José Antonio Mata-Marín

Correlation between HIV viral load and aminotransferases as liver damage markers in HIV infected naive patients: a concordance cross-sectional study.

Abnormalities in liver function tests could be produced exclusively by direct inflammation in hepatocytes, caused by the human immunodeficiency virus (HIV). Mechanisms by which HIV causes hepatic damage are still unknown. Our aim was to determine the correlation between HIV viral load, and serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as markers of hepatic damage in HIV naive infected patients.We performed a concordance cross-sectional study. Patients with antiviral treatment experience, hepatotoxic drugs use or co-infection were excluded. We used a Pearsons correlation coefficient to calculate the correlation between aminotransferases serum levels with HIV viral load. We enrolled 59 patients, 50 men and 9 women seen from 2006 to 2008. The mean (± SD) age of our subjects was 34.24 ± 9.5, AST 37.73 ± 29.94 IU/mL, ALT 43.34 ± 42.41 IU/mL, HIV viral load 199,243 ± 292,905 copies/mL, and CD4+ cells count 361 ± 289 cells/mm3. There was a moderately strong, positive correlation between AST serum levels and HIV viral load (r = 0.439, P < 0.001); and a weak correlation between ALT serum levels and HIV viral load (r = 0.276, P = 0.034); after adjusting the confounders in lineal regression model the correlation remained significant. Our results suggest that there is an association between HIV viral load and aminotransferases as markers of hepatic damage; we should improved recognition, diagnosis and potential therapy of hepatic damage in HIV infected patients.

Risk factors and correlates for anemia in HIV treatment-naïve infected patients: a cross-sectional analytical study

BackgroundHematologic manifestations of the human immunodeficiency virus (HIV) infection are a well-recognized complication of the disease and may be clinically important. Our objective was to determine the risk factors for anemia and its correlation with HIV treatment-naïve infected patients without co-infection or opportunistic diseases.FindingsWe performed a cross-sectional comparative study in which HIV treatment-naïve infected patients with anemia were compared with a control group of HIV patients without anemia. The interrelationship between risk factors and anemia was determined. Odds ratio and 95% confidence intervals were calculated, to adjust for the effects of potential confounders and we used a logistic regression model. Pearsons correlation coefficient was obtained to calculate the correlation between risk factors and hemoglobin.We enrolled 54 men and 9 women. Anemia was found in 13 patients; prevalence .20 (CI 95% 0.12-0.32). Severe anemia was found in only one patient (1.5%). Only CD4+ Cells Count <200 cells/mm3 was associated with increased risk of anemia in the multivariate analysis. There was a moderately strong, positive correlation between WBC and hemoglobin (r = 0.49, P < 0.001) and between CD4+ cell count and hemoglobin (r = 0.595, P < 0.001) and a moderately strong, negative correlation between HIV RNA viral load and hemoglobin (r = - 0.433, P < 0.001).ConclusionsAnemia is a common manifestation in the Mexican population without antiretroviral therapy. In HIV naïve patients a CD4+ Cell Count < 200 cells/mm3 was associated with an increased risk of anemia. There is a positive correlation between hemoglobin and CD4+ cell count.

Effect of antiretroviral therapy on inflammatory markers of endothelial dysfunction in HIV treatment-naïve infected patients.

The aim of this study was to evaluate the effect of antiretroviral therapy on inflammatory markers of endothelial dysfunction in HIV treatment‐naïve infected patients. This was a prospective cohort study in HIV treatment‐naïve infected patients. The patients were assigned to a untreated group or a treatment group according to the therapeutic strategy received. Patients in the treatment group received efavirenz or lopinavir/ritonavir, each given with zidovudine and lamivudine. HIV RNA, CD4+ cell count, and the levels of hsCRP, sCD40L, sICAM‐1, sVCAM‐1, and sE‐selectin were measured before and 12 weeks after treatment. Fifty patients were enrolled: 13 in the untreated group and 37 in the treatment group; 48 (96%) completed the follow‐up. The mean (±SD) age was 33 ± 9 years, and 38 (79%) were men. The median pretreatment CD4+ cell counts were 263 cells/ml (IQR 118–341) in the treatment group and 658 cells/ml (IQR 475–887) in the untreated group. In the treatment group, the median serum sVCAM‐1 and sICAM‐1 levels decreased by a small but significant amount (1,400 and 228 ng/ml, respectively, P < 0.05) from before to after the 12 weeks. These levels did not change in the untreated group. Antiretroviral therapy is associated with a decrease in sVCAM‐1 and sICAM‐1 levels after 12 weeks of treatment. J. Med. Virol. 85:1321–1326, 2013.

Development and validation of a questionnaire to identify patients with sleep apnea in Mexican population: Mexican questionnaire to identify sleep apnea.

PurposeTo develop and validate a questionnaire to identify patients with obstructive sleep apnea (OSA) in Mexican population.MethodsWe performed a cross-sectional study to develop and validate an instrument in Spanish language, consistent in an 18-item questionnaire. We enrolled patients seen from July 2008 to August 2009. We evaluated the internal consistency with the Kuder Richardson coefficient, a value greater than 0.70 was considered a good index correlation. Sensitivity, specificity, and positive and negative predictive factor was obtained with standard methods by comparison with polysomnographic results. Validity of Mexican questionnaire at baseline and follow-up was assessed using Pearson correlations coefficient.ResultsWe enrolled 100 patients. The initial pool comprised 25 items, four items were considered confusing and they were omitted; then, a preliminary questionnaire comprising 21 items was obtained, and three items were removed by presenting a response rate lesser than 90%, yielding a total of 18 items for the final questionnaire. This evaluation was performed stratifying in groups related to severity of illness. Snoring was the question with the greatest sensitivity to detect OSA; and obesity class I was the criteria with greatest specificity to detect OSA.ConclusionThe screening tool proposed in this study has the advantages of being quick, inexpensive, easy to apply and reproducible, and the result has reliability with acceptable sensitivity; this is a symptom-based questionnaire with good predictive ability and it will avoid unnecessary sleep studies in the subjects who are not at high risk for having OSA.

Responses to peginterferon alfa-2a vs alfa-2b plus ribavirin in a Mexican population with chronic hepatitis C

INTRODUCTION The WHO estimates that 180 million people are chronically infected with hepatitis C virus (HCV) throughout the world. Despite the emergence of new therapies, the combination of pegylated interferon and ribavirin remains the accepted standard of care in low-income countries, including Mexico. Two types of peginterferon are available (peginterferon alfa-2a and peginterferon alfa-2b), and both are recommended for the treatment of HCV, although there is controversy over which treatment option is most effective. METHODOLOGY This was a retrospective cohort study at a infectious disease center in Mexico City. Patients were included if they had received peginterferon alfa-2a or peginterferon alfa-2b plus ribavirin. Age, sex, body mass index, AST platelet ratio index, HCV RNA viral load, levels of alanine aminotransferase, aspartate aminotransferase, bilirubin, albumin, and hemoglobin, and platelet and leukocyte counts of the subjects were assessed before treatment and at weeks 4, 12, 24, 48, and 6 months post treatment. RESULTS Eighty-seven patients met the inclusion criteria. A sustained virological response (SVR) occurred in 33 (38%) of them, 11 (33%) given peginterferon alfa-2a and 22 (67%) given peginterferon alfa-2b (p = 0.17). Seventeen patients (20%) relapsed, 7 (41%) of those given peginterferon alfa-2a and 10 (59%) of those given peginterferon alfa-2b (p = 0.76); 27 (31%) patients were non-responders (p = 0.09). The rates of anemia, thrombocytopenia, and leukopenia were similar in both groups. CONCLUSIONS Similar SVR rates and frequencies of adverse events were observed. Either type of interferon can be used to treat HCV infection in the Mexican population.

Dyslipidemia and Fasting Glucose Impairment among HIV-InfectedPatients 48-Weeks after the First Antiretroviral Regimen

Background: People infected with human immunodeficiency virus (HIV) develop lipid and glucose metabolic alterations, which predisposes them to cardiovascular disease. The aim of this study was to evaluate the cumulative incidence of dyslipidemia and fasting glucose impairment after 48 weeks of initiating the first antiretroviral (ART) regimen and the association with the type of ART regimen. Method: Retrospective cohort of HIV-1 infected patients attending in the AIDS clinic of five centers of the country, between February 2009 and March 2013. Lipids (total cholesterol and triglycerides) and fasting glucose, were collected prior and 48 weeks after starting ART. We assessed risk factors for dyslipidemia and fasting glucose. To adjust for the effects of potential confounders of metabolic alterations we used logistic regression model. Results: During the study, 223 patients on ART were evaluated. Median age was 34 years [interquartile range (IQR): 28-43]. Of the total patients, 201 (90%) were men. Most common OBR regimens were tenofovir/emtricitabine (TDF/FTC), and efavirenz (EFV) in 42%, abacavir/lamivudine (ABC/3TC) +EFV in 16.6% and TDF/FTC+nevirapine (NVP) in 11.7% patients. Cumulative incidence per 1,000 patients/year of glucose ≥ 100 mg/dL was 233.1, total cholesterol >200 mg/dL was 273.5 and tryglicerides >200 mg/dL was 372.2. The proportion of patients with hypertriglyceridemia (>200 mg/dL) at 48 weeks of ART initiation was 37.2% (95% CI: 31.1-43.7%), hypercholesterolemia (>200 mg/dL) 32.3% (95% CI: 26.5-38.6%) and impairment of fasting glucose (IFG) (>100 mg/dL) 23.3% (95% CI: 18.2-29.2%), After adjustment in a logistic regression model for IFG, EFV-containing regimen OR 2.9 (95%CI 1.12-7.45); p=0.027; for hypertriglyceridemia, age >40 years old OR=1.9 (95% CI: 1.01-3.63); p=0.044, ABC/LAM-containing regimen OR=2.69 (95% CI: 1.42-5.09); p=0.002 and LPV/r-containing regimen OR=5.04 (95% CI 2.32-10.92); p=0.001 were significant; finally, for hypercholesterolemia age >40 years old OR=2.4 (95% CI: 1.15- 4.9); p=0.004 and ABC/3TC-containing regimen OR=1.87 (95% CI: 1.01-3.49); p=0.05 remain significant. Conclusion: These data show high risk of cumulative incidence of IFG and dyslipidemia after initiation of ART. Age >40 years old, ABC/3TC and LPV/r-containing regimens were independent factors to develop dyslipidemia and EFV-containing regimen for IFG in this cohort.

Case report: Identification of recombinant HCV genotype 1b–2b by viral sequencing in two patients with treatment failure, who responded to re-treatment with sofosbuvir and daclatasvir

Hepatitis C virus (HCV) infection is a global health problem. HCV has been classified into seven genotypes and >67 subtypes. Genotyping is necessary to enable selection of appropriate treatments. The commercial molecular techniques currently used do not identify some HCV subtypes, mixed infections and recombinant forms. In this study, the core-E1 and NS5B regions were sequenced and phylogenetically analysed to identify infections by HCV recombinant genotype 1b-2b in two patients who had initially been diagnosed with HCV genotype 2 infection by reverse hybridization with a Versant HCV Genotype 2.0 Assay. Response to treatment was monitored by viral kinetics. Therapeutic failure occurred with initial treatment with PEGylated interferon-α2b and ribavirin, but the use of sofosbuvir and daclatasvir on a re-treatment regimen after reclassification of the infecting virus resulted in a sustained virologic response. The use of a sequencing approach in treatment-naïve infected patients could enable physicians to select the optimal therapy and avoid possible relapses and adverse reactions associated with antiviral therapy.

Mexican patients with HIV have a high prevalence of vertebral fractures

Low bone mineral density (BMD) and fragility fractures are common in individuals infected with HIV, who are undergoing antiretroviral therapy (ART). In high-income countries, dual energy X-ray absorptiometrry is typically used to evaluate osteopenia or osteoporosis in HIV infected individuals. However, this technology is unavailable in low andmiddle income countries, so a different approach is needed. The aim of this study was to use X-ray scans of the spine to determine the prevalence of and associated risk factors for vertebral fractures in HIVinfected patients in a tertiary-care hospital in Mexico. We conducted a cross-sectional study of outpatients who were >40 years old and receiving ART at the Hospital de Infectología, La Raza National Medical Center in Mexico City, Mexico. We used semi-quantitative morphometric analysis of centrally digitized X-ray images to assess vertebral deformities in the spine. Anterior, middle and posterior vertebral heights were measured, and height ratios were calculated. For each vertebral body, fractures were graded on the basis of height ratio reductions, and a spine deformity index’ (SDI) value was calculated by summing the grades of the vertebral deformities: An SDI>1 was indicative of a vertebral fracture. We included 104 patients, 87% of whom were men. The median age was 49 years [interquartile range (IQR) 42-52]. The most common stage of HIV infection, as defined by the Centers for Disease Control, was B2 in 40 (39%) of patients. Forty seven (45%) patients were on ART regimens that included protease inhibitors (PIs) and 100 (96%) being treated with tenofovir. The median time of ART was 6.5 years (IQR 1.6-9.0). Of the 104 patients in our study, 83 (80%) had undetectable viral load, as assessed by HIV-1 RNA levels, 32 (31%) showed evidence of a previous fracture, 4 (4%) were co-infected with hepatitis C virus, and 57 (55%) had a history of corticosteroid treatment. The prevalence of vertebral fractures was 25%, 95% confidence interval 17-34%. We assessed whether gender, HCV co-infection, previous corticosteroid use, AIDS, total HIV viral load, and current and previous use of PIs were associated with fractures in our study group, but we did not observe a significant association between any of these factors and vertebral fractures. The prevalence of vertebral fractures was high among HIV-infected patients. We propose that screening for bone disease should be performed in HIV individuals who are at risk of fragility fractures. Furthermore, we suggest that X-ray based assessment of the spine should be considered in patients who are at increased risk of fragility fractures, irrespective of BMD levels, particularly in elderly patients in low and middle income countries.

Genotype-guided antiretroviral regimens in children with multidrug-resistant HIV-1 infection

Background:Genotyping tests were developed to attenuate the impact of viral resistance. Information about the efficacy in genotype base antiretroviral therapy in children is rare and even more in low- and middle-income countries.Methods:Sixteen children with antiretroviral therapy (ART) failure and triple-class drug-resistant viruses were included in this study. Protease and retrotranscriptase genotypes were available for all patients. Switch of ART regimen was guided by genotyping data. The primary end point was virological suppression (<50 copies/ml) and immunological improvement after 48 wk of treatment with the new ART regimen.Results:The median age of the patients was 14.5 y (interquartile range (IQR) 11–16.5). Median HIV-1 RNA viral load was 4.2 log10 (IQR: 3.4–4.8). The primary end point was found in 11 children (69%), and 13 children (81%) had an HIV-1 RNA viral load <200 copies/ml. Median (IQR) for the baseline CD4+ cell count was 382 cells/μl (281–686 cells/μl), whereas after 48 wk of treatment with the new ART regimen, it was 640 cells/μl (361–936 cells/μl) (P < 0.001).Conclusion:Darunavir/ritonavir, raltegravir, and etravirine were well tolerated in the present pediatric population. These drugs provide good options for children exposed to extensive ART. Regimens guided by genotyping data were effective for children who had ART failure and multidrug-resistant HIV-1 infection.

Effectiveness of etravirine-based therapy for treatment-experienced HIV-infected patients

INTRODUCTION Treatment options are limited for HIV-1-infected individuals who have received extensive previous antiretroviral therapy. ETV has shown significant clinical benefits in treatment-experienced HIV-1+ patients with antiretroviral resistance. The aim of this study was to evaluate the effectiveness of ETV plus optimized background regimen in real-life conditions in a cohort of highly HIV-1 antiretroviral-experienced patients. METHODOLOGY Retrospective cohort of treatment-experienced HIV-1-infected adults with virological failure who started therapy with an ETV-containing regimen. The effectiveness was evaluated using HIV-1 RNA viral load and changes in CD4+ cell count after 48 weeks of treatment. RESULTS Forty-two patients ≥ 16 years of age were included; 74% were men, and the median age was 45 years (IQR 41-53). All participants had prior non-nucleoside reverse transcriptase inhibitor use (55% nevirapine, 83%, efavirenz, and 28% both). Baseline median HIV-1 RNA viral load was 15,598 copies/mL (IQR 2651-84,175) and CD4+ cell count was 276 cells/mL (IQR 155-436). After 48 weeks of treatment, 90.5% (95% CI 78-96) of patients had HIV-1 RNA viral load < 200 copies/mL and 76% (95% CI 61-86) had < 50 copies/mL. CD4+ cell counts increased from baseline to 48 weeks of treatment to a median of 407 cells/mL (IQR 242-579); p < 0.001. Virological outcome was associated with virological failure at baseline HIV-1 RNA viral load ≥ 100,000 copies/mL (OR 7.6; 95% CI 1.2-44.80; p = 0.025). CONCLUSIONS Our study provides clinically important evidence of the effectiveness and safety of ETV in highly antiretroviral-experienced HIV-1-infected patients.