A HIV Superinfection Diagnosed in a Patient on Intramuscular Long-acting Combination of Cabotegravir and Rilpivirine.

A case of a male with human immunodeficiency virus with plasma genotyping detecting no resistance and a CRF02_AG subtype had a controlled HIV RNA on antiretroviral therapy since 2010. We introduced intramuscular therapy with cabotegravir and rilpivirine. One month later, his HIV RNA was 1500 copies/mL; genotyping found a subtype B with many mutations.

Screening HIV Patients at Risk for NAFLD Using MRI-PDFF and Transient Elastography: A European Multicenter Prospective Study.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is a growing concern in the aging population with human immunodeficiency virus (HIV). Screening for NAFLD is recommended in patients with metabolic risk factors or unexplained transaminitis. This study aimed to prospectively assess the prevalence and associated factors of liver steatosis and advanced fibrosis (AF) in HIV-monoinfected patients at risk of NAFLD. METHODS: We conducted a multicenter study in HIV-monoinfected patients, nonexcessive drinkers with metabolic syndrome, and/or persistently elevated liver enzymes, and/or clinical lipodystrophy. All participants had magnetic resonance imaging proton density fat fraction (MRI-PDFF), Fibroscan/controlled attenuation parameter (CAP), and cytokine and genetic analysis. RESULTS: From March 2014 to November 2015, we enrolled 442 participants and analyzed 402: male (85%); median age, 55 years (interquartile range [IQR], 50-61 years); body mass index, 27.0 kg/m2 (IQR, 23.6-28.7 kg/m2); metabolic syndrome (67%); and CD4 cell count, 630/mm3 (IQR, 510-832/mm3). Overall 257 of 402 (64%) had NAFLD (MRI-PDFF ≥5%). Among them, 11.3% had a liver stiffness ≥9.6 kPa, suggestive of AF. Multivariable analysis identified 7 factors of steatosis: high CD4-cell count (odds ratio [OR], 4.04; 95% confidence interval [CI], 1.92-8.51), high leptin level (OR, 2.12; 95% CI, 1.14-3.93), non-CC PNPLA3s738409 genetic polymorphism (OR, 1.92; 95% CI, 1.11-3.33), low high-density lipoprotein (OR, 1.83; 95% CI, 1.03-3.27), high triglycerides (OR, 1.48; 95% CI, 1.18-1.84), elevated alanine transaminase (OR, 1.23; 95% CI, 1.16-1.31), and hyper ferritinemia (OR, 1.05; 95% CI, 1.03-1.07). Two factors were associated with AF: high body mass index (OR, 1.23 ; 95% CI, 1.07-1.42 ; P = .005, and elevated aspartate aminotransferase (OR, 1.03; 95% CI, 1.01-1.05; P = .001). Using MRI-PDFF as a reference, CAP (best cutoff, 280 dB/m) had good accuracy (area under the receiver operating characteristic curve = 0.86; 95% CI, 0.82-0.90) for the diagnosis of moderate to severe steatosis. CONCLUSIONS: In a large cohort of HIV-moninfected patients at risk of NAFLD, steatosis is present in two-thirds of cases, and around 10% have AF. The CAP technique is accurate for screening steatosis in this population.

Striking differences in weight gain after cART initiation depending on early or advanced presentation: results from the ANRS CO4 FHDH cohort.

BACKGROUND: Many studies have reported weight gain in ART-naive people living with HIV (PWH) initiating an integrase strand-transfer inhibitor-based regimen. We studied the impact of early or advanced presentation and that of individual drugs in PWH initiating combined ART (cART) between 2012 and 2018. METHODS: From the French Hospital Database HIV cohort, we assessed factors associated with a weight gain  ≥10%, weight change after cART initiation or BMI increase  ≥5 kg/m2 up to 30 months. The analyses were conducted overall, and among PWH with early (primary infection or CD4 >350/mm3 and viral load  <100 000 copies/mL, without AIDS) and advanced presentation (AIDS or CD4 <200/mm3, not during primary infection). RESULTS: At 30 months, 34.5% (95% CI: 33.5-35.6) of the 12 773 PWH had a weight gain ≥10%, with 20.9% (95% CI: 19.6-22.2) among the 5794 with early presentation and 63.1% (95% CI: 60.9-65.3) among the 3106 with advanced presentation. Weight gain was 2.8 kg (95% CI: 2.0-3.7) for those with early presentation and 9.7 kg (95% CI: 8.4-11.1) for those with advanced presentation. Most weight gain occurred in the first 12 months. Underweight and obese PWH were at significantly higher risk of a BMI increase  ≥5 kg/m2 than normal-weight PWH. Results differed within classes and by outcome. Raltegravir and dolutegravir were consistently associated with greater weight gain than the other third agents. Tenofovir alafenamide was also associated with higher weight gain than tenofovir disoproxil or abacavir. CONCLUSIONS: After initiating cART, PWH with early presentation exhibited a small weight gain, whereas it was large among those with advanced presentation. The choice of ART should account for the risk of weight gain, especially for PWH who present with advanced disease and/or are obese.

Ultrasensitive Human Immunodeficiency Virus Type 1 Viral Load as a Marker of Treatment Choice for Simplification Strategies.

Background: Using 3 randomized Protease inhibitor (PI) monotherapy studies: Kalesolo, Dream and Monoi, we performed a pooled-analysis. Our objective was to determine in PI monotherapy and standard tritherapy: 1) distribution of ultrasensitive viral load (USVL) at week 96 (W96); 2) factors associated with virological failure (VF) at W96 and 3) factors associated with USVL<1 copy at W96. Methods: VF was defined as 2 consecutive measurements of Human Immunodeficiency Virus Type 1 RNA viral load>50 copies/mL and analysed in Intention-To-Treat. A logistic model was used to investigate which variables were predictive of a VF and Fisher test to investigate differences in USVL at W96. Results: Among 609 patients, 73% were male with median age of 44.4 years (IQR 39.8-52.1), baseline CD4/CD8 ratio was 0.8 (IQR 0.6-1.10), baseline CD4 was 564.5/mm3 (IQR 422-707) and 59% presented a baseline USVL<1 copy/mL. At W96, the proportion of USVL<1 copy/mL was significantly different between PI monotherapy and standard tritherapy in pooled-analysis (65% versus 74%; p=0.04). Overall, baseline USVL<1copy/mL, tritherapy and to be a female were associated with USVL<1 copy/mL at W96 (p<0.0001, p=0.049 and p=0.006). In PI monotherapy receiving DRV/r was associated with USVL<1 copy/mL at W96 (p=0.003). Factors associated to virological succes at W96 were higher baseline CD4 (p=0.034) and baseline USVL<1 copy/mL (p=0.0005). Conclusion: Pooled-analysis of 3 PI monotherapy trials showed better efficacy of tritherapy in terms of USVL at W96. Furthermore regarding USVL at W96, to receive LPV/r seems to be more deleterious than DRV/r. Baseline USVL impacts VF at W96 more specifically in tritherapy arm. Clinical Trials Registration: NCT00421551, NCT00946595, and NCT00140751.

Utility of HIV-1 DNA genotype in determining antiretroviral resistance in patients with low or undetectable HIV RNA viral loads.

Objectives: To investigate the extent to which drug resistance can be evaluated from proviral HIV-1 DNA genotype compared with RNA genotype at different timepoints. Patients and methods: In HIV-1-infected patients routinely seen at a university hospital, who needed to change their current ART, antiretroviral drug resistance was determined from DNA genotype and was compared with past RNA genotype (group 1) or same-day RNA genotype (group 2). A 'resistance sum' was defined as the sum of agents to which resistance was present and was calculated across NRTI, NNRTI and PI. We defined 'loss of information' as when a lower resistance sum was observed in DNA than in RNA samples. Results: Of the 74 and 26 patients included in groups 1 and 2, respectively, most had a long median duration of known HIV-1 infection (17.4 and 14.2 years) and ART (15.3 years and 13.5 years). For group 1, the median (range) resistance sums between DNA/RNA were 0 (0-6)/1 (0-6) for NRTIs, 0 (0-4)/0 (0-4) for NNRTIs and 0 (0-7)/0 (0-8) for PIs, which were comparable with group 2. Loss of information in DNA was substantial for group 1 (37.8%) and less so for group 2 (11.1%). In multivariable analysis, only longer ART duration was significantly associated with loss of information. Results were similar in patients harbouring resistance to one or more agents. Conclusions: In a real-life setting, genotyping DNA from PBMC has some degree of concordance compared with RNA. Loss of information in DNA would appear to coincide with longer periods of ART.

Week 96 efficacy of lopinavir/ritonavir monotherapy in virologically suppressed patients with HIV: a randomized non-inferiority trial (ANRS 140 DREAM).

Background: Sparing of antiretroviral drug classes could reduce the toxicity and cost of maintenance treatment for HIV infection. Objectives: To evaluate the non-inferiority of efficacy and the safety of lopinavir/ritonavir (r) monotherapy versus a single-tablet regimen of efavirenz, emtricitabine and tenofovir (EFV/FTC/TDF) over 2 years. Methods: Adults on stable ART with plasma HIV-1 RNA viral load <50 copies/mL for the past 12 months and no documented treatment failure were randomized to receive either lopinavir/r or EFV/FTC/TDF for 2 years. The primary endpoint was the proportion of patients without treatment failure at week 96 (viral load <50 copies/mL at week 96, confirmed at week 98), without study treatment discontinuation, a new AIDS-defining illness, or death. Results: In the ITT analysis, the primary endpoint was reached by, respectively, 64% and 71% of patients in the lopinavir/r (n = 98) and EFV/FTC/TDF arms (n = 97), yielding a difference of -6.8% (lower limit of the 95% two-sided CI: -19.9%). Sanger and UltraDeep sequencing showed the occurrence of PI mutations in the lopinavir/r arm (n = 4) and of NNRTI and/or NRTI mutations in the EFV/FTC/TDF arm (n = 2). No unexpected serious clinical events occurred. Conclusions: Lopinavir/r monotherapy cannot be considered non-inferior to EFV/FTC/TDF. PI resistance rarely emerged in the lopinavir/r arm and did not undermine future PI options. Two years of lopinavir/r monotherapy had no deleterious clinical impact when compared with EFV/FTC/TDF.

Less-drug regimen including atazanavir in maintenance treatment of HIV infection: how, who, when, why?

For many patients living with HIV-1, the efficacy of combined ART (cART) has made the infection turn to a chronic disease. Because cART is associated with a risk of long-term toxicity, switching patients with virological success to another therapy remains a major issue. Studies undertaken and published over recent years have shown that switching patients exhibiting virological suppression to less-drug regimens (LDR) is a possible option of maintenance strategy. The use of ritonavir-boosted PIs (PI/r) as the backbone of LDR-based maintenance therapy is consistent with their virological potency and a high genetic barrier of resistance. Atazanavir is the most documented PI/r regarding maintenance in dual therapy, with favourable results in terms of virological suppression, tolerance improvement and absence of emergence of mutations. Furthermore, atazanavir is the only commonly prescribed PI that can be used after withdrawal of ritonavir, with maintenance of virological suppression whatever the backbone of associated NRTIs. Based on clinical studies, and taking into account the characteristics of the patients included, one may consider that for any patient with a virological suppression on cART for at least 12 months, with the nadir CD4 >100 cells/mm3 and an absence of encephalitis, an LDR-based maintenance therapy including atazanavir can be considered. Cumulative genotypes must be available to make sure that the LDR will not jeopardize future therapeutic options. The final decision regarding the most appropriate LDR must be guided by the objectives shared by the physician and his/her patient.

Increased prevalence and severity of radiographic hand osteoarthritis in patients with HIV-1 infection associated with metabolic syndrome: data from the cross-sectional METAFIB-OA study.

OBJECTIVE: To determine radiographic hand osteoarthritis (HOA) prevalence in patients with HIV-1 infection in comparison with the general population and to address whether metabolic syndrome (MetS) may increase the risk of HOA during HIV-1 infection. PATIENTS: Patients with HIV-1 infection and MetS (International Diabetes Federation, IDF criteria) aged 45-65 years were matched by age and gender to HIV-1-infected subjects without MetS and underwent hand radiographs. Framingham OA cohort was used as general population cohort. METHODS: Radiographic HOA was defined as Kellgren-Lawrence (KL) score ≥2 on more than one joint. Radiographic severity was assessed by global KL score and number of OA joints. HOA prevalence was compared with that found in the Framingham study, stratified by age and sex. Logistic and linear regression models were used to determine the risk factors of HOA in patients with HIV-1 infection. RESULTS: 301 patients (88% male, mean age 53.4±5.0 years) were included, 152 with MetS and 149 without it. Overall, HOA prevalence was 55.5% and was higher for those with MetS than those without it (64.5% vs 46.3%, p=0.002). When considering men within each age group, HOA frequency was greater in patients with HIV-1 infection than the general population (all ages: 55.8% vs 38.7%; p<0.0001), due to the subgroup with MetS (64.9%; p<0.0001), as well as the subgroup without MetS, although not significant (46.6%; p=0.09). Risk of HOA was increased with MetS (OR 2.23, 95% 95% CI 1.26% to 3.96%) and age (OR 1.18, 95% CI 1.12 to 1.25). HOA severity was greater for patients with MetS than those without. HOA was not associated with previous or current exposure to protease inhibitors or HIV infection-related markers. CONCLUSIONS: HOA frequency is greater in patients with HIV-1 infection, especially those with MetS, than the general population. TRIAL REGISTRATION NUMBER: NCT02353767.

Clostridium difficile associated reactive arthritis: Case report and literature review.

INTRODUCTION: Extra-gastro-intestinal tract manifestations associated with Clostridium difficile infection (CDI), including reactive arthritis (ReA), are uncommon. METHOD: We report a case of ReA associated with a relapse of CDI in a 46-year-old woman. A toxigenic C. difficile strain was isolated from stools and characterized as PCR-ribotype 014/020/077. We conducted a comprehensive literature review of ReA associated with CDI (ReA-CDI). Diagnostic criteria for ReA-CDI were: (i) evidence of aseptic synovitis (confirmed by culture) developing during or immediately after colitis, (ii) presence of a toxigenic C. difficile strain in stool samples, and (iii) absence of other causes of colitis and arthritis. RESULTS: Forty-nine cases of ReA-CDI (excluding the present report) have already been described since 1976. Of these reports, Mean age of patients was 38 years (SD: 18.5), 46% were male, and 68% had HLA B27 genotype. Sixty-nine percent of patients received a ß-lactamin treatment before CDI. ReA-CDI occurred a median 10 days (range 0-55 days) after CDI. Outcome was favorable in 90% of patients and oral non anti-inflammatory drugs were required for 55%. CONCLUSION: ReA-CDI remains uncommon. Compared to the general population, it is more likely observed in younger patients with HLA B27-positive genotype.

Convalescent Plasma Therapy in Immunocompromised Patients Infected With the BA.1 or BA.2 Omicron SARS-CoV-2.

The emergence of SARS-CoV-2 Omicron variant has led to a complete reconfiguration of the therapeutic landscape, with all monoclonal antibodies having lost any neutralization activity. We report here a case series of 75 immunocompromised patients infected by the Omicron variant who benefited from COVID-19 convalescent plasma (CCP). At Day 28, the overall survival was 76% (95% CI 67-86) with no significant difference in the clinical outcome between patients with hematological malignancies, solid organ transplantation or autoimmune diseases. No safety concern was reported during the course of the study. These results showed that CCP is well tolerated and represents a treatment option for immunocompromised patients who remain highly impacted by the COVID19 epidemic.

Human metapneumovirus infection is associated with a substantial morbidity and mortality burden in adult inpatients.

Background: Human metapneumovirus (hMPV) is one of the leading respiratory viruses. This prospective observational study aimed to describe the clinical features and the outcomes of hMPV-associated lower respiratory tract infections in adult inpatients. Methods: Consecutive adult patients admitted to one of the 31 participating centers with an acute lower respiratory tract infection and a respiratory multiplex PCR positive for hMPV were included. A primary composite end point of complicated course (hospital death and/or the need for invasive mechanical ventilation) was used. Results: Between March 2018 and May 2019, 208 patients were included. The median age was 74 [62-84] years. Ninety-seven (47 %) patients were men, 187 (90 %) had at least one coexisting illness, and 67 (31 %) were immunocompromised. Median time between first symptoms and hospital admission was 3 [2-7] days. The two most frequent symptoms were dyspnea (86 %) and cough (85 %). The three most frequent clinical diagnoses were pneumonia (42 %), acute bronchitis (20 %) and acute exacerbation of chronic obstructive pulmonary disease (16 %). Among the 52 (25 %) patients who had a lung CT-scan, the most frequent abnormality was ground glass opacity (41 %). While over four-fifths of patients (81 %) received empirical antibiotic therapy, a bacterial coinfection was diagnosed in 61 (29 %) patients. Mixed flora (16 %) and enterobacteria (5 %) were the predominant documentations. The composite criterion of complicated course was assessable in 202 (97 %) patients, and present in 37 (18 %) of them. In the subpopulation of pneumonia patients (42 %), we observed a more complicated course in those with a bacterial coinfection (8/24, 33 %) as compared to those without (5/60, 8 %) (p = 0.02). Sixty (29 %) patients were admitted to the intensive care unit. Among them, 23 (38 %) patients required invasive mechanical ventilation. In multivariable analysis, tachycardia and alteration of consciousness were identified as risk factors for complicated course. Conclusion: hMPV-associated lower respiratory tract infections in adult inpatients mostly involved elderly people with pre-existing conditions. Bacterial coinfection was present in nearly 30 % of the patients. The need for mechanical ventilation and/or the hospital death were observed in almost 20 % of the patients.

[Focus on pre-exposure prophylaxis]. / Zoom sur la prophylaxie préexposition.

Pre-exposure prophylaxis currently has no market authorisation in France, but is still evaluated. This article presents an additional tool for risk reduction, currently the subject of studies.

Convalescent plasma improves overall survival in patients with B-cell lymphoid malignancy and COVID-19: a longitudinal cohort and propensity score analysis.

Patients with hematological malignancy and COVID-19 display a high mortality rate. In such patients, immunosuppression due to underlying disease and previous specific treatments impair humoral response, limiting viral clearance. Thus, COVID-19 convalescent plasma (CCP) therapy appears as a promising approach through the transfer of neutralizing antibodies specific to SARS-CoV-2. We report the effect of CCP in a cohort of 112 patients with hematological malignancy and COVID-19 and a propensity score analysis on subgroups of patients with B-cell lymphoid disease treated (n = 81) or not (n = 120) with CCP between May 1, 2020 and April 1, 2021. The overall survival of the whole cohort was 65% (95% CI = 56-74.9) and 77.5% (95% CI = 68.5-87.7) for patients with B-cell neoplasm. Prior anti-CD20 monoclonal antibody therapy was associated with better overall survival, whereas age, high blood pressure, and COVID-19 severity were associated with a poor outcome. After an inverse probability of treatment weighting approach, we observed in anti-CD20-exposed patients with B-cell lymphoid disease a decreased mortality of 63% (95% CI = 31-80) in the CCP-treated group compared to the CCP-untreated subgroup, confirmed in the other sensitivity analyses. Convalescent plasma may be beneficial in COVID-19 patients with B-cell neoplasm who are unable to mount a humoral immune response.

Cellular CD4 T cell responses to the diphtheria-derived carrier protein of conjugated pneumococcal vaccine and antibody response to pneumococcal vaccination in HIV-infected adults.

BACKGROUND: The French National Agency for AIDS and Viral Hepatitis Research (ANRS) 114 Pneumovac trial showed that a strategy combining a 7-valent pneumococcal conjugate vaccine (PCV) prime at week 0 followed by a 23-valent pneumococcal polysaccharide vaccine (PPV) boost at week 4 enhances the frequency and magnitude of immunoglobulin (Ig) G responses against Streptococcus pneumoniae polysaccharides (SPPs) compared with PPV alone. CD4 T cell responses specific to the diphtheria-derived carrier protein CRM(197) were evaluated. METHODS: Lymphocyte proliferative responses (LPRs) and T(H)1 cytokine T cell responses against the diphtheria-derived carrier protein CRM(197) contained in the PCV were investigated at weeks 0, 4, and 24. RESULTS: In the prime-boost PCV and PPV group, the magnitude of LPRs to diphtheria toxoid and CRM(197) increased at week 4 (P < .001) and persisted until week 24 (P = .08 and .13, respectively, compared with week 4). Interferon-gamma and interleukin-2 production to CRM(197) increased significantly at week 4 (P = .02 and P < .001, respectively) and remained stable until week 24 (P = .28 and P = .08, respectively). No changes were detected in the PPV group. A strong association among the magnitude of LPRs to CRM(197) at week 4, the breadth of SPP specific IgG responses at week 8 (P = .03), and sustained IgG responses at week 24 was observed. A high frequency of helper follicular CD4(+)CXCR5(+) T cells at baseline was associated with a better LPR response to CRM(197.) CONCLUSIONS: The PCV prime-elicited memory T cell responses were associated with better and sustained humoral SPP specific IgG responses. ClinicalTrials.gov identifier. NCT00148824.

Low frequency of intermittent HIV-1 semen excretion in patients treated with darunavir-ritonavir at 600/100 milligrams twice a day plus two nucleoside reverse transcriptase inhibitors or monotherapy.

HIV-1 RNA level and darunavir concentration in the genital tract were measured in 45 men receiving darunavir-ritonavir mono- or tritherapy. At week 48, a low frequency (3/45) of HIV-1 RNA shedding was observed in patients (1 on monotherapy and 2 on triple therapy), although they had undetectable HIV-1 RNA in plasma. The median darunavir seminal plasma concentration was close to the blood plasma free fraction, demonstrating a good penetration of darunavir into the male genital tract.

Impact of reduced dosing of lopinavir/ritonavir in virologically controlled HIV-infected patients: the Kaledose trial.

BACKGROUND: It is debated whether a risk of protease inhibitor mutation selection in proviral DNA exists during intermittent HIV-1 viraemia thereby impacting long-term virological control. METHODS: Virologically controlled patients treated with lopinavir/ritonavir were included in a 48 week pilot trial during which lopinavir/ritonavir dosage was reduced if lopinavir concentration was >5000 ng/mL at inclusion. Serum lipids were longitudinally assessed and proviral DNA was quantified and sequenced in patients experiencing transient viraemia. RESULTS: Thirty-three virologically suppressed patients while on a lopinavir/ritonavir-containing regimen were included, of whom 28 [20 males, mean age 44.6 years (SD 10.9)] completed the 48 week follow-up as scheduled. A significant decrease in lopinavir level was noted [mean C(min), 7363 ng/mL (min, 5118; max, 12 415) at baseline versus 4319 ng/mL (min, 1427; max, 8683) at week 48, P < 0.03]. A significant decrease in triglycerides was also observed [1.73 mmol/L (SD 1.08) at baseline versus 1.34 mmol/L (SD 0.91) at week 48, P = 0.03], whereas no significant change occurred for total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol. In the 15 patients with transient viraemia, analysis of proviral DNA for antiretroviral resistance showed that mutations had occurred when compared with baseline genotypes in three patients: I47M (n = 2) and M46I (n = 1). Selection of these mutations was not associated with virological failure as all three patients had a sustained virological response without treatment modification after a 3 year follow-up. CONCLUSIONS: This pilot study evaluating the biochemical and virological impact of a reduced dosing of lopinavir/ritonavir suggests that lower exposure to lopinavir/ritonavir could be associated with a significant decrease in triglycerides during treatment, without occurrence of resistance mutations that might impact the virological response to treatment.

Lopinavir/ritonavir monotherapy versus current treatment continuation for maintenance therapy of HIV-1 infection: the KALESOLO trial.

OBJECTIVES: We evaluated a monotherapy maintenance regimen with lopinavir/ritonavir versus continuing current combined antiretroviral treatment (cART) in HIV patients with suppressed plasma HIV-1 RNA. PATIENTS AND METHODS: This was an open-label, non-inferiority, multicentre trial in 23 sites in France. Adults were randomized if they had no history of virological failure while receiving a protease inhibitor, maintained HIV-1 RNA <50 copies/mL for at least 6 months and did not change cART during the last 3 months. The primary endpoint was the proportion of patients with HIV-1 RNA <50 copies/mL at Week 48 (non-inferiority margin set at -12%) with missing data and treatment modification considered as failure. The trial has been registered in ClinicalTrials.gov under the identifier NCT00140751. RESULTS: At Week 48, 84% (73/87) of patients in the lopinavir/ritonavir monotherapy group met the primary endpoint compared with 88% (87/99) in the cART group [difference, -4.0%, lower limit of 90% two-sided confidence interval (CI) for difference, -12.4%]. In secondary analysis with success defined as plasma HIV-1 RNA <400 copies/mL, 87% (76/87) of patients in the lopinavir/ritonavir monotherapy group were virologically suppressed compared with 88% (87/99) in the cART group (difference, -0.5%, lower limit of 90% two-sided CI for difference, -8.5%). If antiretroviral treatment intensification was taken into account, 91% (79/87) of patients in the lopinavir/ritonavir monotherapy group met the primary endpoint compared with 88% (87/99) in the cART group (difference, +2.9%, lower limit of 90% two-sided CI for difference, -4.5%). Failures of lopinavir/ritonavir monotherapy did not show acquired resistance mutations in the protease gene. CONCLUSIONS: Lopinavir/ritonavir monotherapy did not achieve non-inferiority versus cART for maintaining plasma HIV-1 RNA <50 copies/mL. Nevertheless, the incidence of virological failure was low (mostly with HIV-1 RNA <400 copies/mL) and easily managed by treatment intensification.

Switch from enfuvirtide to raltegravir in virologically suppressed multidrug-resistant HIV-1-infected patients: a randomized open-label trial.

BACKGROUND: Among patients with multidrug-resistant human immunodeficiency virus type 1 (HIV-1) infection, salvage regimens including enfuvirtide have demonstrated sustained efficacy. Because of reluctance to use subcutaneous injections, raltegravir may be an alternative to replace enfuvirtide within a suppressive regimen. We conducted a prospective, randomized, open-label trial to compare the antiviral efficacy and safety of a switch to raltegravir with the efficacy and safety of continuing enfuvirtide. METHODS: A total of 170 patients with multidrug-resistant HIV-1 infection and plasma HIV-1 RNA levels <400 copies/mL who were receiving enfuvirtide-based regimens were randomized 1:1 to maintain enfuvirtide or to switch to raltegravir. The primary efficacy end point was the cumulative proportion of patients with virologic failure, defined as a confirmed plasma HIV-1 RNA level >or=400 copies/mL, over 24 weeks. The secondary end points mainly involved safety. RESULTS: The switch to raltegravir was non-inferior to the maintenance of enfuvirtide, with virologic failure rates of 1.2% in both treatment arms in the intention-to-treat analysis (beta = 0.01%; 95% confidence interval, -6.7 to 6.8) and 1.2% and 0%, respectively, in the on-treatment analysis (beta = 1.22%; 95% confidence interval, -5.6 to 8.1). At week 24, 88%-89% of patients in both arms had plasma HIV-1 RNA levels <50 copies/mL. No significant CD4 cell count changes occurred in either arm. Grade 3-4 adverse events and laboratory abnormalities were uncommon and were not different between the treatment arms. CONCLUSION: A switch to raltegravir was safe, well tolerated, and virologically non-inferior to the maintenance of enfuvirtide in patients infected with multidrug-resistant HIV-1 infection who were receiving suppressive antiretroviral therapy. CLINICAL TRIALS REGISTRATION: NCT00454337

Influence of liver fibrosis stage on plasma levels of efavirenz in HIV-infected patients with chronic hepatitis B or C.

OBJECTIVES: Liver function is a key component of efavirenz metabolism and might be altered in severe liver fibrosis induced by HIV/chronic hepatitis co-infection. However, data evaluating the impact of liver fibrosis stages on the plasma efavirenz level are lacking. PATIENTS AND METHODS: In this study, conducted in 134 HIV-infected patients [77, 35 and 22 HIV mono-infected, HIV/hepatitis C virus (HCV) co-infected and HIV/hepatitis B virus (HBV) co-infected, respectively] treated with efavirenz 600 mg once a day in combination with other antiretroviral agents, plasma concentration was measured at least 8 h after the last drug intake using a validated HPLC method. The degree of liver fibrosis was determined by means of either liver biopsy or non-invasive biochemical markers (Fibrotest. The proportions of patients above a threshold of 4000 ng/mL were compared by means of Pearson's chi(2) test or Fisher's exact test. RESULTS: In HIV mono-infected and HIV/HCV and HIV/HBV co-infected patients, mean +/- SD efavirenz plasma concentrations were 3060 +/- 1928, 4108 +/- 3324 and 3163 +/- 2432 ng/mL, respectively. The proportion of patients with an efavirenz concentration above 4000 ng/mL differed significantly according to the presence of hepatitis and the fibrosis stage. A concentration above 4000 ng/mL was found in 14 patients (18.2%) mono-infected with HIV compared with 5 (22.7%, P = 0.01) and 9 (25.7%, P = 0.001) HIV/HBV or HIV/HCV co-infected patients, respectively. When the fibrosis stage was considered in all patients with hepatitis, 3 cirrhotic patients (42.6%) had an efavirenz concentration above the 4000 ng/mL threshold [compared with 14 (18.2%) HIV mono-infected patients, P = 0.001]. CONCLUSIONS: Therapeutic drug monitoring may be of interest in cirrhotic patients more at risk of side effects due to efavirenz overdosing.