Metabolic syndrome in people with HIV from Guatemala: analysis of components and risk factors.

BACKGROUND: People with HIV (PWH) in Latin America are at a greater risk of developing comorbidities due to the increasing burden of obesity and metabolic syndrome in the region. We explored the associations between social, cardiovascular and HIV-related risk factors with metabolic syndrome in PWH from Guatemala. METHODS: Cross-sectional study analyzing demographic, clinical and laboratory data from PWH. Metabolic syndrome diagnosis and components are defined by the harmonized Joint Scientific Statement criteria. Data were collected from July 2019 to March 2020 and analyzed using correlations and logistic regression. RESULTS: Median age was 39 years [IQR 31-48], 56.8% of participants were male and 31.5% (n = 266, 95% CI 0.28-0.34) had metabolic syndrome. Age (adjusted odds ratio (aOR): 1.03, 95% CI 1.02-1.05, p <0.001), urban dweller (aOR: 1.48, 95% CI 1.00-2.18, p = 0.049), low physical activity (aOR: 1.45, 95% CI 1.01-2.08, p = 0.046), hyperuricemia (aOR: 3.31, 95% CI 1.93-5.67, p <0.001), current CD4+ T cell count < 200 cells/mm3 (aOR: 1.96, 95% CI 1.19-3.23, p = 0.009), 6 months of efavirenz (aOR: 1.89, 95% CI 1.29-2.77, p = 0.001), and obesity (aOR: 37.0, 95% CI 7.70-178.2, p < 0.001) were independently associated with metabolic syndrome. CONCLUSIONS: Prevalence of metabolic syndrome in this study was high and driven mainly by social and cardiovascular risk factors such as age, urban dwelling, obesity, hyperuricemia and low physical activity. Efavirenz use and CD4 count were the only HIV-related factors associated with metabolic syndrome.

Factors associated with viremia in people living with HIV on antiretroviral therapy in Guatemala.

INTRODUCTION: Viral suppression prevents HIV transmission and disease progression, but socio-economic and clinical factors can hinder the goal of suppression. We evaluated factors associated with viral non suppression (VNS) and persistent viremia (PV) in people living with HIV (PLHIV) receiving antiretroviral therapy (ART) in Guatemala. METHODS: We conducted a cross sectional analysis using data from an ongoing cohort of PLHIV attending the largest HIV clinic in Guatemala. Univariable and multivariable analyses were conducted between PLHIV with viral suppression and detectable viremia. VNS was defined as most recent HIV RNA ≥ 200 copies/ml and PV as two consecutive HIV RNA ≥ 200 copies/ml. RESULTS: Of 664 participants, 13.3% had VNS and 7.1% had PV. In univariable analysis disaggregated by gender, low income, poor education, perceived difficulty attending healthcare, and alcohol use were associated with VNS in men while low CD4 at diagnosis, multiple prior ART regimens and treatment interruptions were significant in both genders. Multiple prior ART regimens (adjusted Odds Ratio (aOR) 2.82, [95% confidence interval (CI) 1.59, 4.99], p < 0.01), treatment interruptions (aOR 4.51, [95% CI 2.13, 9.58], p < 0.01), excessive alcohol consumption (aOR 2.56, [95% CI 1.18, 5.54], p < 0.05) perceived difficulty attending healthcare (aOR 2.07, [ 95% CI 1.25, 3.42], p < 0.01) and low CD4 at diagnosis (aOR 2.34, 95% [CI 1.30, 4.20], p < 0.01) were independently associated with VNS on multivariable regression. CONCLUSIONS: We conclude that socio-economic and clinical factors influence viral suppression in our cohort and vary between men and women. Gender specific approaches are necessary to achieve the 90% suppression goal.

Accuracy of the tuberculosis point-of-care Alere determine lipoarabinomannan antigen diagnostic test using α-mannosidase treated and untreated urine in a cohort of people living with HIV in Guatemala.

BACKGROUND: Improved point-of-care diagnostic tests for tuberculosis (TB) in severe immune suppressed people living with HIV (PLWH) are needed to decrease morbidity and mortality outcomes. The aim of the study is to evaluate the performance of the lipoarabinomannan antigen test (LAM-test) with and without α-mannosidase pre-treated urine in a cohort of PLWH in primary care clinics in Guatemala. We further determined TB incidence, and mortality rates and its risk factors in PLWH with TB symptoms. METHODS: Prospective longitudinal study of PLWH with TB symptoms. Urine samples were collected at 2 HIV sites to test the sensitivity of the LAM-test in urine with and without α-mannosidase pre-treatment. A composite reference standard of either a positive Mycobacterium tuberculosis complex culture and/or GeneXpert® MTB/RIF (Xpert, Cepheid, Sunnyvale, CA, USA) results was used in the LAM-test diagnostic accuracy studies. Cox proportional hazards regression was used to study mortality predictors. RESULTS: The overall sensitivity of the LAM-test was of 56.1% with 95% CI of (43.3-68.3). There were no differences in the LAM-test sensitivity neither by hospital nor by CD4 T cell values. LAM-test sensitivity in PLWH with < 200 CD4 T cells/µl was of 62.2% (95% CI 46.5-76.2). There were no significant differences in sensitivity when comparing LAM-test results obtained from untreated vs. α-mannosidase treated urine [55.2% (95% CI 42.6-67.4) vs. 56.9% (95% CI 44-69.2), respectively]. TB incidence in our cohort was of 21.4/100 person years (PYs) (95% CI 16.6-27.6), and mortality rate was of 11.1/100 PYs (95% CI 8.2-15.0). Importantly, PLWH with a positive LAM-test result had an adjusted hazard ratio (aHR) of death of 1.98 (1.0-3.8) with a significant p value of 0.044 when compared to PLWH with a negative LAM-test result. CONCLUSIONS: In this study, α-mannosidase treatment of urine did not significantly increase the LAM-test performance, however; this needs to be further evaluated in a large-scale study due to our study limitations. Importantly, high rates of TB incidence and mortality were found, and a positive LAM-test result predicted mortality in PLWH with TB clinical symptoms.

Improved Alere Determine Lipoarabinomannan Antigen Detection Test for the Diagnosis of Human and Bovine Tuberculosis by Manipulating Urine and Milk.

Tuberculosis (TB) disease still kills 1-person every 21-seconds. Few TB diagnostic tests are considered truly appropriate for point of care settings. The WHO-endorsed immunodiagnostic Alere Determine Lipoarabinomannan Ag-test (LAM-test) detects Mycobacterium tuberculosis complex LAM in urine, and its use is recommended for TB diagnosis among HIV co-infected individuals with low CD4 T-cell counts. Here we found that a simple 15-minute enzymatic treatment at room temperature of LAM-spiked urine with α-mannosidase (for human TB), and LAM-spiked milk with combined lactase and caseinase (for bovine TB), enhanced 10-fold the detection levels of the LAM-test and thus, improved the detection of LAM by the LAM-test in urine and milk that otherwise could be missed in the field. Future separate clinical research studies specifically designed to address the potential of these findings are required.

Late Presentation and Missed Opportunities for HIV Diagnosis in Guatemala.

Early HIV diagnosis remains a challenge in many regions with delayed diagnosis resulting in increased morbidity and mortality. We conducted a retrospective cohort study of people living with HIV receiving outpatient care at a large tertiary referral center in Guatemala to describe the proportion of late presenters (LP) and missed opportunities for HIV diagnosis. Of 3686 patients, 2990 (81.1%) were LP who were more likely to be male (60.2% vs. 48.0%, p < 0.0001), heterosexual (88.0% vs. 78.0%, p < 0.0001) and rural dwellers (43.7% vs. 33.8%. p < 0.0001). The proportions of patients who presented late or with AIDS at diagnosis decreased over time. Only 665 patients (18.2%) sought care in the 2 years prior to HIV diagnosis. This study, the first of its kind in Central America to focus on late presenters and missed opportunities for HIV diagnosis, demonstrates extremely high rates of LP in Guatemala. Although in recent years rates of LP have improved somewhat, the need for screening outside of traditional healthcare settings is apparent.

Awareness and attitudes of pre-exposure prophylaxis for HIV prevention among physicians in Guatemala: Implications for country-wide implementation.

INTRODUCTION: HIV continues to be a major health concern with approximately 2.1 million new infections occurring worldwide in 2015. In Central America, Guatemala had the highest incident number of HIV infections (3,700) in 2015. Antiretroviral pre-exposure prophylaxis (PrEP) was recently recommended by the World Health Organization (WHO) as an efficacious intervention to prevent HIV transmission. PrEP implementation efforts are underway in Guatemala and success will require providers that are knowledgeable and willing to prescribe PrEP. We sought to explore current PrEP awareness and prescribing attitudes among Guatemalan physicians in order to inform future PrEP implementation efforts. METHODS: We conducted a cross-sectional survey of adult internal medicine physicians at the main teaching hospital in Guatemala City in March 2015. The survey included demographics, medical specialty, years of HIV patient care, PrEP awareness, willingness to prescribe PrEP, previous experience with post-exposure prophylaxis, and concerns about PrEP. The primary outcome was willingness to prescribe PrEP, which was assessed using a 5-point Likert scale for different at-risk population scenarios. Univariate and multivariate logistic regression was performed to identify predictors for willingness to prescribe PrEP. RESULTS: Eighty-seven physicians completed the survey; 66% were male, 64% were internal medicine residency trainees, and 10% were infectious disease (ID) specialists. Sixty-nine percent of physicians were PrEP aware, of which 9% had previously prescribed PrEP. Most (87%) of respondents were willing to prescribe PrEP to men who have sex with men (MSM), sex workers, injection drug users, or HIV-uninfected persons having known HIV-positive sexual partners. Concerns regarding PrEP included development of resistance (92%), risk compensation (90%), and cost (64%). Univariate logistic regression showed that younger age, being a resident trainee, and being a non-ID specialist were significant predictors for willingness to prescribe PrEP. In multivariate logistic regression, being a non-ID specialist was a significant predictor. CONCLUSIONS: Guatemalan physicians at an urban public hospital were PrEP aware and willing to prescribe, but few have actually done so yet. Future education programs should address the concerns identified, including the low potential for the development of antiretroviral resistance. These findings can aid PrEP implementation efforts in Guatemala.

AIDS-Defining Illnesses at Initial Diagnosis of HIV in a Large Guatemalan Cohort.

BACKGROUND: Anecdotal evidence suggests that a high proportion of patients diagnosed with HIV in Guatemala present with AIDS. There remain limited data on the epidemiology of AIDS-defining illnesses (ADIs) in Central America. METHODS: We conducted a retrospective cohort study of all patients living with HIV at the largest HIV clinic in Guatemala. Charts were analyzed for clinical and demographic data. Presence of an ADI was assessed by US Centers for Disease Control definitions; patients who presented with an ADI were compared with those without ADI using descriptive statistics. RESULTS: Of 3686 patients living with HIV, 931 (25.3%) had an ADI at HIV diagnosis, 748 (80.3%) of whom had CD4 counts lower than 200 cells/mm3. Those with ADIs were more likely to be male (67.5% vs 54.6%; P < .0001) and heterosexual (89.4% vs 85.0%; P = .005). The most common ADIs were Mycobacterium tuberculosis (55.0%), Pneumocystis jirovecii pneumonia (13.7%), esophageal candidiasis (13.4%), and histoplasmosis (11.4%). Histoplasmosis and HIV wasting syndrome were both more common among rural patients. CONCLUSIONS: In this large Guatemalan cohort of patients currently living with HIV, a significant portion presented with an ADI. These data inform the most common ADIs diagnosed among survivors, show that histoplasmosis is more commonly diagnosed in rural patients, and suggest that HIV wasting syndrome may reflect missed histoplasmosis diagnoses.