Chemsex drugs on the rise: a longitudinal analysis of the Swiss HIV Cohort Study from 2007 to 2017.

OBJECTIVES: Chemsex refers to the use of sex-enhancing drugs among men who have sex with men (MSM) in combination with specific sexual and social behaviours. Longitudinal data on this development and the associated health risks are scarce. METHODS: Data on all recreational drugs reported in the Swiss HIV Cohort Study (SHCS) from 2007 to 2017 were collected. Drug use was analysed longitudinally for all drug classes. In addition, potential associations between patient characteristics and the consumption of methamphetamine, γ-hydroxybutric acid/γ-butyrolactone (GHB/GBL), 3,4-methylenedioxymethamphetamine (MDMA/XTC), cocaine and amphetamine were analysed. RESULTS: We analysed 166 167 follow-up entries for 12 527 SHCS participants, including 7101 free text field entries containing information about recreational drugs other than cannabis, cocaine and heroin. Overall, we observed a stable percentage (9.0%) of recreational drug use (excluding cannabis, amyl nitrite and prescription drugs). For MSM, however, there was an increase in overall drug use from 8.8% in 2007 to 13.8% in 2017, with particularly large increases for methamphetamine (from 0.2 to 2.4%; P < 0.001) and GHB/GBL (from 1.0 to 3.4%; P < 0.001). The use of each of the potentially sex-enhancing drugs methamphetamine, GHB/GBL, cocaine, XTC/MDMA and amphetamine was significantly associated with condomless sex with nonsteady partners, and higher prevalences of depression, syphilis and hepatitis C. CONCLUSIONS: The significant increase in the use of chemsex drugs among MSM in the SHCS and the strong association with coinfections and depression highlights the need for harm reduction programmes tailored to MSM. According to our results, improving knowledge about recreational drugs is important for all health care professionals working with people living with HIV.

Decreasing mortality and changing patterns of causes of death in the Swiss HIV Cohort Study.

BACKGROUND: Mortality among HIV-infected persons is decreasing, and causes of death are changing. Classification of deaths is hampered because of low autopsy rates, frequent deaths outside of hospitals, and shortcomings of International Statistical Classification of Diseases and Related Health Problems (ICD-10) coding. METHODS: We studied mortality among Swiss HIV Cohort Study (SHCS) participants (1988-2010) and causes of death using the Coding Causes of Death in HIV (CoDe) protocol (2005-2009). Furthermore, we linked the SHCS data to the Swiss National Cohort (SNC) cause of death registry. RESULTS: AIDS-related mortality peaked in 1992 [11.0/100 person-years (PY)] and decreased to 0.144/100 PY (2006); non-AIDS-related mortality ranged between 1.74 (1993) and 0.776/100 PY (2006); mortality of unknown cause ranged between 2.33 and 0.206/100 PY. From 2005 to 2009, 459 of 9053 participants (5.1%) died. Underlying causes of deaths were: non-AIDS malignancies [total, 85 (19%) of 446 deceased persons with known hepatitis C virus (HCV) status; HCV-negative persons, 59 (24%); HCV-coinfected persons, 26 (13%)]; AIDS [73 (16%); 50 (21%); 23 (11%)]; liver failure [67 (15%); 12 (5%); 55 (27%)]; non-AIDS infections [42 (9%); 13 (5%); 29 (14%)]; substance use [31 (7%); 9 (4%); 22 (11%)]; suicide [28 (6%); 17 (7%), 11 (6%)]; myocardial infarction [28 (6%); 24 (10%), 4 (2%)]. Characteristics of deceased persons differed in 2005 vs. 2009: median age (45 vs. 49 years, respectively); median CD4 count (257 vs. 321 cells/µL, respectively); the percentage of individuals who were antiretroviral therapy-naïve (13 vs. 5%, respectively); the percentage of deaths that were AIDS-related (23 vs. 9%, respectively); and the percentage of deaths from non-AIDS-related malignancies (13 vs. 24%, respectively). Concordance in the classification of deaths was 72% between CoDe and ICD-10 coding in the SHCS; and 60% between the SHCS and the SNC registry. CONCLUSIONS: Mortality in HIV-positive persons decreased to 1.33/100 PY in 2010. Hepatitis B or C virus coinfections increased the risk of death. Between 2005 and 2009, 84% of deaths were non-AIDS-related. Causes of deaths varied according to data source and coding system.

High specificity of line-immunoassay based algorithms for recent HIV-1 infection independent of viral subtype and stage of disease.

BACKGROUND: Serologic testing algorithms for recent HIV seroconversion (STARHS) provide important information for HIV surveillance. We have shown that a patient's antibody reaction in a confirmatory line immunoassay (INNO-LIA HIV I/II Score, Innogenetics) provides information on the duration of infection. Here, we sought to further investigate the diagnostic specificity of various Inno-Lia algorithms and to identify factors affecting it. METHODS: Plasma samples of 714 selected patients of the Swiss HIV Cohort Study infected for longer than 12 months and representing all viral clades and stages of chronic HIV-1 infection were tested blindly by Inno-Lia and classified as either incident (up to 12 m) or older infection by 24 different algorithms. Of the total, 524 patients received HAART, 308 had HIV-1 RNA below 50 copies/mL, and 620 were infected by a HIV-1 non-B clade. Using logistic regression analysis we evaluated factors that might affect the specificity of these algorithms. RESULTS: HIV-1 RNA < 50 copies/mL was associated with significantly lower reactivity to all five HIV-1 antigens of the Inno-Lia and impaired specificity of most algorithms. Among 412 patients either untreated or with HIV-1 RNA ≥ 50 copies/mL despite HAART, the median specificity of the algorithms was 96.5% (range 92.0-100%). The only factor that significantly promoted false-incident results in this group was age, with false-incident results increasing by a few percent per additional year. HIV-1 clade, HIV-1 RNA, CD4 percentage, sex, disease stage, and testing modalities exhibited no significance. Results were similar among 190 untreated patients. CONCLUSIONS: The specificity of most Inno-Lia algorithms was high and not affected by HIV-1 variability, advanced disease and other factors promoting false-recent results in other STARHS. Specificity should be good in any group of untreated HIV-1 patients.

Discontinuation of maintenance therapy against toxoplasma encephalitis in AIDS patients with sustained response to anti-retroviral therapy.

Discontinuation of maintenance therapy against toxoplasma encephalitis (TE) for individuals infected with human immunodeficiency virus (HIV) who are receiving successful anti-retroviral therapy is considered safe. Nevertheless, there are few published studies concerning this issue. Within the setting of the Swiss HIV Cohort Study, this report describes a prospective study of discontinuation of maintenance therapy against TE in patients with a sustained increase of CD4 counts to > 200 cells/microL and 14% of total lymphocytes, and no active lesions on cerebral magnetic resonance imaging (MRI). In addition to clinical evaluation, cerebral MRI was performed at baseline, and 1 and 6 months following discontinuation. Twenty-six AIDS patients with a history of TE agreed to participate, but three patients (11%) could not be enrolled because they still showed enhancing cerebral lesions without a clinical correlate. One patient refused MRI after 6 months while clinically asymptomatic. Among the remaining 22 patients who discontinued maintenance therapy, one relapsed after 3 months. During a total follow-up of 58 patient-years, there was no TE relapse among the patients who had remained clinically and radiologically free of relapse during the study. Thus, discontinuation of maintenance therapy against TE was generally safe, but may fail in a minority of patients. Patients who remain clinically and radiologically free of relapse at 6 months after discontinuation are unlikely to experience a relapse of TE.

Enteric infections and diarrhea in human immunodeficiency virus-infected persons: prospective community-based cohort study. Swiss HIV Cohort Study.

BACKGROUND: Persons infected with human immunodeficiency virus (HIV) are at increased risk for diarrhea and enteric infections. We studied (1) the epidemiology of enteric pathogens associated with diarrhea, (2) the diagnostic yield of stool examination and endoscopic evaluation, (3) risks to develop diarrhea, and (4) the impact of diarrhea on patients' survival. METHODS: A total of 1933 participants in the Swiss HIV Cohort Study were prospectively followed up for a median of 25.5 months. A total of 560 diarrheal episodes were evaluated by standardized stool examination. Endoscopic evaluation was performed in 25% of patients with chronic diarrhea. RESULTS: The incidence of diarrhea was 14.2 per 100 person-years (95% confidence interval, 13.0-15.4). Among patients with CD4 cell counts below 0.05 x 10(9)/L, the probability to develop diarrhea within 1, 2, and 3 years was 48.5%, 74.3%, and 95.6%, respectively. The risk to develop diarrhea was increased among patients with severe immunodeficiency, homosexual men, and patients taking antiretroviral therapy. Pneumocystis carinii chemoprophylaxis did not reduce the risk of diarrhea. Diarrhea was an independent negative predictor of survival. Enteric pathogens were detected in 16.5% of 212 acute diarrheal episodes and in 46% of 348 chronic diarrheal episodes. The sensitivity of histological and stool examination was similar except for the diagnosis of intestinal cytomegalovirus infection and leishmaniasis, which required invasive evaluation. CONCLUSIONS: Intestinal infections were diagnosed in less than 50% of chronic diarrheal episodes. The prevalence of enteric pathogens tended to decrease during the observation period, possibly because of improved antiretroviral therapy. Endoscopic evaluation did not improve the diagnostic yield compared with stool examination except for the diagnosis of cytomegalovirus enteritis and leishmaniasis.

Heat-mediated immune complex dissociation and enzyme-linked immunosorbent assay signal amplification render p24 antigen detection in plasma as sensitive as HIV-1 RNA detection by polymerase chain reaction.

OBJECTIVE: To compare heat denaturation and acidification as immune complex dissociation (ICD) methods in adult HIV-1 infection and to increase the sensitivity by a signal-amplification-boosted HIV-1 p24 antigen enzyme-linked immunosorbent assay (ELISA). DESIGN: Prospective and retrospective blinded study of paired serum and plasma samples from 245 patients (112 of class A, 66 of B, 67 of C of the Centers for Disease Control and Prevention 1993 classification). METHODS: Plasma and sera were prospectively tested for antigen by ELISA using native, acidified, or heat-denatured material. Retrospective tests included batch analysis of heat-denatured samples for antigen by the signal-amplification-boosted ELISA and for viral RNA. RESULTS: With serum, native antigen was reactive in 26.5%. Acidification increased the rate to 53.1% (P < or = 0.0001), but was inefficient at a CD4+ count > or = 500 x 10(6)/l. Heat denaturation further elevated the rate to 67.8% (P < or = 0.0007) and the use of plasma to 78.0% (P < or = 0.008). The boosted ELISA, performed with plasma samples diluted 1 :6, which eliminated the problem of heat-induced sample coagulation, was confirmed positive in 89.5% of serum and 97.8% of plasma samples. RNA was detected in 95.7%. CONCLUSION: Heat-mediated ICD combined with a signal-amplification-boosted ELISA detects HIV-1 expression as sensitively as a polymerase chain reaction kit for viral RNA, but at only a fraction of the cost. The procedure uses a 50 microliters plasma sample and should be fully automatable.

Reasons for failure of prevention of Toxoplasma encephalitis. Swiss HIV Cohort Study.

OBJECTIVE: To study whether absence of prophylaxis is a risk factor for cerebral toxoplasmosis, and to determine the reasons for absence of prophylaxis among AIDS patients diagnosed with Toxoplasma encephalitis (TE). DESIGN: Retrospective chart review and matched case-control study. PATIENTS: Patients (104 first episodes and 26 relapses of TE) were registered in the Swiss HIV Cohort Study from three centres from July 1992 to December 1994; 91 matched controls were included for 52 patients with a first episode, and 17 matched controls for 17 patients with relapse of TE. RESULTS: Prophylaxis was prescribed to 17 patients (16%) with a first episode and 19 patients (73%) with a relapse of TE. Reasons for the absence of prophylaxis included patient refusal (25%), non-proposal by physicians (17%), and drug intolerance (17%). Reduced absorption due to non-compliance, diarrhoea or vomiting was identified among 12 patients with a first episode and 14 patients with a relapse of TE. Absence of prescription of prophylaxis was associated with a 10-fold increased risk of a first episode of TE (odds ratio, 9.8; 95% confidence interval, 2.7-35.4) in the matched case-control study. CONCLUSIONS: TE continues to occur among patients not receiving prophylaxis. At least one-half of the cases may be prevented with better motivation of physicians and increased compliance of patients.

Potent antiretroviral treatment of HIV-infection results in suppression of the seminal shedding of HIV. The Swiss HIV Cohort Study.

OBJECTIVE: The amount of HIV in semen likely influences infectiousness. Antiretroviral therapy decreases HIV-RNA in semen, but data on HIV concentrations in semen in a large cohort of men with suppressed HIV-RNA in blood is unavailable. METHODS: Male patients with a treatment-induced reduction of HIV-RNA load in plasma below 400 copies/ml were asked to donate a semen and blood sample. Blood and seminal plasma were tested for the presence of HIV-RNA by the NucliSens method (detection limit 400 copies/ml). Seminal cell samples from 67 patients were further analysed for the presence of HIV-DNA using a nested DNA-polymerase chain reaction. Results of RNA and DNA testing in semen were compared with 55 HIV-positive antiretroviral therapy-naive men. RESULTS: A total of 114 patients participated in the study. Seminal plasma HIV-RNA was detectable in only two patients [1.8%, 95% confidence ratio (CI), 0-4.2%] compared with a detection frequency of 67% in untreated controls [Odds ratio (OR), 0.01; 95% CI, 0-0.03]. Detection of cell-associated HIV-DNA in semen was significantly less frequent (16 versus 38%) in patients receiving suppressive therapy compared with untreated controls (OR, 0.32; 95% CI, 0.12-0.80). CONCLUSION: In patients with treatment-induced suppression of blood viral load the likelihood of having detectable HIV in semen is very low (< 4%). In addition, seminal shedding of cell-free and cell-associated HIV is significantly lower than in an untreated population of HIV-infected asymptomatic men. On a population basis, this effect of therapy may help to reduce sexual transmission of HIV. However, individual patients may still be infected as evidenced by continued shedding of cells harbouring the HIV provirus.

Effect of antiviral treatment on the shedding of HIV-1 in semen.

OBJECTIVE: The potential role of antiretroviral treatment on the infectiousness of HIV-1-infected men was examined by studying the effect of antiviral treatment on the shedding of HIV-1 in semen. METHODS: Forty-four patients enrolled in various treatment protocols were asked to donate a semen sample before they began a new antiviral treatment and at a follow-up visit after 6 to 15 weeks of treatment. Since most patients were on blinded protocols, patients were stratified by response of blood viral load. The effect of each patient's treatment was classified as good (n = 24), fair (n = 8) and marginal (n = 13) by measurement of the HIV RNA reduction in blood plasma (> 1.0 log10; 0.5-1.0 log10 and < 0.5 log10 HIV RNA copies/ml reduction, respectively). The effect of treatment on shedding of HIV-1 in semen was documented by the reduction of HIV RNA concentration in seminal plasma and by quantitative HIV-1 seminal cell culture. RESULTS: Overall, antiviral treatment resulted in a significant fall in the viral load in semen (RNA and culture) that paralleled the reduction of viral load in blood. More pronounced reductions of HIV RNA in semen were observed as the effectiveness of treatment on blood HIV RNA levels increased (median drop from baseline 0, 0.3 log10 and 0.8 log10 RNA copies/ml in patients with marginal, fair and good treatment effect, respectively). Thirteen patients lost detectable HIV RNA in blood on treatment and all of these had undetectable levels of HIV-1 in semen by culture and RNA analysis at follow-up. In 19 of the 31 patients (62%) who still had HIV RNA in their blood during treatment, semen HIV levels were below detection in semen at follow-up. CONCLUSIONS: Treatment-induced changes of HIV RNA concentration in blood are generally associated with a corresponding change in seminal HIV RNA: If confirmed in larger studies, potent antiretroviral therapy might reduce the spread of HIV-1.

Response to first protease inhibitor- and efavirenz-containing antiretroviral combination therapy. The Swiss HIV Cohort Study.

OBJECTIVE: To compare the response to protease inhibitor (PI) and efavirenz-containing combination therapy among treatment-naive HIV-infected persons. DESIGN: Prospective observational cohort study. METHODS: Response to treatment was analysed according to the intent-to-treat principle among antiretroviral-naive patients who started either efavirenz (n = 89) or PI (n = 183) plus two nucleoside reverse transcriptase inhibitors between February 1999 and March 2000 using Kaplan-Meier and multivariable Cox proportional hazard regression methods. Primary endpoint was time to undetectable plasma viral load. Secondary endpoints included the number of CD4 cells gained, virological rebound, treatment change, and clinical progression. RESULTS: Patients on PI regimens had lower median CD4 counts (165 versus 216 x 5 106/l; P = 0.15) and were more likely to have AIDS at initiation of treatment (25% versus 15% P = 0.048) than patients starting efavirenz regimens. The probability of reaching plasma HIV-1 RNA < 400 copies/ml was higher with efavirenz- than with PI-containing regimens [adjusted hazard ratio, 1.75; 95% confidence interval (CI), 1.34-2.29]. Median times to undetectable viral load were 58 days (95% CI, 44-70 days) for efavirenz-treated and 88 days (95% CI, 79-98 days) for PI-treated patients. The median number of CD4 cells gained in the first 6 months (90 x 10(6) cells/l with efavirenz, 10(7) x 10(6) cells/l with PI; P = 0.63), time to and reasons for treatment change, time to viral rebound, drug intolerance and clinical progression rates were similar in the two treatment groups. CONCLUSIONS: Treatment with efavirenz-, compared with PI-based regimens, appeared to result in a superior virological response but no difference in immunological or clinical efficacy. The relevance of these observations remains to be determined in studies with longer follow-up.

Discontinuation of primary prophylaxis in HIV-infected patients at high risk of Pneumocystis carinii pneumonia: prospective multicentre study.

OBJECTIVES: To assess the safety of discontinuation of primary prophylaxis in HIV-infected patients on antiretroviral combination therapy at high risk of developing Pneumocystis carinii pneumonia. DESIGN: Prospective multicentre study. PATIENTS AND METHODS: The incidence of P. carinii pneumonia after discontinuation of primary prophylaxis was studied in 396 HIV-infected patients on antiretroviral combination therapy who experienced an increase in their CD4 cell count to at least 200 x 10(6)/l and 14% of total lymphocytes; the study population included 191 patients with a history of CD4 cell counts below 100 x 10(6)/l (245 person-years) and 144 patients with plasma HIV RNA above 200 copies/ml (215 person-years). RESULTS: There was one case of Pneumocystis pneumonia, an incidence of 0.18 per 100 person-years [95% confidence interval (CI), 0.005--1.0 per 100 person-years]. No case was diagnosed in groups with low nadir CD4 cell counts (95% CI, 0--1.2 per 100 person-years) or detectable plasma HIV RNA (95% CI, 0--1.4 per 100 person-years). CONCLUSIONS: Discontinuation of primary prophylaxis against Pneumocystis pneumonia is safe in patients who have responded with a sustained increase in their CD4 cell count to antiretroviral combination therapy, irrespective of the CD4 cell count nadir and the viral load at the time of stopping prophylaxis.

Acute HIV infection: impact on the spread of HIV and transmission of drug resistance.

OBJECTIVE: To assess the impact of primary HIV infection (PHI) on the spread of HIV and the temporal trends in transmission of HIV drug resistance between 1996 and 1999 in Switzerland. METHODS: Sequencing of the genes for reverse transcriptase (RT) and protease was performed for 197 individuals with documented PHI. Phylogenetic analyses were confronted with epidemiological data. RESULTS: Significant clustering was demonstrated for 29% of the RT sequences. All these cases occurred closely together in place and time; contact tracing demonstrated transmission at the time of PHI in 30% of them. Genotypic drug resistance was detected in 8.6% of PHI individuals in 1996, 14.6% in 1997, 8.8% in 1998 and 5.0% in 1999. Drug-resistant variants were identified in 11.3% of individuals infected by homosexual contacts, 6.1% by heterosexual contacts, 13% of intravenous drug users and more frequently in men (10.4%) than women (2.6%). Potential factors involved in the recent decrease of transmission of drug-resistant variants include increase of HIV non-B subtypes from 23% in 1996 to 35% in 1999 (only one non-B subtype had resistance mutations) and a steady increase of patients with undetectable viraemia as documented in Swiss HIV Cohort Study (10% in 1996 vs 53% in 1999). CONCLUSIONS: Phylogenetic and epidemiological analyses underline the impact of PHI in the spread of HIV. Moreover, this study indicates that drug resistance transmission may have decreased recently in Switzerland through the increased frequency of infection with HIV non-B subtypes and the steady increase of patients with undetectable viraemia.

Hyperlactatemia and antiretroviral therapy: the Swiss HIV Cohort Study.

The prevalence, clinical presentation, and risk factors for hyperlactatemia among patients receiving antiretroviral therapy was determined during a 1-month period for patients in the Swiss HIV Cohort Study. Overall, 73 (8.3%) of 880 patients presented an increase in serum lactate of >1.1 times the upper normal limit (UNL). For 9 patients (1%), lactate elevation was moderate or severe (>2.2 times the UNL). Patients who presented with hyperlactatemia were more likely to be receiving stavudine with or without didanosine (odds ratio, 2.7; 95% confidence interval, 1.5-4.8), as compared with patients who received zidovudine-based regimens. The risk increased with increasing time receiving stavudine with or without didanosine. The association between hyperlactatemia and stavudine with or without didanosine was not biased by these medications being more recently available and, therefore, being given preferentially to patients who had prolonged use of nucleoside analog reverse-transcriptase inhibitors. Hyperlactatemia was associated with lipoatrophy, hyperlipidemia, and hyperglycemia. Age, sex, or stage of infection with human immunodeficiency virus were not predictive of hyperlactatemia. Determination of lactate levels may prove useful in the screening for mitochondrial toxicity.

Incidence and predictors of virologic failure of antiretroviral triple-drug therapy in a community-based cohort.

Highly active antiretroviral therapy fails to reach its recommended goal of sustained suppression of viral replication in a substantial proportion of patients. We analyzed incidence and predictors of virologic failure of the first regimen of a triple-drug combination therapy, including a protease inhibitor and two nucleoside analog reverse transcriptase inhibitors (NRTIs), in 274 HIV-infected patients. Long-term virologic response to combination therapy including salvage regimens was assessed 2.5 years after treatment initiation. During an initial observation period of up to 1.8 years (median, 0.8 years) 152 patients (55%) experienced sustained suppression of HIV-1 RNA to <500 copies/ml. Failure to reduce viral load to <500 copies/ml within 6 months (initial failure) was observed in 51 patients (19%). Independent risk factors for initial failure included higher baseline viral load; addition of a protease inhibitor to an unchanged NRTI regimen; use of saquinavir hard-gel capsules; and longer duration of prior NRTI treatment. Within a median of 7 months viral load rebound above 500 copies/ml occurred in 71 of 223 patients (32%) whose viral load had initially decreased below this threshold. In proportional hazard analysis none of the potential risk factors was significantly associated with viral load rebound. However, in 40 patients (56%) with viral load rebound, incomplete adherence to therapy or treatment interruptions preceded the rebound. Virologic outcome after 2.5 years correlated with initial response to the first regimen: viral load was <500 copies/ml in 88, 55, and 21% of patients with sustained suppression, viral load rebound, and initial failure, respectively.

Use of HIV-1 p24 as a sensitive, precise and inexpensive marker for infection, disease progression and treatment failure.

HIV RNA is an acknowledged marker of disease activity and predictive of progression, while the p24 antigen is considered unsuitable. This is at odds with the fact that viral pathogenesis is usually mediated by proteins. One might expect that p24, if analyzed properly, might even be superior to RNA. This hypothesis was investigated in clinical studies using a sensitive and precise p24 test (heat-mediated immune complex dissociation with signal amplification-boosted ELISA). This test was as sensitive and specific as the polymerase chain reaction (PCR) for viral RNA (200-400 copy detection), an overall better predictor of CD4 decline and survival, while RNA prevailed in predicting AIDS. The lower costs of p24 testing also permit a closer monitoring of patients with an earlier detection of anti-retroviral treatment failures.

Modern anti-HIV therapy.

Highly active antiretroviral therapies (HAART), usually consisting of two nucleoside reverse transcriptase inhibitors (NRTI) plus an HIV protease inhibitor (PI), have been widely used since 1996. They produce durable suppression of viral replication with undetectable plasma levels of HIV-RNA in more than half of patients. Immunity recovers, and morbidity and mortality fall by more than 80% [1, 2]. Treatment was thought to be particularly effective when started early; therefore, HAART was recommended for essentially all HIV-infected persons willing to commit themselves to lifelong therapy [3, 4]. Besides these successes, however, HAART also produces problems. HIV is not eradicated by present-day drugs, and patients often cannot comply with long-term combination treatment [5, 6]. Moreover, HAART causes unexpected and ill-understood side effects [7]. The dogma of earliest possible treatment has therefore come under attack. Ten principles governing anti-retroviral treatment are summarised in Table 1. Starting and maintaining HAART is complex. Within the last few years, the numbers of antiretrovirals, their known and potential interactions with each other and with non-HIV drugs, and the list of their side effects have all increased exponentially. As a rule a physician specialising in HIV care should be consulted whenever HAART is started or changed. It is his task to ensure that the treatment chosen is optimal for the particular patient.

Disseminated M. avium complex infection in the Swiss HIV Cohort Study: declining incidence, improved prognosis and discontinuation of maintenance therapy.

BACKGROUND: Introduction of potent antiretroviral combination therapy (ART) has reduced overall morbidity and mortality amongst HIV-infected adults. Some prophylactic regimes against opportunistic infections can be discontinued in patients under successful ART. QUESTIONS UNDER STUDY: (1) The influence of the availability of ART on incidence and mortality of disseminated M. avium Complex infection (MAC). (2) The safety of discontinuation of maintenance therapy against MAC in patients on ART. SETTING: The Swiss HIV-Cohort Study, a prospective multicentre study of HIV-infected adults. METHODS: Patients with a nadir CD4 count below 50 cells/mm3 were considered at risk for MAC and contributed to total follow-up time for calculating the incidence. Survival analysis was performed by using Kaplan Meier and Cox proportional hazards methods. Safety of discontinuation of maintenance therapy was evaluated by review of the medical notes. RESULTS: 398 patients were diagnosed with MAC from 1990 to 1999. 350 had a previous CD4 count below 50 cells/mm3. A total of 3208 patients had a nadir CD4 count of less than 50 cells/mm3 during the study period and contributed to a total follow-up of 6004 person-years. The incidence over the whole study period was 5.8 events per 100 person-years. In the time period of available ART the incidence of MAC was significantly reduced (1.4 versus 8.8 events per 100 person-years, p < 0.001). Being diagnosed after 1995 was the most powerful predictor of better survival (adjusted hazard ratio for death: 0.27; p < 0.001). None of 24 patients discontinuing maintenance therapy while on ART experienced recurrence of MAC during a total follow-up of 56.6 person-years (upper 95% confidence limit 5.3 per 100 person-years). CONCLUSION: Introducing ART has markedly reduced the risk of MAC for HIV-infected individuals with a history of very low CD4 counts. Survival after diagnosis of MAC has improved after ART became available. In patients responding to ART, discontinuation of maintenance therapy against M. avium may be safe.

Impact of new antiretroviral combination therapies in HIV infected patients in Switzerland: prospective multicentre study. Swiss HIV Cohort Study.

OBJECTIVES: To examine trends in disease progression and survival among patients enrolled in the Swiss HIV cohort study during 1988-96 and to assess the influence of new antiretroviral combination therapies. DESIGN: Prospective multicentre study, with follow up visits planned at six monthly intervals. SETTING: Seven HIV units at university centres and cantonal hospitals in Switzerland. PATIENTS: 3785 men (mean age 35.0 years) and 1391 women (30.3 years) infected with HIV. 2023 participants had a history of intravenous drug misuse; 1764 were men who had sex with men; 1261 were infected heterosexually; and 164 had other or unknown modes of transmission. 601 participants had had an AIDS defining illness. RESULTS: During more than 15,000 years of follow up, there were 1456 first AIDS defining diagnoses and 1903 deaths. Compared with those enrolled during 1988-90, the risk of progression to a first AIDS diagnosis was reduced by 18% (relative risk 0.82 (95% confidence interval 0.73 to 0.93)) among participants enrolled in 1991-2, by 23% (0.77 (0.65 to 0.91)) among those enrolled in 1993-4, and by 73% (0.27 (0.18 to 0.39)) among those enrolled in 1995-6. Mortality was reduced by 19% (0.81 (0.73 to 0.90)), 26% (0.74 (0.63 to 0.87)), and 62% (0.38 (0.25 to 0.97)) respectively. Compared with no antiretroviral treatment, the risk of an initial AIDS diagnosis after CD4 lymphocyte counts fell to < 200 cells x 10(6)/1 was reduced by 16% (0.84 (0.73 to 0.97)) with monotherapy, 24% (0.76 (0.63 to 0.91)) with dual therapy, and 42% (0.58 (0.37 to 0.92)) with triple therapy. Mortality was reduced by 23% (0.77 (0.68 to 0.88)), 31% (0.69 (0.60 to 0.80)), and 65% (0.35 (0.20 to 0.60)) respectively. CONCLUSIONS: The introduction of antiretroviral combination therapies outside the selected patient groups included in clinical trials has led to comparable reductions in disease progression and mortality.

[The Swiss HIV Cohort Study--multifaceted network supporting patient care as well as large international research projects]. / Die Schweizerische HIV-Kohortenstudie--ein Netzwerk gespannt zwischen individueller Patienten-Betreuung und internationaler Forschungs-Zusammenarbeit.

The Swiss HIV Cohort Study (SHCS) integrates networks at several different levels. Initiated as a national collaboration of five University and a Cantonal hospital the SHCS currently also integrates numerous regional hospitals and specialized physicians in private practice. The standardized anonymous data collection allowed a variety of scientific projects--even beyond strictly medical domains such as psychosocial and legal aspects. Although the SHCS is one of the largest HIV cohorts worldwide some important medical questions cannot readily be answered without collaborating in international networks. These networks on different levels facilitate an efficient information exchange aimed at an optimal and standardized care of patients with HIV and AIDS in Switzerland.

[Fever, headache and paralysis of the left leg]. / Status febrilis, Cephalaea und Parese des linken Beins.

A 17 year old man was hospitalized because of fever, headache and a paresis of his left leg. Radiologic findings demonstrated a subdural interhemispheric empyema on the right side as a complication of ipsilateral pansinusitis. Streptococcus milleri was cultured as the only pathogen from maxillary sinus suppuration. Pathogenesis and therapy of subdural empyema are discussed. Cure was achieved with ceftriaxone, flucloxacilline and ornidazole during one week followed by ceftriaxone as monotherapy during further five weeks. The importance of streptococcus milleri as causing agent of purulent lesions in internal organs is stressed.