Background. The benefits of continuing antiretroviral therapy are questionable in human immunodeficiency virus (HIV) type 1–infected patients with profound immunodeficiency and multiple treatment ...failure due to viral resistance. Methods. From the French Hospital Database on HIV, we selected 12,765 patients with a CD4+ cell count <200 cells/mm3 who received a combination antiretroviral therapy (cART) during 2000–2005. Three groups of patients were defined: patients who interrupted cART at least once, patients who had at least 2 consecutive detectable viral loads (VLs) while receiving cART, and patients who had undetectable VL during treatment with cART. Incidence rates and risks of new acquired immunodeficiency syndrome-defining events (ADEs) were assessed among the 3 groups of patients, overall and after CD4+ cell count stratification (<50 and 50–200 cells/mm3). Results. The estimated incidence rates ± standard deviation of ADEs were 18.5±1.9, 14.5±0.7, and 4.9±0.5, respectively, for patients who interrupted cART, patients who had detectable VL during treatment with cART, and patients who had undetectable VL during treatment with cART. These differences were observed in both CD4+ cell count strata. Overall, after adjustment, risks of a new ADE in patients who had detectable VL and in patients who had undetectable VL while receiving cART were 22% and 62% lower, respectively, than in patients who stopped cART. Among patients with CD4+ cell count <50 cells/mm3, the risk of a new ADE was 22% lower in patients who continued to receive a failing cART regimen than in patients who stopped treatment with cART. Likewise, among patients with a CD4+ cell count of 50–200 cells/mm3, the risk was 34% lower in patients who continued to receive a failing cART regimen than in those who stopped taking cART. Conclusions. Even when effective virological control is no longer achievable, cART still reduces the risk of ADEs in profoundly immunodeficient HIV-infected patients.
Summary
Background Kaposi's sarcoma (KS) is a potentially life‐threatening multifocal neoplasm. Despite the significant decline in the incidence of acquired immune deficiency syndrome (AIDS)‐related ...KS with the use of highly active antiretroviral therapy (HAART), some patients, even those with a good immune restoration, still have aggressive disease. Liposomal anthracyclines or combination chemotherapy are widely used but adverse effects limit their utilization.
Objectives We studied the efficacy and tolerance of docetaxel in the treatment of AIDS‐related KS after pretreatment with anthracycline.
Patients/methods and main outcome measure A retrospective cohort study was done. Nine human immunodeficiency virus (HIV)‐infected patients were treated from 1997 to 2002 with docetaxel. Tumour response was evaluated using the AIDS Clinical Trial Group (ACTG) staging criteria. Clinical and biological toxicity was evaluated. AIDS status with HIV viral load and CD4 T‐cell count were measured at the beginning and at the end of the treatment.
Results A major (complete or partial) response and a stabilization of the disease were demonstrated in seven and two patients, respectively. Grade 4 neutropenia and thrombocytopenia were observed in four of nine and one of nine patients, respectively. One patient died after sepsis.
Conclusions Docetaxel has a good and rapid efficacy in anthracycline‐pretreated patients with severe AIDS‐related KS. Phase II/III trials should be done to compare docetaxel with liposomal anthracyclines as a first‐line treatment.
Our study describes the prevalence of transmitted drug resistance (TDR) among 1318 French patients diagnosed at the time of primary HIV-1 infection (PHI) in 2007-12.
HIV-1 resistance-associated ...mutations (RAMs) were characterized using both the 2009 WHO list of mutations and the French ANRS algorithm. A genotypic susceptibility score was estimated for each first-line recommended ART combination.
Patients were mainly MSM (72.6%). Non-B variants were identified in 33.7% of patients. The proportion of TDR was estimated as 11.7% (95% CI 10.0-13.5). The prevalences of PI-, NRTI-, first-generation NNRTI and etravirine/rilpivirine-associated RAMs were 2.5%, 5.2%, 3.9% and 3.2%, respectively. Single, dual and triple class resistance was found in 9.6%, 1.0% and 1.1% of cases, respectively. Additionally, 5/331 strains isolated in 2010-12 had integrase inhibitor (II)-related RAMs (isolated E157Q mutation in all cases). TDR was more common among MSM than in other groups (12.9% versus 8.6%, P = 0.034), and in case of B versus non-B subtype infections (13.6% versus 7.9%, P = 0.002). The proportions of fully active combinations were ≥99.2%, ≥97.3% and ≥95.3% in cases of PI-, II- and NNRTI-based regimens, respectively. In 2010-12, the proportion of fully active efavirenz-based ART was lower in cases of subtype B versus non-B infection (P = 0.021).
Compared with our previous studies, the proportion of NRTI- and first-generation NNRTI-related TDR has continued to decline in French seroconverters. However, subtype B-infected MSM could drive the spread of resistant HIV strains. Finally, we suggest preferring PI- or II- to NNRTI-based combinations to treat PHI patients.
The objectives of this study were to determine the prevalence and patterns of resistance to integrase strand transfer inhibitors (INSTIs) in patients experiencing virological failure on ...raltegravir-based ART and the impact on susceptibility to INSTIs (raltegravir, elvitegravir and dolutegravir).
Data were collected from 502 treatment-experienced patients failing a raltegravir-containing regimen in a multicentre study. Reverse transcriptase, protease and integrase were sequenced at failure for each patient. INSTI resistance-associated mutations investigated were those included in the last ANRS genotypic algorithm (v23).
Among the 502 patients, at failure, median baseline HIV-1 RNA (viral load) was 2.9 log10 copies/mL. Patients had been previously exposed to a median of five NRTIs, one NNRTI and three PIs. Seventy-one percent harboured HIV-1 subtype B and the most frequent non-B subtype was CRF02_AG (13.3%). The most frequent mutations observed were N155H/S (19.1%), Q148G/H/K/R (15.4%) and Y143C/G/H/R/S (6.7%). At failure, viruses were considered as fully susceptible to all INSTIs in 61.0% of cases, whilst 38.6% were considered as resistant to raltegravir, 34.9% to elvitegravir and 13.9% to dolutegravir. In the case of resistance to raltegravir, viruses were considered as susceptible to elvitegravir in 11% and to dolutegravir in 64% of cases. High HIV-1 viral load at failure (P < 0.001) and low genotypic sensitivity score of the associated treatment with raltegravir (P < 0.001) were associated with the presence of raltegravir-associated mutations at failure. Q148 mutations were selected more frequently in B subtypes versus non-B subtypes (P = 0.004).
This study shows that a high proportion of viruses remain susceptible to dolutegravir in the case of failure on a raltegravir-containing regimen.
Objectives
To evaluate the impact on peripheral fat tissue of a nucleoside reverse transcriptase inhibitor (NRTI)‐sparing regimen in lipoatrophic HIV‐1 infected patients.
Methods
This 96‐week ...prospective, randomized study compared lipoatrophic patients switched to an NRTI‐sparing regimen with patients remaining on an NRTI‐containing regimen. The primary endpoint was the change in thigh subcutaneous fat tissue volume between baseline and week 48, as assessed by computerized tomography.
Results
One hundred patients were included, 50 in each arm. At baseline, patients had been on highly active antiretroviral therapy (HAART) for a median time of 6.6 years (4.9–9.7); 71% of the patients had received thymidine analogues stavudine (37%), zidovudine (34%). The mean change in fat volume between baseline and week 48 significantly favoured the NRTI‐sparing arm over the NRTI‐maintaining arm in the intent‐to‐treat analysis, with a last‐observation‐carried‐forward approach +34 cm3; 95% confidence interval (CI) 5–63 cm3; P=0.002. This was confirmed in the intent‐to‐treat analysis of available data, with a mean difference of +109 cm3 (95% CI 34–185 cm3) at week 96 (n=53; P=0.001). This corresponded to increases of 12 and 30% in fat volume at weeks 48 and 96, respectively, in the NRTI‐sparing arm.
Conclusions
Switching from an effective NRTI‐containing regimen to an NRTI‐sparing regimen preserves immunovirological status and increases subcutaneous fat volume at weeks 48 and 96.
We report the case of a 25-year-old female patient with intractable complex partial seizures characterized by repetition of certain religious statements and a rather compulsive kissing behavior. ...Presurgical evaluation revealed a right-sided, mesial temporal focus and hippocampal sclerosis on MRI. After selective amygdalohippocampectomy, she has only occasional auras. Her rare and peculiar ictal manifestations are discussed in the context of semiology and pathogenesis. Published with videosequences.
Immune restoration following combination antiretroviral therapy (cART) questions the maintenance of prophylaxis among HIV-infected patients with cryptococcosis.
To describe the long-term outcome ...after the diagnosis of cryptococcosis at the cART era.
Multicentre cohort of patients with a diagnosis of cryptococcosis between 1996 and 2000, follow-up until December 2002. Comparison with a historical cohort (1990-1994) for survival.
Eighty-four French AIDS clinical centres.
Two-hundred and forty HIV-infected adult patients at the cART era and 149 at the pre-cART era experiencing a first episode of culture-confirmed cryptococcosis.
In the cART era, 82/189 patients surviving more than 3 months after initiation of antifungal therapy had their maintenance therapy interrupted with a subsequent median follow-up of 19 months. Their relapse rate per 100 person-years was 0.9 95% confidence interval (CI),0.0-2.0. When considering the whole cART cohort, probability of reaching negative serum cryptococcal antigen was 71% after 48 months of follow-up. A CD4 cell count < 100/microl relative risk (RR), 5.5; 95% CI, 1.3-22.2, antifungal therapy < 3 months over the past 6 months RR, 5.0; 95% CI, 1.1-22.3 and serum cryptococcal antigen titre > or = 1/512 RR, 3.5; 95% CI, 1.1-10.8 were associated with a higher rate of cryptococcosis relapse. The mortality rate per 100 person-years was 15.3 95% CI,12.2-18.4 in the cART era versus 63.8 95% CI,53.0-74.9 in the pre-cART era although early mortality did not differ between the two periods.
Overall survival after cryptococcosis has dramatically improved at the cART era. Immune restoration and low serum cryptococcal antigen titres are associated with lower cryptococcosis relapse rates.
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