Weight gain and metabolic disturbances in people living with HIV who start antiretroviral therapy with, or switch to, bictegravir/emtricitabine/tenofovir alafenamide after 48 weeks of treatment: A real-world prospective study.

BACKGROUND: People living with HIV (PLWH) starting or switching to an integrase strand transfer inhibitor-based regimen are more likely to experience weight gain than other classes of antiretroviral regimens. The aim of this study was to evaluate the weight gain and metabolic disturbances in PLWH who start antiretroviral therapy (ART) with bictegravir/emtricitabine/tenofovir alafenamide and in individuals who switch from another ART to BIC/FTC/TAF after 48 weeks. METHODS: A prospective longitudinal study was conducted in an HIV clinic in Mexico. Weight and metabolic parameters were measured at baseline, 24 and 48 weeks. A paired t test and Wilcoxon signed-rank test were applied to evaluate weight and metabolic changes. RESULTS: 160 participants completed measurements, median age was 29 (IQR 26-32) and 30 (IQR 27-34) years old for the treatment-naïve and switch group respectively. In the treatment-naïve group, mean weight change was 3.8 kg (±5.8) (p < .001) and BMI increased 1.3 kg/m2 (±2) (p < .001) at 48 weeks. Incidence of BMI >25 kg/m2 was 28% (95%CI; 18%-40%) and BMI >30 kg/m2 was 7% (95%CI; 2%-16%) at 48 weeks in treatment-naïve individuals. In the switch group, mean weight gain and BMI change at 48 weeks was 2.8 kg (±5.9) and 0.9 kg/m2 (±2.0) respectively (p < .001). Incidence of BMI >25 kg/m2 was 17% (95%CI; 8%-32%) and BMI >30 kg/m2 12.8% (95%CI; 5%-26%) at 48 weeks respectively. CONCLUSIONS: Weight gain should be considered when men PLWH are treated with BIC/FTC/TAF regimen. They should be informed about this possible adverse event and strategies of intervention.

Reversibility of Neuropsychiatric Adverse Events after Switching to Darunavir/Cobicistat or Doravirine in Men on INSTI-Based Regimen.

Integrase strand transfer inhibitors (INSTI) are associated with neuropsychiatric adverse events (NPAEs). The aim of this study was to evaluate improvements in NPAEs after switching an INSTI-based regimen to darunavir/cobicistat (DRV/c) or doravirine (DOR). Methods: A prospective cohort study was conducted to evaluate the reversibility of NPAEs via the Patient Health Questionnaire (PHQ-9), the Insomnia Severity Index (ISI), and the Hospital Anxiety and Depression Scale (HADS-A and D) in patients who started antiretroviral therapy with dolutegravir (DTG) or bictegravir (BIC). These patients were switched to DRV/c or DOR. Scales were compared at the moment of the switch and 12 weeks later. Results: We included 1153 treatment-naïve men, 676 (58.7%) with BIC and 477 (41.3%) with DTG. A total of 32 (2.7%) experienced NPAEs that led to discontinuation. Insomnia was found in 20 patients; depression via PHQ-9 in 21 patients, via HADS-D in 5 patients, and anxiety via HADS-A in 12 patients. All of them were evaluated by a psychiatrist at the moment of the symptoms; 7 (21.8%) started psychotropic drugs. After 12 weeks of follow-up, PHQ-9, ISI, HADS-A, and HADS-D decreased, with a p-value ≤ 0.05. Conclusions: NPAEs seem to improve after switching to a DRV/c- or DOR-based regimen after the first 4 and 12 weeks.

Risk factors for mortality and clinical presentation of monkeypox.

OBJECTIVES: To describe risk factors for mortality and clinical characteristics in patients with mpox infection at a reference hospital in Mexico. DESIGN: A prospective cohort study was conducted from September to December 2022 at Hospital de Infectología La Raza National Medical Center. METHODS: Study participants were patients that met operational definition of confirmed case of mpox according to WHO criteria. Information was obtained through a case report form that included epidemiological, clinical, and biochemical information. The follow-up period was from initial evaluation for hospitalization until discharge due to clinical improvement or death. Written informed consent was obtained from all participants. RESULTS: Seventy-two patients were included in the analysis, 64 of 72 (88.9%) were people with HIV (PWH). Of the total of patients 71 of 72 (98.6%) were male, with a median age of 32 years old [95% confidence interval (CI), interquartile range (IQR) 27-37]. Coinfection with sexually transmitted infections was reported in 30 of 72 (41.7%). The overall mortality was five of 72 (6.9%). The incidence of mortality rate in PWH was 6.3%. Median days from onset of symptoms to death from any cause during hospitalization was 50 days (95% CI, IQR 38-62). Risk factors for mpox mortality in the bivariate analysis were CD4 + cells count ≤100 cells/µl at the time of assessment RR 20 (95% CI, IQR 6.6-60.2) ( P  < 0.001), absence of antiretroviral therapy RR 6.6 (95% CI, IQR 3.6-12.1) ( P  = 0.001) and ≥50 skin lesions at presentation RR 6.4 (95% CI, IQR 2.6-15.7) ( P  = 0.011). CONCLUSIONS: The clinical presentation between PWH and non-HIV patients was similar in this study, however, reported mortality was associated with advanced-HIV disease.

Diagnostic accuracy of antigen detection in urine and molecular assays testing in different clinical samples for the diagnosis of progressive disseminated histoplasmosis in patients living with HIV/AIDS: A prospective multicenter study in Mexico.

BACKGROUND: The progressive disseminated histoplasmosis (PDH) has been associated with severe disease and high risk of death among people living with HIV (PLWHIV). Therefore, the purpose of this multicenter, prospective, double-blinded study done in ten Mexican hospitals was to determine the diagnostic accuracy of detecting Histoplasma capsulatum antigen in urine using the IMMY ALPHA Histoplasma EIA kit (IAHE), clarus Histoplasma GM Enzyme Immunoassay (cHGEI IMMY) and MiraVista Histoplasma Urine Antigen LFA (MVHUALFA); as well as the Hcp100 and 1281-1283220SCAR nested PCRs in blood, bone-marrow, tissue biopsies and urine. METHODOLOGY/PRINCIPAL FINDINGS: We included 415 PLWHIV older than 18 years of age with suspicion of PDH. Using as diagnostic standard recovery of H. capsulatum in blood, bone marrow or tissue cultures, or histopathological exam compatible, detected 108 patients (26%, [95%CI, 21.78-30.22]) with proven-PDH. We analyzed 391 urine samples by the IAHE, cHGEI IMMY and MVHUALFA; the sensitivity/specificity values obtained were 67.3% (95% CI, 57.4-76.2) / 96.2% (95% CI, 93.2-98.0) for IAHE, 91.3% (95% CI, 84.2-96.0) / 90.9% (95% CI, 87.0-94.0) for cHGEI IMMY and 90.4% (95% CI, 83.0-95.3) / 92.3% (95% CI, 88.6-95.1) for MVHUALFA. The Hcp100 nested PCR was performed on 393, 343, 75 and 297, blood, bone marrow, tissue and urine samples respectively; the sensitivity/specificity values obtained were 62.9% (95%CI, 53.3-72.5)/ 89.5% (95%CI, 86.0-93.0), 65.9% (95%CI, 56.0-75.8)/ 89.0% (95%CI, 85.2-92.9), 62.1% (95%CI, 44.4-79.7)/ 82.6% (95%CI, 71.7-93.6) and 34.9% (95%CI, 24.8-46.2)/ 67.3% (95%CI, 60.6-73.5) respectively; and 1281-1283220SCAR nested PCR was performed on 392, 344, 75 and 291, respectively; the sensitivity/specificity values obtained were 65.3% (95% CI, 55.9-74.7)/ 58.8% (95%CI, 53.2-64.5), 70.8% (95%CI, 61.3-80.2)/ 52.9% (95%CI, 46.8-59.1), 71.4% (95%CI, 54.7-88.2)/ 40.4% (95%CI, 26.4-54.5) and 18.1% (95%CI, 10.5-28.1)/ 90.4% (95%CI, 85.5-94.0), respectively. CONCLUSIONS/SIGNIFICANCE: The cHGEI IMMY and MVHUALFA tests showed excellent performance for the diagnosis of PDH in PLWHIV. The integration of these tests in clinical laboratories will certainly impact on early diagnosis and treatment.

Diagnostic accuracy cohort study and clinical value of the Histoplasma urine antigen (ALPHA Histoplasma EIA) for disseminated histoplasmosis among HIV infected patients: A multicenter study.

BACKGROUND: The Histoplasma urine antigen (HUAg) is the preferred method to diagnose progressive disseminated histoplasmosis (PDH) in HIV patients. In 2007, IMMY ALPHA Histoplasma EIA was approved for clinical for on-site use, and therefore useful for regions outside the United States. However, ALPHA-HUAg is considered inferior to the MVista-HUAg which is only available on referral. We aim to evaluate the diagnostic accuracy of ALPHA-HUAg. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a multicenter, prospective, diagnostic test study in two secondary and eight tertiary-care facilities in Mexico. We included HIV patient with PDH suspicion and evaluated ALPHA-HUAg diagnostic accuracy using as reference standard the Histoplasma capsulatum growth on blood, bone marrow, and tissue cultures or compatible histopathologic exam (PDH-proven). We evaluated the results of 288 patients, 29.5% (85/288; 95% confidence interval [CI], 24.3-35.1) had PDH. The sensitivity of ALPHA-HUAg was 67.1% (95% CI, 56-76.8%) and the specificity was 97.5% (95% CI, 94.3%-99.1%). The positive likelihood ratio was 27.2 (95% CI; 11.6-74.4). In 10.5% of the PDH-proven patients, a co-existing opportunistic infection was diagnosed, mostly disseminated Mycobacterium avium complex infection. CONCLUSIONS/SIGNIFICANCE: We observed a high specificity but low sensitivity of IMMY-HUAg. The test may be useful to start early antifungals, but a culture-based approach is necessary since co-infections are frequent and a negative IMMY-HUAg result does not rule out PDH.

Effectiveness of tipranavir versus darunavir as a salvage therapy in HIV-1 treatment-experienced patients.

INTRODUCTION: Although both tipranavir (TPV) and darunavir (DRV) represent important options for the management of patients with multi-protease inhibitor (PI)-resistant human immunodeficiency virus (HIV), currently there are no studies comparing the effectiveness and safety of these two drugs in the Mexican population. The aim of this study was to compare the effectiveness of TPV versus DRV as a salvage therapy in HIV-1 treatment-experienced patients. METHODOLOGY: This was a comparative, prospective, cohort study. Patients with HIV and triple-class drug resistance evaluated at the Hospital de Infectología "La Raza", National Medical Center, were included. All patients had the protease and retrotranscriptase genotype; resistance mutation interpretation was done using the Stanford database. RESULTS: A total of 35 HIV-1 triple-class drug-resistant patients were analyzed. All of them received tenofovir and raltegravir, 22 received darunavir/ritonavir (DRV/r), and 13 received tipranavir/ritonavir (TPV/r) therapies. The median baseline RNA HIV-1 viral load and CD4+ cell count were 4.34 log (interquartile range [IQR], 4.15-4.72) and 267 cells/mm3 (IQR, 177-320) for the DRV/r group, and 4.14 log (IQR, 3.51-4.85) and 445 cells/mm3 (IQR, 252-558) for the TPV/r group. At week 24 of treatment, 91% of patients receiving DRV/r and 100% of patients receiving TPV/r had an RNA HIV-1 viral load < 50 copies/mL and a CD4+ cell count of 339 cells/mm3 (IQR, 252-447) and 556 cells/mm3 (IQR, 364-659), respectively. CONCLUSIONS: No significant difference was observed between DRV/r and TPV/r in terms of virological suppression in HIV-1 patients who were highly experienced in antiretroviral therapy.

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.

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.

Risk factors associated with mortality in patients infected with influenza A/H1N1 in Mexico.

BACKGROUND: Influenza virus pandemics vary dramatically in their severity and mortality. Thus, it is very important to identify populations with high risks of developing severe illness to reduce mortality in future pandemics. The purpose was to determine the mortality-associated risk factors in hospitalized Mexican patients infected with influenza A/H1N1. RESULTS: The risk factors associated with mortality were: male sex [odds ratio (OR) = 5.25, confidence interval (CI) = 1.22-28.95], medical attention delayed >3 days (OR = 9.9, CI = 1.51-64.52), anti-flu therapy delayed >3 days (OR = 10.0, CI = 1.07-93.43), admission to intensive care unit (ICU) (OR = 9.9, CI = 1.51-64.52) and creatinine levels >1.0 mg/dL when admitted to hospital (OR = 11.2, CI = 1.05-120.32). After adjusting for the effects of potentially confounding variables in a logistic regression model, delayed medical attention (OR = 13.91, CI = 1.09-41.42, p = 0.044) and ICU hospitalization (OR = 11.02, CI = 1.59-76.25, p = 0.015) were the only predictors of mortality. CONCLUSION: Early medical attention is essential for reducing the mortality risk in patients with influenza A/H1N1, while a requirement for ICU management increases the risk.