Type Of Antiretroviral Therapy Research Articles

Erectile dysfunction in men with human immunodeficiency virus: prevalence and associated factors.

Male sexuality plays a crucial role in determining the overall quality of life, and it involves complex interactions between physical systems and psychosocial dimensions. Erectile dysfunction (ED) has a particularly notable impact on men's well-being, especially among those living with human immunodeficiency virus (HIV). This study's aim was to explore the prevalence of ED and its associated factors in men with HIV. Cross-sectional research was conducted in a specialized care unit in Paraná, involving 120 adult men living with HIV. Data collection occurred from March 2021 to December 2023, and ED was assessed using the 6-item version of International Index of Erectile Function (IIEF-6) questionnaire. Psychological factors were assessed using the Depression, Anxiety and Stress Scales-21 (DASS-21). The primary outcome was ED. The prevalence of ED was 37.5% [95% confidence interval (CI): 28.8% to 46.2%]. A significant association was observed between advanced age and ED. Regarding the type of antiretroviral therapy (ART), the data revealed a significant association with ED, the differences were particularly notable when comparing the therapeutic regimens of nucleoside reverse transcriptase inhibitor (NRTI) + Integrase inhibitor (INI) vs. NRTI + protease inhibitor (PI) and NRTI + NRTI. Furthermore, mental health factors were analyzed, with anxiety demonstrating a significant association with ED [odds ratio (OR) =2.35; 95% CI: 1.02 to 5.43; P=0.046]. The findings highlight the urgent need for an integrated approach to clinical management that considers both medical and emotional aspects in men living with HIV. It has also a potential to subside further investigations, particularly those adopting a longitudinal design to capture casual mechanisms of ED in men with HIV.

Vitamin D and HIV: Description and correlation of serum levels with clinical and paraclinical variables

Introduction: Vitamin D (VD) has many extra-skeletal functions, such as immune regulation. It is important to recognize its role in patients infected by the human immunodeficiency virus (HIV). The objective of this study was to determine possible correlations between serum VD levels and multiple clinical and paraclinical variables in HIV-infected patients in the city of Bogotá, Colombia. Materials and methods: An observational, cross-sectional study was carried out on 161 HIV-infected patients in the city of Bogotá. VD levels were analyzed in relation to anthropometric classification of nutritional status, clinical and metabolic profile. Results: It was found a prevalence of low VD levels of 60.87%. Statistically significant correlations were detected between VD and the time of sun exposure reported by the patient and the type of antiretroviral therapy. In addition, using a linear regression model, it was found that the use of 2 nucleoside reverse transcriptase inhibitors + 1 integrase inhibitor correlates with hypovitaminosis, even with adequate time of sun exposure. No associations were found with age, sex, race, co morbidities, immune, or metabolic profile. Discussion: Although the pathophysiology of VD deficiency is multifactorial, low VD levels should be considered among the possible adverse effects of antiretro viral therapy and should be included in the usual follow-up of these patients.

Ocular and Adnexal Diseases in Human Immunodeficiency Virus-Infected Pregnant Women Attending HIV Clinics in Ibadan, Nigeria.

Human immunodeficiency virus (HIV) is a lentivirus. It is transmitted through sexual intercourse, shared intravenous drugs, contaminated needle use, blood transfusion, and mother-to-child transmission. Of the patients with HIV, 50%-75% have ocular manifestations and this may be the primary presentation. This study was carried out in two prevention of mother-to-child transmission (PMTCT)/HIV clinics. The aim was to determine the incidence, patterns of presentation, and determinants of ocular and adnexal diseases in HIV-positive pregnant women attending HIV clinics to develop an eye care protocol for them. The study was a cross-sectional study of HIV-positive pregnant women attending the PMTCT/HIV Clinics at University College Hospital and Adeoyo Maternity Teaching Hospital, Ibadan. Patients were interviewed using a structured questionnaire. Blood samples were taken for CD4+ count and viral load. The stage of the disease, type of antiretroviral therapy (ART), and the interval between HIV diagnosis and commencement of ART were recorded. Comprehensive ocular examination, which included visual acuity check unaided and with pinhole, lid, anterior segment examination with slit lamp and posterior segment examination with dilated binocular indirect ophthalmoscopy, was conducted. Statistical Package for Social Sciences version 23 was used to analyse the data. A total of 153 pregnant women aged 23-42 years (mean, 33.5; standard deviation, ±5.6) were recruited. One hundred and fifteen (75.2%) of them were married in a monogamous setting. Multiple sexual partners (48.4%; n = 74-some women married in monogamous settings at the time of recruitment for this study had multiple sexual partners in the past) and the use of unsterilised objects (46.4%; n = 71) were major high-risk behaviours. Ocular and adnexal diseases were found in 81 (53%) participants. HIV-related ocular and adnexal diseases were found in 16 (10%) participants. Of the 16 HIV-related diseases, optic atrophy was found in seven (43.8%), presumed toxoplasmosis in three (18.7%), presumed cytomegalovirus retinitis in three (18.7%) lid warts in two (12.5%), and conjunctival microangiopathy in one (6.3%) participant. The association between HIV- related ocular and adnexal diseases and gestational age, CD4+ count, viral load and type of ART was not statistically significant. The few HIV-related findings in this study could be a result of the improved CD+ count/low viral load of most of the recruited participants. Ensuring that patients attending PMTCT/HIV clinic have at least one ocular examination during pregnancy by collaborating with eyecare professionals could ensure prompt detection and treatment of eye diseases, to improve the quality of life of HIV-positive pregnant women.

Unique Profile of Inflammation and Immune Activation in Pregnant People With HIV in the United States.

Little is known about inflammation/immune activation during pregnancy in people with HIV (PWH) and growth in their children who are HIV-exposed and uninfected (CHEU). Using data from the Pediatric HIV/AIDS Cohort Study and an HIV-seronegative comparison group, we assessed associations of (1) HIV status, mode of HIV acquisition (perinatally vs nonperinatally acquired), and type of antiretroviral therapy (ART) with inflammation/immune activation in pregnancy; and (2) inflammation/immune activation in pregnancy with growth of CHEU at 12 months. Interleukin 6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), soluble(s) TNF-α receptor 1 and 2 (sTNFR1, sTNFR2), sCD14, and sCD163 were measured between 13 and 27 weeks' gestation. Linear regression models were fit to estimate differences between groups for each log-transformed biomarker, adjusted for confounders. Pregnant PWH (188 total, 39 perinatally acquired, 149 nonperinatally acquired) and 76 HIV-seronegative persons were included. PWH had higher IL-6, sTNFR1, sCD14, and sCD163 and lower sTNFR2 compared to HIV-seronegative persons in adjusted models. Among PWH, sCD163 was higher in those with perinatally versus nonperinatally acquired HIV and on PI-based versus INSTI-based ART. Higher maternal concentrations of IL-6, sTNFR2, and hs-CRP were associated with poorer growth at 12 months. Maternal HIV status is associated with a distinct profile of inflammation/immune activation during pregnancy, which may influence child growth.

Bone Mineral Content Prediction by Bioelectrical Impedance Analysis in Children and Adolescents Diagnosed with HIV Infection: Comparison with Dual Energy X-ray Absorptiometry: A Cross-Sectional Study

A body composition analysis has been used to investigate alterations on body tissues in children and adolescents diagnosed with human immunodeficiency virus (HIV) infection, such as low bone mineral content (BMC). The study aimed to developed equations to estimate the BMC in children and adolescents diagnosed with HIV based on a bioelectrical impedance analysis (BIA) using dual energy X-ray absorptiometry (DXA) as a reference method. This is a cross-sectional study conducted with children and adolescents diagnosed with HIV infection. Their body composition was evaluated by BIA and DXA. Linear multiple regression models were constructed to estimate the BMC. Sixty-four children and adolescents aged 8–15 years (12.22 ± 2.13) who were diagnosed with HIV infection participated in the study. The models were substantially correlated with the BMC values, and they explained 82–91% of the BMC, with no differences between DXA and values as estimated by the models. The model with the highest estimate of the BMC (91% of explanation) and the lowest error (SEE of 0.011 kg) included the following variables: body mass, fat mass, total 50 kHz reactance, TCD4 lymphocytes, antiretroviral therapy type, and %TCD4 lymphocytes. The models had a clinically acceptable correlation and low SEE values. The BIA was suitable to estimate the BMC in children and adolescents diagnosed with HIV.

Immune markers and microbial factors are related with periodontitis severity in people with HIV

ObjectiveThe objective of the study is to assess systemic immune markers and microbial factors related to periodontitis severity in people living with HIV.MethodsEighty people living with HIV (PLWH), who exhibited in the last two viral load measurements < 40 copies/mL, underwent full-mouth periodontal examinations and sub-gingival plaque sampling. Periodontitis was classified according to the CDC-AAP case definition. Inflammation, immune-activation, and immunosenescence markers were assessed, microbiological analyses were performed, and oral care routines and HIV characteristics were noted.ResultsFrom our group of PLWH, 42.5% and 57.5% suffered from moderate and severe periodontitis, respectively. Oral care habits did not differ between PLWH with moderate and severe periodontitis. Bacterial subgingival plaque loads were higher, and Porphyromonas gingivalis was more prevalent in PLWH with severe periodontitis than with moderate periodontitis (53% vs 7%, respectively). Mean C-reactive protein levels [CRP, 1.6 mg/L versus 0.8 mg/L, p = 0.020] and percentages of senescent CD28-CD57 + CD8 + T-cells in peripheral blood [16.5 versus 8.9, p = 0.035] were higher with severe periodontitis. Infection duration, CD4 count, CD4/CD8 ratio and type of antiretroviral therapy did not differ between both groups.ConclusionsPeriodontitis severity is related to increased prevalence of Porphyromonas gingivalis, elevated CRP levels, and higher frequencies of circulating CD8 + senescent cells in PLWH.

Association between bone mineral density and content and physical growth parameters among children and adolescents diagnosed with HIV: a cross-sectional study.

ABSTRACTBACKGROUND:During childhood and adolescence, there are significant increases in bone mineral content (BMC) and bone mineral density (BMD).OBJECTIVE:To investigate physical growth parameters associated with BMD and BMC among children and adolescents diagnosed with human immunodeficiency virus (HIV).DESIGN AND SETTING:Cross-sectional study conducted in Florianópolis, Brazil, among 63 children and adolescents (aged 8-15 years) diagnosed with HIV.METHOD:BMD, BMC and fat percentage z score were evaluated using dual X-ray absorptiometry. Age/height z score and body mass index (BMI)/age z score were obtained in accordance with international recommendations, and bone age was obtained through hand-wrist radiography. Sex, family income, information on HIV infection (T CD4+ lymphocyte count, viral load and type of antiretroviral therapy, moderate-vigorous physical activity and sedentary behavior) were used as adjustment variables in the analyses. Simple and multiple linear regression analyses were performed, with a significance level of P ≤ 0.05.RESULTS:Subtotal BMD (without the head region) was directly associated with bone age, BMI/age z score and fat percentage z score, even after adjusting for covariates. Subtotal BMC/height was directly associated with bone age, height/age z score, BMI/age z score and fat percentage z score, even after adjusting for covariates.CONCLUSION:Subtotal BMD and subtotal BMC/height were directly associated with physical growth indicators among children and adolescents diagnosed with HIV.

COVID-19 Severity and COVID-19-Associated Deaths Among Hospitalized Patients with HIV Infection - Zambia, March-December 2020.

The effect of HIV infection on COVID-19 outcomes is unclear. Studies in South Africa (1) and the United Kingdom (2) found an independent association between HIV infection and COVID-19 mortality; however, other studies have not found an association between poor COVID-19 outcomes and either HIV status among hospitalized patients (3-5) or HIV-associated factors such as CD4 count, viral load, or type of antiretroviral therapy (ART) (6). The effect of HIV infection on COVID-19 outcomes remains an urgent question in sub-Saharan Africa, where many countries are experiencing dual HIV and COVID-19 epidemics, and capacity to treat severe COVID-19 is limited. Using data from patients with probable or confirmed COVID-19 admitted to specialized treatment centers during March-December 2020 in Zambia, the Zambian Ministry of Health and CDC assessed the relationship between HIV infection and severe COVID-19 and COVID-19-associated death. Among 443 patients included in the study, 122 (28%) were HIV-positive, and of these, 91 (89%) were receiving ART at the time of hospitalization. HIV status alone was not significantly associated with severe COVID-19 at admission or during hospitalization or with COVID-19-associated death. However, among HIV-positive persons, those with severe HIV disease were more likely to develop severe COVID-19 and were at increased risk for COVID-19-associated death. Ensuring that persons maintain HIV disease control, including maintaining ART continuity and adherence, achieving viral suppression, and addressing and managing underlying medical conditions, could help reduce COVID-19-associated morbidity and mortality in sub-Saharan Africa.

376. COVID-19 Severity in HIV+ Patients Receiving Tenofovir

BackgroundEarly in the COVID-19 pandemic, tenofovir (TAF/TDF) was identified as a potential agent for SARS-CoV-2 due to binding to RNA-dependent RNA polymerase similarly to remdesivir. This led to the hypothesis that TAF/TDF may be lessening the severity and improving outcomes of COVID-19 infection.COVID-19 Severity COVID-19 Infection Outcomes MethodsPatients were identified by searching for HIV infection and SARS-CoV2 PCR testing. Type of antiretroviral therapy (ART), CD4+ cell count, HIV viral load (VL), comorbidities, presenting symptoms, severity of COVID infection, and outcomes were analyzed. COVID disease was classified as mild, moderate, severe, or critical based on World Health Organization criteria. We primarily sought to determine the effect of TAF/TDF on the severity of COVID infection. The secondary endpoint was to determine the effect of low CD4 count and HIV VL on the severity of infection.Results39 HIV+ patients were tested at least once for SARS-CoV2 by PCR at VA NJ Health Care System. 18 of 39 patients were PCR positive. In those, common presenting symptoms included: fever (15/18), cough (7/18), and lethargy/fatigue (6/18). 16 of the 39 HIV+ patients’ ART included TAF/TDF; 8 of 18 COVID+ and 8 of 21 COVID-. In the COVID- group, 2 patients had CD4 count < 200 cells/mm3, 3 patients had HIV VL >200, and 19 of 21 had at least 1 comorbidity. In the COVID+ group, 3 had CD4 count < 200 cells/mm3, none had detectible HIV viremia, and all but one had comorbidities. Of COVID+ infections, 7 were mild, 3 moderate, 8 severe, and 5 patients died. 4 of the 5 patients that did not survive were in non-TAF/TDF group. All 3 patients with CD4 count < 200 cells/mm3 had severe disease. 6 out of 8 patients developed mild disease in TAF/TDF group vs. 1 out of 10 patients in non-TAF/TDF group. 1 out of 8 and 7 out of 10 patients had severe or critical disease in TAF/TDF vs non-TAF/TDF groups respectively.ConclusionIn this sample of 18 HIV+ patients with COVID-19 infection, patients receiving TAF/TDF were more likely to develop mild disease and have full recovery than those who were on TAF/TDF-free regimens (75% vs. 10% and 87.5% vs. 50%, respectively). Patients not on TAF/TDF-based regimens had a higher rate of developing severe and critical COVID-19 disease (40% vs. 0% and 30% vs. 12.5%, respectively).Disclosures All Authors: No reported disclosures

The association of nadir CD4-T cell count and endothelial dysfunction in a healthy HIV cohort without major cardiovascular risk factors.

Objectives:HIV-infected population may have increased risk of cardiovascular disease. The prevalence of traditional cardiovascular disease risk factors such as hypertension, diabetes and dyslipidemia in HIV-infected individuals has made it difficult to assess the direct effects of HIV and immune factors on endothelial dysfunction and associated increased risk of atherosclerosis. The purpose of this study was to investigate indicators of endothelial dysfunction in an HIV cohort without hypertension and diabetes.Methods:We studied 19 HIV-infected patients between the ages of 25–76 years old with effectively suppressed viral load and without diagnosis of hypertension or diabetes. Endothelial function was measured by digital thermal monitoring of vascular reactivity using the VENDYS technique. Endothelial function was reported as vascular reactivity index. Systolic blood pressure and diastolic blood pressure at the time of VENDYS test were measured and latest lipid panels were recorded. The association between vascular reactivity index and CD4-T cells count, different antiretroviral therapy types (non-nucleoside reverse transcriptase, nucleoside reverse transcriptase, protease inhibitors, integrase inhibitors), vitamins use, systolic blood pressure, diastolic blood pressure, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol was investigated.Results:Mean vascular reactivity index was 1.87 ± 0.53. Vascular reactivity index, marker of endothelial dysfunction, showed a significant correlation with lower nadir CD4 count (p = 0.003) as well as low-density lipoprotein cholesterol (p = 0.02). No additional significant correlation between vascular reactivity index and the rest of the investigated variables was found.Conclusion:Vascular reactivity index, a clinical predictor of endothelial dysfunction, is associated with lower nadir CD4-T cell and low-density lipoprotein cholesterol in HIV-infected men with no history of hypertension or diabetes and before clinical evidence of cardiovascular disease.

Stillbirth in Women Living With HIV Delivering in the United Kingdom and Ireland: 2007-2015.

Women living with HIV have a higher risk of adverse birth outcomes, but questions remain regarding their specific risk factors for stillbirth and the extent to which maternal HIV is associated with stillbirth. Using data on pregnant women with HIV reported within population-based surveillance in the United Kingdom/Ireland, we described stillbirth rates in 2007-2015 stratified by type of antiretroviral therapy (ART) and evaluated risk factors using Poisson regression. General population stillbirth rates by maternal world region of origin were derived from national annual birth statistics, and compared with rates in women with HIV, using standardized stillbirth ratios with the general population as the reference. Between 2007 and 2015, there were 10,434 singleton deliveries in 8090 women with HIV; 75% of pregnancies were in women of African origin; and 49% were conceived on ART. The stillbirth rate was 8.5 (95% confidence interval: 6.9 to 10.5) per 1000 births. Risk factors for stillbirth included pre-eclampsia, diabetes, Asian maternal origin (versus United Kingdom/Ireland), CD4 count <350 cells/mm, older maternal age, and primiparity. Conceiving on ART did not increase the risk. The stillbirth rates (per 1000 births) by type of ART were 14.3, 11.7, 8.3, and 6.0, respectively for NVP + XTC/TDF-, LPV/r + 3TC/ZDV-, NVP + XTC/ABC-, and NVP + XTC/ZDV-exposed pregnancies (P value = 0.40). The standardized stillbirth ratio was 129 (95% confidence interval: 101 to 165) in women with HIV compared with the general population. After adjusting for maternal origin, the stillbirth rate remained higher in women with HIV than the general population. We recommend further studies to understand and prevent this excess.

Diagnosis, prevention, and treatment of bone fragility in people living with HIV: a position statement from the Swiss Association against Osteoporosis.

Life expectancy of people living with HIV (PLWH) is reaching similar length as in the general population. Accordingly, age-related comorbidities, including osteoporosis, are increasing. Fracture risk is higher and increases approximately 10years earlier in PLWH. Classical risk factors of bone fragility are highly prevalent in PLWH but factors specific for HIV infection itself and the type of antiretroviral therapy (ART) (triple combination antiretroviral therapy) regimen (especially tenofovir and protease inhibitors) also contribute to bone loss. The majority of bone loss occurs during virus activity and at initiation of ART (immune reconstitution) and is associated with an increase of bone resorption (upregulation RANKL). Recent data indicate that calcium and vitamin D supplements as ART initiation lower BMD loss. The reduction of tenofovir plasma concentrations with tenofovir alafenamide attenuates BMD loss but it remains unknown whether it will contribute to reduce fracture risk. Hence, special considerations for the management of bone fragility in PLWH are warranted. Based on the current state of epidemiology and pathophysiology of osteoporosis in PLWH, we provide the consensus of the Swiss Association against Osteoporosis on best practice for diagnosis, prevention, and management of osteoporosis in this population. Periodic assessment of fracture risk is indicated in all HIV patients and general preventive measures should be implemented. All postmenopausal women, men above 50years of age, and patients with other clinical risk for fragility fractures qualify for BMD measurement. An algorithm clarifies when treatment with bisphosphonates and review of ART regimen in favour of more bone-friendly options are indicated.

The association between oral disease and type of antiretroviral therapy among perinatally HIV-infected youth.

This study explores the association between combination antiretroviral therapy (cART) and oral health outcomes (dental and periodontal) among perinatally HIV-infected (PHIV) youth. We conducted a cross-sectional study of oral health among PHIV youth participating in the Oral Health substudy of the Pediatric HIV/AIDS Cohort Study (PHACS). Dentists at research sites were trained/calibrated on how to perform a standardized oral mucosal, dental and periodontal examination. They assessed the decayed-missing-filled-surfaces and teeth index (DMFS/T). The number of decayed surfaces and teeth and the number of teeth with gingival bleeding on probing for each participant were derived from the examination. Data for analysis included lifetime measurements of CD4 cell count and viral load, sociodemographic information and current/past history of ART. Among 209 PHIV youth, 95% were on ART at the time of enrolment. Among 143 PHIV youth on the same cART for at least 1 year, we found that the mean decayed teeth score of those receiving cART containing an integrase inhibitor was 86% higher than that of those on cART without an integrase inhibitor after adjusting for age, lifetime proportion of unsuppressed viral load and CD4 cell count nadir. Initiating protease inhibitors before age 6 years was associated with a significantly lower DMFT score than participants who initiated at age 6 years and older. Our study revealed that PHIV youth who received cART containing an integrase inhibitor had a significantly higher number of untreated active caries than those on cART without an integrase inhibitor. This may warrant closer dental surveillance of those receiving an integrase inhibitor.

Contribution of HIV Infection, AIDS, and Antiretroviral Therapy to Exocrine Pathogenesis in Salivary and Lacrimal Glands.

The structure and function of exocrine glands are negatively affected by human immunodeficiency virus (HIV) infection and its co-morbidities, including innate and adaptive immune responses. At the same time, exocrine function may also be influenced by pharmacotherapies directed at the infectious agents. Here, we briefly review the role of the salivary glands and lacrimal glands in normal physiology and exocrine pathogenesis within the context of HIV infection and acquired immune deficiency syndrome (AIDS), including the contribution of antiretroviral therapies on both. Subsequently, we discuss the impact of HIV infection and the types of antiretroviral therapy on disease management and therapy development efforts.

MONITORING OF IMMUNE RESPONSE IN VIROLOGIC SUCCESSFULLY TREATED HIV-INFECTED PATIENTS IN SOUTHEASTERN SERBIA

The number of CD4 lymphocytes defines the evolutional stage of HIV-infection and is the most important for a reliable estimation of the individual risk of developing AIDS. However, it is difficult to predict the degree of immune reconstitution during antiretroviral therapy, as it varies significantly from one person to another. Further investigations to better understand the limitations of immunological success are necessary to improve the response to treatment and regimen durability. The current study includes HIV-infected patients in Southeastern Serbia with achieved virologic suppression of HIV infection. The CD4 count was determined by flow cytometry, and was correlated with the duration of treatment, initial number of CD4 cells, type of antiretroviral therapy, mode of transmission of infection, age and gender of examinees. The resulting arithmetic mean and standard deviation of CD4 number was 473±259 cells/µl (range, 1130 cells/µl). There was no statistically significant correlation between the values of CD4 count and length of treatment, stage of the infection at which the therapy was started, treatment profile, method of infection, age or gender. The obtained results are comparable with the existing studies that follow immunological response to antiretroviral therapy and primarily point out the issue of substantial individual response variability, which has not yet been fully elucidated.

Genetic polymorphisms in fatty liver disease in HIV positive patients receiving combined antiretroviral therapy (cART)

Background and aims: Hepatic steatosis possibly occurs with any type of antiretroviral therapy (cART). Genome wide association studies have identified 7 single nucleotide polymorphisms (SNPs) predisposing to fatty liver disease in obesity. In this study, we analyzed if the risk of developing fatty liver under cART is associated to single nucleotide polymorphisms in HIV positive patients.

Interaction Between Alcohol Consumption Patterns, Antiretroviral Therapy Type, and Liver Fibrosis in Persons Living with HIV.

We examined the longitudinal association between alcohol use and liver fibrosis, measured by FIB-4 Score, among HIV-infected individuals by (1) antiretroviral therapy (ART) class, and (2) the presence of hepatitis C (HCV) co-infection. This was a prospective cohort study of 550 individuals in the Johns Hopkins HIV Clinical Cohort initiating ART between 2000 and 2012. The relationship between alcohol consumption (defined using NIAAA categories of non-, moderate, and hazardous drinkers) and liver fibrosis (FIB-4 score) by ART class was assessed using linear mixed effects models. Additionally, we examined whether the presence of HCV modified and whether viral load mediated the relationship between alcohol use and liver fibrosis. Overall, FIB-4 levels were 15.6% higher in hazardous drinkers compared to moderate drinkers (p = 0.025) after adjusting by age, sex, and race. Hazardous drinkers on PI-based regimens had FIB-4 scores 26.9% higher than moderate drinkers (p = 0.015). However, there was no difference in FIB-4 levels between hazardous drinkers on non-PI-based regimens compared to moderate drinkers (1.83% versus moderate drinkers, p = 0.848). There was no significant difference in FIB-4 between nondrinkers and moderate drinkers, irrespective of ART regimen. These associations were not modified by HCV status or mediated by viral load changes. Individuals with hazardous alcohol consumption and on PI-based regimens had significantly increased liver fibrosis, as measured by the FIB-4. These data suggest that providers should consider level of alcohol consumption when choosing an ART regimen to minimize detrimental effects on the liver.

L-carnitine supplementation in patients with HIV/AIDS and fatigue: a double-blind, placebo-controlled pilot study.

BackgroundThe purpose of this study was to determine the effect of L-carnitine supplementation on fatigue in patients with terminal human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS).MethodsIn this randomized, double-blind, placebo-controlled, parallel-group study, patients who had end-stage HIV/AIDS with carnitine deficiency and fatigue received 3 g of oral L-carnitine or placebo for 2 weeks, followed by a 2-week, open-label phase with the same amount of L-carnitine for all patients. The primary outcome was the degree of fatigue according to the Brief Fatigue Inventory. Secondary outcomes included serum carnitine and lactate levels, physical, emotional, social, and functional well-being, performance status, mood, and CD4 count.ResultsEighteen patients in the treatment arm and 17 in the placebo arm completed the trial. At the end of the double-blind phase, total and free carnitine levels in the treatment arm rose from 28±9 to 48±17 nM/L (P<0.001) and from 24±8 to 40±13 nM/L (P<0.001) respectively, with no changes in the placebo arm. The primary outcome, ie, fatigue measured at the end of the blinded phase, did not improve. Secondary outcomes of function, quality of life, and mood did not show improvement either. The secondary outcome of serum lactate decreased from baseline in the treatment group (1.45±0.76 to 1.28±0.52 mmol/L) and increased in the placebo group (1.38±0.62 to 1.84±0.74 mmol/L; P<0.005).ConclusionOur study suggests that 3 g of oral L-carnitine supplementation for 2 weeks in terminally ill HIV/AIDS patients does not improve fatigue. This study might help to determine the dose and duration of treatment used in future clinical trials, as higher doses and/or longer periods of supplementation might be needed in order to detect an improvement. The reduction in serum lactate levels suggests a potential role for L-carnitine supplementation in patients undergoing certain types of antiretroviral therapy. This study contributes evidence-based data to the field of alternative and complementary medicine, a multibillion dollar industry in which controlled studies are not the norm.

Concurrent use of comedications reduces adherence to antiretroviral therapy among HIV-infected patients.

The use of highly active antiretroviral therapy has significantly reduced morbidity and mortality, thus increasing life expectancy of human immunodeficiency virus (HIV)-infected individuals, transforming HIV into a chronic disease. Accordingly, there has been an increase in the number of comorbidities concomitantly present in these individuals and also an increased use of comedications, which may negatively impact antiretroviral therapy adherence. These factors can affect adherence to antiretroviral therapy. The role of the HIV clinical pharmacist is essential to achieve therapeutic objectives and enhance adherence. To determine the influence of the comorbidities and comedications on antiretroviral therapy adherence among HIV-infected patients receiving services from a clinical pharmacist. We conducted a prospective observational study that included HIV-infected outpatients who attended the pharmaceutical care office of a hospital pharmacy service, which initiated antiretroviral treatment between January 2002, and December 2011. The variables analyzed in the study were demographics (sex and age), HIV transmission mode, and the following variables at the time of comedication collection: hepatitis C virus or hepatitis B virus coinfection, HIV plasma viral load (copies/mL) and CD4+ T-cell count (cells/µL), Centers for Disease Control and Prevention HIV classification, number of hospital admissions and emergency room visits, and antiretroviral therapy-related features (type at baseline, treatment-naïve status, and number of changes since starting antiretroviral therapy). For follow-up at 12 months, antiretroviral therapy adherence was measured through pharmacy dispensing records and the Morisky Medication Adherence Scale (MMAS). Patients were considered adherent if antiretroviral therapy adherence through dispensing records was greater than 90%, and the MMAS score was 4. Other variables were number of comorbidities and number of comedications for other chronic diseases (non-HIV drugs). According to the number of comorbidities, patients were categorized as having multiple chronic conditions (polypathology) if they had 2 or more chronic diseases. Polypharmacy was defined specifically as the use of 5 or more prescription medications in a medication regimen. In addition, a complexity therapeutic index of antiretroviral therapy was calculated for each patient. We determined the risk of drug-related problems using the tool Predictor Index. To identify independent predictors of adherence to antiretroviral therapy, we performed a univariate logistic regression. Afterward, those variables that showed statistical significance in the univariate analysis and those with P less than 0.25 were included in a multivariate model. The sample size was estimated by the Freeman equation. We included 594 patients in the study (80.1% men, median age 47 years). In the univariate analysis, the variables that showed statistically significant relationships with antiretroviral therapy adherence were HIV transmission mode, detectable viral load, CD4+ T-cell count, AIDS-defining condition, hospital admission, antiretroviral therapy-naïve treatment, type of antiretroviral therapy, high risk of drug-related problems, polypathology, and polypharmacy. Multivariate analysis showed that independent predictors of nonadherence to antiretroviral therapy were HIV transmission by intravenous drug use (OR = 0.56, 95% CI = 0.35-0.90), previous treatment with antiretroviral therapy (OR = 0.09, CI = 0.04-0.24), nontreatment changes (OR = 0.12, CI = 0.05-0.31), high risk of drug-related problems (OR = 0.38, CI = 0.23-0.63), and polypharmacy (OR = 0.36, CI = 0.21-0.61). The value of the Hosmer and Lemeshow test confirmed the validity of this model (P = 0.378). Recently, the number of HIV-infected patients with polypharmacy has been higher, increasing the risk of nonadherence. Furthermore, previous treatment with antiretroviral therapy, HIV transmission by intravenous drug use, and high risk of drug-related problems are also associated with lower adherence.

Survival probabilities for HIV infected patients through semi-Markov processes

SUMMARY In this paper we apply a parametric semi-Markov process to model the dynamic evolution of HIV-1 infected patients. The seriousness of the infection is rendered by the CD4+ T-lymphocyte counts. For this purpose we introduce the main features of nonhomogeneous semi-Markov models. After determining the transition probabilities and the waiting time distributions in each state of the disease, we solve the evolution equations of the process in order to estimate the interval transition probabilities. These quantities appear to be of fundamental importance for clinical predictions. We also estimate the survival probabilities for HIV infected patients and compare them with respect to certain categories, such as gender, age group or type of antiretroviral therapy. Finally we attach a reward structure to the aforementioned semi-Markov processes in order to estimate clinical costs. For this purpose we generate random trajectories from the semi-Markov processes through Monte Carlo simulation. The proposed model is then applied to a large database provided by ISS (Istituto Superiore di Sanità, Rome, Italy), and all the quantities of interest are computed.