Psychiatric and substance use disorders in HIV/hepatitis C virus (HCV)-coinfected patients: does HCV clearance matter? [Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) HEPAVIH CO13 cohort].

OBJECTIVES: The objective of this nested study was to assess the prevalence of psychiatric disorders in a sample of HIV/hepatitis C virus (HCV)-coinfected patients according to their HCV status. METHODS: The nested cross-sectional study, untitled HEPAVIH-Psy survey, was performed in a subset of HIV/HCV-coinfected patients enrolled in the French Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) CO13 HEPAVIH cohort. Psychiatric disorders were screened for using the Mini International Neuropsychiatric Interview (MINI 5.0.0). RESULTS: Among the 286 patients enrolled in the study, 68 (24%) had never received HCV treatment, 87 (30%) were treatment nonresponders, 44 (15%) were currently being treated and 87 (30%) had a sustained virological response (SVR). Of the 286 patients enrolled, 121 patients (42%) screened positive for a psychiatric disorder other than suicidality and alcohol/drug abuse/dependence, 40 (14%) screened positive for alcohol abuse/dependence, 50 (18%) screened positive for drug abuse/dependence, 50 (17.5%) were receiving an antidepressant treatment and 69 (24%) were receiving an anxiolytic. Patients with an SVR did not significantly differ from the other groups in terms of psychiatric disorders. Patients receiving HCV treatment screened positive less often for an anxiety disorder. The highest rate of drug dependence/abuse was among HCV treatment-naïve patients. CONCLUSIONS: Psychiatric disorders were frequent in HIV/HCV-coinfected patients and their rates were comparable between groups, even for patients achieving an SVR. Our results emphasize the need for continuous assessment and care of coinfected patients, even after HCV clearance. Drug addiction remains an obstacle to access to HCV treatment. Despite the recent advent and continued development of directly acting antiviral agents (DAAs), it is still crucial to offer screening and comprehensive care for psychiatric and addictive disorders.

Factors associated with guideline-based hepatitis C virus (HCV) treatment initiation in HIV/HCV-coinfected patients: role of comorbidities and physicians' perceptions.

OBJECTIVES: Many HIV-infected patients with chronic hepatitis C virus (HCV) infection do not receive treatment for HCV infection, often because of contraindications or poor adherence to anti-HIV therapy. The aim of this study was to identify factors influencing guideline-based HCV treatment initiation in a large cohort of HIV/HCV-coinfected patients. METHODS: Between 2005 and 2011, 194 (40.5%) of 479 coinfected patients not previously treated for HCV infection started this treatment based on current recommendations, i.e. a Metavir score >F1 for liver fibrosis; HCV genotype 2 or 3 infection; or HCV genotype 1 or 4 infection and low HCV viral load (<800000 IU/mL), whatever the fibrosis score. Clinical and biological data were compared between patients who started HCV therapy during follow-up and those who did not. RESULTS: In multivariate analyses, good adherence to treatment for HIV infection, as judged by the patient's physician, was associated with HCV treatment initiation [odds ratio (OR) 2.37; 95% confidence interval (CI) 1.17-4.81; P=0.017], whereas patients with children (OR 0.53; 95% CI 0.30-0.91; P=0.022) and those with cardiovascular disease or respiratory distress (OR 0.10; 95% CI 0.01-0.78; P=0.03) were less likely to be treated. CONCLUSIONS: Adherence to treatment for HIV infection, as judged by the patient's physician, appears to have a major influence on the decision to begin treatment for HCV infection in coinfected patients. This calls for specific therapeutic education and adherence support in order to ensure timely anti-HCV therapy in this population.

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.

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.

Comparison of resistance mutation patterns in historical plasma HIV RNA genotypes with those in current proviral HIV DNA genotypes among extensively treated patients with suppressed replication.

OBJECTIVES: Heavily treatment-experienced patients with good virological control could be at risk of virological failure on switching to a new regimen if pre-existing drug resistance is not taken into account. We examined whether genotyping based on cellular HIV-1 DNA during controlled viraemia identifies resistance mutations detected in plasma HIV-1 RNA during treatment with previous antiretroviral regimens. PATIENTS AND METHODS: All 169 patients enrolled in the Agence Nationale de Recherche sur le SIDA (ANRS) 138-intEgrase inhibitor MK_0518 to Avoid Subcutaneous Injections of EnfuviRtide (EASIER) trial had already received three antiretroviral drug classes [nucleoside reverse transcriptase inhibitor (NRTI), nonnucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitor (PI)] and had plasma HIV-1 RNA<400 copies/ml at baseline. The results of previous resistance genotyping of plasma HIV-1 RNA in individual patients were compared with those of resistance genotyping of whole-blood HIV-1 DNA at randomization. RESULTS: A median of 4 plasma RNA genotypes were available for the 169 patients. The median numbers of resistance mutations in HIV-1 RNA and DNA were, respectively, 5 and 4 for NRTIs, 2 and 1 for NNRTIs, and 10 and 8 for PIs. The difference was significant for all three drug classes (P=0.001). Resistance to at least one antiretroviral drug was detected exclusively in HIV-1 RNA or in DNA in 63% and 13% of patients for NRTI, 47% and 1% of patients for NNRTI, and 50% and 7% of patients for PI, respectively. CONCLUSION: This study shows that, among highly treatment-experienced patients on effective highly active antiretroviral therapy, resistance genotyping of HIV-1 DNA detects fewer resistance mutations than previous analyses of HIV-1 RNA. These results have implications for patient management and for the design of switch studies.

Investigation of the significance of Oil Red O-positive macrophage excess in bronchoalveolar lavage fluid during HIV infection.

OBJECTIVE: To assess the significance of increased levels of Oil Red O-positive macrophages (ORO-PM) in bronchoalveolar lavage fluids (BALFs) from HIV-positive patients. METHODS: Cytological data for seventy BALF samples from 66 consecutive HIV-infected patients were analysed according to antiretroviral therapy regimen, presence of Pneumocystis jiroveci infection, blood CD4(+) T cell count, HIV-1 viral load and plasma lipid levels. Non-parametric tests were used to compare the values between groups. RESULTS: The percentages of ORO-PM were high in this group: 40% [6-80] (median [interquartile range]). They were positively correlated with the BALF total cell count, 21% [5-48.5] for <300 cells/mm(3) and 60% [26.5-80] for >300 cells/mm(3) (P<0.01) but inversely correlated with the percentage of BALF lymphocytes, 50% [20-80] for <15% lymphocytes and 11.5% [2-47] for ≥15% lymphocytes (P<0.01). Antiretroviral therapy with or without protease inhibitors, plasma lipid levels, HIV-1 viral load, blood CD4(+) T cell count or presence of a Pneumocystis jiroveci infection were not correlated with the ORO-PM status. CONCLUSION: Significantly increased numbers of ORO-PM were correlated with high total cell counts and low lymphocyte counts in BALF, irrespective of disease activity or treatment. Extended work on a larger series of patients needs to be conducted.

[Hyperreactive malarial splenomegaly: three clinical cases and literature review]. / Splénomégalie palustre hyperimmune : à propos de trois cas cliniques et revue de la littérature.

Hyperreactive malarial splenomegaly (HMS) is the chronic stage of a long-term stimulation of the immune system secondary to plasmodial infections, more frequently in genetically predisposed patients. HMS is a leading cause of large tropical splenomegaly in endemic zones but has been described in immigrants from Africa and in some European expatriates living in endemic countries. Diagnostic criteria include: long-term stay in a endemic zone, often large splenomegaly, high IgM titer, high antiplasmodial antibody titer, regression by at least 40% of splenomegaly six months after curative antimalarial treatment. In tropical settings, B-cell lymphoma and splenic lymphoma are the main differential diagnoses, which may be identified by a clonality analysis. Recent studies suggest that HMS can be treated by a short-term antimalarial therapy as long as the patient resides out of a malarial endemic country.

[Quinquina and man]. / Du quinquina et des hommes.

Many great discoveries have been made by chance but some have been the result of human perseverance and ingenuity. A sterling example of the second case is quinquina that was discovered in Peru and is now produced in Java. Quinquina has gone through centuries without losing its medical efficacy that efficacy allowed the exploration and colonization of Africa and played a key role in the ability to conduct overseas military campaigns. Because of its strategic importance, it was a coveted resource. It led to the discovery of homeopathy and dyes, allowed the development of organic chemistry, and has been used to make alcoholic bitters and soft drinks.

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.

Prevalence of Plasmodium falciparum cytochrome b gene mutations in isolates imported from Africa, and implications for atovaquone resistance.

The atovaquone resistance of malaria parasites correlates with mutations in the cytochrome b gene. We sequenced the Plasmodium falciparum cytochrome b gene of 135 African isolates. Our data showed a high mutation rate (8.9%); however, the risk of emergence spreading of atovaquone-resistant P. falciparum strains could be limited.

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.

[Human babesiosis]. / Babésioses humaines.

Babesia is one of the most ubiquitous and widespread blood parasite in the world based on numbers and distribution of species in animals. The clinical presentation may vary according to the incriminated species. In some states of the USA this kind of infection is endemic; the number of cases reported in Europe is inferior but more life-threatening. A better understanding of parasite specificities such as cycle and pathogenicity allowed to suggest treatment guidelines adapted to the different clinical and microbiological situations.

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.

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.

Treatment of imported malaria in adults: a multicentre study in France.

BACKGROUND: Data about anti-malarial drugs prescription practices in Europe and the safety of imported malaria treatments are scanty. In 1999, a French consensus development conference published guidelines for the prevention and treatment of imported P. falciparum malaria. The impact of these guidelines has not been evaluated. AIM: To investigate the impact of these guidelines on the prescription of anti-malarials, and to evaluate the incidence of acute drug events (ADEs) leading to discontinuation of treatment. DESIGN: Cross-sectional survey. METHODS: Members of the medical staff in 14 French infectious and tropical disease wards completed a standardized form for each patient treated for imported malaria in 2001. A propensity score matching technique was used to estimate the risk of ADEs leading to discontinuation of the regimen. RESULTS: In the 474 patients studied, quinine was the first-line anti-malarial most often prescribed. Only 3% of patients received halofantrine. Mefloquine was associated with a RR of 4.9 (95%CI 3.2-7.4, p < 0.00001) risk of discontinuation of treatment due to ADEs. DISCUSSION: The very limited use of halofantrine indicates that the main practice recommendations of the guidelines have been taken into account. Mefloquine was associated with a substantial risk of discontinuing the treatment because of ADEs. This is a serious limitation for the use of mefloquine in the treatment of out-patients with imported malaria.

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.

Ex vivo and in vitro impairment of CD36 expression and tumor necrosis factor-alpha production in human monocytes in response to Plasmodium falciparum-parasitized erythrocytes.

Severe malaria is associated with the failure of host defenses to control parasite replication, with the excessive secretion of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), and with the sequestration of parasitized erythrocytes (PEs) in the microcirculation of vital organs. The scavenger receptor CD36, known as a major sequestration receptor, has also been identified as an important factor in mediating nonopsonic phagocytosis of PEs by monocytes and macrophages. The specific consequence of this phagocytosis is a decrease in parasite-induced TNF-alpha secretion. We evaluated the variations in CD36 level and in lipopolysaccharide (LPS)-induced TNF-alpha production in monocytes from Plasmodium falciparum-infected patients and in vitro in the presence of PEs. Both the monocytes from infected patients and from in vitro culture showed a decrease of CD36 expression and a reduced production of TNF-alpha induced by LPS. Using incubation assays with no contact between monocytes and PEs, or in the presence of a soluble supernatant obtained from the incubation of monocytes and PEs, this study shows that decreased CD36 expression was posttranscriptional and not directly related to PEs phagocytosis. In addition, these culture models suggest that the reduced capacity of TNF-alpha production occurred in 2 phases. The early phase (24 hr) appeared to be CD36 dependent and the second phase (48 hr) was due to a soluble factor produced by PEs. These observations suggest that the control of the TNF-alpha production in malaria by monocytes was not entirely dependent on the phagocytosis of PEs by CD36 and that soluble factors produced by PEs could play a role in this process.

[The Nadis cohort: 6236 HIV-infected patients followed up in French university hospitals]. / Cohorte Nadis: 6236 patients séropositifs suivis dans des CHU de France.

OBJECTIVE: The Nadis electronic medical patient record allows real time constitution of a database including the clinical, therapeutic, biological, and epidemiological features of HIV-positive patients. METHODS: Data concerning HIV-infected patients followed-up in 6 French University Hospitals was collected. Data quality was assessed on a regular basis in each center. RESULTS: The 6 first University hospitals using Nadis agreed to group their data on March 15, 2004, concerning 6236 patients having consulted at least once in the previous year. Among these, 29% were female patients, 80% were under treatment on March 15, 2004, 9% were off treatment, 29% were co-infected by hepatitis B or C virus, 57% had an undetectable viral load, 15% of the treated patients were in a worrying immunovirological situation, 358 were diagnosed HIV-positive in 2003. 35% of these "new patients" were women, the mode of infection was sexual in 80%, 45% were under treatment on March 15, 04. This recent data allowed us to have an accurate assessment of this population's management in 2004.

Minority resistant HIV-1 variants and the response to first-line NNRTI therapy.

BACKGROUND: The presence of low-frequency HIV-1 variants with mutations making them resistant to non-nucleoside reverse-transcriptase inhibitors (NNRTI) could influence the virological response to first-line NNRTI therapy. OBJECTIVES: This study was designed to describe the proportions and quantities of NRTI and NNRTI-resistant variants in patients with successful first-line NNRTI therapy. STUDY DESIGN: We evaluated the presence of drug-resistance mutations (DRMs) prior to treatment initiation in 131 naive chronically HIV-1-infected patients initiating NNRTI-based first-line therapy. DRMs were detected by ultradeep pyrosequencing (UDPS) on a GS Junior instrument (Roche). RESULTS: The mean HIV RNA concentration was 4.78 ± 0.74 log copies/mL and the mean CD4 cell count was 368 ± 184 CD4 cells/mm(3). Patients were mainly infected with subtype B (68%) and 96% were treated with efavirenz. The sensitivity threshold for each mutation was 0.13-1.05% for 2000 reads. Major NRTI-resistant or NNRTI-resistant mutations were detected in 40 patients (33.6%). The median frequency of major NRTI-resistant mutations was 1.37% [IQR: 0.39-84.1], i.e.: a median of 556 copies/mL [IQR: 123-37,553]. The median frequency of major NNRTI-resistant DRMs was 0.78% [IQR: 0.67-7.06], i.e.: a median of 715 copies/mL [IQR: 391-3452]. The genotypic susceptibility score (GSS) of 9 (7.3%) patients with mutations to given treatment detected by UDPS was 1.5 or 2. CONCLUSIONS: First-line NNRTI-based treatment can produce virological success in naïve HIV-1-infected patients harboring low-frequency DRMs representing <1% of the viral quasispecies. Further studies are needed to determine the clinical cut-off of low-frequency resistant variants associated to virological failure.