Reported here is a case of a patient with pulmonary arterial hypertension related to HIV (PAHRH) in which lipodystrophy necessitated interruption of highly active antiretroviral therapy (HAART) and long-term survival was the outcome. Although previous studies have suggested antiretroviral therapy may benefit patients with this rare complication of HIV infection, no worsening of PAHRH was observed when HAART was interrupted. Clinical and echocardiographic parameters remained stable during 7 months of follow up. In cases in which HAART is associated with relevant toxicity, interruption of HAART in patients with PAHRH can be considered, but should be used only if no alternatives are available. Close follow-up is warranted.

Because of high death rates in the past, patients with HIV-1 cannot obtain life insurance. We measured mortality rates in the Swiss HIV Cohort Study (SHCS) from 1997 to 2001 and compared them with those of the Swiss reference population. In patients who were successfully treated with highly active anti-retroviral therapy (HAART), and who were not also infected with the hepatitis C virus, excess death rates were below five per thousand per year. Patients with successfully treated cancer have much the same excess death rates but are not excluded from life insurance policies.

OBJECTIVES:The study investigates associations between socio-demographic or lifestyle factors and the progression of HIV.METHODS:We recruited a Swiss cohort (n = 56) of long-term survivors and conducted a cross-sectional study of laboratory data as well as factors concerning socio-demography, life-style, and psychology. On the basis of laboratory results, the cohort was divided into 2 subgroups, non-progressors (n = 31) and slow progressors (n = 25), which were subsequently compared.RESULTS:The comparison of socio-demographic factors showed that non-progressors were younger and had a higher income than slow progressors. Our data do not show an association between lifestyle and disease progression.DISCUSSION:Younger age as a cofactor of non-progression confirms various other studies. The association between income and disease progression, also found in another cohort, cannot be explained by unequal access to therapies since, in accordance with the inclusion criteria, no one in our cohort had received antiretroviral therapies. Further research in this field seems important to determine possible links between socio-economic status and disease progression. The lack of association between disease progression and lifestyle factors such as drug use, physical activity or nutrition is in contrast to a common view of HIV in our study population, but is confirmed by a majority of the research in this field.

Background and aims:The aim of the study was to determine the thiamin status in HIV-positivepatients.Methods:Measurement of erythrocyte transketolase activity (ETK) and thiaminpyrophosphate (TPP)effect in 55 consecutive HIV-positive patients of a specialized outpatient clinic were grouped into five groups according to their CD4 counts. Comparison of results of HIV-positive patients with age-matched control group of 22 healthy subjects.Results:Of the patients, 27% had a pathologically-increased TPP effect, 18% of the patients had pathologically-low ETK. The percentage of pathological values of TPP effect in the patients was significantly higher compared with the control group. There was no statistically significant correlation between pathological thiamin status and stage of the disease, zidovudine therapy or nutritional status of the patients.Conclusions:Thiamin deficiency in HIV-positive patients was found in a higher percentage than previouslyreported. Thiamine deficiency is not only present in advanced stages of HIV-infection, but also in clinically asymptomatic patients.

Objectives: To study whether syncytium-inducing (Sl)/non-SI (NSI) phenotype of HIV-1 is associated with CD4+ lymphocyte count, plasma HIV RNA level, clinical stage and sociodemographic characteristics in antiretroviral-naive HIV-1-infected patients.Design: Cross-sectional analysis of single centre cohort study data.Methods: SI/NSI phenotype was determined using a cocultivation assay using patients' peripheral blood mononuclear cells and MT2 cells. Standard procedures were used for CD4+ cell counts and viral load measurements in plasma. Univariate and multivariate analyses of association of CD4+ cell counts, viral load, clinical stage, age, sex and mode of HIV transmission were performed.Results: In univariate analysis, SI phenotype was significantly associated with lower CD4+ cell counts, higher HIV RNA plasma levels, symptomatic HIV disease, male sex and age 32-36 years (middle tercile). In multivariate analysis, only lower CD4+ cell counts were associated with SI phenotype (odds ratio per increase of 100 x 10(6)/l, 0.54; 95% confidence interval, 0.38-0.78).Conclusions: HIV-1 SI phenotype was associated with lower CD4+ cell counts but not with higher plasma viral load, clinical stage or sociodemographic variables. (C) 1998 Lippincoit-Raven Publishers.

Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality in transplant and HIV-infected patients. However, CMV can also cause asymptomatic infection. An elevated blood viral load as assessed by various methods appears to be a predictor for symptomatic infections, and can be used to identify patients at the highest risk of developing CMV disease. We developed a single tube competitive quantitative PCR assay for CMV DNA, using as a competitor a plasmid carrying the target sequence for amplification with an internal deletion. The analysis of data from repeated extractions and amplifications of samples showed that the coefficient of variation of the assay was typically less than 20%. Clinical samples from 14 HIV-infected and 13 solid organ transplant patients were analyzed. Widely varying CMV DNA levels were found in leukocytes, with a positive correlation with the measure of infectivity in the leukocytes by quantitative culture on fibroblasts. The highest CMV DNA content in leukocytes was found in two patients with presumptive CMV disease. In HIV patients, the amount of DNA in leukocytes was much larger than in solid organ transplant recipients, when standardized for infectivity. Although based on a very limited number of patients, this observation probably points to a difference in the biology of CMV infection in these two categories of susceptible individuals. CMV DNA was also found in the plasma of some of the patients with a high CMV DNA leukocyte load. The present test should be useful for identifying patients at high risk of developing CMV disease, for monitoring therapeutic efficacy of antiviral regimens and to improve the understanding the pathogenesis of CMV infection.

Homozygous (delta ccr5/delta ccr5) and heterozygous (CCR5/delta ccr5) deletions in the beta-chemokine receptor 5 (CCR5) gene, which encodes for the major co-receptor for macrophage-tropic HIV-1 entry, have been implicated in resistance to HIV infection and in protection against disease progression, respectively. The CCR5/delta ccr5 genotype was found more frequently in long-term nonprogressors (LTNP) (31.0%) than in progressors (10.6%, p < 0.0001), in agreement with previous studies. Kaplan-Meier survival analyses showed that a slower progression of disease, i.e. higher proportion of subjects with CD4+ T cell counts > 500/microl (p = 0.0006) and a trend toward a slower progression to AIDS (p = 0.077), was associated with the CCR5/delta ccr5 genotype. However, when LTNP were analyzed separately, no significant differences in CD4+ T cell counts (p = 0.12) and viremia levels (p = 0.65) were observed between the wild-type (69% of LTNP) and the heterozygous (31.0%) genotypes. Therefore, there are other factors which play a major role in determining the status of nonprogression in the majority of LTNP. Furthermore, there was no evidence that the CCR5/delta ccr5 genotype was associated with different rates of disease progression in the group of progressors. Taken together, these results indicate that the CCR5/delta ccr5 genotype is neither essential nor sufficient for protection against the progression of HIV disease.

During the last 18 months, our knowledge and possibilities in the field of HIV infections have progressed in four principal domains: (1) better understanding of the dynamics of HIV infections and in particular of the importance of viral replication during the phase of latency, (2) possibility of measuring the viral charge and its use for diagnosis and to follow treatment, (3) access to very effective new anti-retroviral substances which permit hope of long-term stabilization of the infection, (4) clinical demonstration that combined treatments are superior to monotherapy. While, at the beginning of 1996, only three medications were commercialized, there were eight at the end of that year. This paper describes the implications for daily practice of recent scientific discoveries in the field of HIV infection. The importance of compliance is discussed, as well as that of clinical research.

To evaluate combined prophylaxis for Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis, 533 patients with symptomatic human immunodeficiency virus infection and/or CD4 lymphocyte counts of < 200/microL were randomized to receive dapsone/pyrimethamine (200/75 mg once weekly) or aerosolized pentamidine (300 mg every 4 weeks). The median CD4 lymphocyte count was 110/microL; 47.5% were seropositive for toxoplasma antibodies. The median duration of follow-up was 483 days. In the intent-to-treat analysis, 12 cases of PCP and 14 of toxoplasmic encephalitis occurred in the dapsone/pyrimethamine group and 13 and 20 cases, respectively, in the aerosolized pentamidine group (adjusted relative risk for toxoplasmosis, 0.56; P = .10). However, only two of the 14 cases of toxoplasmic encephalitis in the dapsone/pyrimethamine group developed during actual treatment. The mortality among the two groups was similar. Dapsone/pyrimethamine was not tolerated by 30% of participants. A subanalysis of 240 matched, tolerant patients yielded a relative risk for toxoplasmosis of 0.21 (P = .014), a result favoring the use of dapsone/pyrimethamine. Dapsone/pyrimethamine was as effective as aerosolized pentamidine as prophylaxis for PCP and significantly reduced the incidence of toxoplasmic encephalitis among those participants who tolerated it.

Disseminated nontuberculous mycobacteriosis is a frequent and late complication of HIV infection. All the 13 patients described here had CD4-lymphocyte counts < 20/mm3. The causative agent was mainly M. avium complex. But we also found, for the first time, a double infection with M. avium complex and M. "genavense" and one patient with growth of M. shimoidei in the blood culture. Clinical signs are nonspecific (fever, reduced performance, anemia). Positive cultures of blood or tissue biopsies are diagnostic. The therapeutic approach is the combination of new macrolides with other antimycobacterial agents. Prognosis is poor, mainly due to advanced immunodeficiency, but two of our patients survived more than one year after diagnosis. Prophylactic treatment should be considered in patients with CD4-counts less than 50/mm3.

Objective:To examine survival differences in HIV-infected individuals between the sexes and the categories of transmission. Patients and setting:Subjects assumed to have been infected by injecting drug use, by male homosexual contact or by heterosexual contact and enrolled in the Swiss HIV Cohort Study, a national multicentre cohort study of adult HIV-infected patients. Methods:Kaplan–Meier lifetable and Cox regression analyses were performed (time 0=date of study entry) and survivors were censored at their last follow-up visit. Results:A total of 4428 patients (mean duration of follow-up, 2.1 years) were considered. At entry, men were older and had lower CD4+ counts than women (P<0.0001). Homosexual men were the oldest group with the lowest CD4+ counts and the most advanced disease at study entry (P<0.0001). Crude hazard ratios indicated a 28% lower mortality from all causes in women compared with men (P<0.0001) and, among men but not in women, a 28 and 32% higher mortality in homosexuals and heterosexuals compared with injecting drug users (IDU) (P=0.0002 and P=0.008, respectively). After adjusting for differences at entry, the mortality difference between the sexes disappeared (P=0.5) and differences across transmission categories were reversed. Mortality in homosexual men was an estimated 13% (P=0.057) lower than in male IDU; mortality was 22% lower in heterosexual women than in female IDU (P=0.098). In stratified analysis the increased risk in IDU was confined to subjects with CD4+ cell counts > 500×106/l cells at study entry. Conclusions:These results indicate a uniform mortality risk across the sexes but indicate an increased risk in IDU without CD4+ cell depletion at entry, the latter probably attributable to causes not related to progression of HIV infection. This study underscores the importance of adjusting for prognostic factors when comparing survival between different patient groups.

The differential diagnosis of recently acquired cough, diarrhea, headaches, odynophagia and fever in AIDS-Patients is discussed. The aim is to find the most frequent, the treatable and the most dangerous diseases. We discuss the empirical and the symptomatic treatment in special situations.

Sulfadiazine-nephropathy and -nephrolithiasis were well known complications of high dose sulfadiazine therapy 50 years ago. In the last few years high dose sulfadiazine therapy has been widely used for treatment of toxoplasmic encephalitis in AIDS patients. As a consequence sulfadiazine-nephropathy and -nephrolithiasis have become increasingly common. We describe 2 patients with the typical picture of these complications. Therapy is based on the fact that the solubility of sulfadiazine and its acetylated metabolite are markedly improved at higher urine-pH levels. Urine alkalinization is also effective for prophylaxis during sulfadiazine treatment. We present our guidelines for prophylaxis and treatment of these complications.

Accidental exposure to blood carries with it a definite risk for the health care worker of infection by various bloodborne pathogens, especially the hepatitis B, hepatitis C, and human immunodeficiency virus. The risk of transmission from exposure to HIV is lower than that associated with exposure to HBV and HCV. Should HIV infection occur, however, the outcome is likely to be fatal. Although general infection control precautions, safer use of needles, gloves, and other procedures may substantially reduce the incidence of occupational exposures, they cannot eliminate the risk completely. The post-exposure management is discussed. Neither the efficacy nor the safety of AZT (zidovudine) for use as a chemoprophylactic agent following occupational exposures to HIV has been established. Nevertheless in selected cases it can be proposed to health care workers.

Traveller's diarrhea is a common problem without consequences for a healthy patient. Correct information, especially about hygiene habits during the trip, is most important. The prescription of an anti-diarrheal medication is usually justified but should not be given without proper information about the possible dangers. A prophylactic antibiotherapy is very seldom necessary. Antibiotic self-medication can be a pragmatic alternative. Patients at risk must be identified before the trip, and appropriate measures are essential. Once the patient is back home again diarrhea will subside spontaneously and both patient and physician should therefore know to be patient.