Dramatic decline in new HIV diagnoses in persons born in France in a large nationwide HIV cohort.

OBJECTIVES: As trends in new HIV diagnoses represent a measure of the HIV epidemic, we conducted a 6-year longitudinal study to evaluate the change in rates of new HIV diagnosis, stratified by birthplace, HIV risk groups and CD4 cell count at diagnosis in a large French multicentre cohort. STUDY DESIGN: We performed a retrospective cohort study using data from the mainland French Dat'AIDS cohort. METHODS: Data were obtained for subjects with a new HIV diagnosis date between 2013 and 2018. HIV diagnosis date was defined as the date of the first known positive HIV serology. RESULTS: Between 2013 and 2018, a total of 68,376 people living with HIV (PLHIV) were followed in the Dat'AIDS cohort; 9543 persons were newly diagnosed with HIV. The annual number of new HIV diagnoses decreased from 1856 in 2013, to 1149 in 2018 (-38.1%), P = 0.01; it was more pronounced among subjects born in France, from 858 to 484 (-43.6%), P < 0.01, than in those born abroad (-23.8%, from 821 to 626, P = 0.13). Among subjects born in France, the decrease over the period was -46.7% among men who have sex with men (MSM), -43.5% for heterosexual women and -33.3% for heterosexual men. CONCLUSION: Our findings show changes in HIV epidemiology in PLHIV born in France, with a decline around 40% in new HIV diagnoses, and a more pronounced decrease among MSM and heterosexual women. Our results support the long-term effectiveness of the antiretroviral therapy as a prevention strategy among the various tools for HIV prevention.

Kaposi sarcoma among people living with HIV in the French DAT'AIDS cohort between 2010 and 2015.

BACKGROUND: Although antiretroviral therapy (ART) has reduced the risk of Kaposi sarcoma (KS), KS cases still occur in HIV-infected people. OBJECTIVE: To describe all KS cases observed between 2010 and 2015 in a country with high ART coverage. METHODS: Retrospective study using longitudinal data from 44 642 patients in the French Dat'AIDS multicenter cohort. Patients' characteristics were described at KS diagnosis according to ART exposure and to HIV-plasma viral load (HIV-pVL) (≤50 or >50) copies/mL. RESULTS: Among the 209 KS cases diagnosed during the study period, 33.2% occurred in ART naïve patients, 17.3% in ART-experienced patients and 49.5% in patients on ART, of whom 23% for more than 6 months. Among these patients, 24 (11.5%) had HIV-pVL ≤50 cp/mL, and 16 (66%) were treated with a boosted-PI-based regimen. The distribution of KS localization did not differ by ART status nor by year of diagnosis. LIMITATIONS: Data on human herpesvirus 8, treatment modalities for KS and response rate were not collected. CONCLUSION: Half of KS cases observed in the study period occurred in patients not on ART, reflecting the persistence of late HIV diagnosis. Factors associated with KS in patients on ART with HIV-pVL ≤50 cp/mL remain to be explored.

Missed opportunities of HIV pre-exposure prophylaxis in France: a retrospective analysis in the French DAT'AIDS cohort.

BACKGROUND: HIV pre-exposure prophylaxis (PrEP) was implemented in France in November 2015 based on individual-level risk factors for HIV infection. We evaluated the proportion of missed opportunities for PrEP among newly HIV-diagnosed people entering the Dat'AIDS cohort in 2016. METHODS: Multicenter retrospective analysis in 15 French HIV clinical centers of patients with a new diagnosis of HIV infection. Among them we differentiated patients according to the estimated date of infection: those occurring in the PrEP area (a previous negative HIV test in the last 12 months or those with an incomplete HIV-1 western blot (WB) with no HIV-1 anti-Pol-antibody at time of HIV diagnosis) and those in the pre-PrEP area (older infections). Epidemiological, biological and clinical data at HIV diagnosis were collected. Clinicians retrospectively identified potential eligibility for PrEP based on individual-level risk factors for HIV infection among those infected in the PrEP area. RESULTS: Among 966 patients with a new HIV diagnosis, 225 (23.3%) were infected in the PrEP area and 121 (53.8%) had complete data allowing evaluation of PrEP eligibility. Among them, 110 (91%) would have been eligible for PrEP, median age 31 years, with 68 (75.6%) born in France and 10 (11.1%) in Central/West Africa, with more than one previous STI in 19 (15.7%). The main eligibility criteria for PrEP were being a man who had sex with men or transgender 91 (82.7%) with at least one of the following criteria: unprotected anal sex with ≥2 partners in the last 6 months: 67 (60.9%); bacterial sexually transmitted infection in the last 12 months: 33 (30%); Use of psychoactive substances in a sexual context (chemsex): 16 (14.5%). PrEP was indicated for other HIV risk factors in 25 (22.7%). CONCLUSION: With 91% (110/121) of patients infected in the PrEP area eligible for PrEP, this study highlights the high potential of PrEP in avoiding new infection in France but also shows a persistent delay in HIV testing. Thus, an important limit on PrEP implementation in France could be insufficient screening and care access.

E-health. Patterns of use and perceived benefits and barriers among people living with HIV and their physicians. Part 2: Health apps and smart devices.

OBJECTIVES: To evaluate patterns of use and perceived benefits and barriers to health/wellness applications (apps) and smart devices among people living with HIV (PLHIV) and their physicians. METHODS: Online multicenter observational survey (October 15-19, 2018). RESULTS: Study participation was accepted by 229 physicians and 838/1377 PLHIV followed in 46 centers, of which 325 (39%) responded online. Overall, 83/288 (29%) PLHIV had already downloaded at least one app: these 'downloaders' were younger (OR0.96±0.01, P=0.004), educated to at least university entry level (OR2.27±0.86, P=0.03), and more frequently used geolocation-based dating websites (OR3.00±1.09, P=0.002). However, 227/314 (72%) PLHIV claimed they were ready to use an app recommended by a physician. For the 60/83 PLHIV who answered, the ideal app would be a vaccination tracker (76%) to better communicate with their physician (68%). However, 96/277 (42%) physicians were unable to answer this question and for 94/227 (41%) of them, the ideal patient app would be for schedule management. Although PLHIV used smart devices, 231/306 (75%) would want to report the data to their physicians and 137/225 (61%) of physicians would welcome this exchange. The main physician-side barrier to this exchange was concerns over data security. CONCLUSION: mHealth apps and smart devices have failed to garner adoption by PLHIV. There is a case for good-quality health data sharing and exchange if PLHIV are provided with appropriately secure tools and physicians are backed up by adapted legislation.

E-health. Patterns of use and perceived benefits and barriers among people living with HIV and their physicians. Part 1: Information retrieval on the Internet and social networks.

OBJECTIVES: To identify patterns of use, perceived benefits, and barriers among people living with HIV (PLHIV) of online searches for health information and via social media. METHODS: Online multicentre observational survey (October 15th-19th, 2018). RESULTS: Study participation was accepted by 838/1377 PLHIV followed in 46 centres, of which 325 (39%) responded online: 181 (56%) had already used the Internet to search for health information; 88/181 (49%) on HIV infection and 78 (43%) on nutrition. These 56% were characterised by a higher educational level (OR=1.82±0.50; P=0.028) and more often consulted other specialists (OR=3.14±1.26; P=0.004). A subset of 87/180 (48%) PLHIV had changed the way they looked after their health based on their online research, and were more often in material/social deprivation (P=0.02) and diabetic (P=0.02). A small subset of 19/180 (11%) had already asked or answered a question on a forum; these people tended to be women (P=0.03) in material/social deprivation (P=0.009). 296/322 (92%) PLHIV trusted their physician whereas only 206 (64%) trusted information sourced on medical websites. 238/323 (74%) PLHIV expected their physicians to recommend websites if asked, whereas only 23/323 (7%) had actually been given this guidance. CONCLUSION: More than half of PLHIV surveyed had already searched for health information on the Internet, and one in two had changed their behaviour based on the online search. PLHIV did not see the Internet as an alternative to physicians but they wanted their physicians to guide them on how to find quality health information to better self-manage their condition.

E-health. Patterns of use and perceived benefits and barriers among people living with HIV (PLHIV) and their physicians - Part 3: Telemedicine and collection of computerized personal information.

OBJECTIVES: To evaluate the patterns of use and perceived benefits and barriers among people living with HIV and their physicians concerning telemedicine and the collection of computerized personal information. METHODS: Multicenter online observational survey from October 15 to 19, 2018. RESULTS: Study participation was accepted by 229 physicians and 838/1,377 PLHIV followed in 46 centers, of which 325 (39%) responded online. We found that while 226/302 (75%) PLHIV accept online prescription renewals and 197/302 (65%) accept online medical certificates, 182/302 (60%) PLHIV-who were more often in material/social deprivation (OR=1.70±0.45; P=0.045), less often born in Île-de-France (OR=0.43±0.15; P=0.018), with lower CD4 T-cell counts (OR=0.999±0.0004; P=0.038), and less often on psychiatric treatment (OR=0.50±0.18; P=0.047)-were receptive to teleconsultations. However, 137/225 (61%) physicians would be uncomfortable teleconsulting due to inadequate data security without it reducing the number of consultations or offering economic benefit. Asked about collection of computerized personal information, 197/296 (67%) PLHIV and 139/223 (62%) physicians agreed it improved quality of care, but 144 (49%) PLHIV and 94/222 (42%) physicians thought it was not sufficiently framed by the law. eHealth was seen as improving coordination between health professionals by 240/296 (81%) PLHIV and seen as a good thing by 181/225 (81%) physicians. CONCLUSION: More than half of PLHIV were ready for telemedicine. PLHIV and physicians endorsed the advantage of e-health in terms of better coordination across health professionals but mistrust the data collection factor, which warrants either clarification or stronger legal protections.

High rate of virologic suppression with raltegravir plus etravirine and darunavir/ritonavir among treatment-experienced patients infected with multidrug-resistant HIV: results of the ANRS 139 TRIO trial.

BACKGROUND: The introduction of 2 or 3 fully active drugs in human immunodeficiency virus (HIV)-infected patients receiving failing antiretroviral therapy is a key determinant of subsequent treatment efficacy. The aim of this study was to assess the safety and efficacy of a regimen containing raltegravir, etravirine, and darunavir/ritonavir for treatment-experienced patients infected with multidrug-resistant HIV. METHODS: Patients enrolled in this phase II, noncomparative, multicenter trial were naive to the investigational drugs and had plasma HIV RNA levels >1000 copies/mL, a history of virologic failure while receiving nonnucleoside reverse-transcriptase inhibitors (NNRTI), > or =3 primary protease inhibitor and nucleoside reverse transcriptase inhibitor (NRTI) mutations, and < or =3 darunavir and NNRTI mutations. The primary end point was the proportion of patients with plasma HIV RNA levels <50 copies/mL at 24 weeks. RESULTS: A total of 103 patients enrolled in the study. At baseline, genotypic resistance profiles showed a median of 4 primary protease inhibitor mutations, 1 NNRTI mutation, and 6 NRTI mutations. In addition to the investigational drugs, 90 patients (87%) received optimized background therapy that included NRTIs (86 patients) or enfuvirtide (12 patients). At week 24, 90% of patients (95% confidence interval, 85%-96%) had an HIV RNA level <50 copies/mL. At week 48, 86% (95% confidence interval, 80%-93%) had an HIV RNA level <50 copies/mL. The median CD4 cell count increase was 108 cells/mm(3). Grade 3 or 4 clinical adverse events were reported in 15 patients (14.6%). Only 1 patient discontinued the investigational antiretroviral regimen, because of an adverse event. CONCLUSION: In patients infected with multidrug-resistant virus who have few remaining treatment options, the combination of raltegravir, etravirine, and darunavir/ritonavir is well tolerated and is associated with a rate of virologic suppression similar to that expected in treatment-naive patients.

Persistently normal alanine aminotransferase levels in HIV/HCV-coinfected patients: the role of steatosis.

OBJECTIVE: The frequency and significance of, and liver biopsy findings associated with, a persistently normal alanine aminotransferase (ALT) level in HIV/hepatitis C virus (HCV)-coinfected patients are poorly characterized. We analysed factors associated with persistently normal ALT levels, defined as at least three consecutive normal ALT values over a 6-month period, in a group of 381 HIV/HCV-coinfected patients. METHODS: Patients were categorized into two groups according to ALT values: group 1, patients with persistently normal ALT levels; and group 2, patients with elevated ALT values. Possible interactions with host factors, HIV and HCV viral factors, antiretroviral treatment and histological features were examined. RESULTS: Thirty-six patients (9.4%) had persistently normal ALT levels. None of the 36 patients had cirrhosis. Seven patients (19.4%) had a METAVIR fibrosis score of F3. In multivariate analysis, a lower mean METAVIR inflammation score [odds ratio (OR) 0.50, 95% confidence interval (CI) 0.28-0.89; P=0.017], the absence of steatosis (OR 0.43, 95% CI 0.20-0.90; P=0.026) and HCV genotype 4 infection (OR 2.81, 95% CI 1.15-6.68; P=0.023) were associated with persistently normal ALT levels. CONCLUSION: The slower progression of chronic hepatitis in patients with persistently normal ALT levels could be related, in part, to a lower frequency of steatosis.

[Thromboembolic events at the time of highly active antiretroviral therapies against human immunodeficiency virus]. / Evénements thromboemboliques à l'ère des trithérapies antirétrovirales hautement actives contre le virus de l'immunodéficience humaine.

PURPOSE: Vein thrombosis risk and pulmonary embolism seem to be more important among human immunodeficiency virus (HIV) infected patients. METHOD: We performed a retrospective study including 780 HIV positive patients followed-up between January 2000 and June 2005 at the University Hospital of Clermont-Ferrand. RESULTS: Among the 780 HIV-infected patients, six cases of thromboembolic events were identified including, four with pulmonary embolism. All the patients were receiving lopinavir/ritonavir combination. CONCLUSION: Although uncommon, pulmonary embolism occurs more frequently among HIV positive patients than in general population. Clinicians must remain aware about the possibility of the occurrence of a thromboembolic event especially during the first few months after introduction of the antiretroviral therapy.

[Non Hodgkin's and Hodgkin's lymphomas and HIV: frequency, outcome and immune response under HAART; Clermont-Ferrand University Hospital, 1991-2003]. / Lymphomes non hodgkiniens et hodgkiniens et infection VIH: fréquence, pronostic et reconstitution immune sous trithérapie antirétrovirale; CHU de Clermont-Ferrand, 1991-2003.

OBJECTIVES: The authors had for aim to identify cases of non Hodgkin's (NHL) and Hodgkin's (HL) lymphomas in HIV1-infected patients to assess 1) their incidence, before and after 1996, 2) the clinical features and outcome under treatment together with the survival rate of the patients, 3) the immune reconstitution of lymphoma-free patients under HAART. PATIENTS AND METHODS: A retrospective study was made of HIV1-infected patients managed at the Clermont-Ferrand University Hospital from 1991 to 2003 for the diagnosis and treatment of HIV1-related lymphomas. RESULTS: Forty-one patients were included: 35 NHL and 6 HL giving a cumulative incidence rate estimate from 2.4% between 1991 and 1996 to 3.4% between 1997 and 2003 while other opportunistic diseases were decreasing. A high proportion of aggressive and disseminated disease was observed among NHL cases. Complete remission was achieved in 17 (49%) and 5 (83%) NHL and HL cases respectively. The mean survival was 109+/-54 months and was correlated with CD4 cell count at lymphoma diagnosis (univariate analysis). Among responding patients, 5 died: 3 from opportunistic infections, 1 commited suicide, and 1 from hepatic carcinoma. For responding patients, the mean increase of CD4 cell count under HAART was 58/mm3 over a 2 year-period and 192/mm3 over a 5 year-period of follow-up. CONCLUSIONS: The incidence of lymphomas in HIV-infected patients has not decreased since the introduction of HAART. The immune status assessed by CD4 cell count on diagnosis is correlated with survival. Immune restoration in lymphoma-free patients under HAART is poor.

Prevalence of aortic valve dystrophy and insufficiency in a cohort of 255 HIV-positive patients followed-up in a cardiology department between 2012 and 2014.

OBJECTIVES: To study valve appearance and the presence of valve disease in a cohort of people living with HIV (PLHIV). DESIGN: A prospective study of PLHIV examined at the cardiology department of the Clermont Ferrand university hospital group (CHU) between January 1, 2012, and December 31, 2014. Were excluded those with a history of infection associated with a possible endocarditis. METHODS: Demographic, medical characteristics and cardiovascular disease risk factors at time of cardiovascular examination and Doppler-echocardiography were recorded and analyzed. RESULTS: In total, 903 PLHIV were examined in the infectious diseases department, 255 of whom were included. These consisted of 67 women (26.3%) and 188 men, of a mean age of 51.2±9.7years, in whom coronary artery disease was diagnosed in 18 patients (7.0%), two women and 16 men, representing a prevalence of 3.0% in females and 8.5% in males. The appearance of the aortic cusps was considered dystrophic in 14.1% of cases (36/255), dysplastic in two cases (0.8%), exhibiting a bicuspid deformity in one case. The prevalence of aortic valve abnormality was therefore 6.0% in the women (4/67) and 17.0% in the men (32/188). On facing off this data with the Kora Monica study findings, an increase in prevalence appears only to truly manifest after 50years of age. We registered 35 aortic insufficiency cases (13.7%), representing a higher incidence than that of the Framingham cohort, with age and masculine gender being the determining factors. CONCLUSION: Valve disease, along with coronary artery disease, should be closely monitored in PLHIV.

Impact of Age-related Comorbidities on Five-year Overall Mortality among Elderly HIV-Infected Patients in the Late HAART Era--Role of Chronic Renal Disease.

OBJECTIVES: To identify main prognostic factors for 5-year mortality among age-related comorbidities (ARCs) in older people living with HIV (PLHIV). DESIGN: A prospective, multicentre cohort study with a 5-year follow-up period in the late HAART era (from January 2008 to December 2012). SETTING: The Dat'AIDS cohort involving 12 French hospitals. PARTICIPANTS: All actively followed HIV-1 infected patients aged 60 or older. MEASUREMENTS: The study endpoint was all-cause five-year mortality. The following ARCs were considered: chronic renal disease, cardiovascular diseases, cancer, chronic pulmonary disease, cirrhosis, diabetes and nutritional status. Hepatitis C (HCV), hepatitis B (HBV) co-infection and sociodemographic characteristics were also evaluated. Cox's Proportional Hazards model was used for multivariate analysis. RESULTS: Among 1415 PLHIV aged 60 or more patients included, mean age was 66±5.5 years; 154 died (mortality rate 2.47/100 patient-years). The most prevalent ARCs were chronic renal disease (20.1%), diabetes (14.2%) and cardiovascular diseases (12.2%). By multivariate analysis, chronic renal disease (adjusted hazard ratio (aHR)=2.25; 95% confidence interval (CI) [1.58-2.21]; p<10-4), cardiovascular diseases (aHR=2.40; 95%CI[1.64-3.52]; p<10-4), non-HIV related cancer (aHR=1.91; 95%CI[1.20-3.05]; p=0.007), cirrhosis (aHR=2.99; 95%CI[1.68-5.33]; p<10-3), HCV co-infection (aHR=2.00; 95%CI[1.18-3.38]; p=0.009), low body mass index (aHR=2.42; 95%CI[1.46-4.01]; p<10-3) and CD4 cell count < 200 cells/µl (aHR=2.23; 95%CI[1.36-3.65]; p=0.002) were independently associated with 5 year mortality. CONCLUSION: Due to a high prevalence, chronic renal disease and cardiovascular disease are main prognostic factors for 5-year mortality among aged PLHIV.

Autocrine interferon-beta synthesis for gene therapy of HIV infection: increased resistance to HIV-1 in lymphocytes from healthy and HIV-infected individuals.

OBJECTIVE: To explore the possibility of gene therapy of HIV infection based on the multiple antiretroviral activities of interferon (IFN)-beta. DESIGN: We introduced into HIV target cells an IFN-beta gene placed under an expression control ensuring a low and constitutive expression, sufficient to confer a permanent antiviral state without impeding normal cell function. METHODS: We transformed, with an efficacy ranging from 20-55%, peripheral blood lymphocytes (PBL) derived from healthy, seronegative donors, and from asymptomatic HIV-infected individuals by the HMB-KbHuIFN beta retroviral vector carrying the human IFN-beta coding sequence driven by a fragment of the murine H-2Kb gene promoter. RESULTS: The replication rate of the IFN-beta-expressing cells was no different from that of untransformed controls during the 21-day period of in vitro observation. When IFN-beta-transformed, purified CD4+ lymphocytes from healthy donors were HIV-1LAI-infected, virus replication was inhibited and most of the cells survived, in contrast to untransformed CD4+ cells which were all destroyed 12 days after infection. Protection of CD4+ cells from the same donors was also observed in suspensions of IFN-beta-transformed total PBL that were infected with HIV-1LAI. In IFN-beta-transformed PBL from four HIV-infected donors, endogenous HIV replication was decreased and 28-69% of the CD4+ cells survived at the end of the 21 days in culture. In the untransformed control PBL suspensions, all CD4+ cells were destroyed. In long-term experiments, HIV-infected, IFN-beta-transformed cell populations of the lymphocytic CEM and the promonocytic U937 line were kept in culture for 60 days, during which time they remained resistant to HIV infection. CONCLUSION: These results indicate that further exploration of autocrine IFN-beta production for somatic cell gene therapy of HIV infection is warranted.

Intravenous methotrexate for primary central nervous system non-Hodgkin's lymphoma in AIDS.

OBJECTIVE: To evaluate high-dose intravenous methotrexate in primary central nervous system (CNS) lymphoma in HIV-infected patients. DESIGN: An uncontrolled pilot trial. SETTING: An infectious diseases department in Paris, France. PATIENTS: All consecutive AIDS patients with primary CNS lymphoma attending the same unit from August 1994 to March 1996. INTERVENTIONS: Methotrexate was intravenously administered at a dose of 3 g/m2 every 14 days with leucovorin rescue. A maximum of six cycles was planned. Steroids were given to all patients and haematological growth factors were administered as required. MAIN OUTCOME MEASURES: Rate of response, time to response and survival. RESULTS: Fifteen patients (10 with histological documentation) were recruited. The median time since clinical onset was 27 days (range, 7-69 days), median Karnofsky score was 51 (range, 30-70), and mean CD4+ cell count was 30 +/- 19 x 10(6)/l (range, 7-69 x 10(6)/l). Complete responses, defined as clinical improvement and disappearance of contrast-enhancing brain abnormalities on computed tomography or magnetic resonance imaging, were obtained in seven out of 15 patients (three out of 10 patients with histological diagnosis and four out of five patients without histological confirmation). The Karnofsky score of these seven patients improved to 80 +/- 10 (range, 70-100). The mean time taken to respond was 62 +/- 20 days (range, 45-90 days). One patient relapsed at 6 months. Six patients failed to respond, and two died of severe sepsis on days 15 and 45. The median survival time was 290 days (range, 11-570 days): 73 days (range, 11-570 days) in the 10 patients with histological diagnosis, and 347 days (range, 286-409 days) in the five patients without histological confirmation. Side-effects occurred in 10 patients, with gastrointestinal disorders in five, mucositis and skin rash in two, and fever in three patients; however, these events were mild and did not require cycle postponement or dose changes. No cognitive dysfunction occurred. CONCLUSION: Methotrexate appears to be an attractive alternative to radiation therapy for primary CNS lymphoma and is associated with a far greater improvement in quality of life relative to historical series of radiation therapy.

A prospective evaluation of clinical criteria and polymerase chain reaction assay of cerebrospinal fluid for the diagnosis of cytomegalovirus-related neurological diseases during AIDS.

OBJECTIVE: To study the predictive value of clinical criteria and polymerase chain reaction (PCR) assay of cerebrospinal fluid (CSF) for the diagnosis of cytomegalovirus (CMV)-related neurological disorders during AIDS. SETTING: Four infectious diseases departments in two tertiary referral teaching hospitals in Paris, France. DESIGN AND PARTICIPANTS: One-year prospective study involving 164 consecutive immunosuppressed HIV-seropositive patients undergoing lumbar puncture (LP). METHODS: A tentative diagnostic classification, based on strict operational criteria and PCR assay of CSF, was performed at the time of LP. At the end of the study, tentative diagnoses and PCR results were blindly and independently compared with the firm diagnoses, based on central nervous system histology, clinical outcome and/or viral culture of CSF. RESULTS: The tentative diagnosis showed CMV-related neurological disease in 38 patients, and CMV DNA was detected in 42. Among the 88 patients for whom a firm diagnosis was possible, 26 had a diagnosis of CMV-related neurological disease. The concordance between the tentative and firm diagnoses was 61%, with a kappa index of 0.40. In contrast, the sensitivity and specificity of PCR were respectively 92 and 94%, with positive and negative predictive values of 86 and 97%. The presence of CMV DNA in CSF was associated with an increased risk of death (P < 0.0001). CONCLUSIONS: Unlike clinical criteria, PCR detection of viral DNA in CSF can be used reliably for antemortem diagnosis of CMV-related neurological disease, a frequent complication of AIDS in this study. This rapid method should make a major impact on the management of these patients.

Cytomegalovirus multifocal neuropathy in AIDS: analysis of 15 consecutive cases.

A severe multifocal neuropathy caused by cytomegalovirus (CMV-MN) can occur in the late stage of human immunodeficiency virus (HIV) infection. In a retrospective study, we identified 15 consecutive HIV-positive patients with a diagnosis of CMV-MN based on (1) markedly asymmetric neuropathy, (2) fewer than 100 CD4+ cells per mm3, (3) exclusion of other causes of neuropathy, and (4) characteristic CMV cytopathic changes on neuromuscular biopsy (2 patients), positive CSF culture for CMV (2 patients), or clinical improvement on anti-CMV therapy given for concurrent extraneurologic CMV disease (8 patients) or neuropathy (3 patients). All patients were men and had severe immunosuppression (mean CD4+ cell count, 18 per mm3). The initial symptoms were numbness and painful paresthesias showing a patchy, multifocal distribution. After a mean of 11 weeks (range, 1 to 10 months), the patients developed moderate or severe sensorimotor asymmetric neuropathy. Extraneurologic CMV infection occurred in 10 patients before diagnosis. Electrophysiologic studies showed axonal neuropathy and CMV DNA was present in CSF by the polymerase chain reaction (PCR) technique in 90% of patients tested. Fourteen patients showed a marked improvement 1 to 4 weeks after starting ganciclovir or foscarnet therapy. During follow-up on maintenance therapy (13 patients), the neuropathy relapsed in three patients and probable or confirmed CMV encephalitis occurred in five. Twelve patients died during follow-up, at a mean interval of 9.5 months after their first symptoms. These results extend the clinical spectrum of CMV-MN and show that PCR detection of CMV DNA in CSF may be a useful diagnostic marker.

[Development of an anti-HIV gene therapy based on the antiviral properties of beta interferon]. / Développement d'une génothérapie anti-VIH basée sur les propriétés antivirales de l'interféron bêta.

The aim of our work is to explore the use of IFN-beta for gene therapy in the HIV-infection. Transduction of various HIV target cells with a retroviral vector that carries the Hu-IFN-beta coding sequence under constitutive low expression control, confers resistance to HIV without affecting cell replication or function. After transduction, lymphocytes from HIV-infected patients develop resistance to the endogenous virus, provided the cells are derived from individuals with a CD4 cell count higher than 200 per mm3.

Clinical and laboratory findings of disseminated Mycobacterium avium complex infection (DMAC) in a pair matched case-control study.

A pair matched case/control study was conducted from January 1991 to 30 June 1992 in order to define clinical and laboratory findings associated with DMAC infection in AIDS patients. Since DMAC infection is usually associated with advanced immunodeficiency, and therefore also with other opportunistic illnesses, in addition to the number of CD4+ lymphocytes, cases and controls were matched using the following criteria: date of AIDS diagnosis and antiretroviral therapy, number and severity of associated opportunistic infections and, whenever possible, type of Pneumocystis carinii prophylaxis, age and gender, in this order of relevance. Cases (defined as patients presenting at least one positive culture for MAC at a normally sterile site) and controls presented CD4+ lymphocyte counts below 50 cel/mm3. A significantly higher prevalence of general, digestive and respiratory signs, increased LDH levels, low hemoglobin levels and CD4+ cell counts were recorded for cases when compared to controls. Increases in gammaGT and alkaline phosphatase levels seen in cases were also recorded for controls. In conclusion, the strategy we used for selecting controls allowed us to detect laboratory findings associated to DMAC infection not found in other advanced immunosupressed AIDS patients without DMAC.

[Septicemia associated with the presence of a pacemaker with endocavitary electrode]. / Septicémie associée à la présence d'un cardiostimulateur avec sonde endocavitaire.

Septicaemia on endovenous pacemaker electrodes is infrequent and difficult to detect. We report the case of a 64-year old woman with a diagnosis of prolonged fever that dragged on for several months before infection of her pacemaker was considered, then confirmed. Repeated Staphylococcus epidermidis isolates from blood cultures were no longer regarded as contaminations, and transoesophageal echocardiography revealed the presence of a "mass" on her endocavitary electrode, which had not been visualized on several previous échocardiographies. Surgical removal of the electrode was soon required in view of multiple septic emboli despite a bacteriologically effective antibiotic therapy. The outcome is favourable after a 6-month follow-up. The authors review the diagnostic and therapeutic problems created by infections on electrosystolic exciting electrodes.

[Bilateral uveitis with definitive hypotony caused by systemic cidofovir]. / Uvéite bilatérale et hypotonie définitive due au cidofovir intraveineux. A propos d'un cas.

We report the case of a 52-year-old man with AIDS and CMV bilateral retinitis, treated first with ganciclovir (cymevan) and then with cidofovir. During the treatment, the patient complained of a sharp decrease in visual acuity. Cycloplegics and topical corticosteroids were given. Then cidofovir was stopped and replaced with intravenous Foscavir because of the clinical inefficacy. The anterior uveitis resolved but the ciliary secretion has not stopped after 12 months of follow-up. The patient presented +11 hypermetropia with a choroidal edema and bilateral cataract. This case is interesting for its permanent hypotony and bilateral uveitis. A literature search has brought out a rate of only 3% of chronic hypotony. We hypothesize bilateral iatrogenic ciliary body necrosis, as described in the animal models.