Symptomatic Human Immunodeficiency Virus Infection Research Articles

Symptomatic HIV infection and in-hospital outcomes for patients with acute myocardial infarction undergoing percutaneous coronary intervention from national inpatient sample

Human immunodeficiency virus (HIV) infection increases the risk of acute myocardial infarction (AMI). However, little is known about its association with in-hospital outcomes and temporal trends in patients with AMI undergoing percutaneous coronary intervention (PCI). We queried patients with AMI who underwent PCI from the National Inpatient Sample Database (2003–2015) and stratified them into three groups: symptomatic, asymptomatic, and HIV-negative. After 1:2 case–control matching (CCM), logistic regression analysis was conducted to determine how HIV infection affected in-hospital outcomes. We also evaluated their recent trends from 2003 to 2015. The total weighted national estimate of 2,191,129 AMI cases included 2,178,995 HIV/AIDS-negative, 4994 asymptomatic, and 7140 symptomatic HIV cases. Symptomatic but not asymptomatic patients with HIV suffered more than triple the in-hospital mortality (adjusted odds ratio (aOR) 3.6, 95% confidence interval (CI) 2.5–5.2), over one-fold incidence of acute kidney injury (aOR 2.6 95% CI 1.9–3.4) and cardiogenic shock risk (aOR 1.9, 95% CI 1.3–2.7), a longer length of hospital stay (beta 1.2, 95% CI 1.0–1.5), and had more procedures (beta 1.3, 95% CI 1.2–1.5). These disparities relating to symptomatic HIV infection persisted from 2003 to 2015. In patients with AMI who underwent PCI, symptomatic HIV infection was associated with higher in-hospital mortality and more severe outcomes.

Symptomatic human immunodeficiency virus infection is associated with advanced presentation and perioperative mortality in patients undergoing surgery for peripheral arterial disease

ObjectivePrior studies have demonstrated an increased risk of developing cardiovascular and peripheral arterial disease (PAD) in patients with human immunodeficiency virus (HIV). However, the effect of chronic HIV infection in patients with preexisting PAD and requiring vascular intervention is unclear. In the present study, we assessed the differences in clinical presentation and perioperative outcomes for patients with PAD who had undergone revascularization or amputation with and without HIV infection. MethodsInternational Classification of Diseases, 9th and 10th Revisions, Clinical Modification, codes were used to identify patients with a prior diagnosis of PAD who had undergone lower extremity revascularization or amputation in the National Inpatient Sample (2003-2017). From this group, the patients were divided for analysis into those with and without HIV infection. Of the patients with HIV infection (PWHs), we identified additional subsets of patients: those with any prior or current diagnosis of an HIV-related illness, including acquired immunodeficiency syndrome, designated as symptomatic HIV, and those without such a diagnosis, designated as asymptomatic HIV infection. Propensity score matching was performed to create matched cohorts. Population-based comparative analyses were performed of the clinical characteristics of the HIV-infected and HIV-uninfected groups. Univariate and multivariate logistic regression analyses of the perioperative in-hospital outcomes were performed on the matched cohorts. ResultsA total of 224,912 patients aged 18 to 85 years were identified who had been admitted with an established diagnosis of PAD and had undergone a lower extremity procedure. Of these patients, 1264 (0.56%) also had a diagnosis of HIV infection. Symptomatic PWHs were more likely to present with critical limb ischemia than were the HIV-uninfected patients or asymptomatic PWHs (66.2% vs 46.3% and 43.6%; P < .01). However, both asymptomatic and symptomatic PWHs were more likely to have required minor (7.5% and 6.7% vs 2.6%; P < .01) and major (12.9% and 27.4% vs 7.0%; P < .01) amputations than were matched HIV-uninfected controls. Although adjusted multivariate logistic regression analysis demonstrated symptomatic HIV infection to be a significant, independent predictor of in-hospital mortality (odds ratio, 2.46; 95% confidence interval, 1.37-4.40; P = .003), the perioperative mortality for the asymptomatic PWH was comparable to that of matched HIV-uninfected controls. ConclusionsSymptomatic PWHs, including patients living with acquired immunodeficiency syndrome, who had required a PAD-related procedure had presented with more advanced vascular disease and were most at risk of early perioperative mortality. However, the presentation and mortality between asymptomatic PWHs with well-controlled disease and HIV-uninfected patients were comparable. All PWHs with PAD were more likely to undergo lower extremity amputations than were HIV-uninfected matched controls. Asymptomatic, well-controlled HIV infection should not be a contraindication to elective PAD-related procedures because the mortality was similar to that of HIV-uninfected controls. However, the limb salvage rates might be lower for all PWHs with PAD, regardless of HIV disease severity. Taken together, these findings can improve perioperative risk stratification and surgical management of PAD in this high-risk population.

Impact of sickle cell disease on presentation and progression of paediatric HIV: a retrospective cohort study.

HIV and sickle cell disease (SCD) are significant causes of morbidity and mortality in sub-Saharan Africa. Given their separate roles in immune dysregulation, our objective was to characterise the impact that SCD has on the presentation and progression of paediatric HIV. The study was a retrospective cohort study (study period 2004-2018). Cases of HIV+and SCD-afflicted patients (HIV+/SCD+) were obtained via electronic chart review from a paediatric HIV clinic in Kampala, Uganda and matched 1:3 with HIV+controls without SCD (HIV+/SCD-). Thirty-five HIV+/SCD+subjects and 95 HIV+/SCD- controls were analysed (39% female (51/130), age 3.6years (SD3.9)). At baseline, WHO clinical stage (64% total cohort Stage III/IV) and nutritional status (9.4% severe acute malnutrition) were similar for both groups, whereas HIV+/SCD+had higher though non-significant baseline CD4 count (1036 (SD713) vs 849 (SD638) cells/microlitre, P=0.20, two-tailed t-test). There were 19 deaths, 6 (17%) HIV+/SCD+and 13 (14%) HIV+/SCD-, with unadjusted/adjusted models showing no significant difference. Nutritional progression and clinical stage progression showed no significant differences between groups. Kaplan-Meier analysis showed a slower rate of treatment failures in the HIV+/SCD+cohort (P=0.11, log-rank survival test). Trajectory analysis showed that in the time period analysed, the HIV+/SCD+cohort showed a more rapid rise and higher total CD4 count (P=0.012, regression analysis). The study suggests that SCD does not adversely affect the progression of HIV in patients on ART. Further, HIV+/SCD+achieved higher CD4 counts and fewer HIV treatment failures, suggesting physiological effects due to SCD might mitigate HIV progression.

3039 Esophageal Ulcers: A Presenting Symptom of Acute HIV Infection

INTRODUCTION: Dysphagia and odynophagia are commonly encountered in patients who are immunocompromised from chronic Human Immunodeficiency Virus (HIV) infection. Acute HIV infection can also cause odynophagia due to abrupt onset of oropharyngeal mucosal disease. We describe the eventual diagnosis of acute HIV infection in a patient presenting with dysphagia and odynophagia following endoscopic finding of esophageal ulceration. CASE DESCRIPTION/METHODS: A 43-year-old man presented with one week of epigastric pain, dysphagia, and odynophagia in the setting of recent fever (TMax 102.8F) and chills. He had intermittently taken a PPI following an emergency room visit the previous week. Oropharyngeal exam was negative for ulcers or thrush and abdominal exam was benign. Initial labs were normal aside from mild leukopenia (WBC 3,100/uL) with a low absolute neutrophil count. He underwent EGD showing several deep distal esophageal ulcers. Pathology showed acute esophagitis with mild to severe neutrophilic infiltrate and neutrophilic microabscesses. Staining of the ulcer biopsy specimens was negative for cytomegalovirus (CMV), herpes simplex virus (HSV) and fungal elements. The unknown etiology of his esophageal ulcers prompted testing for HIV. HIV immunoassay was positive however antibody differentiation was indeterminate. A subsequent HIV viral load was positive indicating acute HIV-1 infection. He was placed on anti-retroviral therapy soon after. A repeat EGD was performed three months later, demonstrating complete resolution of the previously seen ulcers. DISCUSSION: Presenting signs and symptoms of acute symptomatic HIV infection are nonspecific and the diagnosis is often missed or delayed. Esophageal ulceration may be underrecognized as an acute manifestation of illness. In one study of 16 men presenting with odynophagia who were eventually found to have acute HIV infection (HIV serology negative at presentation), all 16 were found to have esophageal ulceration during index endoscopy. Identification of viral particles resembling HIV-1 within ulcer biopsies with electron microscopy and isolation of HIV-1 from an ulcer biopsy specimen raise the possibility of direct viral infection of esophageal cells. With this in mind, endoscopists and gastroenterology providers should have a high index of suspicion for acute HIV infection in patients with odynophagia secondary to esophageal ulcer of unknown etiology.

Current Use and In-Hospital Outcomes of Mechanical Circulatory Support in HIV-Infected Patients: A Friend or a Foe?

Current Use and In-Hospital Outcomes of Mechanical Circulatory Support in HIV-Infected Patients: A Friend or a Foe?

Measles Seroprevalence and Vaccine Responses in Human Immunodeficiency Virus-infected Adolescents and Adults: A Systematic Review.

The World Health Organization (WHO) recommends an additional dose of measles-containing vaccine (MCV) for human immunodeficiency virus (HIV)-infected children receiving highly active antiretroviral therapy following immune reconstitution. We conducted a systematic review to synthesize available evidence regarding measles seroprevalence and measles vaccine immunogenicity, efficacy, and safety in HIV-infected adolescents and adults to provide the evidence base for recommendations on the need for measles vaccination. We conducted searches of 8 databases through 26 September 2017. Identified studies were screened independently by 2 reviewers. The search identified 30 studies meeting inclusion criteria. Across studies, measles seroprevalence among HIV-infected adolescents and adults was high (median, 92%; 27 studies), with no significant difference compared to HIV-uninfected participants (10 studies). In 6 studies that evaluated the immunogenicity of MCVs among seronegative HIV-infected adults, measles seropositivity at end of follow-up ranged from 0% to 56% (median, 39%). No severe adverse events were reported following measles vaccination in HIV-infected patients. Based on similar measles seroprevalence between HIV-infected and HIV-uninfected adolescents and adults, and the low response to vaccination, these studies do not support the need for an additional dose of MCV in HIV-infected adolescents and adults. These findings support WHO guidelines that measles vaccine be administered to potentially susceptible, asymptomatic HIV-infected adults, and may be considered for those with symptomatic HIV infection if not severely immunosuppressed. Measles-susceptible adolescents and adults, regardless of HIV status, may require targeted vaccination efforts to reach critical vaccination thresholds and achieve regional elimination goals.

181 Clinical Knowledge of Human Immunodeficiency Virus Among Emergency Providers at Two Level 1 Trauma Centers in Cleveland, Ohio

Emergency departments (ED) are targeted areas for prevention and diagnosis of early human immunodeficiency virus (HIV) and sexually transmitted infections (STI) given increased prevalence in this setting. Clinical knowledge and recognition of these diseases is required for identifying those at risk. Previous studies show that STI knowledge is sup-optimal among general practitioners, and acute HIV infection is frequently misdiagnosed in the ED. The purpose of this study was to assess the correlation between self-reported STI knowledge and HIV test ordering practices among emergency medicine providers in a survey study of simulated scenarios. We modified 2 surveys previously published in the literature that assess knowledge of acute HIV infection and STIs. The survey was divided into 2 sections: a 29-point score for STIs and a 10-point score for HIV. This modified survey was administered to all emergency physicians, residents, and advanced practice providers affiliated with 2 level 1 trauma centers in Cleveland, Ohio. The primary outcome of ordering an HIV test was analyzed using Spearman’s correlation coefficient (SC) to assess strength of correlation with STI knowledge. Subgroup analyses were conducted using SC and ANOVA. This study was powered to estimate the SC using an effect size of 0.3 at an alpha of 0.05 for 90% power requiring a sample size of 90 respondents. A total of 75 providers (31.3%) completed the survey. Respondents were primarily physicians (54.6%), male (56%), white (83.7%), with a median of 8 years in practice (IQR: 2,16). The majority of respondents (57%) report formal HIV training as part of their professional education. Spearman’s correlation of HIV and STIs showed a monotonic relationship with a weak positive correlation (r = 0.3513, p = 0.002). A similar analysis comparing length of time as an emergency medicine provider with HIV and STI scores was monotonic with a weak negative correlation that was not statistically significant. There was no association between HIV scores and provider type (p=0.67) or provider sex (p=0.89); however, those with formal HIV training scored higher than those without formal HIV training (p=0.003). There was no association between STI scores and provider type (p=0.10) or provider sex (p=0.79). The movement in emergency medicine to screen patients at risk of undiagnosed HIV focuses on universal or targeted screening. The results of our study reveal that when presented with a patient at high-risk for undiagnosed HIV or with undiagnosed symptomatic HIV infection, most providers either do not screen or do not have HIV in the differential diagnosis. Similarly, knowledge of STIs is only weakly correlated with knowledge of HIV risk factors and symptomatic HIV infection. Further research and screening efforts may benefit by focusing on HIV education among EM providers.

Higher HIV RNA Viral Load in Recent Patients with Symptomatic Acute HIV Infection in Lyon University Hospitals.

IntroductionIncreased human immunodeficiency virus (HIV) virulence at infection has been suggested by a meta-analysis based on viral load and CD4 T lymphocytes (CD4) count during acute infection. This result was obtained after secondary analyses of large databases, facilitating the detection of differences. Similar finding in cohorts of more modest sample size would indicate that the effect could be more substantial.MethodsChange from initial CD4 count and HIV viral load after acute HIV infection by calendar year was explored in patients treated at Lyon University hospitals. All patients admitted to our hospitals with acute HIV infection between 1996 and 2013 were included in our study. Initial CD4 count and viral load before the start of anti-retroviral treatment were analyzed. Trends over time were assessed in linear models.ResultsInitial CD4 count remained similar over time. However, in 2006–2013, initial viral load rose significantly (+1.12 log10/ml/year, p = 0.01).ConclusionOur data, obtained from a single hospital cohort, confirmed findings from a large meta-analysis, showed increased initial viremia at acute HIV infection since 2006 and suggesting potentially higher HIV virulence in recent years.

PREVALENCE OF AUTOANTIBODIES REVEALS A PREDOMINANT SMA AND ANCA-PR3/MPO PATTERN IN HIV INFECTION AND SMA IN HAV-INFECTED CHILDREN

Hepatitis A Virus (HAV) and Human Immunodeficiency Virus (HIV) have been associated with development of autoantibodies and autoimmune manifestations in children. Autoimmune Hepatitis (AIH) is particularly aggressive in children/adolescents with a more severe outcome. Thus, studying the mechanisms of virus-related autoimmune disorders in children is a relevant topic of research. We aimed to study the prevalence of autoantibodies in plasma of children infected with either HAV or HIV comparing to healthy children. The relationship bet ween the presence of autoantibodies and biochemical markers of hepatic damage was also investigated. De tection of autoantibodies (SMA) was associated with HAV infection with a prevalence of 35%. Similar levels of hepatic enzymes were observed in sera of HAV-infected patients with reactivity against autoa ntigens as compared to those without autoantibodies . On the other hand, HIV infection showed broader aut oantibodies reactivities than HAV-infected patients and was associated with SMA (18%), ANCA (20%), ANCA-PR3 (15%) and ANCA-MPO (13%). Moreover, either RF or ANA was detected in 8% of HIV-infected children. Prevalence of autoantibodies was not associated with either gender or age of inf ected children. A high prevalence of SMA was observed in HAV- and HIV-infected patients. As HAV and SMA may persit in some patients and AIH can develop in susceptible children, it is recommen ded a follow up of virus infected patients. Since ANCA-PR3 and ANCA-MPO have been shown to be pathogenic, proinflammatory and associated with symptomatic HIV infection, further studies are requ ired to determine the role of these autoantibodies in the pathogenesis associated with viral infection in children.

Host–Epstein–Barr virus relationship affected by immunostimulation in HIV-infected patients representing distinct progressor profile groups

Human immunodeficiency virus (HIV) infection with pronounced immunosuppression disrupts Epstein-Barr virus (EBV)-host balance with increased lymphoma risk. We explored whether different host responses to HIV are reflected in the EBV-host balance. Eleven unvaccinated HIV-positive patients and 16 participants in a vaccine trial were included in the study. Blood samples were collected, B cells extracted, and EBV DNA load was determined using a semiquantitative polymerase chain reaction (PCR) method. Treatment-naïve patients with a history of symptomatic primary HIV infection showed non-significant, but higher EBV load compared to untreated long-term non-progressors. A significant difference in HIV RNA titres between these groups correlated weakly to EBV DNA load. Patients in the vaccine trial with recombinant HIV gp160 and/or adjuvant and with a history of symptomatic primary HIV infection, showed a 1-log increase in EBV load compared to patients with long-lasting HIV disease. Different host responses to HIV infection, especially in combination with vaccination, can be reflected in the EBV-host balance.

Documento de consenso del Grupo de Estudio de Sida/Plan Nacional sobre el Sida respecto al tratamiento antirretroviral en adultos infectados por el virus de la inmunodeficiencia humana (actualización enero 2010)

This consensus document is an update of antiretroviral therapy recommendations for adult patients with human immunodeficiency virus infection. To formulate these recommendations a panel made up of members of the Grupo de Estudio de Sida (Gesida, AIDS Study Group) and the Plan Nacional sobre el Sida (PNS, Spanish AIDS Plan) reviewed the advances in the current understanding of the pathophysiology of human immunodeficiency virus (HIV) infection, the efficacy and safety of clinical trials, and cohort and pharmacokinetic studies published in biomedical journals or presented at scientific meetings. Three levels of evidence were defined according to the data source: randomized studies (level A), cohort or case-control studies (level B), and expert opinion (level C). The decision to recommend, consider or not to recommend ART was established in each situation. Currently, the treatment of choice for chronic HIV infection is the combination of three drugs of two different classes, including 2 nucleosides or nucleotide analogs (NRTI) plus 1 non-nucleoside (NNRTI) or 1 boosted protease inhibitor (PI/r), but other combinations are possible. Initiation of ART is recommended in patients with symptomatic HIV infection. In asymptomatic patients, initiation of ART is recommended on the basis of CD4 lymphocyte counts, plasma viral load and patient co-morbidities, as follows: 1) therapy should be started in patients with CD4 counts below 350 cells/microl; 2) When CD4 counts are between 350 and 500 cells/microl, therapy should be started in case of cirrhosis, chronic hepatitis C, high cardiovascular risk, HIV nephropathy, HIV viral load above 100,000 copies/ml, proportion of CD4 cells under 14%, and in people aged over 55; 3) Therapy should be deferred when CD4 are above 500 cells/microl, but could be considered if any of previous considerations concurs. Treatment should be initiated in case of hepatitis B requiring treatment and should be considered for reduce sexual transmission. The objective of ART is to achieve an undetectable viral load. Adherence to therapy plays an essential role in maintaining antiviral response. Therapeutic options are limited after ART failures but undetectable viral loads maybe possible with the new drugs even in highly drug experienced patients. Genotype studies are useful in these situations. Drug toxicity of ART therapy is losing importance as benefits exceed adverse effects. Criteria for antiretroviral treatment in acute infection, pregnancy and post-exposure prophylaxis are mentioned as well as the management of HIV co-infection with hepatitis B or C. CD4 cells counts, viral load and patient co-morbidities are the most important reference factors to consider when initiating ART in asymptomatic patients. The large number of available drugs, the increased sensitivity of tests to monitor viral load, and the ability to determine viral resistance is leading to a more individualized therapy approach in order to achieve undetectable viral load under any circumstances.

Evaluation of immunoglobulin classes (IgA, IgG and IgM) levels and complement fixation activity in HIV infected subjects

The study was designed to evaluate the immunoglobulin A, G and M levels and complement fixation activity in HIV infected participants, who were not administered antiretroviral therapy (ART). Eighty (80) HIV infected participants, aged between 15 – 55 years (38 ±10 years), were recruited for the study. Forty five (45) of the participants were classified as symptomatic HIV (stage ii), while the remaining 35 were classified asasymptomatic HIV (stage i). Similarly, 40 seronegative participants served as control. Blood samples were collected from the participants for the determination of HIV status by immunochromatography, HIV confirmation by Western blot, determination of immunoglobulin levels by immunoturbidimetry, and complement activity by complement fixation test. The IgG and IgA were significantly increased in symptomatic HIV infection compared with asymptomatic HIV infection (p0.05). The complement fixation activities decreased in HIV infected patients compared with the values in HIV seronegatives. The increase in IgA concentration with HIV infected participants may suggest existence of mucosal infections, while theincrease in IgG concentration in HIV infected participants may suggest evidence of increased opportunistic infection requiring IgG response. The low level of complement activity in HIV infected participants maypredispose individuals with HIV infection to disease commonly controlled through immunological activity of the complement. Keywords: Human Immunodeficiency Virus (HIV), immunoglobulins (IgA, IgG and IgM), complements.

HIV Infection Presenting in Older Children and Adolescents: A Case Series from Harare, Zimbabwe

Symptomatic human immunodeficiency virus (HIV) infection during late childhood and adolescence may be an emerging problem in southern Africa, but it is one that is poorly described. We investigated social and clinical features in patients of this age group presenting to a HIV treatment clinic with special adolescent services in Harare, Zimbabwe. All patients aged 8-19 years and their guardians who attended an adolescent HIV treatment clinic were asked to consent to an interview and a review of medical notes. Of 32 patients, 17 (53%) were male. The median CD4 cell count at presentation was 101 cells/microL (interquartile range, 35-197 cells/microL). Sixty-two percent experienced stunting (mean Z score for height-for-age, -2.55; 95% CI, -2.00 to -3.10), and all presented with World Health Organization stage 3 or 4 HIV infection. The median age at the first HIV test was 11 years, with a median of 3.5 years delay since the first HIV-related illness. Recurrent respiratory tract infections, skin complaints, diarrhea, and past tuberculosis were the most common HIV-related complaints. Seventeen patients (55%) were double orphans, and 10 (62%) surviving parents were known to be HIV positive. In this small study, HIV-infected adolescents were profoundly immunosuppressed, with characteristics suggesting long-standing HIV infection. The equal sex distribution and high incidence of parental and sibling mortality were consistent; the majority of children had HIV-infected parents and, therefore, were potentially long-term survivors of HIV infection due to mother-to-child transmission. Greater recognition of the substantial burden of undiagnosed HIV infection and acquired immunodeficiency syndrome in this age group is needed, together with services aimed at reducing barriers to earlier diagnosis and initiation of treatment.

Rhabdomyolyse aiguë associée à une primo-infection à VIH-1 : une nouvelle observation

Introduction Acute human immunodeficiency virus type 1 infection is a clinical and biological misleading and often undiagnosed illness. Laboratory studies frequently demonstrate abnormalities. Acute rhabdomyolysis is rarely reported. Exegesis Authors report the case of an African man who presented with acute fever, cough, diarrhea, conjunctivitis, thrombocytopenia, lymphopenia, and rhabdomyolysis without other possible cause. HIV test and detection of plasma p24 antigen were initially negative but were controlled positive and associated with high level of viral RNA. Conclusion Symptomatic primary human immunodeficiency virus infection presenting with acute rhabdomyolysis was diagnosed. Diagnosis of primary HIV-1 infection must be considered in young people and patients at risk who present with acute rhabdomyolysis and fever.

Non-condylomatous, perianal disease in homosexual men.

This retrospective study details the findings and outcome in 34 homosexual men, out of a total of 177 patients, who underwent surgery for non-condylomatous perianal disease over a 2-year period. Of 34 homosexuals 20 presented with anorectal sepsis compared with 11 of 79 heterosexual male patients (X2 = 24.07, P less than 0.001). Lesions included chronic intersphincteric abscess (eight patients), anal fistula (seven patients) and chronic intersphincteric abscess and fistula (five patients). Anal fissure occurred in 15 patients, anal ulcer in three, skin tags in six, haemorrhoids in two and Kaposi's sarcoma in one. Eight patients were human immunodeficiency virus (HIV) antibody negative, four were asymptomatic HIV antibody positive, 12 had symptomatic HIV infection using the Centers for Disease Control classification and in ten patients HIV status was unknown. Irrespective of the type of surgery performed, healing occurred within 6 weeks of operation in all HIV antibody negative patients, all asymptomatic HIV antibody positive and in only one of nine patients with symptomatic HIV infection. Eight of nine patients with symptomatic HIV infection failed to heal by this time (X2 = 8.98, P less than 0.05). These findings suggest that the prevalence of anorectal sepsis in homosexual men is high and that symptomatic HIV infection is an important determinant of progress after surgery.

Acute Pancreatitis Associated with Different Combination Therapies in Patients Infected with Human Immunodeficiency Virus

To assess the risk of acute pancreatitis in patients receiving various combinations of protease inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs), and nonnucleoside reverse transcriptase inhibitors (NNRTIs) for treatment of human immunodeficiency virus (HIV) infection. Retrospective cohort study. Ohio Medicaid claims database, January 1997-December 2002. Four thousand nine hundred seventy-two patients with HIV infection who had received at least one antiretroviral drug. Three combination regimens were evaluated: didanosine plus other antiretroviral agents, protease inhibitors plus NRTIs or NNRTIs, and NRTI combinations (no didanosine) or NRTIs plus NNRTIs. We used Cox proportional hazard regression and Kaplan-Meier plots to examine the risk for acute pancreatitis. We identified 159 (3.2%) cases of acute pancreatitis during the study period. For patients who were newly treated for HIV, the incidence of acute pancreatitis was 1.95/100 person-years. Half of these cases developed within 500 days of the start of drug therapy. Hazard ratios (HRs) for acute pancreatitis were 39-54% higher for nonwhite patients than Caucasians and 240-290% higher for symptomatic versus nonsymptomatic patients. Hazard ratios also were significantly associated with increased age, liver injuries (HR 2.94, 6.73), and cardiovascular diseases (HR 1.68, 2.36), respectively, for both newly treated and previously diagnosed patients with HIV. The risk for patients receiving either protease inhibitors plus an NRTI or an NNRTI, or NRTI plus NNRTI combinations was not significantly different from the risk associated with didanosine combination therapy (p>0.10). The risk of acute pancreatitis was significantly associated with age, race, symptomatic HIV infection, and liver and cardiovascular diseases. However, risk did not differ significantly among patients with different antiretroviral regimens. Our results can be used by the medical community to enhance patient safety and minimize costly adverse drug reactions among patients with HIV infection.

Age-related macular degeneration: economic burden and value-based medicine analysis

Age-related macular degeneration (AMD) is a major public health problem. It can be estimated that 17 100 new cases of neovascular (wet) AMD and 180 000 new cases of geographic-atrophy (dry) AMD occur in Canada annually. In addition to having a devastating effect on patients' lives, the condition causes significant adverse consequences for the economy. The deleterious effect of AMD on quality of life is markedly underestimated by ophthalmologists who treat patients with AMD, by non-ophthalmic physicians and by the public. In fact, patients with different degrees of severity of AMD have a perceived impairment of their quality of life that is 96% to 750% greater than the impairment estimated by treating ophthalmologists. Mild AMD causes a 17% decrease in the quality of life of the average patient, a decrease similar to that encountered with symptomatic human immunodeficiency virus infection or moderate cardiac angina. Moderate AMD produces a 40% decrease in quality of life, a decrease similar to that associated with permanent renal dialysis or severe cardiac angina. Very severe AMD causes a 63% decrement in quality of life, a decrease similar to that encountered with advanced prostatic cancer with uncontrollable pain or a severe stroke that leaves a person bedridden, incontinent and requiring constant nursing care. The adverse economic consequences of AMD include an annual $2.6 billion negative impact on Canada's gross domestic product. The return on investment is high for both current AMD therapies and research into new treatment modalities.

Difficulties in assessing cytomegalovirus-associated gastric perforation in an HIV-infected patient

BackgroundActive Cytomegalovirus (CMV) infection is a common complication in advanced symptomatic Human Immunodeficiency Virus (HIV) infection. CMV-induced intestinal perforations are hard to diagnose and may be observed throughout the gastrointestinal tract. Isolated stomach perforation is exceptional.Case presentationA 47-year-old man was admitted to our intensive care unit with multiorgan failure. Gastrointestinal endoscopic examination showed erythematous gastritis but normal duodenum and colon. CMV blood culture was positive. Histologic examination of a gastric biopsy showed inflammatory infiltrate and immunostaining typical intranuclear CMV inclusion bodies. Concomitant abdominal CT scan disclosed large peripancreatic hypodensities without pneumoperitoneum. The patient died despite supportive therapies and ganciclovir infusion. Postmortem examination showed a 4-cm gastric perforation adhering to the transverse colon and liver, with a thick necrotic inflammatory coating around the pancreas. The whole GI tract, except the stomach, was normal. As other causes, especially Helicobacter pylori infection could be ruled out, a causal relationship between CMV and gastric disease was assumed.ConclusionCMV may be responsible for gastric perforations, with difficulties in assessing the diagnosis. Early diagnosis based on cautious endoscopy and histopathologic examination is needed to make a favorable outcome possible.

High Prevalence of Hepatitis B Virus Markers in Romanian Adolescents With Human Immunodeficiency Virus Infection

BackgroundWe evaluated the frequency of hepatitis coinfection in Romanian adolescents who were diagnosed with human immunodeficiency virus (HIV) infection prior to 1995.MethodsOne hundred sixty-one adolescents (13–18 years of age) with symptomatic HIV infection, but without signs of hepatic dysfunction, and 356 age-matched, HIV-uninfected controls underwent laboratory testing for markers of parenterally acquired hepatitis virus infection.ResultsSeventy-eight percent of HIV-infected adolescents had markers of past or present hepatitis B virus (HBV) infection, as compared with 32% of controls (P = .0001). The prevalence of HBV replicative markers was more than 5-fold higher in HIV-infected adolescents as compared with controls: 43.4% vs 7.9% (P = .0001), respectively, for hepatitis B surface antigen (HBsAg); and 11.2% vs 2.2% (P = .0001), respectively, for hepatitis B e antigen (HBeAg). The prevalence of HBsAg chronic carriers and the presence of HBV replicative markers was significantly higher in patients with immunologically defined AIDS (CD4+ cell counts < 200 cells/mcL): 59.6% vs 34.6% (P = .02) for HBsAg and 22.8% vs 5.7%, (P = .002) for HBV DNA. After 1 year of follow-up, the proportion of those who cleared the HBeAg was considerably lower in severely immunosuppressed coinfected patients: 4.7% vs 37.1% (P = .003). Four additional HIV-infected adolescents became HBsAg-positive over the term of follow-up (incidence rate, 24.9/1000 person-years), despite a record of immunization against hepatitis B.ConclusionA substantial percentage of HIV-infected and HIV-uninfected Romanian adolescents have evidence of past or present HBV infection. In HIV-infected adolescents, the degree of immunosuppression is correlated with persistence of HBV replicative markers, even in the absence of clinical or biochemical signs of liver disease.

Recomendaciones de GESIDA/Plan Nacional sobre el Sida respecto al tratamiento antirretroviral en pacientes adultos infectados por el VIH (octubre 2004)

This consensus document is an update of antiretroviral therapy (ART) recommendations for adult patients infected with the human immunodeficiency virus (HIV). To formulate these recommendations, a panel composed of members of the Grupo de Estudio de Sida (GESIDA; AIDS Study Group) and the Plan Nacional sobre el Sida (PNS; Spanish AIDS Plan) reviewed the advances in current understanding of the pathophysiology of HIV, the safety and efficacy findings from clinical trials, and the results from cohort and pharmacokinetic studies published in biomedical journals or presented at scientific meetings over the last years. Three levels of evidence were defined according to the source of the data: randomized studies (level A), cohort or case-control studies (level B), and expert opinion (level C). The decision to recommend, consider or not recommend ART was established in each of these situations. ART consisting of at least three drugs is currently the initial treatment of choice for chronic HIV infection. These regimens should include 2 NRTI + 1 NNRTI or 2 NRTI + 1 PI. Initiation of ART is recommended in patients with symptomatic HIV infection. In asymptomatic patients, initiation of ART is recommended on the basis of CD4+ lymphocyte counts per L and plasma viral load, as follows: 1) Therapy should be started in patients with CD4+ counts of < 200 cells/microL; 2) Therapy should be started in most patients with CD4+ counts of 200-350 cells/microL, although it can be delayed when CD4+ count persists at around 350 cells/microL and viral load is low; and 3) Initiation of therapy can be delayed in patients with CD4+ counts of > 350 cells/microL. The initial objective of ART is to achieve an undetectable viral load. Adherence to therapy plays an essential role in maintaining the antiviral response. Because of the development of cross resistance, therapeutic options are limited when ART fails. Genotype studies are useful in these cases. Toxicity is a limiting factor in the use of ART, although the benefits outweigh the risks. In addition, the criteria for the use of ART are discussed in situations of acute infection, pregnancy, and post-exposure prophylaxis, and in the management of co-infection of HIV with HCV or HBV. CD4+ lymphocyte count is the most important reference factor for initiating ART in asymptomatic patients. The large number of available drugs, the increased sensitivity of tests to monitor viral load, and the possibility to determine viral resistance is leading to a more individualized approach to therapy.