Cardiometabolic health in people with HIV: expert consensus review.

OBJECTIVES: To develop consensus data statements and clinical recommendations to provide guidance for improving cardiometabolic health outcomes in people with HIV based on the knowledge and experience of an international panel of experts. METHODS: A targeted literature review including 281 conference presentations, peer-reviewed articles, and background references on cardiometabolic health in adults with HIV published between January 2016 and April 2022 was conducted and used to develop draft consensus data statements. Using a modified Delphi method, an international panel of 16 experts convened in workshops and completed surveys to refine consensus data statements and generate clinical recommendations. RESULTS: Overall, 10 data statements, five data gaps and 14 clinical recommendations achieved consensus. In the data statements, the panel describes increased risk of cardiometabolic health concerns in people with HIV compared with the general population, known risk factors, and the potential impact of antiretroviral therapy. The panel also identified data gaps to inform future research in people with HIV. Finally, in the clinical recommendations, the panel emphasizes the need for a holistic approach to comprehensive care that includes regular assessment of cardiometabolic health, access to cardiometabolic health services, counselling on potential changes in weight after initiating or switching antiretroviral therapy and encouraging a healthy lifestyle to lower cardiometabolic health risk. CONCLUSIONS: On the basis of available data and expert consensus, an international panel developed clinical recommendations to address the increased risk of cardiometabolic disorders in people with HIV to ensure appropriate cardiometabolic health management for this population.

Commercially Available Prenatal Vitamins Do Not Meet American College of Obstetricians and Gynecologists Nutritional Guidelines.

OBJECTIVE: This study aimed to evaluate the reported amount of the American College of Obstetricians and Gynecologists (ACOG) recommended nutrients in commercially available, over-the-counter prenatal vitamins (PNVs) in the United States, to assess their adequacy compared with the ACOG guidelines, and to compare these supplements by cost. STUDY DESIGN: The top 30 online Amazon and Google shopping items found using "prenatal vitamins" in September 2022 were included for analysis if they included the words "prenatal" and "vitamin" in the label and contained multiple nutrients. Duplicates between Amazon and Google were excluded as well as vitamins that did not list all ingredients. The reported amounts of 11 key nutrients, as recommended by the ACOG, for each product were recorded, as well as supplemental form and cost per 30-day supply. A cost analysis was done of PNVs that met the ACOG recommendations for the highlighted nutrients compared with those that did not. Five out of the 11 key nutrients (folic acid, iron, docosahexaenoic acid, vitamin D, and calcium) were specifically highlighted, as deficiencies in these nutrients are known to correlate with significant clinical outcomes in pregnancy. RESULTS: A total of 48 unique PNVs were included for final analysis. Of these PNVs, none were compliant with suggested amounts of all five key vitamins and nutrients. No products met daily recommendations for calcium. Only five PNVs were compliant with recommendations with ⅘ key nutrients. Of note, 27% of PNVs did not have the recommended amount of folic acid (13/48). The median cost of PNVs that were not compliant with the four nutrients mentioned above was $18.99 (interquartile range [IQR]: $10.00-$30.29), which was not statistically different from the median cost of the PNVs that did meet compliance with the four nutrients, which was $18.16 (IQR: $9.13-$26.99), p = 0.55. CONCLUSION: There were significant variations in the level of nutrients and cost of commercially available, over-the-counter PNVs in the United States. This raises concern that there should be more regulation of PNVs. KEY POINTS: · Commercially available over the counter PNVs vary in their content of the ACOG recommended nutrients and vitamins for pregnancy.. · None of these studied PNVs contain adequate amounts of all five key nutrients.. · Cost is not correlated with more compliance with the ACOG recommendations..

Treatment challenges and health conditions among people living with HIV with or without substance use disorder in the Russian Federation.

We quantified treatment challenges faced by people living with HIV (PLHIV) in Russia. Cross-sectional data of 150 PLHIV in Russia were from the 2019 Positive Perspectives Survey. Mean age was 38.3 y. Two-thirds (68.0%[102/150]) had ever disguised their HIV pills, and 43.3%[65/150] said they would be stressed if someone saw their HIV pills. Overall, 14.7%[22/150] reported being ever diagnosed with substance use disorder (SUD). Self-rated optimal health was significantly lower among those with vs without a report of SUD on multiple health domains: sexual (40.9%[9/22] vs. 70.3%[90/128], p = 0.007), physical (22.7%[5/22] vs. 68.0%[87/128], p < 0.001), and overall health (27.3%[6/22] vs. 68.8%[88/128], p < 0.001). Those reporting SUD were more likely to miss HIV medication ≥ 1 time in the past month because they used recreational drugs (age and gender-adjusted prevalence ratio [APR] = 8.23, 95%CI = 6.99-9.68), could not afford their medication (APR = 3.28, 95%CI = 2.90-3.72), had to work (APR = 3.27, 95%CI = 2.97-3.60), or to avoid side effects (APR = 2.62, 95%CI = 2.37-2.89). Furthermore, self-reported SUD was strongly associated with numerous poor health conditions, including self-reported diagnosis of cancer (APR = 6.67, 95%CI = 5.24-8.48), mental illness (APR = 5.01, 95%CI = 4.53-5.55), and liver disease (APR = 4.29, 95%CI = 3.98-4.61). The distinct patterns of poorer health-related outcomes among PLHIV with SUD underscore the need to address behavioral and psychosocial challenges as part of holistic HIV care.

An epidemiologic analysis of clinical practice guidelines for non-arthroplasty treatment of osteoarthritis of the knee.

PURPOSE: To analyze the current practice patterns of non-arthroplasty treatment of knee osteoarthritis (OA) and to assess the impact of the American Academy of Orthopaedic Surgeons clinical practice guidelines on the management of OA of the knee, particularly as they relate to the use of arthroscopic treatment. METHODS: The United Healthcare Database (2004-2009, 11 million patients, 216 million records) was used for the study and was searched using Boolean language for International Classification of Diseases, Ninth Edition, Clinical Modification and Current Procedural Terminology, fourth revision codes. A reference group was defined as patients treated with knee arthroplasty in 2009 and diagnosed with knee OA in the same record. Clinical practice patterns in the 5 years preceding arthroplasty were analyzed in this group. RESULTS: The reference group consisted of 12,806 patients undergoing total knee arthroplasty in 2009 with a documented diagnosis of OA at the time of surgery, with prior nonoperative treatment strategies analyzed during the preceding 5 years (2004-2009); 10.0% of patients were prescribed physical therapy specific to OA, 2.6% received an unloader brace, 0.52% underwent acupuncture, 43.5% were administered intra-articular corticosteroids, and 15.4% received viscosupplementation injections. During the 5 years before arthroplasty, 2,505 patients (19.6%) underwent arthroscopy and debridement/lavage, 35% of whom did not have a diagnosis code for mechanical pathology. Within 1 year of knee arthroplasty, 2,028 of the 2,505 knee arthroscopies (80.9%) were performed. CONCLUSIONS: The findings show that significant gaps do exist between the evidence-based American Academy of Orthopaedic Surgeons recommendations and actual practice patterns in the United States between 2004 and 2009. LEVEL OF EVIDENCE: Level IV, diagnostic study.

Transmission of integrase strand-transfer inhibitor multidrug-resistant HIV-1: case report and response to raltegravir-containing antiretroviral therapy.

We report the case of an integrase strand-transfer inhibitor (INI)-resistant and four-drug-class-resistant HIV-1 variant infecting an antiretroviral therapy-naive man. The virus harboured INI drug resistance substitutions (Q148H and G140S) along with multiple reverse transcriptase and protease inhibitor resistance mutations. This case illustrates an emerging need to consider the possibility of acquired INI resistance among newly diagnosed treatment-naive individuals harbouring multidrug-resistant HIV-1.

Broadly reactive pan-paramyxovirus reverse transcription polymerase chain reaction and sequence analysis for the detection of Canine distemper virus in a case of canine meningoencephalitis of unknown etiology.

Despite the immunologic protection associated with routine vaccination protocols, Canine distemper virus (CDV) remains an important pathogen of dogs. Antemortem diagnosis of systemic CDV infection may be made by reverse transcription polymerase chain reaction (RT-PCR) and/or immunohistochemical testing for CDV antigen; central nervous system infection often requires postmortem confirmation via histopathology and immunohistochemistry. An 8-month-old intact male French Bulldog previously vaccinated for CDV presented with multifocal neurologic signs. Based on clinical and postmortem findings, the dog's disease was categorized as a meningoencephalitis of unknown etiology. Broadly reactive, pan-paramyxovirus RT-PCR using consensus-degenerate hybrid oligonucleotide primers, combined with sequence analysis, identified CDV amplicons in the dog's brain. Immunohistochemistry confirmed the presence of CDV antigens, and a specific CDV RT-PCR based on the phosphoprotein gene identified a wild-type versus vaccinal virus strain. This case illustrates the utility of broadly reactive PCR and sequence analysis for the identification of pathogens in diseases with unknown etiology.

First small molecular inhibitors of T. brucei dolicholphosphate mannose synthase (DPMS), a validated drug target in African sleeping sickness.

Drug-like molecules with activity against Trypanosoma brucei are urgently required as potential therapeutics for the treatment of African sleeping sickness. Starting from known inhibitors of other glycosyltransferases, we have developed the first small molecular inhibitors of dolicholphosphate mannose synthase (DPMS), a mannosyltransferase critically involved in glycoconjugate biosynthesis in T. brucei. We show that these DPMS inhibitors prevent the biosynthesis of glycosylphosphatidylinositol (GPI) anchors, and possess trypanocidal activity against live trypanosomes.

Short-term safety and tolerability of didanosine combined with high- versus low-dose tenofovir disproxil fumarate in ambulatory HIV-1-infected persons.

Coadministration of didanosine (ddI) and tenofovir (TDF) results in increased ddI serum concentrations, which may lead to increased risk of ddI-associated toxicities. To evaluate the safety and tolerability of ddI/TDF, we performed a retrospective cohort analysis of patients seen in the HIV Outpatient Study, an ongoing dynamic cohort study of HIV-infected persons in clinical care. Study subjects were those who received at least 14 days of combined ddI/TDF before October 2003. Of 260 subjects who received ddI/TDF-based antiretroviral therapy, 155 (60%) received high-dose ddI (400 mg daily dose) and 105 (40%) received low-dose ddI (100-250 mg daily). Forty-two of the high-dose ddI recipients were later switched to low-dose ddI. The median time of observation for those on high-dose ddI only was 5 months, high-dose ddI switched to low-dose ddI was 16 months, and low-dose ddI only was 5 months (p < 0.05). Discontinuations because of toxicity were more frequent on high-dose ddI regimens (34/155, 22%) than on low-dose ddI regimens (9/105, 9%) (unadjusted odds ratio [OR(unadj)] 3.0, 95% confidence interval [95% CI] 1.30-7.09; p = 0.007). Among subjects without preexisting peripheral neuropathy, 12 (12%) of 101 subjects ever on high-dose ddI regimens had treatment-emergent peripheral neuropathy compared to 2 (4%) of 55 subjects on low-dose ddI regimens (OR(unadj) 3.57; 95% CI, 0.72-24.1; p = 0.14). Among patients without a history of pancreatitis, 6 (4%) of 153 subjects developed pancreatitis after starting high-dose ddI regimens, compared to none of the 103 subjects on low-dose ddI regimens (OR(adj) and 95% CIs undefined; p = 0.08). Severe laboratory abnormalities of creatinine, phosphorous, and bicarbonate were not different between the groups. A summary variable for any event--discontinuation for toxicity, treatment- emergent adverse event or abnormal laboratory values--indicated that 44 (28%) of 155 of those on high-dose ddI versus 13 (12%) of 105 on low-dose ddI developed any event (OR(unadj) 2.81; 95% CI, 1.36-5.86; p = 0.004). In conclusion, high-dose ddI/TDF-based therapy was more frequently associated with drug-related toxicity, adverse events, and treatment discontinuation than low-dose ddI/TDF regimens; low-dose ddI with TDF was generally well tolerated in these HIV-infected persons.