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Introduction: Little is known about the epidemiology of coronary artery disease (CAD) in sub-Saharan Africa, where the majority of people living with HIV (PLHIV) live. We assessed the association of HIV with CAD and explored relationships with monocyte activation in sex-stratified analyses of older PLHIV and people without HIV (PWOH) in Uganda. Methods: The Ugandan Study of HIV effects on the Myocardium and Atherosclerosis (mUTIMA) follows 100 PLHIV on antiretroviraltherapy (ART) and 100 age- and sex-matched PWOH controls in Kampala, Uganda; all>45 years of age with >1 cardiovascular disease risk factor. At the year 2 exam (2017-2019), 189 participants had available coronary calcium score and 165 had coronary CT angiography (CCTA) for this analysis. A subset of participants (n = 107) had both CCTA and fresh whole blood flow cytometry for monocyte phenotyping. Results: Median age was 57.8 years and 63% were females. Overall, 88% had hypertension, 37% had diabetes and 4% were smokers. Atherosclerotic cardiovascular disease (ASCVD) risk was modestly higher for PWOH, but not statistically significant (median 10-year ASCVD risk 7.2% for PLHIV vs. 8.6% for PWOH, p = 0.09). Median duration of ART was 12.7 years and 86% had suppressed viralload. Despite a high prevalence of risk factors, only 34/165 (21%, 95% CI 15-28%) had any coronary plaque. After adjustment for ASCVD risk score, HIV status was not associated with CAD (OR 0.55, 95% CI 0.23-1.30) but was associated with more severe CAD (segment severity score>3) among those with disease (OR 10.9, 95% CI 1.67-70.45). Females had a trend towards higher odds of CAD among PLHIV (OR 4.1, 95% CI 0.4-44.9), but a trend towards lower odds of CAD among PWOH (OR 0.30; 95% CI 0.07-1.3; HIV*sex interaction p = 0.019). CAD was positively correlated with classical monocytes (r = 0.3, p = 0.012) and negatively correlated with CX3CR1 expression (r = -0.31, p = 0.011) in PLHIV and negatively correlated with patrolling monocytes (r = -0.36, p = 0.031) and tissue factor expression (r = -0.39, p = 0.017) in PWOH. Conclusions: Our results suggest that HIV may be associated more with severity rather than the presence of CAD in Uganda. Sex differences in the HIV effect suggest that tailored CAD prevention strategies may be required in this setting. Keywords: HIV; sex; Uganda; cardiovascular diseases; monocytes; computed tomography angiography, 1 | INTRODUCTION There are currently over 6 million persons living with HIV (PLHIV) aged 50 years and older, over half of whom live in sub-Saharan Africa (SSA) [1]. Additionally, [...]

Central fat accumulation is increasingly recognized as a problem for patients with HIV infection. The term 'lipodystrophy' has been used to describe collectively a constellation of body habitus changes and metabolic abnormalities commonly observed in HIV-infected patients, particularly since the advent of highly active antiretroviral therapy. Visceral fat accumulation can place patients at increased risk of coronary artery disease. Furthermore, body shape changes are a source of distress to patients that may compromise treatment adherence. Reduction of abdominal obesity can therefore be considered part of therapy in HIV-positive patients with visceral adipose tissue (VAT) accumulation. Currently, there are no drugs approved by the Food and Drug Administration for the treatment of HIV-associated central fat accumulation. Lifestyle modifications such as diet and exercise and switching antiretroviral therapies appear to be of limited value in reducing VAT. Metformin has shown some benefit in reducing VAT but at the expense of accelerating peripheral fat loss, and the thiazolidinediones have no effect on VAT. Similarly, testosterone does not appear to reduce VAT in these patients, and there are no data on anabolic steroids. Two large, randomized controlled trials have demonstrated the efficacy of recombinant human growth hormone (rhGH) in reducing visceral adipose tissue. There are also promising data regarding treatment with growth hormone releasing hormone (GHRH).

Background: Statins are increasingly used in HIV-infected patients, but the effect of their immunomodulatory properties on antiretroviral-induced immune reconstitution is unknown. Methods: The authors compared 6-month and 1-year changes in [...]

The relationships between oxidant stress and nucleoside reverse transcriptase inhibitor (NRTI)-induced peripheral neuropathy were explored by quantifying plasma [F.sub.2]-Isoprostanes among AIDs Clinical Trials Group (ACTG) 384 participants. The findings suggest that symptomatic NRTI-associated peripheral neuropathy was not associated with increased plasma [F.sub.2]-Isoprostanes among ACTG 384 participants.

The utility of quantitative and qualitative analysis of mitochondrial DNA (mtDNA) in longitudinal peripheral blood samples from the same individual, with the performance of mtDNA depletion and extensive mutation analysis, is assessed. The conclusive mtDNA depletion is detected in the blood samples of with HIV-infected subjects with lipoatrophy by using extensive mitochondrial testing.

Background: Treatment has improved HIV infection prognosis, but whether risk and health care seeking behavior have improved is unclear. Methods: New entrants to HIV care at University Hospitals of Cleveland, [...]

The degree and reversibility of adipocyte apoptosis in patients with lipoatrophy before and 48 weeks after substituting abacavir or zidovudine for stavudine is assessed. It is concluded that increased apoptosis is present in fat samples from patients with lipoatrophy treated with stavudine.

Mitochondrial toxicity has been implicated in the development of a variety of nucleoside reverse transcriptase inhibitors-associated syndromes. Clinical syndromes mediated by mitochondrial toxicity include hyperlactatemia and lactic acidosis, lipoatrophy, peripheral nephropathy, HANWS, and hepatic steatosis.

The prevalence of asymptomatic hyperlactatemia among HIV-infected individuals has been reported to be 4% to 36%. The prevalence of elevated venous lactate among HIV-infected and nucleoside analoguetreated subjects was examined, and the findings indicate that asymptomatic hyperlactatemia is either very rare or artifact of collection technique.

The authors compared samples of cerebrospinal fluid (CSF) and plasma in which levels of HIV virus had been measured with samples from patients treated with lamivudine. They found a mutation which resists lamivudine in both CSF and plasma, which indicates that CSF and plasma HIV levels are related.

The benefits of long‐term antiretroviral therapy (ART) are recognized all over the world with infected children maturing into adults and HIV infection becoming a chronic illness. However, the improved survival is associated with serious metabolic complications, including lipodystrophy (LD), dyslipidemia, insulin resistance, lactic acidosis and bone loss. In addition, the dyslipidemia mainly seen with protease inhibitors may increase the risk of cardiovascular disease in adulthood and potentially in children as they mature into adults. Nucleoside reverse transcriptase inhibitors, particularly stavudine, zidovudine and didanosine are linked to development of LD and lactic acidosis. Perinatally infected children initiate ART early in life; they require lifelong therapy with multiple drug regimens leading to varying toxicities, all potentially impacting their quality of life. LD has a significant impact on the mental health of older children and adolescents leading to poor self‐image, depression and subsequent poor adherence to therapy. Reduced bone mineral density (BMD) is reported in both adults and children on ART with the potential for children to develop more serious bone complications than adults due to their rapid growth spurts and puberty. The role of vitamin D in HIV‐associated osteopenia and osteoporosis is not clear and needs further study. Most resource‐limited settings are unable to monitor lipid profiles or BMD, exposing infected children and adolescents to on‐going toxicities with unclear long‐term consequences. Improved interventions are urgently needed to prevent and manage these metabolic complications. Longitudinal cohort studies in this area should remain a priority, particularly in resource‐limited settings where the majority of infected children reside., Introduction Potent antiretroviral therapy (ART) has significantly reduced the morbidity and mortality of HIV‐infected adults [1] and children [1–3]. The long‐term benefits of ART are associated with metabolic complications, including [...]

The benefits of long-term antiretroviral therapy (ART) are recognized all over the world with infected children maturing into adults and HIV infection becoming a chronic illness. However, the improved survival is associated with serious metabolic complications, including lipodystrophy (LD), dyslipidemia, insulin resistance, lactic acidosis and bone loss. In addition, the dyslipidemia mainly seen with protease inhibitors may increase the risk of cardiovascular disease in adulthood and potentially in children as they mature into adults. Nucleoside reverse transcriptase inhibitors, particularly stavudine, zidovudine and didanosine are linked to development of LD and lactic acidosis. Perinatally infected children initiate ART early in life; they require lifelong therapy with multiple drug regimens leading to varying toxicities, all potentially impacting their quality of life. LD has a significant impact on the mental health of older children and adolescents leading to poor self-image, depression and subsequent poor adherence to therapy. Reduced bone mineral density (BMD) is reported in both adults and children on ART with the potential for children to develop more serious bone complications than adults due to their rapid growth spurts and puberty. The role of vitamin D in HIV-associated osteopenia and osteoporosis is not clear and needs further study. Most resource- limited settings are unable to monitor lipid profiles or BMD, exposing infected children and adolescents to on-going toxicities with unclear long-term consequences. Improved interventions are urgently needed to prevent and manage these metabolic complications. Longitudinal cohort studies in this area should remain a priority, particularly in resource-limited settings where the majority of infected children reside. Keywords: children; adolescents; HIV; antiretroviral therapy; metabolic complications; cardiovascular disease., Introduction Potent antiretroviral therapy (ART) has significantly reduced the morbidity and mortality of HIV-infected adults [1] and children [1-3]. The long-term benefits of ART are associated with metabolic complications, including [...]

Objective. Simplification of antiretroviral regimen in human immunodeficiency virus (HIV)-infected children has not yet been investigated. In general, children have a more difficult time maintaining viral suppression because of many factors, including frequent nonadherence and less availability of antiretrovirals in palatable forms. In addition, many serious metabolic complications have emerged in HIV-infected adults and are believed to be attributable to antiretroviral therapy. Some of these complications--hypercholesterolemia, hypertriglyceridemia, and insulin resistance--are believed to be the result of the use of protease inhibitor (PI) therapy, whereas the cause of others, such as lipodystrophy, remains undetermined. Recent reports underline that children experience long-term metabolic abnormalities in the same manner that adults do, and perhaps these consequences are even more worrisome in children secondary to long-term expected survival. We report here the results of the first open-label PI-switch study in HIV-infected children. Methods. Seventeen children, 24 to 160 months of age (median: 120), were enrolled into the study. All were receiving a stable PI-containing antiretroviral regimen that containing 2 to 3 nucleoside analogue reverse transcriptase inhibitors (NRTIs) in addition to 1 to 2 Pis for a median duration of 21 months (range: 5-50) before study entry. All children had HIV-1 RNA Results. All children were heavily pretreated; 88% of the patients had previous NRTIs, and 41% had previous PI use. The most common PI at study entry was nelfinavir (47%), followed by ritonavir (29%), then amprenavir (18%); only 1 was on saquinavir/ritonavir. At study entry, the duration of previous antiretroviral therapy was between 21 and 123 months (median: 88). All patients completed the 48-week study. No acquired immunodeficiency syndrome-defining events occurred. There were no rashes and no changes in liver transaminases. Mild, transient insomnia and dizziness each occurred in 1 child. Two other subjects (6 and 8 years old) experienced unusual vivid dreams, mostly pleasant, which decreased in intensity and frequency after the first 12 weeks of the study. One subject, a 10-year-old girl, had an episode of generalized seizure at week 6; study drugs were not interrupted, and seizure never recurred. The patient had a strong family history of epilepsy, although she had never experienced previous seizures. No anticonvulsants were given. Sixteen of 17 patients had HIV-1 RNA levels of Conclusion. This is the first study in children to evaluate the substitution of PI in a virologically successful regimen with efavirenz, a potent once-daily nonnucleoside reverse transcriptase inhibitor therapy. We were able to show significant improvement in fasting total cholesterol, low-density lipoprotein cholesterol, triglycerides, and, more important, the cholesterol:HDL ratio. In addition, switching to an efavirenz-containing regimen was well tolerated and successfully maintained virologic suppression in all HIV-infected children in this study. This study should encourage large randomized trials to investigate simplification strategies in HIV-infected children. Pediatrics 2003;111:e27S-e281. URL: http://www. pediatrics.org/cgi/content/full/111/3/e275; HIV, AIDS, simplification, lipodystrophy, switch studies, metabolic complications.

Cellulitis is a rare manifestation of meningococcal disease. We describe the case of a previously healthy 4-month-old female infant who developed periorbital cellulitis associated with meningococcal meningitis. meningitis, meningococcal disease.