Ocular syphilis and HIV infection.

Syphilitic ocular involvement is thought to be rare in HIV infected patients. During a 5-year study in 509 HIV-positive patients, syphilis was diagnosed in 3.9%, and the eye was involved in one-fifth of these. The high risk for sequelae emphasizes the need for prevention and for early diagnosis.

Treatment of chronic hepatitis C in HIV-infected patients: from clinical trials to field practice.

In a prospective cohort of 87 HIV coinfected patients with chronic hepatitis C, 63% had been treated for HCV, with global success rate (47%, 95% CI 34-61) close to or higher than that reported in therapeutic trials. These results argue for earlier, more frequent and improved HCV treatment in HIV-infected patients.

Concentration of circulating oxidized LDL in HIV-infected patients treated with antiretroviral agents: relation to HIV-related lipodystrophy.

BACKGROUND: Circulating oxidized LDL (ox-LDL) is associated with clinical manifestations of atherosclerosis. The aim of the study was to investigate the concentrations of ox-LDL in HIV-infected patients under antiretroviral therapy with (HIV-LD) or without (HIV-nLD) HIV-related lipodystrophy. METHOD: A total of 44 HIV-infected men were enrolled in the study. Half of them had HIV-LD. The control group included 12 age- and body mass index (BMI)-matched HIV-uninfected men. Ox-LDL concentration and C-reactive protein level were determined. Insulin sensitivity was measured using the homeostasis model assessment (HOMA-IR). LD was assessed by using a validated score calculated from clinical and biological data. RESULTS: HIV-infected patients had significantly higher ox-LDL concentrations when compared to HIV-negative controls (0.8 +/- 0.3 mg/dL vs. 0.60 +/- 0.1 mg/dL; p = .007). HIV-LD patients had significantly higher ox-LDL concentrations than HIV-nLD patients (0.91 +/- 0.38 and 0.69 +/- 0.16; p = .04). In HIV-LD patients, current therapy with protease inhibitors (PIs); duration of PI therapy; HOMA-IR; and time exposure to stavudine, efavirenz, ritonavir, saquinavir, and amprenavir were significantly higher than in HIV-nLD patients. In multivariate analysis, time exposures to stavudine and ox-LDL concentration were independently related to lipodystrophy. CONCLUSION: The high concentration of ox-LDL was found in HIV-infected patients under antiretroviral therapy, especially in those with lipodystrophy.

Low trough plasma concentrations of nevirapine associated with virologic rebounds in HIV-infected patients who switched from protease inhibitors.

BACKGROUND: The substitution of a nonnucleoside reverse-transcriptase inhibitor (NNRTI) for protease inhibitors (PIs) has demonstrated its suitability to maintain virologic response. However, the switch from PIs to an NNRTI could fail for a number of reasons, including NNRTI-associated toxicity and emergence of NNRTI-resistant variants. OBJECTIVE: To describe the virologic failures among 74 HIV-infected patients who switched from PIs to nevirapine. METHODS: Virologic failure was defined as any rebound of the plasma HIV-RNA (pVL) levels >1000 copies/mL on one occasion or 2 consecutive intermittent viremia episodes defined as increases of the pVL >20 copies/mL but <1000 copies/mL. Virologic failures were investigated retrospectively by determining nevirapine trough concentrations and performing genotypic resistance analysis. RESULTS: The mean nevirapine concentration was significantly lower in patients with virologic failure in comparison with patients with virologic response (2572 +/- 1642 vs 4550 +/- 2084 ng/mL, respectively; p = 0.003). In multivariate analysis, the mean duration of undetectable pVL before the switch and the mean plasma concentration of nevirapine were significantly associated with virologic success with relative rates of 1.39 (95% CI 1.10 to 1.76, p = 0.006) and 2.7 (95% CI 1.37 to 5.41, p = 0.01), respectively. In patients with pVL >1000 copies/mL, nevirapine mutations and nucleoside reverse-transcriptase inhibitor mutations were found in 80% of the cases. CONCLUSIONS: The risk of virologic failure after the switch from PI to nevirapine is higher in cases of inadequate nevirapine plasma concentrations. Our data support prospective monitoring of nevirapine plasma concentrations to detect low concentrations prior to the emergence of resistance mutations.

Usefulness of therapeutic drug monitoring of antiretrovirals in routine clinical practice.

BACKGROUND: Clinical trials have shown that therapeutic drug monitoring (TDM) of antiretrovirals (ARV) improves patient care. However, little is known about the usefulness of TDM in routine practice. METHOD: We reviewed all the trough concentrations of protease inhibitors and nonnucleoside reverse transcriptase inhibitors that were performed for therapeutic failure, suspected drug toxicity, or routine purposes. RESULTS: Between 1998 and 2001, 146 TDMs were done in 109 HIV patients. Of the 48 patients with therapeutic failure, 62% had resistance to ARV with adequate ARV concentrations, 16% had insufficient drug exposure without any ARV resistance mutations, and 16% combined both resistance and suboptimal drug concentrations. Subsequent therapeutic interventions (increasing adherence and/or changing HAART) resulted in an undetectable viral load in 37.5% of the patients (14/48). Five (24%) of 21 patients with suspected drug toxicity had high drug concentrations associated with side effects. In all the cases, adverse events regressed after reduction of drug dosage. Of the 77 TDMs done for routine purposes, 26% were outside the therapeutic range. CONCLUSION: The data show that TDM of ARVs in the clinical setting provides important information that can be used to improve the management of HIV patients receiving antiretroviral therapy.

Clinical, immunological and virological evolution in patients with CD4 T-cell count above 500/mm3: is there a benefit to treat with highly active antiretroviral therapy (HAART)?

To assess the clinical, immunological and virological evolution in HIV-1 infected patients with CD4 T-cell count above 500/mm3, a historical cohort of 202 untreated and 96 patients treated with HAART was longitudinally studied (median follow-up 36 months). Fourteen untreated and 2 treated patients experienced clinical progression (p = 0.09). The difference between baseline CD4 T-cell count and after 3 years, was -240/mm3 in the untreated group +19/mm3 in the HAART group (p < 10(-3)). A better immunological outcome was significantly associated with a HIV sexual contamination (p = 0.01), HAART (p = 0.01), high baseline CD4 T-cell count (p < 10(-3)) and low baseline HIV viral load (p = 0.01). In the HAART group, the incidence rate of antiretroviral modification due to tolerance difficulties was 0.23+/-0.36/patient year. A sustained undetectable HIV viral load was correlated with a low baseline HIV viral load (p = 0.003) and to be antiretroviral naive (p < 10(-3)). Thus, HAART provide a better immunological outcome in patients with high CD4 T-cell count. However, the CD4 decay slope after 3 years, the risk of therapeutic side-effects and the low risk of clinical progression do not support systematic treatment of those patients.

Acute liver enzyme elevations in HIV-1-infected patients.

BACKGROUND: Acute liver enzyme elevations (ALEE) have been associated with a first-line highly active antiretroviral therapy (HAART) and/or viral hepatitis coinfections in HIV-infected patients. By comparison, the frequency and the risk factors of ALEE in untreated patients and in patients treated with several antiretroviral regimens need to be assessed. PURPOSE: To describe the long-term frequency and the characteristics of ALEE in antiretroviral treated and untreated patients and to define risk factors for ALEE in a retrospective cohort of HIV-1-infected patients. METHOD: An HIV-infected cohort was retrospectively examined. ALEE was defined as levels of alanine amino transferase and/or alkaline phosphatase rising to at least 2.5 times above baseline values. Hazard ratios (HR) for ALEE were estimated using an extension of the Cox proportional model taking into account recurrent events. RESULTS: Out of 239 assessable patients, 12 (5%) were coinfected with hepatitis B virus (HBV) and 34 (14.2%) with hepatitis C virus (HCV). The incidence rate of ALEE was 9.9/100 patients-year and the cumulative incidence was 20.9%. HCV genotype 3 tended to give a higher risk of ALEE. Independent factors for developing ALEE in multivariate logistic regression were HBV (HR = 4.0) and HCV (HR = 3.4) coinfections, antiretroviral therapy (HR = 2.6), CDC stage C (HR = 2.5), and high alkaline phosphatase baseline values (HR = 1.7). CONCLUSION: The occurrence of ALEE is influenced more by the past medical history and the clinical background of the patients than by antiretroviral therapy. These patient-linked variables must be taken into account to avoid unwarranted treatment withdrawal.

[Acute Gemella haemolysans spondylodiscitis in an immunocompetent patient]. / Spondylodiscite aiguë à Gemella haemolysans chez une patiente immunocompétente.

INTRODUCTION: Gemella is a commensal bacterium of the upper respiratory tract responsible for rare infections such as acute endocarditis and meningitis. We report the case of an acute Gemella haemolysans spondylodiscitis. OBSERVATION: A 72 year-old woman was hospitalised for an etiological control and treatment of acute L4-L5 spondylodiscitis with epiduritis, confirmed on MRI. The clinical picture was composed of backache with shivering and alteration in general status of health. The peripheral bacteriological samples, intra-dermal reaction and brucella serology were all negative. The surgical L5 biopsy, following bacteriological enrichment, isolated Gram-positive cocci, later identified as Gemella haemolysans. The antibiogram showed good sensitivity to amoxicillin, dalacin and erythromycin, and strong resistance to aminosides. The search for a contamination point was negative. The patient rapidly improved with antibiotics combining 6 g/d of amoxicillin and 1200 mg/d of clindamycin, and the biological and clinical signs regressed. The antibiotic bi-therapy was continued for two and a half months and then relayed to amoxicillin alone for two further weeks. COMMENTS: The first descriptions of Gemella haemolysans infection were made in the seventies. Cases of infectious endocarditis were succeeded by septicaemia on cirrhosis and later a few cases of acute post-neurosurgical meningitis. In the majority of cases, a dental contamination point was found. The difficulties in its etiological diagnosis, related to the problems in identifying this germ that has similar characteristics to Streptococcus viridans, suggests that the prevalence of Gemella haemolysans infections is greatly underrated. The sensitivity profile generally observed is sensitivity to penicillins and aminosides--the association of which is synergic--, to cyclines and glycopeptides, and resistance to trimethoprime-sulfamethoxazole.

[New strategies for angina case management in France]. / Nouvelle stratégie de prise en charge des angines en France.

Old French recommendations were to treat all pharyngitis cases to prevent acute rheumatic fever. 85 to 90% of cases were treated (8 to 9 millions/year), of which 3/4 unnecessary. Furthermore, penicillin V the drug of first choice was prescribed only to 5 to 10% of patients. Considering the preocupating increase of bacterial resistances and the disponibility of performane Group A Beta-Hemolytic Streptococcus Rapid Diagnostic Test (Negative Predictive Value above 95%), the new management strategy is proposed in two ways. Firstly, the free delivery of RDT to practitioners which was associated in Burgundy with a dramatic prescription decrease to 41% without benefice lost for patients. Considering these good results the French authorities decided the generalization of RDT use in 2002 and more than 15,000 practitioners have been concerned by the formations delivered in 3 months. Secondly, the short course treatment assays initiated by our group have been validated and since 2002 the AFSSAPS recommend the preferential use of compounds which obtained the authorization of use in short course with a new indication incitating to document GABHS pharyngitis by the RDT use.

The evolution of hepatitis B virus serological patterns and the clinical relevance of isolated antibodies to hepatitis B core antigen in HIV infected patients.

BACKGROUND/AIMS: The evolution of hepatitis B virus (HBV) serological patterns and the clinical relevance of isolated anti-HBc pattern are not well established in HIV infected patients. METHODS: A cohort of 240 patients was followed for 6.9+/-3.4 years, with iterative HBV serologic assays performed (mean interval of 2.2 years). RESULTS: Five patients without HBV markers at baseline subsequently developed positive anti-HBs (incidence 0.66/100 patient-year), as did two patients with chronic HBs antigenemia (incidence 1.66/100 patient-year). Only one patient with isolated anti-HBc pattern developed HBs chronic antigenemia. Persistent isolated anti-HBc pattern was observed in 37 patients (13 with detectable blood HBV DNA) and was strongly associated with positive hepatitis C virus (HCV) viremia (hazard ratio=9.5, confidence interval 95%: 4.5-20.0, P<0.0001). Hepatic lesions were more severe in HCV infected patients with persistent isolated anti-HBc pattern than in those without (Knodell score 9.2+/-4.6 versus 6.7+/-5.0, P=0.04). In time updated analysis, this pattern was not associated with an increased risk of hepatotoxicity, by contrast with HCV infection or positive HBs antigenemia. CONCLUSIONS: In HIV infected patients, HBV serological status must be systematically and regularly assessed, and systematic HBV vaccination must be proposed in those without HBV marker. Isolated anti-HBc pattern must be considered in the management of hepatitis C, but not for antiretroviral therapy.

Role of long-term nucleoside-analogue therapy in lipodystrophy and metabolic disorders in human immunodeficiency virus-infected patients.

The role of nucleoside analogues (NAs) in lipodystrophy (LD) syndrome in human immunodeficiency virus (HIV)-infected patients remains controversial. We studied the prevalence of LD in previously untreated patients randomized to receive different NA combinations (in the ALBI-ANRS 070 trial) for 6 months. At month 30 of follow-up, 37 (31%) of 120 patients had >/=1 morphologic change, and 21 (57%) of 37 had isolated peripheral lipoatrophy; corresponding values for the patients who received only NAs throughout follow-up were 20 (30%) of 66 and 14 (67%) of 21, respectively. In multivariate analysis, factors associated with presence of LD at month 30 were initial assignment to the group receiving stavudine and didanosine (odds ratio [OR], 6.7; P=.02), age (OR for being 10 years older, 3.6; P=.002), and HIV RNA level at month 30 (OR, 0.4; P=.007). No difference was observed in cholesterol and glucose levels as a function of any pattern of antiretroviral exposure. Exposure to stavudine and didanosine was associated with LD syndrome (predominantly lipoatrophy).