CCR6(-) regulatory T cells blunt the restoration of gut Th17 cells along the CCR6-CCL20 axis in treated HIV-1-infected individuals.

The gut CD4(+) T cells, particularly the T helper type 17 (Th17) subset, are not completely restored in most HIV-1-infected individuals despite combined antiretroviral therapy, when initiated at the chronic phase of infection. We show here that the CCR6-CCL20 chemotactic axis is altered, with reduced CCL20 production by small intestine epithelial cells in treated HIV-1-infected individuals. This leads to impaired CCR6(+)CD4(+) T-cell homing, particularly Th17 cells, to the small intestine mucosa. In contrast, the frequency of gut FoxP3(+) T regulatory (Treg) cells, specifically the CCR6(-) subset, was increased. The resulting imbalance in the Th17/CCR6(-) Treg ratio and the associated shift from interleukin (IL)-17 to IL-10 and transforming growth factor-ß (TGF-ß) blunts CCL20 production by enterocytes, perpetuating a negative feedback for the recruitment of CCR6(+)CD4(+) T cells to the small intestine in treated HIV-1-infected individuals.

FDG-PET/CT findings during immune reconstitution in an HIV-1 patient infected with visceral leishmaniasis.

Visceral leishmaniasis can rarely be unmasked by immune reconstitution in human immunodeficiency virus (HIV)-1-infected patients. We report the first case of immune reconstitution associated with leishmaniasis in an HIV patient to be imaged with [(18)F]fluorodeoxyglucose positron emission tomography (FDG/PET), at both baseline and after therapy.

Minority variants associated with resistance to HIV-1 nonnucleoside reverse transcriptase inhibitors during primary infection.

BACKGROUND: Recent data suggest that subjects harbouring low-frequency variants of HIV that are resistant to non-nucleoside reverse-transcriptase inhibitors (NNRTI) could suffer virological failure when treated with NNRTI-based therapy. Rilpivirine, a second-generation NNRTI, will be used in first-line regimen therapy, but the prevalence of minority variants that are resistant to rilpivirine is unknown. OBJECTIVES: We evaluated the presence of low-frequency NNRTI resistance associated mutations (RAMs) in 27 patients with a primary HIV-1 infection. STUDY DESIGN: We performed genotypic resistance test at baseline and used ultradeep pyrosequencing (UDPS) to detect minority RAMs. RESULTS: Bulk genotyping identified NNRTI-resistant RAMs in 3/27 (11%) patients while UDPS identified NNRTI-resistant RAMs in 10/27 (37%) patients. The 11 RAMs not detected by bulk sequencing were A98G (n=2), L100I (n=3), K101E (n=2), V106I (n=3) and E138G (n=1). The prevalence of these minority variants was 0.34-18.26%. The absolute copy numbers of minority resistant variants were 3.21-5.53 log copies/mL. CRF02 harboured more minority resistant variants than subtypes B (P<0.05). Four samples (15%) had a major rilpivirine resistant mutation (E138G, K101E and E138A), 3 of which were detected by UDPS. CONCLUSION: In these primary HIV infected patients, as regards to the detection of RAMs at the cut-off level>15-25% of the virus population, the concordance between bulk genotypic and UDPS was perfect. UDPS detected additional major NNRTI-resistant mutations, including rilpivirine resistant variants. Further studies are needed to assess the impact of these minority variants on treatment efficacy.

Factors associated with a strictly undetectable viral load in HIV-1-infected patients.

OBJECTIVES: The aim of the study was to identify factors associated with a strictly undetectable viral load (VL) using a routine sensitive real-time polymerase chain reaction (RT-PCR) technology. METHODS: From a large prospective cohort, 1392 patients with a VL<50 HIV-1 RNA copies/mL while receiving a three-drug suppressive regimen for at least 1 year were included in a cross-sectional analysis. Patients were classified into three groups and compared by univariate and multivariate analysis: 479 patients with a strictly undetectable VL (group 1; 34%), 617 patients with detectable VL below the threshold of 20 copies/mL (group 2; 44%), and 296 patients with a VL of 20-50 copies/mL (group 3; 12%). RESULTS: Comparing groups 1 and 2, VL zenith<5 log(10) copies/mL [odds ratio (OR) 1.51; 95% confidence interval (CI) 1.15-1.99; P=0.003], current CD4 T-cell count<500 cells/µL (OR 1.44; 95% CI 1.08-1.92; P=0.01), and duration of viral suppression<50 copies/mL longer than 2 years (OR 2.32; 95% CI 1.20-4.54; P=0.01) were associated with undetectable VL. Comparing groups 1 and 3, VL zenith<5 log(10) copies/mL (OR 2.48; 95% CI 1.75-3.50; P<0.001), duration of viral suppression<50 copies/mL longer than 1 year (OR 3.33; 95% CI 1.66-6.66; P=0.0006), and nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens (OR 1.45; 95% CI 1.03-2.04; P=0.03) were associated with undetectable VL. No individual drug effect was found within NNRTI molecules. CONCLUSIONS: Longer duration of viral suppression<50 copies/mL, lower viral load zenith and NNRTI-based regimen were independently associated with a strictly undetectable viral load. This routinely used RT-PCR assay may prove to be a valuable tool in further large-scale studies.

[Penicilliosis in Vietnam: a series of 94 patients]. / La pénicilliose au Vietnam: une série de 94 cas.

PURPOSE: Haiphong is the second city of Vietnam most affected by HIV infection. Penicilliosis represents the third leading cause of opportunistic infection. However, this systemic fungal infection remains poorly knew by practitioners. This study aimed to clarify the clinical, diagnostic and therapeutic aspects of penicilliosis. METHODS: It is a descriptive study, prospective and retrospective, conducted over a 3-year period in Viet Tiep hospital, Haiphong. RESULTS: With 94 cases, penicilliosis represented 11% of opportunistic infections. The patients were young (mean: 33 years) and male (87%). The main symptoms were persistent fever (99%), weight loss (88%), skin lesions (86%), hepatomegaly (69%) and lymphadenopathy (68%). Anemia was noted in 77% of cases. The average CD4 count was 29/µL. The culture of skin biopsies and blood culture were positive for Penicillium marneffei in 94% and 90% of cases, respectively. Despite antiretroviral and antifungal therapy, the mortality rate was 18%. Itraconazole monotherapy, administered in 53 patients due to the unavailability of amphotericin B, did not significantly affect the survival compared to the recommended treatment received by the 41 other patients. CONCLUSION: In Haiphong, penicilliosis is one of the most frequent and severe opportunistic infections of AIDS. The diagnosis should be considered in all febrile and immunocompromised patients having spent time in Vietnam. The prognosis can be improved by early diagnosis through the blood culture and a good adherence to an appropriate antifungal therapy.

[Impact of malaria on HIV infection]. / Impact du paludisme sur l'infection par le VIH.

Malaria and HIV are two major public health issues, especially in sub-Saharan Africa. HIV infection increases the incidence of clinical malaria, inversely correlated with the degree of immunodepression. The effect of malaria on HIV infection is not as well established. Malaria, when fever and parasitemia are high, may be associated with transient increases in HIV viral load. The effect of subclinical malaria on HIV viral load is uncertain. During pregnancy, placental malaria is associated with higher plasma and placental HIV viral loads, independently of the severity of immunodeficiency. However, the clinical impact of these transient increases of HIV viral load remains unknown. Although some data suggests that malaria might enhance sexual and mother-to-child transmissions, no clinical study has confirmed this. Nevertheless pregnant women and children with malaria-induced anemia are also exposed to HIV through blood transfusions. Integrated HIV and malaria control programs in the regions where both infections overlap are necessary.

[Infection due to Mycobacterium malmoense in an immunocompetent patient]. / Infection à Mycobacterium malmoense chez un patient immunocompétent.

INTRODUCTION: Mycobacterium malmoense (MM) is an atypical mycobacterium responsible for opportunistic infection. The clinical and radiological picture is non-specific. The infection develops most frequently in a dystrophic lung. CASE REPORT: A patient of 52 years was admitted with an extensive multifocal pneumonia which later proved to be due to infection with MM. Empirical treatment was started with the combination of rifampicin, isoniazid, pyrazinamide (rifater) and ethambutol (myambutol). Subsequently, cultures showed sensitivity to rifampicin, ethambutol, oxfloxacin, clarithromycin (MIC < 2 mg/l) and rifabutin (MIC < 0.5 mg/l). More than two weeks after the start of treatment, material aspirated at fibroscopy showed the persistence of numerous acid-alcohol fast bacilli, an increase, compared with the original examination, from 5 to 25 per field on day 2, to 20 to 100 per field on day 19. Despite the late addition of clarithromycin there was a progressive deterioration in the pulmonary condition. CONCLUSION: There is little correlation between the in vivo and in vitro sensitivities of MM to antibiotics. In our patient the progress was unfavourable, even though the mycobacterium was sensitive to the combination of antibiotics used, with the exception of isoniazid that was not tested. In vitro isoniazid does not seem to be active against MM. There is no consensus of opinion on the antibiotic treatment of MM infections.

[Evaluation of clinical practice: audit of prophylactic antibiotics in urology]. / Evaluation des pratiques professionnelles: audit portant sur l'antibioprophylaxie en urologie.

OBJECTIVE: To evaluate compliance with clinical practice guidelines concerning prophylactic antibiotics in urological surgery. MATERIAL AND METHODS: Thirty per cent of the medical charts for the first 288 patients operated in 2005 and requiring prophylactic antibiotics were selected at random. On this sample of 84 patients, compliance with the CHU de Toulouse (Toulouse teaching hospital) and société française d'anesthésie et de réanimation (SFAR) (French Society of Anaesthesia and Intensive Care), prophylactic antibiotic guidelines were investigated according to the method recommended by the Centre de coordination de da lutte dontre des infections nosocomiales (CCLIN) Ouest (Nosocomial Infection Control Coordination Centre) which analyses the indication, type of antibiotic, time of administration and duration of treatment. RESULTS: The compliance rate with the indication was 88.1%. When prophylactic antibiotics were effectively administered, compliance with guidelines were 91.9% for type of antibiotic and 72.9% for time of administration. The duration was excessive in one case. The overall compliance rate was 58.3%. CONCLUSION: Prophylactic antibiotic guidelines were inadequately applied, especially concerning the time of administration. Further progress must be made in terms of compliance with guidelines and recording of administration, which must be repeatedly evaluated.

Impact of HIV infection on total body composition in treatment-naive men evaluated by dual-energy X-ray absorptiometry comparison of 90 untreated HIV-infected men to 241 controls.

The aim of this study was to establish the contribution of human immunodeficiency virus (HIV) itself on body composition changes evaluated by dual-energy X-ray absorptiometry (DXA). Body composition evaluated by DXA in 90 HIV never treated men, without comorbidity, or current or past opportunistic infections were compared with 241 healthy volunteers. The mean duration of seropositivity from HIV diagnosis was 41+/-62 mo, mean CD4 and viral load at the time of DXA were 402/mm(3)+/-263 (control values 500-1200/mm(3)) and 4.2 log copies/mL+/-1.3. Mean age (41 vs 39 yr, respectively, for HIV never treated patients and controls) and mean height (174.5 vs 176 cm) were not different, but mean weight was lower among HIV never treated patients (69.8 vs 78.7 kg). Mean total body bone mineral density (BMD) of naive HIV-infected patients was lower than that of controls (1.20 vs 1.23 g/cm(2), p=0.01) but not after adjustment on age, height, lean mass (LM), and fat mass ratio (FMR=% trunk fat mass/% lower limb fat mass). Fat mass (13.2 vs 16.5 kg, p<0.0001) and LM (53.5 vs 59 kg, p<0.0001) of naive HIV-infected patients were lower whatever the adjustment variables. The FMR was lower in naive HIV-infected men (1.0 vs 1.3, p<0.0001) because of a decreased trunk fat mass. After adjustment on age, height, LM, and fat mass, the lower limbs fat mass percentage was higher in HIV-infected men. The profile of naïve HIV-infected patients displayed low lean and fat masses, and a fat mass repartition characterized by a predominant loss in the trunk. Those alterations may result from the catabolic effect of the chronic HIV infection.

[Impact of HIV infection on malaria in adults]. / Impact de l'infection VIH sur l'infection palustre chez l'adulte.

Malaria and HIV are two major public health issues, especially in sub-Saharan Africa. The impact of HIV infection on malaria depends on the patient's immune status: immunodepression level but also immunity against Plasmodium. HIV infection increases the incidence of clinical malaria, inversely correlated with the degree of immunodepression, but the severity and mortality are increased only in areas of unstable malaria. In severe malaria the level of parasitemia is similar in HIV-positive and HIV-negative patients. During pregnancy, HIV infection increases the incidence of clinical malaria, maternal morbidity, and fetal and neonatal morbi-mortality. Sulfa-based therapies reduce the risk of malaria, most importantly in pregnancy. HIV infection increases the risk of treatment failure, mainly with sulfa-based therapies, due to re-infection or parasitic recrudescence. Further studies are needed to determine the pathophysiological interactions between HIV infection and malaria.

Streptococcus milleri group infection associated with digestive fistula in patients with vascular graft: report of seven cases and review.

We described seven patients with Streptococcus milleri group aortic (six patients) or vena cava (one patient) graft infection secondary to a vasculo-digestive fistula. Time between vascular graft setting and first clinical signs varied from eight months to more than thirteen years. Six patients had fever. Three patients presented with recurrent fever for more than nine months and in two of these cases, delay before diagnosis was long because repeated blood cultures were sterile. Three patients had abdominal pain and/or digestive haemorrhage. Abdominal CT-scan S. milleri was not contributive for the diagnosis in four patients. Streptococcus anginosus was isolated in four patients, Streptococcus constellatus in three patients. One patient died before surgical management. The other six patients were cured by a surgical management associated with a prolonged antibiotic (lactams) treatment. S. milleri group graft infections are rare (or misdiagnosed) while we found only 4 similar cases in the English medical literature. We conclude that a peri-prosthetic infection secondary to a digestive fistula must be insistently searched (and blood cultures must be repeated many times) in any patient with an aortic (or any other vascular) graft presenting prolonged or recurrent fever or acute digestive symptoms.

Long-term evolution of CD4 count in patients with a plasma HIV RNA persistently <500 copies/mL during treatment with antiretroviral drugs.

BACKGROUND: The increase in CD4 count may reach a plateau after some duration of virological response to highly active antiretroviral therapy (HAART). METHODS: A total of 1281 HIV-infected patients initiating HAART were enrolled in the AntiPROtease (APROCO) cohort. We investigated determinants of increase in CD4 count using longitudinal mixed models in patients who maintained a plasma HIV RNA <500 HIV-1 RNA copies/mL. RESULTS: A total of 870 patients had a virological response at month 4. The median follow-up time was 57 months. Mean estimated increases in CD4 count in patients with persistent virological response were 29.9 cells/muL/month before month 4, 6.4 cells/microL/month between months 4 and 36, and 0.7 cells/microL/month (not significantly different from 0) after month 36. Three factors were associated with a significantly positive CD4 count slope after month 36: male gender (+0.9), no history of antiretroviral therapy at baseline (+1.7) and baseline CD4 count <100 cells/microL (+2.6). In patients who maintained a virological response after 5 years of HAART, a CD4 count >500 cells/microL was achieved in 83% of those with a baseline CD4 count >or=200 cells/microL and in 45% of those with a baseline CD4 count <200 cells/microL. CONCLUSION: The increase in CD4 count reaches a plateau after 3 years of virological response. Even if patients initiating HAART with low CD4 counts still show a CD4 count increase after 3 years, it remains insufficient to overcome immune deficiency in all patients.

Scedosporium apiospermum mycetoma with bone involvement successfully treated with voriconazole.

Treatment of Scedosporium apiospermum mycetoma usually requires limb amputation. A 49-year-old woman, from Ivory Coast, was diagnosed with Madura foot in 1995. She failed to respond to several treatments including itraconazole, fluconazole and co-trimoxazole, and refused limb amputation. In December 2002 she was admitted to hospital in France with a painful, swollen right leg and foot. She had no fever and C-reactive protein was 120 mg/l. Magnetic resonance imaging (MRI) confirmed the destruction of tarsus bones with a tibia extension. Voriconazole (400 mg/day) treatment was initiated in March 2003; a significant clinical improvement was observed within 4 months as confirmed by C-reactive protein (16 mg/l) and MRI. Voriconazole was maintained for 18 months with good tolerance. Cholestasis appeared after the first month and remained stable. In October 2004 voriconazole was discontinued due to side effects on the liver (alanine aminotransferase 17 times the normal level); MRI showed impressive regression of bone lesions. As of July 2005, the patient remains clinically well. Voriconazole appears to be a promising drug for the treatment of S. apiospermum mycetomas.

Predictive factors of treatment interruption duration in a cohort of HIV-1 infected patients with CD4 count greater than 350 cells per mm3.

OBJECTIVE: To determine predictive factors of treatment interruption (TI) duration within a cohort of HIV-1 infected patients having stopped their treatment with CD4 above 350 cells per mm(3). DESIGN: Data were collected from computerized medical records. Patients were selected if they were HIV-1 positive, 18 years of age or older, and had stopped their treatment between January 1st, 1999 and July 1st, 2003, with CD4 count above 350 cells per mm(3). The study period was censored on October 1st, 2003. Patients were assessed every 3 months from inclusion to censure. A survival analysis using the Cox proportional hazard model was performed. RESULTS: One hundred eighty-five patients were included. The median duration of TI was 43 weeks. Sixty-three patients remained off-treatment at censure. In the multivariate analysis, TI duration was shorter if CD4 nadir was below 250 cells per mm(3) before TI (relative hazard, 2.10), age superior to 40 (relative hazard, 1.72), viral load higher than 2.3 log.copies per ml (relative hazard, 1.52), and CDC class C (relative hazard, 1.78) at TI. Neither CD4 cell count at TI, numbers of treatments, nor duration of treatment and infection before TI were independent predictive factors of early treatment resumption (TR). CONCLUSION: Some clinical and biological data may be used as predictive factors of early TR. Our results can have implications on future therapeutic strategies, in which the goal of therapy is to maintain CD4 cell count above a predetermined threshold using cycles of therapy followed by prolonged interruption according to CD4 count.

Triple nucleoside reverse transcriptase inhibitor- vs. nonnucleoside reverse transcriptase inhibitor-containing regimens as first-line therapy: efficacy and durability in a prospective cohort of French HIV-infected patients.

OBJECTIVE: Based on the short-term results of the AIDS Clinical Trials Group (ACTG) A5095 trial, zidovudine (ZDV)/lamivudine (3TC)/abacavir (ABC) is no longer recommended as a first-line antiretroviral regimen. Data on the efficacy of this triple nucleoside reverse transcriptase inhibitor (NRTI) combination compared with the gold-standard nonnucleoside reverse transcriptase inhibitor (NNRTI) regimen could provide important information. METHODS: Patients were selected from three prospective cohorts of patients who received first-line therapy with ZDV/3TC plus an NNRTI or ABC, started after January 1998. Immunovirological changes and the proportion of treatment discontinuations were compared between groups. RESULTS: Of the 380 patients, 190 started on ABC [the triple-NRTI group (3N)] and 190 on NNRTI. At baseline, there was no statistical difference between the NNRTI and 3N groups for age (mean=38 years), sex (66% male) or CD4 cell count (mean=305 cells/muL). Mean baseline plasma HIV-1 viral load (pVL) was higher in the 3N group (4.6 vs. 4.3 log10 HIV-1 RNA copies/mL: P<0.01). Lower and higher estimates of median pVL decrease at month 24 were 2.05 and 4.76 log10 copies/mL in the 3N group, and 1.73 and 4.31 log10 copies/mL in the NNRTI group (not significant). CD4 cell count evolution did not differ between groups. Treatment discontinuation occurred in 45% vs. 44% of patients in the NNRTI and 3N groups, respectively, after median durations of 9 and 4 months, respectively (P=0.02). CONCLUSIONS: In this prospective cohort, 3N and NNRTI regimens as first-line therapy produced similar immunovirological responses.

Total body composition by DXA of 241 HIV-negative men and 162 HIV-infected men: proposal of reference values for defining lipodystrophy.

The aim of this study was to define standard values for fat mass distribution by dual-energy X-ray absorptiometry in human immunodeficiency virus (HIV)-negative men and to analyze factors associated with lipodystrophy in HIV-infected men. Total-body composition was analyzed in 241 HIV-negative men (controls) and 162 HIV-infected men. We created a fat mass ratio (FMR) as the ratio of the percentage of the trunk fat mass to the percentage of the lower limbs fat mass. We defined the FMR standard values as the mean value+/-standard deviation. We compared body mass index (BMI), fat mass percentage (%FM), lean mass (LM), bone mineral density (BMD), and FMR between the control group and HIV-infected men, by age range, according to prescription of treatment and presence of clinical lipodystrophy. The FMR standard value is equal to 1.3+/-0.2. The FMR was higher in treated HIV-infected men with or without clinical lipodystrophy. The FMR was similar for naïve HIV-infected men and controls. It was positively correlated with age, cumulative time on treatment, zidovudine, stavudine, or indinavir. BMD and fat mass were lower for treated and naïve HIV-infected men than for HIV-negative men. The FMR seems to be a valuable index for measuring fat mass distribution. We defined FMR standard values from the largest group of HIV-negative men to our knowledge. Applying FMR to HIV patients could help physicians to diagnose lipodystrophy earlier.

[Management of occupational and sexual exposure to HIV in the Toulouse teaching hospital]. / Prise en charge des accidents d'exposition au VIH d'origine professionnelle et sexuelle: etat des lieux au centre hospitalo-universitaire de Toulouse.

OBJECTIVE: This study had aim to describe the management of occupational and sexual HIV exposure in the Toulouse teaching hospital. DESIGN: A prospective descriptive study was made of patients reporting with potential HIV exposure in Toulouse between 01/01/2000 and 12/31/2002. RESULTS: Six hundred and ninety three cases were reported, 236 after occupational and, 457 after sexual exposure. The frequency of sexual exposures increased with time. 61.2% of patients received post-exposure treatment and no seroconversion was diagnosed during their follow-up. Eighty-four percent of treated patients received three anti-retroviral drugs, with a protease inhibitor in 57%. Treatment was more frequently prescribed in sexual exposures than in occupational ones. For occupational exposures, the median time between exposure and consultation was 4 h and was decreased by spontaneous bleeding but not affected by source patient serostatus or injury deepness. Treatment was more frequent when injury was deep, when there was spontaneously bleeding, and when the source patient serostatus was positive or unknown. For sexual exposures, the median time between exposure and consultation was significantly superior to 4 h. That was diminished by positive source person serostatus but not affected by the partner's gender, nature of intercourse, or rape. Treatment was more frequently prescribed in case of positive or unknown source person serostatus, rape and homosexual intercourse. CONCLUSIONS: Given the delay before consultation for sexual exposures and out of delay treatment in occupational exposures, discussion with health professionals on implementing procedures and means seems mandatory.