to-face in-depth interviews and focus group discussions based on open-ended and semi-structured questions. The data were analyzed using thematic analysis. RESULTS: The assessment identified the following PROMs of concern: psychological well-being, concerns about stigma, physical health, social well-being, sexual well-being, medication uptake, managing other medications with antiretrovirals (ARVs), and growing old. The assessment identified the following PREMs: helping patients understand their own health status, proving an opportunity for patients to discuss physical health, psychological and sexual well-being, supporting the uptake of ARVs, assisting patients with medication use, showing compassion towards patients, and empowering patients against stigma. CONCLUSION: These findings of the study can be used to develop domain-specific PROM and PREM questions for the national HIV quality care register.

Gut microbiota alterations after switching from a protease inhibitor or efavirenz to raltegravir in a randomized, controlled study.

OBJECTIVE: To study gut microbiota before and 24 weeks after a single antiretroviral agent switch. DESIGN: HIV-positive patients with efavirenz (EFV) or a protease inhibitor (PI)-based antiretroviral therapy (ART) were randomized to switch EFV or PI to raltegravir (RAL group, n = 19) or to continue unchanged ART (EFV/PI group, n = 22). Age and weight-matched HIV-negative participants (n = 10) were included for comparison. METHODS: Microbiota was analyzed using 16S rRNA sequencing. Serum intestinal fatty acid-binding protein (I-FABP) and serum lipopolysaccharide-binding protein (LBP) were measured as gut permeability markers. Three-day food diaries were collected. RESULTS: At week 24, microbiota diversity (Chao1 index) was higher in RAL than the EFV/PI group (P = 0.014), and RAL group did not differ from HIV-negative participants. In subgroup analysis switching from EFV (P = 0.043), but not from a PI to RAL increased Chao1. At week 24, RAL and EFV/PI group differed in the relative abundance of Prevotella 9 (higher in RAL, P = 0.01), Phascolarctobacterium and Bacteroides (lower in RAL, P = 0.01 and P = 0.03). Dietary intakes did not change during the study and do not explain microbiota differences. Also, I-FABP and LBP remained unchanged. CONCLUSION: Here we demonstrate that a single ART agent switch caused microbiota alterations, most importantly, an increase in diversity with EFV to RAL switch. Previously, we reported weight gain, yet reduced inflammation in this cohort. The observed microbiota differences between RAL and EFV/PI groups may be associated with reduced inflammation and/or increase in weight. Further studies are needed to evaluate inflammatory and metabolic capacity of microbiota with ART switches.

Switching from tenofovir alafenamide to tenofovir disoproxil fumarate improves lipid profile and protects from weight gain.

BACKGROUND: Switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) increases low-density lipoprotein cholesterol (LDL-C) and body weight. Metabolic effects of the opposite TAF-to-TDF switch are unknown. OBJECTIVES: To investigate the effect of TAF-to-TDF switch on plasma lipids, body weight, and atherosclerotic cardiovascular disease (ASCVD) risk score. DESIGN: A retrospective chart review. METHODS: One hundred and forty-six patients with TAF-to-TDF switch (Switch group) were compared with 146 patients matched for sex, age, and third antiretroviral agent class who continued unchanged TAF-containing regimen (Control group). Data were collected at approximately 1 year (follow-up FU-1) and 2 years (follow-up FU-2) after baseline values. RESULTS: In Switch group at FU-1, total cholesterol (TC) and LDL-C decreased 12.1% and 12.4% ( P  < 0.001 in both), respectively. High-density lipoprotein cholesterol (HDL-C) also decreased 8.2% ( P  < 0.001) in Switch group, but TC/HDL-C ratio did not change. No statistically significant changes were observed in Control group in any lipid values. TC remained similarly decreased through FU-2 in Switch group, but LDL-C increased from FU-1 to FU-2 in both groups. ASCVD risk score decreased from 6.3% at baseline to 6.0% at FU-2 ( P  = 0.012) in Switch group but increased from 8.4 to 9.1% ( P  = 0.162) in Control group. Body weight increased from 83.4 kg at baseline to 84.9 kg at FU-2 ( P  = 0.025) in Control group but remained stable in Switch group (83.1-83.7 kg, P  = 0.978). CONCLUSIONS: TAF-to-TDF switch improved plasma lipid profile and ASCVD risk score, as well as prevented weight gain, when compared with ongoing TAF-based antiretroviral therapy.

Liver Fat, Adipose Tissue, and Body Composition Changes After Switching from a Protease Inhibitor or Efavirenz to Raltegravir.

Integrase inhibitors appear to increase body weight, but paradoxically some data indicate that raltegravir (RAL) may decrease liver fat. Our objective was to study the effects of switching from a protease inhibitor (PI) or efavirenz (EFV) to RAL on liver fat, body composition, and metabolic parameters among people living with HIV (PLWH) with high risk for nonalcoholic fatty liver disease (NAFLD). We randomized overweight PLWH with signs of metabolic syndrome to switch a PI or EFV to RAL (n = 19) or to continue unchanged antiretroviral therapy (control, n = 24) for 24 weeks. Liver fat was measured by magnetic resonance spectroscopy (MRS), body composition by magnetic resonance imaging, and bioimpedance analysis; subcutaneous fat biopsies were obtained. Median (interquartile range) liver fat content was normal in RAL 2.3% (1.1-6.0) and control 3.1% (1.6-7.3) group at baseline. Liver fat and visceral adipose tissue remained unchanged during the study. Body weight [from 85.9 kg (76.1-97.7) to 89.3 (78.7-98.7), p = 0.019], body fat mass [from 20.3 kg (14.6-29.7) to 22.7 (17.0-29.7), p = 0.015], and subcutaneous adipose tissue (SAT) volume [from 3979 mL (2068-6468) to 4043 (2206-6433), p = 0.048] increased, yet, adipocyte size [from 564 pL (437-733) to 478 (423-587), p = 0.019] decreased in RAL but remained unchanged in control group. Circulating lipids and inflammatory markers improved in RAL compared to control group. The median liver fat measured by MRS was unexpectedly within normal range in this relatively small study population with presumably high risk for NAFLD contradicting high prevalence of NAFLD reported with other methods. Despite weight gain, increase in SAT together with decreased adipocyte size and reduced inflammation may reflect improved adipose tissue function. Clinical Trial Registration number: NCT03374358.

Natural Course of Nonalcoholic Fatty Liver Disease and Type 2 Diabetes in Patients With Human Immunodeficiency Virus With and Without Combination Antiretroviral Therapy-associated Lipodystrophy: A 16-Year Follow-up Study.

BACKGROUND: Abnormal glucose metabolism and nonalcoholic fatty liver disease (NAFLD) are common in patients with human immunodeficiency virus (HIV+ patients), but longitudinal data are lacking. We determined the natural course of NAFLD (liver fat [LFAT]) and type 2 diabetes mellitus (T2DM) in HIV+ patients with and without lipodystrophy (LD+ and LD-, respectively) during a 16-year longitudinal study. METHODS: LFAT (by proton magnetic resonance spectroscopy) and clinical characteristics were measured in 41 HIV+ patients at baseline and after 16 years. Liver fibrosis was estimated by measuring liver stiffness using transient elastography (TE) and magnetic resonance elastography (MRE) at 16 years. We also longitudinally studied 28 healthy subjects. RESULTS: During follow-up, the HIV+ patients gained more body fat (8.6% ± 0.7%) than the control patients (4.5% ± 0.6%, P < .001). Features of insulin resistance increased significantly in the HIV+ patients but not the control patients. A significant proportion (20%, P < .01 vs 0% at baseline) of the HIV+ but none of the control patients developed T2DM. LFAT was significantly higher at baseline in the LD+ (4.3 [1.9-11.8]) than the LD- (1.0 [0.5-1.5]; P < .001) HIV+ patients. LFAT remained stable during follow-up in all groups. At follow-up, liver stiffness measured with TE was similar among all HIV, LD+, LD-, and control patients and between the LD+ and LD- patients measured with MRE. Advanced fibrosis by MRE was observed in 3 of LD+ and none of LD- patients. CONCLUSIONS: During 16 years of follow-up, progression of NAFLD is rare compared to development of T2DM in HIV+ patients.

Switching from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide Significantly Worsens the Lipid Profile in a Real-World Setting.

Tenofovir disoproxil fumarate (TDF) has increasingly been replaced by tenofovir alafenamide (TAF) because of reduced kidney and bone toxicity with TAF. This switch has, however, caused worsening of lipid concentrations in clinical trials, but data from any real-world setting are scarce. The objective of this study was to characterize the effect of TDF to TAF switch on plasma lipid concentrations in a real-world clinic population. This is a retrospective study comparing lipid concentrations and other laboratory parameters between the last visit on TDF and the first visit after at least a 2-month exposure to TAF. A total of 490 HIV-positive subjects were included in the study. The median (interquartile range) increase was 23.2 (0-38.7) mg/dL in total cholesterol (p < 0.001) and 15.5 (0-30.9) mg/dL in low-density lipoprotein (LDL) cholesterol (p < 0.001). The ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol increased by 0.2 (-0.2 to 0.6), p < 0.001. The proportion of patients having optimal LDL cholesterol concentration by National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) decreased from 30.8% to 17.8% and proportion having dyslipidemia or severe dyslipidemia increased from 30.2% to 50.3% after the switch. Demographic characteristics, antiretroviral agents, or comedication did not affect the changes in lipid concentrations. Plasma creatinine decreased by 0.03 (-0.09 to 0.03) mg/dL (p < 0.001) and estimated glomerular filtration rate increased by 0.5 (-2.3 to 3.2) mL/min (p = 0.009). Switching from TDF to TAF caused a statistically significant worsening of the lipid profile that may have clinical relevance. The benefit of the lipid-lowering effect of TDF should be considered in selected patients with low risk for kidney and bone toxicity.

Most women living with HIV can deliver vaginally-National data from Finland 1993-2013.

INTRODUCTION: Vaginal delivery has been recommended for more than ten years for women living with HIV (WLWH) with good virological control. However, in Europe most WLWH still deliver by cesarean section (CS). Our aim was to assess the rate of vaginal delivery and the indications for CS in WLWH over 20 years in a setting of low overall CS rate. MATERIALS AND METHODS: This was a retrospective study of all WLWH delivering in Finland 1993-2013. We identified the women by combining national health registers and extracted data from patient files. RESULTS: The study comprised 212 women with 290 deliveries. Over 35% of the women delivered several children during the study years. During 2000-2013, with consistent viral load monitoring, 80.0% showed HIV viral loads <50 copies/mL in the last measurement preceding the delivery. Altogether 74.5% of all WLWH delivered vaginally and the rate of both elective CS and emergency CS was 12.8% each. For most CSs (63.5%) the indication was obstetrical, for 28.4% it was avoiding HIV transmission and for 0.7% it was mother's request. In hospitals with less than ten HIV-related deliveries during the study period, the rate of elective CS was higher than in more experienced hospitals (22.7% versus 10.6% [p = 0.024]). No perinatal HIV transmissions occurred. CONCLUSIONS: Most WLWH can achieve good virological control and deliver vaginally. This will help them to maintain their future child bearing potential and reduce CS-related morbidity.

HIV-Related Self-Stigma and Health-Related Quality of Life of People Living With HIV in Finland.

We examined how HIV-related self-stigma was associated with different domains of quality of life (QoL), as measured by the World Health Organization Quality of Life in HIV-infected persons instrument (WHOQOL-HIV-Bref), and health-related quality of life (HRQoL) as measured by the generic 15D (15-dimensional measure of HRQoL), to identify the factors associated with self-stigma of people living with HIV (PLWH). The study sample included 440 patients living with HIV followed at the Infectious Disease Clinic of Helsinki University Hospital. Participants with more severe self-stigma reported significantly lower QoL and HRQoL. Male gender, cohabiting with a partner, and disclosure of HIV status were associated with less self-stigma; high education level and financial difficulties were associated with greater self-stigma. Having lived longer with HIV, being unemployed, and living alone were also predictors of self-stigma via financial difficulties. The findings suggest that self-stigma is a complex and multidimensional phenomenon that impacts the HRQoL of PLWH. Psychosocial interventions to enhance the well-being of PLWH are increasingly needed.

Declining prevalence of cytological squamous intraepithelial lesions of the cervix among women living with well-controlled HIV - Most women living with HIV do not need annual PAP smear screening.

INTRODUCTION: Cervical screening by means of annual Papanicolaou (PAP) smears has been recommended for all women living with HIV. We analysed the results of our annual PAP smear screening program to identify low-risk subgroups for less rigorous screening. MATERIAL AND METHODS: The study comprised 369 women followed at the Helsinki University Hospital 2002-2013, with a total of 2033 PAP smear results. We analyzed the temporal changes in PAP smear findings. Logistic regression analysis for binominal dependent variables was used for assessing risk factors for ever having cytological squamous intraepithelial lesions (hereafter referred as SIL) using generalized estimating equations taking into account multiple observations of each patient. RESULTS: Most women had well-controlled HIV, especially towards the end of the study. PAP smear results improved substantially. At the time of each individual's last PAP smear, 90.0% of the findings displayed normal results. Conversely, the rate of SIL decreased from 16.8% to 4.6% from 2002 to 2013. In multivariate analysis the risk of SIL was significantly lower in women with consecutive normal PAP smear findings during the first two years of follow up [odds ratio (OR) 0.21, 95% confidence interval (CI) 0.10-0.45, p < 0.001] and with CD4 counts >500 cells/µL (OR 0.11, 95% CI 0.05-0.26, p < 0.001). CONCLUSIONS: Widespread use of combination antiretroviral therapy (cART) and systematic cervical screening has reduced the rate of abnormal PAP smears. It seems feasible to identify low-risk women by combining HIV-related information and PAP smear results. Screening low-risk women living with HIV at three-year intervals similar to HIV-negative women appears justified.

Factors associated with the quality of life of people living with HIV in Finland.

In recent years, the concept of quality of life (QoL) has received significant attention in the HIV/AIDS literature. In Finland, however, the factors associated with the QoL of people living with HIV/AIDS (PLWHA) still remain unknown. The aim of this study was to identify the sociodemographic and HIV-related factors associated with the different domains of QoL of PLWHA in Finland. The sample of this cross-sectional study consisted of 453 HIV-infected patients (Mean age = 46.5 years; 76.5% male) followed at the Infectious Disease Clinic of Helsinki University Hospital. Participants completed a self-reported questionnaire covering sociodemographic and HIV-related information, and the Finnish version of the WHOQOL-HIV-Bref questionnaire. Participants reported rather high scores in the six QoL domains, which ranged between 68.48 (Social relationships) and 78.05 (Environment) on a 0-100 scale. Multiple regression analyses revealed that male gender, being married or living in a partnered relationship, being employed, having fewer financial concerns, and not having depression and other medical comorbidities were the main factors positively and consistently associated with higher scores in the different domains of the QoL. HIV-related variables were not significantly associated with QoL ratings. Sociodemographic factors were independently associated with the QoL of PLWHA in Finland. Psychosocial support should reflect these factors in order to improve the health status and well-being of PLWHA.

Quality of life of people living with HIV/AIDS: a cross-country comparison study of Finland and Portugal.

The premises underlying the development of the World Health Organization Quality of Life (WHOQOL) instruments provide a convincing rationale for comparing quality of life (QoL) across countries. The aim of the present study was to compare the QoL of patients living with HIV infection in Finland and in Portugal, and to examine the contribution of the QoL domains to the overall QoL in these two countries. The sample comprised 453 patients from Finland (76.3% male; mean age = 46.50) and 975 from Portugal (69.2% male; mean age = 40.98), all living with HIV. QoL data were collected by use of the WHOQOL-HIV-Bref questionnaire. Significant country differences were found in QoL domains and specific facets. Patients from Finland reported markedly higher scores on all six QoL domains and general facet, than did their Portuguese counterparts. Regarding the specific facets of the WHOQOL-HIV-Bref, patients from Finland also reported significantly higher scores on 24 out of 29. The exceptions were dependence on medications and treatment, positive feelings, personal relationships, sexual activity, and on spirituality, religion and personal beliefs. Regression analyses showed that physical, psychological, and independence domains contributed to overall QoL among the Finnish patients (R(2) = 0.63), whereas among the Portuguese, the domains significantly associated with overall QoL were physical, psychological, independence, and environment (R(2) = 0.48). Country differences in QoL domains and specific facets may reflect sociocultural differences between southern and northern Europe.

HIV infection and cancer.

Cancers in HIV-infected patients are divided into the AIDS-defining and non-AIDS defining cancers. In the era of effective antiretroviral therapy there has been a significant decrease in the incidence of AIDS-defining cancers, whereas the number of non-AIDS defining cancers is on the rise. This is partly explained by the frequent occurrence of conventional risk factors for cancers, but also HIV infection itself seems to further increase the risk. If an HIV-infected person is diagnosed early enough, his/her life expectancy corresponds to that of the general population. Therefore the treatment goal of cancers in HIV-infected patients should be the same as for HIV negative subjects. Antiretroviral agents have significant drug-drug interactions with many other medicines. These must always be taken into account when planning the treatment of HIV-infected patients.

[HIV--from a lethal disease to a chronic illness]. / HIV--tappavasta taudista krooniseksi sairaudeksi.

Combination anti-HIV therapies revolutionized patient life expectancy in the mid-1990's. Afterwards, in the early 2000's, research focused on the adverse effects caused by HIV drugs. Among these, the most serious ones are myocardial infarction at young age, disturbances of kidney function, liver disorders, pancreatitis and osteoporosis. The worsening of prognosis, for instance in respect of cardiac diseases, observed approximately five years ago in patients due to pauses in HIV medication, has changed perspective. Currently it is being discussed whether the overall prognosis will be improved with HIV medication started as early as possible.

[When should a patient be tested for HIV?]. / Milloin pyydän potilaastani HIV-testin?

Thanks to current drug therapy, the prognosis of an early diagnosed HIV-positive patient is almost equivalent to the life expectancy of the general population. Because HIV-positive persons remain typically symptomless for years, suspicion of the infection should be remembered not only on the basis of symptoms compatible with the disease, but also on the basis of mere exposure. A symptomatic HIV patient may be encountered in any special field. The possibility of a symptomless HIV infection should be always kept in mind with patients having a known sexually transmitted disease or chronic viral hepatitis. Diagnosis of HIV is based on the demonstration of antibodies and/ or HIV antigen.

Comparison of dorsocervical with abdominal subcutaneous adipose tissue in patients with and without antiretroviral therapy-associated lipodystrophy.

OBJECTIVE: Combination antiretroviral therapy (cART) is associated with lipodystrophy, i.e., loss of subcutaneous adipose tissue in the abdomen, limbs, and face and its accumulation intra-abdominally. No fat is lost dorsocervically and it can even accumulate in this region (buffalo hump). It is unknown how preserved dorsocervical fat differs from abdominal subcutaneous fat in HIV-1-infected cART-treated patients with (cART+LD+) and without (cART+LD-) lipodystrophy. RESEARCH DESIGN AND METHODS: We used histology, microarray, PCR, and magnetic resonance imaging to compare dorsocervical and abdominal subcutaneous adipose tissue in cART+LD+ (n=21) and cART+LD- (n=11). RESULTS: Albeit dorsocervical adipose tissue in cART+LD+ seems spared from lipoatrophy, its mitochondrial DNA (mtDNA; copies/cell) content was significantly lower (by 62%) than that of the corresponding tissue in cART+LD-. Expression of CD68 mRNA, a marker of macrophages, and numerous inflammatory genes in microarray were significantly lower in dorsocervical versus abdominal subcutaneous adipose tissue. Genes with the greatest difference in expression between the two depots were those involved in regulation of transcription and regionalization (homeobox genes), irrespective of lipodystrophy status. There was negligible mRNA expression of uncoupling protein 1, a gene characteristic of brown adipose tissue, in either depot. CONCLUSIONS: Because mtDNA is depleted even in the nonatrophic dorsocervical adipose tissue, it is unlikely that the cause of lipoatrophy is loss of mtDNA. Dorsocervical adipose tissue is less inflamed than lipoatrophic adipose tissue. It does not resemble brown adipose tissue. The greatest difference in gene expression between dorsocervical and abdominal subcutaneous adipose tissue is in expression of homeobox genes.

Skeletal muscle mitochondrial DNA content and aerobic metabolism in patients with antiretroviral therapy-associated lipoatrophy.

OBJECTIVES: To assess whether mitochondrial dysfunction in skeletal muscle characterizes antiretroviral therapy (ART)-associated lipoatrophy (LA). METHODS: A cross-sectional study comparing HIV-infected, antiretroviral-treated patients with LA (n = 5; LA+) and without LA (n = 5; non-LA) was conducted. Positron emission tomography was used to measure blood flow, oxygen extraction and oxygen consumption in quadriceps femoris muscle during rest and aerobic exercise. Mitochondrial DNA (mtDNA) was quantified by PCR. Body composition was measured by dual-energy X-ray absorptiometry and magnetic resonance imaging. All data are given as means +/- SEM. RESULTS: Compared with the non-LA group, the LA+ group had significantly less limb fat and more intra-abdominal fat, but similar leg muscle mass. The LA+ group versus the non-LA group had reduced mtDNA content per nucleus in adipose tissue (173 +/- 38 versus 328 +/- 62; P = 0.067), but not in skeletal muscle (2606 +/- 375 versus 2842 +/- 309; P = 0.64). Perfusion in resting muscle (34 +/- 7 versus 28 +/- 6 mL/kg/min in the LA+ group versus the non-LA group; P = 0.5), and the mean absolute (277 +/- 30 versus 274 +/- 43 mL/kg/min, respectively; P = 0.95) and relative (10.6 +/- 2.5- versus 11.9 +/- 1.5-fold change, respectively; P = 0.67) increases in perfusion during exercise were similar between the groups. Oxygen consumption at rest (2.2 +/- 0.7 versus 2.1 +/- 0.3 mL/kg/min in the LA+ group versus the non-LA group; P = 0.9), and the mean absolute (14.6 +/- 1.7 versus 24.3 +/- 8.8 mL/kg/min, respectively; P = 0.3) and relative (10.3 +/- 2.8- versus 11.7 +/- 2.4-fold change, respectively; P = 0.73) exercise-induced increases in oxygen consumption were similar between the groups. The oxygen extraction fraction was comparable between the groups, both at rest and during exercise. Plasma lactate concentrations remained unchanged in both groups during exercise. CONCLUSIONS: HIV-infected patients with ART-associated LA have similar mtDNA content in skeletal muscle and comparable skeletal muscle aerobic exercise metabolism to antiretroviral-treated non-lipoatrophic patients.

A meta-analysis of six placebo-controlled trials of thiazolidinedione therapy for HIV lipoatrophy.

OBJECTIVE: To determine the impact of thiazolidinediones (TZD) on changes in limb fat mass in HIV-infected individuals, particularly in those not receiving a thymidine analogue. METHODS: Individual patient data from placebo-controlled, randomized trials of rosiglitazone (n = 5) or pioglitazone (n = 1) were combined. Generalized estimating equation (GEE) models were used to estimate the treatment effect on changes in limb fat mass. RESULTS: In the combined dataset of 427 patients, the baseline median age was 45 years, 86% were male, 80% were Caucasian, 63% were receiving stavudine (d4T) or zidovudine (AZT), 66% were on protease inhibitors, and median body mass index was 23 kg/m(2). In a univariate GEE model, TZD was associated with an increase in limb fat mass (coeff = 0.14 kg vs placebo, P = .04). In a multivariable GEE model, patients receiving pioglitazone had significantly higher limb fat mass gains (coeff = 0.35 kg, P < or = .01) compared to patients receiving placebo, while patients on rosiglitazone did not (coeff = 0.05 kg, P = .48). Interactions between thymidine analogue use and rosiglitazone and pioglitazone were not significant. CONCLUSIONS: In this meta-analysis, pioglitazone therapy was more effective than placebo to increase limb fat mass whereas rosiglitazone was not significantly better than placebo. The effectiveness of these drugs did not vary according to whether the patients were receiving thymidine analogues.