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Disseminated Mycobacterium genavense infection in Canadian AIDS patients.

Mycobacterium genavense is a recently described mycobacterial species which thus far has been identified only in persons with advanced HIV disease. It appears to be a rare pathogen with an undefined reservoir. We describe the first two cases of M. genavense infection in Canadian AIDS patients. The clinical presentation of fever and wasting with extremely low CD4 lymphocyte counts was indistinguishable from disseminated M. avium complex (MAC) infection. However, blood cultures in BACTEC 13A medium required a mean of 58 days (range 41-87) to detect growth of M. genavense in contrast to a mean of 10 days for MAC in our laboratory. M. genavense infection is underdiagnosed due to the lack of universal use of BACTEC liquid medium and the use of relatively short incubation times (only 6 weeks) by some laboratories. The value of antimycobacterial therapy for M. genavense is unknown, but anecdotal data suggest that treatment with a regimen appropriate for MAC may be beneficial.

Acquired Immunodeficiency Syndrome↗

Histological and ultrastructural study of one case of oral bacillary angiomatosis in HIV disease and review of the literature.

Bacillary angiomatosis (BA) is a new clinicopathological entity defined as a pseudo-neoplastic capillary proliferation secondary to an opportunistic infection by one of two Rochalimaea sp.: R. quintana or R. henselae. Although BA is a recently recognised entity, numerous cases have been reported. Most of the patients affected are reported to have low absolute CD4 lymphocyte counts associated with AIDS. Yet, very few oral cases associated or not with cutaneous lesions have been reported or simply identified. Histopathological and ultrastructural features of one case of oral BA with gingival and palatal lesions are presented. Clinical aspects of oral BA do not hold pathognomonic features and the lesions may resemble either a reactive lesion of the gingiva, pyogenic granuloma or Kaposi's sarcoma. The lesion is characteristically composed of circumscribed lobular capillary proliferations and the presence of granular amphophilic material on haematoxylin and eosin sections surrounded by neutrophils and neutrophilic debris is a clue to diagnosis. Demonstration of bacilli in the interstitium by the Warthin-Starry silver method or, better, by electron microscopy is diagnostic. BA may contribute to the death of the patient but erythromycin has proved to be very effective treatment.

AIDS-Related Opportunistic Infections↗

Current guidelines for the management of UK Infants born to HIV-1 infected mothers.

Transmission of the Human Immunodeficiency Virus type 1 (HIV-1) from mother to child has been associated with maternal plasma viral load and CD4 lymphocyte count, prematurity, the mode of infant delivery, length of rupture of membranes and breast feeding. Without intervention, the transmission of HIV-1 occurs in a quarter to a third of infants born to infected mothers. During the last decade, mother-to-child transmission of HIV-1 has been reduced to less than 1%, through formula feeding, prelabour Caesarean section (PLCS) and antiretroviral therapy. With such an impressive reduction in the transmission of HIV-1, attention is turning towards the minimisation of possible drug side effects both in mothers and their infants. HIV-1-infected women are increasingly choosing to conceive on combination antiretroviral therapy, hence, infants are exposed to increasing numbers, combinations and classes of drugs, often from conception. Current guidelines on the prevention of mother to child transmission of HIV-1 are discussed.

Anti-HIV Agents↗

Heart rate variability in human immunodeficiency virus-positive individuals.

BACKGROUND: Heart rate variability (HRV) is a marker of cardiac autonomic tone. Depressed HRV has been reported in patients with AIDS. We conducted this study to find out if HRV is depressed in human immunodeficiency virus (HIV)-positive individuals without AIDS. METHODS: We studied prospectively HRV by spectral analysis of short-term electrocardiography (ECG) monitoring in 21 HIV-positives (33+/-11 years) and in 18 healthy volunteers (31+/-9 years). None of the HIV-positives had any clinical evidence of autonomic or cardiac dysfunction. Echocardiography was also performed in HIV-seropositives to rule out left ventricular (LV) systolic dysfunction. All these individuals did not have any evidence of AIDS. RESULTS: Mean CD4+ lymphocyte count was 426+/-166/mm(3). The ejection fraction (EF%) of HIV patients was 62.4+/-6.4. The total power of HRV was reduced significantly in HIV-positive individuals (p<0.00001). All the components of HRV were reduced. CONCLUSIONS: HRV is reduced in HIV-seropositive individuals in early stages of infection as well without any clinical evidence of autonomic dysfunction. This may serve as an early marker of future global sympatho-vagal imbalance.

Adult↗

Hepatitis C virus viral recurrence and liver mitochondrial damage after liver transplantation in HIV-HCV co-infected patients.

BACKGROUND/AIMS: As life expectancy in HIV-HCV co-infected patients improves, end stage liver disease requiring liver transplantation (LT) may become an emerging problem. We report the Paul Brousse Hospital experience of transplantation for end stage cirrhosis in HIV-HCV co-infected patients. METHODS: Seven consecutive HIV-HCV co-infected patients were transplanted between December 1999 and December 2002 for end stage liver disease due to HCV. All patients were treated by highly active antiretroviral therapy (HAART), HIV plasma viral load was <400 copies/ml and median CD4 lymphocyte count was 306 cells/mm3 (range, 103-510) before LT. At the time of evaluation (March 2003), the median follow-up was 21 months (range, 4-40). RESULTS: Two patients died, 4 and 22 months, respectively after LT. At the last biopsy, METAVIR score was staged F4 in two patients, F3 in two, and F1 in one. Microvesicular steatosis was noted in nearly all patients. The ratio of mitochondrial to nuclear DNA was low in three of four patients examined as compared with the amount of liver mtDNA found in eight HIV-negative, HCV-infected controls (P=0.01). CONCLUSIONS: A significant defect in the activity of the respiratory chain complex IV was noted in all five patients studied. Mitochondrial hepatotoxicity and severe HCV recurrence occur in HIV-HCV co-infected patients after LT.

Adult↗

VH3 gene expression in children with HIV infection.

OBJECTIVE: To study immunoglobulin heavy chain variable region (V(H)) gene expression in HIV-uninfected (HIV-) and HIV-infected (HIV+) children. METHODS: A retrospective, observational study was performed by PCR-ELISA to examine IgM and IgG V(H) gene family expression among peripheral CD19-positive B cells. The subjects were 10 HIV+ children with, and 11 HIV+ children without a history of invasive pneumococcal disease (IPD) and 12 HIV- children. The ages of the HIV+ and HIV- children, and the CD4 lymphocyte counts and viral loads (VL) of the HIV+ /IPD- and HIV+ /IPD- children were statistically similar. Rearranged V(H)3 gene libraries were constructed from 3 HIV+ /IPD- children to examine individual gene expression. RESULTS: The proportion of IgG V(H)3 expression among HIV+ /IPD- was lower than that of HIV- children, but the proportion of IgG V(H)3 expression among HIV+ /IPD+ children was not significantly different from that of HIV- children. IgG V(H)3 expression was positively, whereas IgM V(H)3 expression was inversely correlated with the VL among HIV+ /IPD+, but not HIV+ /IPD- children. IgM V(H) gene family expression did not differ between HIV+ and HIV- children. CONCLUSION: HIV+ children manifest qualitative and quantitative differences in V(H)3 expression, which may be influenced by IPD.

Bacteremia↗

Persistence of psychiatric disorders in a cohort of HIV/AIDS patients in South Africa: a 6-month follow-up study.

BACKGROUND: Psychiatric disorders in HIV/AIDS are common, emerging soon after diagnosis or during the subsequent course of illness. However, there are few prospective studies on the rates of psychiatric disorders in HIV/AIDS, particularly in the context of the developing world. METHODS: Sixty-five patients with recently diagnosed HIV were interviewed on presentation to a hospital-based HIV clinic and then 6 months later. On both interviews, the patients were assessed using the MINI International Neuropsychiatric Interview, the Carver Brief COPE, and the Sheehan Disability Scale. Exposure to negative life events and risk behaviors was also evaluated. RESULTS: The overall prevalence of psychiatric disorders in the follow-up period remained high (56% of patients had at least one psychiatric disorder at baseline, and 48% of patients had at least one psychiatric disorder at 6 months). Depression and posttraumatic stress disorder (PTSD) were the most prevalent disorders at both baseline (34.9% and 14.8%) and follow-up (26% and 20%), respectively. More than half of all patients with depression at baseline improved (16 of 29; 55.1%). However, there was a new onset of both depression (4 of 49; 8.1%) and PTSD (12 of 17; 70.5%) on follow-up. In univariate analysis, depression on follow-up was significantly associated with: (a) disability in work/social/family functioning, (b) greater number of negative life events, and (c) a decline in CD4 lymphocyte count. Univariate analysis also revealed that a diagnosis of PTSD on follow-up was significantly associated with (a) a longer duration of infection and (b) baseline disability in work/social/family functioning. However, in multivariate analysis, only disability scores predicted the diagnoses of major depression and PTSD on follow-up assessment. Persistence of risky sexual behaviour was also noted, with a significantly higher number of participants reporting nonuse of condom on follow-up. There appeared to be a shift from maladaptive coping behaviors to more adaptive coping behaviors over the 6-month period. CONCLUSION: The rate of psychiatric disorders in HIV/AIDS patients was consistent over time. These findings emphasize the importance of regular evaluation for psychiatric disorders in HIV/AIDS patients, not only at the commencement of treatment but also during subsequent follow-up visits.

Acquired Immunodeficiency Syndrome↗

Who is accessing antiretroviral therapy during national scale-up in Malawi?

Malawi is scaling-up provision of free antiretroviral therapy (ART) in the public sector. In the fourth quarter of 2004 and the first quarter of 2005, 3261 and 4530 new patients, respectively, were started on ART. Of these patients, approximately 40% were male and 95% were adults aged > or =13 years. The age group data show that women who accessed ART were in general 10 years younger than men. Between 84% and 90% of patients were started on ART because of being clinically assessed as being in WHO stages III or IV, with the remainder started on ART owing to a low CD4 lymphocyte count. The number of tuberculosis (TB) patients started on ART was 351 (11% of ART patients) in the fourth quarter of 2004 and 702 (15% of ART patients, and 16% of registered TB patients) in the first quarter of 2005. Twenty-nine pregnant women were referred to ART from prevention of mother-to-child transmission programmes in the first quarter of 2005. Between 56% and 62% of patients were subsistence farmers, housewives or in business. Steady progress is being made with national scale-up, although more attention needs to be directed to children, pregnant women and patients with TB to improve their access to ART.

Adolescent↗

Evaluation of feline immunodeficiency virus ORF-A mutants as candidate attenuated vaccine.

Feline immunodeficiency virus (FIV) made defective in the accessory gene ORF-A were previously shown to be greatly attenuated in its ability to replicate in lymphocytes but to grow normally or near normally in other cell types. Here, we examined whether FIV thus mutated could protect specific pathogen-free cats against challenge with ex vivo fully virulent homologous virus. No reversion of the vaccinating infections to wild type ORF-A was noted over 22 months of in vivo infection. Following challenge, 6/6 unvaccinated control cats became readily and heavily infected. In contrast, 3/9 vaccinees showed no evidence of the challenge virus over a 15-month observation period. In the other vaccinees, the challenge virus was predominant for various periods of time, but pre-existing viral loads and CD4 lymphocyte counts were either unaffected or altered only marginally and transiently. These findings show that ORF-A-defective FIV should be further examined as a candidate live attenuated vaccine.

Amino Acid Sequence↗

Sub-cortical white-grey matter contrast on MRI as a quantitative marker of diffuse HIV-related parenchymal abnormality.

White matter change occurs in human immunodeficiency virus (HIV) encephalopathy, which may be difficult to assess subjectively especially in the early stages of disease. This study applies a quantitative approach to the assessment of this finding. Sixty-three HIV seropositive subjects, 47 seronegative blood donors and 17 seronegative homosexual men underwent axial T2 weighted MRI of the brain at 1.5T. Quantitative analysis was performed by obtaining the pixel contrast between parieto-occipital white matter and head of caudate grey matter (Cwg). Highest values of Cwg were found in a subgroup of subjects with AIDS who had diffuse/patchy white matter abnormalities and atrophy on qualitative image assessment. Statistically significant differences were found in Cwg between subjects with high (> or = 200 x 10(6)/I) and low (< 200 x 10(6)/I) CD4 lymphocyte counts (P < 0.05) and between subjects with and without HIV-1 associated cognitive/motor complex (P < 0.05). This technique provides an objective measure of diffuse HIV-related parenchymal abnormality seen on T2 weighted MRI.

AIDS Dementia Complex↗

Cytomegalovirus colitis in acquired immunodeficiency syndrome: a clinical and endoscopic study.

BACKGROUND: Cytomegalovirus colitis is an important complication of the acquired immunodeficiency syndrome (AIDS), although the clinical and colonoscopic manifestations of this disease have not been systematically characterized. METHODS: Patients with AIDS and cytomegalovirus colitis were prospectively identified at two medical centers. The diagnosis of cytomegalovirus disease was based on established endoscopic and histologic criteria. At the time of sigmoidoscopic and/or colonoscopic examination, clinical features were recorded; the location, size, and appearance of all endoscopic abnormalities were documented; and multiple biopsies of any lesions were performed. RESULTS: Fifty-six patients were studied. The majority of the patients were homosexual men with severe immunodeficiency (median CD4 lymphocyte count 15/mm3, range 1 to 294/mm3). Chronic diarrhea and abdominal pain were the most frequent clinical manifestations, seen in 45 (80%) and 28 (50%) patients, respectively. Five patients (9%) presented with lower gastrointestinal hemorrhage, three of whom had no antecedent history of diarrhea. The colonoscopic abnormalities could be categorized into three main groups: colitis associated with ulcer (39%), ulceration alone (38%), or colitis alone (20%). Subepithelial hemorrhage was a prominent endoscopic manifestation of disease. Of the 31 patients undergoing colonoscopy to the cecum, in four (13%) endoscopic evidence of disease was limited to the colon proximal to the splenic flexure. CONCLUSIONS: Cytomegalovirus colitis in AIDS appears to have variable but stereotypical clinical and colonoscopic manifestations. Distal colitis associated with ulceration is the most common colonoscopic pattern.

Acquired Immunodeficiency Syndrome↗

Delayed somatic growth and pubertal development in human immunodeficiency virus-infected hemophiliac boys: Hemophilia Growth and Development Study.

As part of the Hemophilia Growth and Development Study, we investigated the impact of human immunodeficiency virus (HIV) infection on statural growth, weight gain, and skeletal and sexual maturity in more than 300 boys with moderate to severe hemophilia, of whom 62% were infected with HIV. Age-adjusted height and weight were reduced in the HIV-infected subjects (p < 0.001). However, mean weight for height and triceps skin-fold thickness of the infected-boys closely resembled those of the uninfected group. In HIV-infected boys, height for age was positively related to the CD4+ lymphocyte count when the count was < 200 cells/mm3. Age-adjusted serum testosterone levels did not differ by HIV status, but in the infected participants the mean age-adjusted bone age was significantly reduced (p = 0.038) and the distribution of Tanner stages, adjusted for age, differed significantly (p = 0.003). The probability of advancing one or more Tanner stages in the first study year was significantly slowed in HIV-infected boys more than 14 years of age (p = 0.0003). We conclude that linear growth was significantly impaired in boys with hemophilia and HIV infection, but the wasting of malnutrition was not found. The delays in bone age and pubertal maturation strongly suggest that part of the growth failure seen in acquired immunodeficiency syndrome can be attributed to pubertal delay. We speculate that the lack of demonstrable difference in age-adjusted testosterone concentrations might reflect subtle differences in the pattern of secretion of testosterone or in the concentration of sex-hormone binding globulin.

Adolescent↗

Antiviral agents.

In recent years, the antiviral armamentarium has expanded considerably. Currently available agents are virustatic, inhibiting specific steps in the process of viral replication. No agent is active against nonreplicating or latent viruses. Acyclovir is useful in the treatment of genital herpes, herpes simplex encephalitis, mucocutaneous herpetic infection, varicella infection in the immunosuppressed host, and herpes zoster infection in the normal and the immunosuppressed host. It can also be used for prevention of herpesvirus infection in immunocompromised patients. Ganciclovir is indicated for the treatment of cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome (AIDS) and is effective in the management of organ-specific cytomegalovirus infection in other immunocompromised patients. Chronic hepatitis C and condyloma acuminatum due to human papillomavirus respond to therapy with interferon alfa-2b. Patients with human immunodeficiency virus infection and CD4 lymphocyte counts of less than 500 cells/mm3 should be treated with zidovudine. Amantadine is useful in a therapeutic and prophylactic role in the management of influenza A virus infection. With the expanded use of and indications for antiviral therapy, clinically significant resistance to these agents has been encountered with increasing frequency.

Age Factors↗

[Legionnaires' disease and HIV infection: an opportunistic infection?].

BACKGROUND AND OBJECTIVE: Legionella infections are not frequent in HIV-infected patients, although clinical manifestations and outcome are particularly severe in this subset. This manuscript analyzes the clinical features and immunological situation of HIV-infected patients with Legionnaires' disease (LD). PATIENTS AND METHOD: The clinical files of HIV-infected patients diagnosed with LD from 1983 to December 2003 were reviewed. The incidence of hospital-acquired Legionella pneumonia (HALP) from 1997-2000 in HIV-infected patients was compared with that of non infected patients. RESULTS: Eighteen patients were included. 72.2% were diagnosed by the Legionella urinary antigen assay. The incidence of HALP in HIV-infected and non infected patients was 0.3 and 0.25/1000 admissions/year, respectively (p = 0.42). 83.3% received appropriate antibiotic treatment at the Emergency department. The mean lymphocyte CD4 count was 348.1/microl, 53.8% had an undetectable viral load and 64.7% were on antiretroviral therapy. 72.2% were smokers, 38.8% had cancer and 16.7% were on chemotherapy. 93.8% had cough, 75% dyspnea, 62.5% extrarespiratory symptoms, 76.5% increased AST, 50% increased CK and 56.3% hyponatremia. Moreover, 50% developed bilateral pulmonary infiltrates, 83.3% respiratory failure and 22.2% died. CONCLUSIONS: Although LD is not more frequent in HIV-infected than in non infected patients, its clinical severity suggests that it is an opportunistic infection.

AIDS-Related Opportunistic Infections↗

Histologic endometritis in asymptomatic human immunodeficiency virus-infected women: characterization and effect of antimicrobial therapy.

OBJECTIVE: To estimate the prevalence, risk factors, clinical symptoms and signs, and response to antimicrobial therapy of histologic endometritis in human immunodeficiency virus (HIV)-infected women without clinical salpingitis. METHODS: This was a cross-sectional study of 42 HIV-infected women enrolled from a single clinic. Subjects underwent standardized history, examination, and laboratory determinations, including endometrial biopsy. Women with suspected pelvic inflammatory disease were excluded. All women were given antibiotics and repeat evaluation in 5-7 weeks. Histologic endometritis was defined by at least one stromal plasma cell per 120x field and five or more surface polymorphonuclear leukocytes per 400x field. Chi-square and Fisher exact tests were used as appropriate. RESULTS: Histologic endometritis was present among 16 (38%) of 42 evaluable HIV-infected women, none of whom had Chlamydia trachomatis or Neisseria gonorrhoeae. Douching three or more times per month, history of ectopic pregnancy, and two or more prior urinary tract infections were associated with endometritis, as was elevated erythrocyte sedimentation rate (P < or = .05). Physical examination findings and mean CD4+ lymphocyte count were similar among those with and without endometritis. In the nine HIV-infected women with a repeat biopsy, endometritis decreased from four (44%) to two (22%) after treatment (P = .30). CONCLUSION: The prevalence of histologic endometritis in HIV-infected women was high despite few examination findings and no demonstrated pathogens. Endometritis in HIV-infected women might be related to pathogens not evaluated, to prior infection, or to reduced immunity from HIV.

Adult↗

Invasive fungal sinusitis in the acquired immunodeficiency syndrome.

Invasive fungal sinusitis can present as either an indolent or fulminant process that primarily affects immunocompromised individuals. In this article, the clinical characteristics of four cases of invasive fungal sinusitis in patients with AIDS are analyzed and 22 additional previously reported cases in the literature are reviewed. In addition to HIV infection, other variables common to these cases include facial pain or headache out of proportion to clinical or radiographic findings, CD4 lymphocyte count less than 50 cells/mm(3), absolute neutrophil count less than 1,000 cells/mm(3), subtle radiographic evidence suggesting invasion and an indolent clinical course of the invasive infection. The most common pathogen detected was Aspergillus fumigatus. Maintaining a high index of suspicion, critically assessing these clinical findings, and prudently reviewing CT scans may facilitate early diagnosis and prompt intervention in these patients.

Acquired Immunodeficiency Syndrome↗

"Buffalo hump" in men with HIV-1 infection.

BACKGROUND: Enlargement of the dorsocervical fat pad ("buffalo hump") has been reported in numerous HIV-1-infected patients. Some investigators have speculated that this finding is associated with protease-inhibitor treatment. METHODS: Between June, 1995, and October, 1997, we studied eight HIV-1-infected men who had developed a buffalo hump while otherwise stable on antiretroviral therapy. Measurement of 24 h urinary free cortisol excretion and an overnight low-dose dexamethasone suppression test were done to screen for Cushing's syndrome. In one patient, plasma cortisol concentrations were measured every 4 h for 24 h to assess the circadian rhythm of cortisol. Results of total and regional body-composition analysis by dual-energy X-ray absorptiometry, and glucose, cholesterol, triglyceride, and cortisol concentrations were compared with those obtained in a control population of 15 HIV-1-positive men whose age, body-mass index (BMI), and CD4-lymphocyte count were within the range of values in the eight study patients. FINDINGS: The eight patients with a buffalo hump were clinically stable on various antiretroviral regimens, four of which included a protease inhibitor. No other signs of Cushing's syndrome were observed, and plasma cortisol values did not differ significantly from those of controls. 24 h urinary free cortisol excretion was normal in seven patients and slightly raised in one (248 nmoles). In this patient, a repeat 24 h urinary free cortisol was 175 nmoles and plasma cortisol concentrations over 24 h showed a normal circadian pattern (nadir 83 nmol/L at 2400 h). All eight patients had normal suppression of cortisol values after dexamethasone 1 mg (plasma cortisol less than 83 nmol/L). When compared with HIV-1-positive controls, men with a buffalo hump had a significantly greater proportion of fat in the trunk region, suggesting central fat accumulation. Triglyceride but not cholesterol values were higher in the patients than in controls but this difference was not significant. Fasting glucose values did not differ significantly. INTERPRETATION: The development of a buffalo hump cannot be attributed to hypercortisolism in these eight men. Furthermore, its occurrence is not unique to patients on protease inhibitors. Although the mechanism for dorsocervical fat accumulation is unclear, we speculate that regional abnormalities in lipogenesis and lipolysis occur, possibly influenced by the hormonal and metabolic changes seen with HIV-1 infection and its treatment.

Adipose Tissue↗