AIDS

Improvement of chronic diarrhoea in patients with advanced HIV-1 infection during potent antiretroviral therapy.

Foudraine NA. Weverling GJ. van Gool T. Roos MT. de Wolf F. Koopmans PP. van den Broek PJ. Meenhorst PL. van Leeuwen R. Lange JM. Reiss P.
Municipal Health Service, Department of Public Health and Environment, Amsterdam, The Netherlands.
BACKGROUND: A substantial number of patients with advanced HIV infection suffer from intractable diarrhoea. The aim of this study was to evaluate whether potent antiretroviral therapy could alleviate such diarrhoea. METHODS: In an open randomized study the effect of the HIV protease inhibitor indinavir in combination with nucleoside analogue reverse transcriptase inhibitors on chronic HIV-related diarrhoea was investigated in 14 late-stage (CD4+ lymphocyte count < or = 50 x 10(6) cells/l) HIV-infected patients. Data concerning stool frequency, stool consistency and antidiarrhoeal drug use were collected in daily diaries over a 24-week period. Endpoints of the study were reduction of stool frequency, improvement of stool consistency, weight gain, and in case of diarrhoea due to Enterocytozoon bieneusi or Cryptosporidium sp. disappearance of these parasites from stool. RESULTS: Thirteen patients started the study drug indinavir. One patient died after 1 week and one patient withdrew prematurely after 18 weeks. Median stool frequency declined from 5.8 daily at baseline to 2.3 daily after 24 weeks (P=0.04). Stool consistency improved considerably over the study period: before treatment 56% of stools were watery and 0% were formed; at week 24 these figures were 0 and 35%, respectively. Body weight increased significantly with a median increment of 6.6 kg at week 24 (P=0.0006). In two out of six patients with microsporidiosis and both patients with cryptosporidiosis, stools were free of parasites at week 24. Five out of six patients who used non-specific antidiarrhoeal medication on a regular basis prior to the study had ceased to do so at the end. CONCLUSION: The use of potent antiretroviral therapy in patients with advanced HIV infection can improve chronic HIV-related diarrhoea and in some cases lead to disappearance of E. bieneusi and Cryptosporidium sp. from the stools.

Duodenal biopsies of HIV-infected patients with diarrhoea exhibit epithelial barrier defects but no active secretion.

Stockmann M. Fromm M. Schmitz H. Schmidt W. Riecken EO. Schulzke JD.
Department of Gastroenterology, Universitatsklinikum Benjamin Franklin, Freie Universitat Berlin, Germany.
OBJECTIVES: To characterize diarrhoeal mechanisms in HIV-infected patients, epithelial transport and barrier function of the duodenal mucosa was investigated in vitro. PATIENTS: Twenty-one HIV-seropositive patients (13 asymptomatic and eight with diarrhoea) and 12 controls from an urban referral-based tertiary care centre in Berlin who underwent duodenoscopy. METHODS: A new miniaturized Ussing chamber allowed measurements on duodenal forceps biopsies. Epithelial barrier function was characterized by alternating current impedance analysis, which allows differentiation of epithelial and subepithelial resistance and by 3H-lactulose and 3H-mannitol flux measurements. Na+-glucose cotransport was quantified as phlorizin-sensitive short circuit current (Isc) and active ion secretion by baseline and bumetanide-sensitive Isc. RESULTS: Duodenal biopsies from asymptomatic HIV-infected patients were no different from controls, whereas biopsies from HIV-infected patients with diarrhoea showed a decrease in epithelial resistance from 21.2+/-1.9 to 12.9+/-1.3 omega cm2 (P

Does hepatitis C virus co-infection accelerate clinical and immunological evolution of HIV-infected patients?

Year 1998
Piroth L. Duong M. Quantin C. Abrahamowicz M. Michardiere R. Aho LS. Grappin M. Buisson M. Waldner A. Portier H. Chavanet P.
Service des Maladies Infectieuses et Tropicales, Hopital d'Enfants, CHU Dijon, France.
OBJECTIVE: To study the influence of hepatitis C virus (HCV) co-infection on clinical and immunological evolution of HIV-infected patients. DESIGN: A longitudinal study of HIV-infected individuals with or without HCV infection, identified at the Infectious Diseases Department of Dijon University Hospital and enrolled in a historical cohort, was performed. METHODS: One hundred and nineteen HIV-infected people co-infected with HCV and 119 matched individuals infected with HIV alone were included in the cohort (median participation time 3 years; range, 2 months to 11.5 years). Clinical progression was defined as one or more of the following: a 30% decrease in the Karnofsky index; a 20% loss of body weight; an AIDS-defining illness (for non-AIDS patients); death (except by accident, suicide or overdose). Immunological progression was defined as a 50% decrease in the initial CD4 T-cell count (for patients with an initial count > 100 x 10(6) cells/l). Effects of HCV co-infection were evaluated using Kaplan-Meier survival analysis and significance was tested using univariate (log-rank and Peto's tests) and multivariate methods (Cox's model). RESULTS: In univariate analysis, immunological progression was not statistically different between the HCV-positive group and the HCV-negative group, whereas clinical progression was significantly faster in HCV-positive patients (P < 0.005, log-rank test). In a multivariate Cox model, clinical progression remained significantly associated with infection by HCV [hazard ratio (HR), 1.64; 95% confidence interval (CI), 1.06-2.55; P < 0.05]. Stratified multivariable analysis retained HCV as a significant prognostic factor of clinical progression (HR, 10.9; 95% CI, 1.09-109.3; P < 0.05) and immunological progression (HR, 2.31; 95% CI, 1.16-4.62; P < 0.02) for patients with an initial CD4 count above 600 x 10(6) cells/l. CONCLUSIONS: Clinical progression is more rapid in HIV-HCV co-infected patients than in HIV-seropositive patients are not infected by HCV. The prognostic value of HCV infection for both clinical and immunological progression is significant at early stages of HIV infection. These findings may argue for active management of hepatitis C infection in co-infected individuals, especially for asymptomatic patients whose CD4 count is above 600 x 10(6) cells/l, to predict and prevent accelerated progression of HCV and HIV diseases.

High incidence of anal high-grade squamous intra-epithelial lesions among HIV-positive and HIV-negative homosexual and bisexual men.

Year 1998
Palefsky JM. Holly EA. Ralston ML. Jay N. Berry JM. Darragh TM.
Department of Laboratory Medicine, University of California San Francisco, 94143, USA.
OBJECTIVE: The incidence of anal cancer among homosexual men exceeds that of cervical cancer in women, and HIV-positive homosexual men may be at even higher risk than HIV-negative men. Cervical cancer is preceded by high-grade squamous intra-epithelial lesions (HSIL) and anal HSIL may similarly be the precursor to anal cancer. In this study, we describe the incidence of and risk factors for HSIL in HIV-positive and HIV-negative homosexual and bisexual men. DESIGN: Prospective cohort study of HIV-positive and HIV-negative homosexual men. SETTING: The University of California, San Francisco. PATIENTS: 346 HIV-positive and 262 HIV-negative men enrolled at baseline, 277 HIV-positive and 221 HIV-negative homosexual men followed after baseline. STUDY DESIGN: A questionnaire was administered detailing lifestyle habits, medical history and sexual practices. Anal swabs for cytology and human papillomavirus studies were obtained, followed by biopsies of visible lesions. Human papillomavirus testing was performed using polymerase chain reaction (PCR) and 'hybrid capture'. Blood was obtained for HIV testing and measurement of CD4 levels. MAIN OUTCOME MEASURES: Incident HSIL. RESULTS: HIV-positive men were more likely to develop HSIL than HIV-negative men relative risk (RR), 3.7; 95% confidence interval (CI), 2.6-5.7. Life-table estimates of the 4-year incidence of HSIL was 49% (95% CI, 41-56) among HIV-positive men and 17% (95% CI, 12-23) among HIV-negative men. Among HIV-positive men, those with lower baseline CD4 counts (P = 0.007) and persistent infection with one or more human papillomavirus types, determined using PCR (P = 0.0001), were more likely to develop HSIL. CONCLUSIONS: HIV infection, lower CD4 levels and human papillomavirus infection were associated with high rates of incident HSIL among homosexual men. However, high rates were found at all CD4 levels among HIV-positive men and among HIV-negative men.

Effect of combination antiretroviral therapy upon rectal mucosal HIV RNA burden and mononuclear cell apoptosis.

Year 1998
Kotler DP. Shimada T. Snow G. Winson G. Chen W. Zhao M. Inada Y. Clayton F.
Department of Medicine, St Luke's-Roosevelt Hospital Center, Columbia College of Physicians and Surgeons, New York, New York 10025, USA.
BACKGROUND: Pathogen-negative diarrhea is common in HIV infection and has been associated with clinical symptoms, histopathology, HIV expression, CD4+ lymphocyte depletion, cytokine mRNA expression, and apoptosis of lamina propria mononuclear cells. OBJECTIVES AND METHODS: To examine the short-term (7-day) effects of treatment with combination antiretroviral therapies upon gastrointestinal symptoms and rectal mucosa in 15 HIV-infected subjects. RESULTS: Treatment was associated with significant decreases in the perception of abdominal bloating and cramps. Similar declines in RNA burden and rises in CD4+ lymphocyte counts were found in blood and mucosa. Treatment was also associated with a fall in the number of lamina propria mononuclear cells undergoing apoptosis by in situ labeling, a change that correlated with the change in mucosal viral burden. CONCLUSIONS: Peripheral blood and mucosal compartments are equally responsive to effective antiretroviral therapies. The detection of significant changes within 7 days of starting antiviral therapy implies that intestinal dysfunction may be a direct result of local HIV infection.

Pre-AIDS mortality in HIV-infected individuals in England, Wales and Northern Ireland, 1982-1996.

Year 1998
Laurichesse HA. Mortimer J. Evans BG. Farrington CP.
Public Health Laboratory Service AIDS and Sexually Transmitted Diseases Centre, Communicable Disease Surveillance Centre, London, UK.
OBJECTIVE: To assess pre-AIDS mortality in HIV-infected patients in England, Wales and Northern Ireland during the period 1982-1996. DESIGN: Surveillance data on pre-AIDS and AIDS deaths reported to the PHLS-AIDS Centre were analysed. METHODS: Pre-AIDS mortality was estimated as the proportion of pre-AIDS deaths among all deaths in HIV-infected people. Trends over time in the number of pre-AIDS and AIDS deaths were compared using Poisson regression with logarithmic link. Causes of pre-AIDS deaths were recorded. Comparisons were made between the pre-AIDS and the AIDS death groups by logistic regression for: age, location of residence at death, year of death and risk exposure. RESULTS: Four-hundred and sixty-eight pre-AIDS deaths and 8574 AIDS deaths were identified. Pre-AIDS mortality accounted for 5.0% of HIV-related deaths. Trends over time in the number of pre-AIDS and AIDS deaths were not significantly different (P=0.11). Reported causes of pre-AIDS death included pneumonia (92), liver disease (62), septicaemia (51), malignancies (49), suicide (45), cardiopulmonary causes (46), haemorrhage (42), overdose (24) and accidental causes (24). Factors positively associated with pre-AIDS death were injecting drug use, haemophilia and blood transfusion, residence outside the Thames regions, and death at an older age. CONCLUSIONS: Pre-AIDS mortality represents a substantial proportion of HIV mortality, particularly where injecting drug use is a frequent route of HIV transmission.