Poly-l-lactic acid for HIV-1 facial lipoatrophy: 48-week follow-up

Objectives

Poly‐l ‐lactic acid (PLA) injections modestly increase objectively assessed facial thickness but not facial soft tissue volume (FSTV) over 24 weeks. The durability of this response has not been well defined objectively.

Methods

HIV‐infected lipoatrophic adults were randomized to four open‐label PLA treatments administered every 2 weeks from week 0 (immediate group, n=50) or from week 24 (deferred group, n=50). Endpoints included FSTV assessed by computed tomography, facial lipoatrophy severity, quality of life (QoL) and safety. Analyses were by intention to treat.

Results

Between weeks 24 and 48, soft tissue thickness increased modestly in injection planes, at the maxillary [mean 0.9 mm; 95% confidence interval (CI) 0.3–1.5 mm; P=0.007] and base of nasal septum levels (mean 0.4 mm; 95% CI 0.1–0.8; P=0.021), but not in untreated areas (P=0.79 and P=0.24). PLA durability assessed at week 48 in immediate group participants showed a mean change in FSTV of 14 cm³ (95% CI?1 to 29 cm³; P=0.060) and increased tissue depth at the maxillary (P<0.0001), base of nasal septum (P<0.0001) and mandibular (P=0.0035) levels. At week 48, clinicians and patients subjectively assessed facial lipoatrophy severity as reduced in immediate participants (83 and 91%, respectively), and the Mental Health scale score of the Short Form‐36 Health Survey improved significantly in immediate participants relative to deferred participants (P=0.027). Subcutaneous injection‐site nodule incidence at 48 weeks was 10%.

Conclusions

PLA treatment benefits were durable, with objectively assessed modest increases in facial volume and tissue thickness sustained over 48 weeks in injection planes but not in other facial areas. Improvements in some QoL domains were maintained.

     

Hyaluronic acid treatment of facial fat atrophy in HIV-positive patients

OBJECTIVES: Facial lipoatrophy can be devastating for HIV-infected patients, with negative effects on self-esteem. In this study, we treated facial fat atrophy in the nasogenian area with hyaluronic acid (Restylane SubQ; Q-Med AB, Uppsala, Sweden). METHODS: Twenty patients were included in the study. Treatment effects were evaluated at baseline, and at weeks 6, 24 and 52 using ultrasound, the Global Aesthetic Improvement Scale, the Visual Analogue Scale and the Rosenberg Self-Esteem Scale. RESULTS: Mean (+/-standard deviation) total cutaneous thickness increased from 6+/-1 mm at baseline to 15+/-3 mm at week 6 (P<0.001), and declined to 10+/-2 mm at week 52 (P<0.001 vs baseline). The response rate (total cutaneous thickness >10 mm) was 100% at week 6, 85% at week 24 and 60% at week 52. At week 6, all of the patients classified their facial appearance as very much improved or moderately improved. They also reported increased satisfaction with their facial appearance and had higher self-esteem scores. At week 52, 15 of 19 patients still classified their facial appearance as very much improved or moderately improved, although the mean total cutaneous thickness had gradually declined. CONCLUSIONS: Our results indicate that Restylane SubQ is a useful and well-tolerated dermal filler for treating HIV-positive patients with facial lipoatrophy.     

Long-term safety and efficacy of poly-L-lactic acid in the treatment of HIV-related facial lipoatrophy

OBJECTIVE: We evaluated the long-term safety and efficacy of injectable poly-L-lactic acid (PLLA) for the correction of facial lipoatrophy. METHODS: This was a randomized, open-label, comparative, single-centre study of injected PLLA in patients with HIV-related facial lipoatrophy. Thirty subjects were randomized to immediate or delayed PLLA treatments, administered as three sets of bilateral injections, 2 weeks apart, into the deep dermis above the buccal fat pad. Week 24 results have been published previously (Moyle et al, HIV Medicine 2004, Vol. 5, pp. 82-87). Long-term efficacy was assessed at a recall visit using visual analogue scales (VASs) to record patient satisfaction, and by the Hospital Anxiety and Depression Scale (HADS). Patients also reported any adverse events (AEs) during the treatment period and at the recall visit. RESULTS: Twenty-seven patients returned for the recall visit, a minimum of 18 months post final study treatment. Fourteen of these patients were excluded from the recall visit because of additional treatment with PLLA. Improvements in VAS scores for facial appearance were sustained from baseline to the recall visit in both randomization groups (P<0.05 and P<0.001). Trends in improvement in HADS scores were also noted, with patients in the delayed group experiencing significant improvements in depressive symptoms (P<0.05). One case of injection-site induration and nine cases of injection-site nodules were noted at the recall visit, none of which was described as serious or severe. CONCLUSIONS: Physical and psychological benefits of PLLA are sustained over at least 18 months. Delayed AEs include mild nodularity at the treatment site.     

Laser scanning as a tool for assessment of HIV-related facial lipoatrophy: evaluation of accuracy and reproducibility

BACKGROUND: Facial lipoatrophy (LA) is a common complication of highly active antiretroviral therapy (HAART). Research into causes and treatment of facial LA is hindered by the lack of an objective measurement tool. OBJECTIVE: To evaluate the accuracy and reproducibility of three-dimensional laser scanning (LS) for estimating cheek volume changes. METHODS: Paired laser scans were performed and the images superimposed using commercial software. The volume difference between images was computed within a circle of radius 25 mm placed in a standardized position over the cheek area. Accuracy was tested by scanning before and after known volumes of plasticine (0.5--5 mL) were applied to the cheek area of a mannequin to simulate volume change. Reproducibility was tested by repeated scanning of the mannequin with and without 2 mL of plasticine, and repeated scanning of 10 healthy subjects over the course of 1 week. RESULTS: The mean difference between actual and estimated volume change was small across the range of volumes tested [mean difference 0.08 mL; 95% confidence interval (CI)-0.36 to 0.20 mL). The coefficient of variation for repeated measurements of 2-mL volume change was 5.8%. The intraclass correlation coefficient for scan-to-scan variability was 0.812 (95% CI 0.515--0.947) and for day-to-day variability it was 0.764 (95% CI 0.332--0.935). Conclusions LS is an accurate and reproducible method for estimating cheek volume changes. It may be useful as an objective tool for assessment of facial LA in clinical research studies.     

‘Active chronic visceral leishmaniasis’ in HIV‐1‐infected patients demonstrated by biological and clinical long‐term follow‐up of 10 patients

Objectives

The aim of the study was to describe a new evolutionary form of visceral leishmaniasis observed in immunocompromised patients.

Methods

We carried out long‐term clinical and biological follow‐up of 10 HIV‐1/Leishmania‐coinfected patients presenting numerous secondary visceral leishmaniasis episodes despite treatment, with the follow‐up time ranging from 0.5 to 10 years.

Results

Analysis of polymerase chain reaction (PCR) and blood culture results demonstrated continuous multiplication and circulation of parasites despite treatment, both during asymptomatic periods and during secondary visceral leishmaniasis episodes. This condition may be termed ‘chronic’ because of the presence of relapses over a period of several years and ‘active’ because of the continuous blood circulation of the parasite.

Conclusion

We wish to define ‘active chronic visceral leishmaniasis’ as a novel nosological entity observed in HIV‐1/Leishmania‐coinfected patients.     

Long‐term follow‐up of 11 protease inhibitor (PI)‐naïve and PI‐treated HIV‐infected patients harbouring virus with insertions in the HIV‐1 protease gene

Objectives

Amino acid insertions in the protease gene have been reported rarely, and mainly in patients receiving protease inhibitors (PIs). The aim of the study was to assess the long‐term viro‐immunological follow‐up of HIV‐infected patients harbouring virus with protease insertions.

Methods

Cases of virus exhibiting protease insertions were identified in routine resistance genotyping tests. Therapeutic, immunological and virological data were retrospectively collected.

Results

Eleven patients harbouring virus with a protease gene insertion were detected (prevalence 0.24%), including three PI‐naïve patients. The insertions were mainly located between codons 33 and 39 and associated with surrounding mutations (M36I/L and R41K). The three PI‐naïve patients were infected with an HIV‐1 non‐B subtype. Follow‐up of these PI‐naïve patients showed that the insert‐containing virus persisted for several years, was archived in HIV DNA, and displayed a reduced viral replicative capacity with no impact on resistance level. Of the eight PI‐experienced patients, 63% were infected with HIV‐1 subtype B; one had been antiretroviral‐free for 5 years and seven were heavily PI‐experienced (median duration of follow‐up 24 months; range 10–62 months). The protease insertion was selected under lopinavir in four patients and under darunavir in one, in the context of major PI‐resistance mutations, and following long‐term exposure to PIs. The insert‐containing virus persisted for a median of 32 months (range 12–62 months) and displayed no specific impact on phenotypic resistance level or viral replicative capacity.

Conclusion

Our data, obtained during long‐term follow‐up, show that insertions in the protease gene do not seem to have an impact on resistance level. This finding supports the recommendation of PI‐based regimens, although further work is required to confirm it.     

Increased risk of parkinsonism among patients with cirrhosis: a 7‐year follow‐up study

Background/Aims: Previous studies have suggested that hepatic (toxic‐metabolic) encephalopathy, the major complication of cirrhosis, is a neuropsychiatric disorder typically seen in patients with liver dysfunction after exclusion of other known brain disease. This study aims to investigate the risk for parkinsonism during a 7‐year follow‐up period after a diagnosis of cirrhosis. Methods: In total, 1361 patients with cirrhosis and 6805 comparison patients without cirrhosis were included in this study. Each patient was then individually tracked for 7 years from the time of their initial diagnosis of cirrhosis to identify those who developed parkinsonism during the follow‐up period. Stratified Cox proportional hazard regressions were conducted to calculate the hazard of parkinsonism for the two groups during the follow‐up period, after adjusting for patient's age, monthly income, level of urbanization and geographic location. Results: Of the total 8166 sampled patients, 141 (1.7%) developed parkinsonism during the follow‐up period, 48 from the study group (3.5% of the patients with cirrhosis) and 93 from the comparison group (1.4% of patients in the comparison group). Stratified Cox proportional hazard regressions show that the hazard for parkinsonism for patients with cirrhosis was 2.65 times as high (95% confidence interval=1.85–3.80, P<0.001) as the patients in the comparison group over the 7‐year follow‐up period, after adjusting for patient's age, monthly income, level of urbanization and the geographic location of the community in which the patient resided. Conclusions: We concluded that cirrhosis significantly increased the risk of parkinsonism.     

Intra-articular hyaluronic acid in the treatment of haemophilic chronic arthropathy

We report our preliminary experience with the use of hyaluronic acid (Synvisc) in 29 joints from 25 different haemophilic patients (17 knees, six shoulders, four ankles, one elbow and one hip). All the joints were grade III of our classification, characterized by synovial thickening, axial deformities and muscle atrophy (chronic arthropathy). In view of the very satisfactory results obtained with this procedure, we have substituted Synvisc for the previous use of intra-articular long-standing corticosteroids that we had been used for some years. This method is theoretically more physiological and does not destroy the joint cartilage further, as corticosteroids can.     

Bone marrow micrometastases in esophageal carcinoma: a 10‐year follow‐up study

Detection of bone marrow micrometastases (BMMs) in patients with esophageal carcinoma may indicate a metastatic phenotype. We assessed if the presence of BMMs had adverse prognostic significance in a 10‐year follow‐up study. Patients undergoing surgery for esophageal cancer were prospectively recruited between February 1999 and August 2000. Bone marrow aspirates were obtained from the iliac crest of patients under general anesthesia at the time of surgery. Immunocytochemical analysis using anticytokeratin antibodies CAM 5.2 and AE1/AE3 was undertaken to determine the presence of BMMs. Union International Contre le Cancer staging was recorded for all patients. Patient follow‐up was completed over a 10‐year period through analysis of the Northern Ireland Cancer Registry. Forty‐two patients (male = 35) were included, with a mean age of 67.2 years (range 39–83). BMMs were detected in 19 patients (45.2%). International Contre le Cancer tumor staging was stage I = 6, stage II = 10, stage III = 24, and stage IV = 2. BMMs were associated with lymphovascular invasion (P= 0.02) and advanced T stage (P= 0.02). Overall, 10‐year survival was 21.4% (n= 9), with a median follow‐up of 877.5 days (interquartile range 391.5–2546.3). There was no statistically significant difference between the survival of patients with or without BMMs (1451.4 vs. 1431.6 days, P= 0.99). Univariate analysis demonstrated a trend toward decreased survival for patients with positive lymph nodes (P= 0.07), an increased T stage (P= 0.06), and lymphovascular invasion (P= 0.07). Multivariate analysis demonstrated that none of the variables were significant predictors of mortality. Although the presence of BMMs correlates with recognized adverse tumor characteristics in patients with esophageal cancer, micrometastases detected in the bone marrow at time of surgery does not influence long‐term survival.     

Long‐term (96‐week) follow‐up of antiretroviral‐naïve HIV‐infected patients treated with first‐line lopinavir/ritonavir monotherapy in the MONARK trial*

Background

The toxicities, cost and complexity of triple combinations warrant the search for other treatment options, such as boosted protease inhibitor (PI) monotherapy. MONotherapy AntiRetroviral Kaletra (MONARK) is the first randomized trial comparing lopinavir/ritonavir monotherapy to triple combination therapy with zidovudine/lamivudine and lopinavir/ritonavir in antiretroviral‐naïve patients.

Methods

A total of 136 antiretroviral‐naïve patients, with a CD4 cell count above 100 cells/μL and a plasma HIV RNA below 100 000 HIV‐1 RNA copies/mL, were randomized and dosed with either lopinavir/ritonavir monotherapy (n=83) or lopinavir/ritonavir+zidovudine/lamivudine (n=53). We focus here on patients in the lopinavir/ritonavir monotherapy arm followed to week 96. The intent‐to‐treat (ITT) analysis initially involved all patients randomized to lopinavir/ritonavir monotherapy (n=83), and then focused on patients who had an HIV RNA <50 copies/mL at week 48 (n=56).

Results

At week 96, 39 of 83 patients (47%) had HIV RNA <50 copies/mL, five of 83 had HIV RNA between 50 and 400 copies/mL, and three of 83 had HIV RNA >400 copies/mL. Focusing on the 56 patients with an HIV RNA <50 copies/mL at week 48, 38 of 56 patients (68%) had a sustained HIV RNA <50 copies/mL to week 96. To week 96, a total of 28 patients (34%) had discontinued the study treatment. In addition, the allocated treatment was changed for seven patients. PI‐associated resistance mutations were evident in five of 83 patients in the monotherapy arm from baseline to week 96.

Conclusion

By ITT analysis, 39 of the 83 patients initially randomized to lopinavir/ritonavir monotherapy had HIV RNA <50 copies/mL at week 96. The occurrence in some patients of low‐level viraemia (50–500 copies/mL) may increase the risk of drug resistance. First‐line lopinavir/ritonavir monotherapy cannot be systematically recommended.     

Malignant lymphoma in the HIV‐positive patient

The introduction of combination antiretroviral therapy (cART) drastically improved performance status, immune function, and life expectancy of HIV‐infected individuals. In addition, incidence of opportunistic infections and of AIDS‐defining malignancies declined. Nevertheless, aggressive non‐Hodgkin’s lymphoma still remains the leading cause of AIDS‐related deaths. The availability of cART, however, significantly improved the therapeutic options for HIV‐positive patients with lymphomas. Diffuse large B‐cell lymphoma, Burkitt’s lymphoma, or Hodgkin lymphoma has increasingly become curable diseases. In light of these favorable developments in the treatment of HIV and HIV‐associated lymphomas, reduction in treatment‐associated toxicities and further improvement of outcome of patients with advanced immune suppression are major requirements for future clinical trials. This review summarizes the current treatment landscape and gives an overview on future needs in HIV‐positive patients with lymphoma.     

Monitoring of kidney function in HIV‐positive patients

HIV‐positive patients are at increased risk of developing chronic kidney disease. Although guidelines recommend regular monitoring of renal function in individuals living with HIV, the optimal frequency remains to be defined. In this review, we discuss the renal syndromes that may be identified at an earlier stage via routine assessment of kidney function, and provide guidance in terms of the frequency of monitoring, the most useful tests to perform, and their clinical significance. Specifically, we address whether annual monitoring of kidney function is appropriate for the majority of HIV‐positive patients.