Highly Active Antiretroviral Therapy In Combination Research Articles

1068PD - Non-Hodgkin lymphoma in HIV-positive patients treated with antiretroviral therapy and chemotherapy: A single institution retrospective study

BackgroundHIV+ pts have a 25-fold higher risk of developing NHL. Two independent prognostic factors influence incidence and prognosis: highly active antiretroviral therapy (HAART) and CD4+ lymphocyte count. Diagnosis of NHL can occur simultaneously (naive pts), or after diagnosis of HIV infection (experience-pts). MethodsSingle institution retrospective cohort study conducted in ASST FBF-Sacco Polo Luigi Sacco (Milan, Italy). Pts aged>=18 years, diagnosis of HIV infection and NHL, on HAART treated with first line R-CHOP-like chtp from Jan 2007 to Jan 2017. Chi-square, Fisher’s exact or Wilcoxon Rank-sum test, log-rank test or Cox regression model for OS, PFS and RR were used. ResultsWe enrolled 46 HIV+ pts: 11 naive-pts, 35 experience-pts (exp-pts). No difference in median age at diagnosis (49vs48ys p=0.40), sex (male 72.7vs85.7% p=0.37), histological types: DLBCL (2vs24), BL (3vs3), PEL (1vs0), PCNSL (1vs0), PBL (2vs2) low-grade NHL (2vs4) T-cell NHL(0 vs 2) (p=0.13). Naïve-pts higher stage (stage IV 90.9vs41.2% p=0.05). No difference in frequency of B symptoms (40vs41% p=0.99), bulky masses (18.2vs20.6% p=0.99), ≥2 extranodal sites (45.5vs40% p=0.61), CNS involvement (44.4vs38.2% p=0.99), AIDS-definig diseases (44.4vs28.6% p=0.43) HCV/HBV infection (p=0.08/0.99). Naive-pts aaIPI intermediate-high risk (90.0vs58.1% p=0.11). CD4+ count at NHL diagnosis(102vs222/mcl p=0.05). During R-CHOP-like chtp naïve-pts more infectious toxicity (50% vs 10.7% p=0.02). During a median (IQR 2-44) follow-up of 12 mts no difference in RR (CR 60% vs 62.5% p=0.85), median OS (67 mts vs 69.4 mts p=0.3) and PFS (p=0.8). ConclusionsThe compromised immune status in naïve-pts may explain their worst NHL conditions at diagnosis and toxicity during chtp. The immediate start of HAART in combination with chemotherapy probably reduce the impact of these factors in term of response to treatment and survival (RR, PFS and OS). CD4+ count together with HAART remain the independent prognostic factor with the greatest influence on OS [exp vs naïve-pts: OS HR 0.83 (95% CI); OS/CD4+ HR 1.80 (95% CI)]. Naive-pts should be treated with standard chtp regimens, without modification of dose or schedule. Legal entity responsible for the studyASST-FBF-SACCO. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Impact of Herbal Preparations on Outcomes of Highly Active Antiretroviral Therapy: A One-Year Prospective Cohort Study.

To investigate the impacts of two herbal preparations for human immunodeficiency virus/aquired immune deficiency syndrome (HIV/AIDS) patients, Shenling Fuzheng Capsule (, SLFZC) and Qingdu Capsule (, QDC), on the efficacy of highly active antiretroviral therapy (HAART). HIV/AIDS patients met the criteria were all enrolled in a 1-year cohort study, in which patients receiving HAART alone were designated as Group A, those receiving HAART in combination with SLFZC were designated as Group B, and those receiving HAART in combination with QDC were designated as Group C, 100 cases in each group. The dose of SLFZC was 1.48 g (4 capsules), 3 times daily, and QDC 1.56 g (4 capsules), 3 times daily. T cell subsets, HIV RNA and HIV-1 drug resistance were detected at enrollment and 1 year after treatment. Patients were followed up every 3 months, during which side-effects and other clinical data were recorded. After 1-year treatment, the median increment in CD4 counts was 165.0, 178.0 and 145.0 cells/μL for Group A, B and C, respectively. HIV RNA was undetectable in 94% of patients in Group A, 96% in Group B and 92% in Group C. There were no differences regarding the increment in CD4 counts, HIV RNA and frequency of HIV-1 drug resistance mutations. Two of the 14 suspected side-effect symptoms, i.e. fatigue and dizziness, were lower in Groups B and C than in Group A (P<0.05, respectively) CONCLUSIONS: SLFZC and QDC do not have a negative impact on immunological and virological response to HAART; however, these preparations are not as potent in reducing HAART-associated side-effects as anticipated.

Plasma cell neoplasms in HIV-Infected Patients: A Literature Review and Case Series

Aim. Analysis of 37 published and 2 author's cases of multiple myeloma (MM) in HIV-positive patients. Materials &amp; Methods. Description of 37 patients and 2 author's previously unpublished observations. Results. The median age of patients was 37 years (66 in the general population), only 2 % being under 40 years. Abnormal MM progression was observed including the emergence of extramedullary lesions, low levels of M-gradient, and the development of plasmoblastic leukemia. Historically, before highly active antiretroviral therapy (HAART) was introduced, a rapid progression of MM with a short life expectancy was observed. HAART in combination with chemotherapy showed the best results of MM treatment in terms of overall and relapse-free survival. According to the literature data HAART may also be used to treat HIV-negative patients with MM. The cytological analysis of MM showed atypical myeloma cells with no lysozyme, leukocyte common antigen, CD19, and CD20. The CD38 was clearly identified. Anaplastic MM may be regarded as the first manifestation of AIDS. The author's results were similar to the published data. Conclusion. MM in HIV-infected patients in stage with secondary diseases is still considered to be not HIV-related. In HIV-positive MM patients on HAART overall and relapse-free survival rates were higher than that in HIV-negative patients with MM. The serum levels M-gradient was shown to decrease or even become indeterminate in MM patients receiving HAART for HIV infection. Thus, the HAART was proposed for MM HIV-negative patients.

Orogastric administration of crushed darunavir tablets for a critically ill patient.

When HIV-positive patients are critically ill and unable to take medications orally, administration of highly active antiretroviral therapy (HAART) becomes challenging. The foremost issue is the lack of parenteral formulations and oral suspensions. Only limited clinical evidence directly addresses the conversion of antiretroviral drugs from the oral to the enteral route. Interruption of HAART is not an acceptable alternative, as this results in HIV viral rebound, immunodeficiency, opportunistic infections, and development of resistance to antiretroviral treatment. Altering the route of administration may affect the plasma concentration of antiretrovirals, which also affects clinical outcomes. For example, as described in one case report, a 28-year-old HIV-positive man with diffuse large B cell–type lymphoma of the duodenum was taking the liquid or powder formulations of lopinavir–ritonavir, abacavir, and lamivudine (at standard adult doses) by oral ingestion, with suppression of the viral load to less than 400 copies/mL. Development of a duodenal obstruction necessitated insertion of a percutaneous jejunal feeding tube (located ≥ 35 cm distal to the ligament of Treitz). HAART was reinitiated via the jejunostomy, leading to HIV viral rebound (to 11 000 copies/mL), undetectable serum concentration of lopinavir, and development of resistance to lamivudine (M184V mutation). Gastric bypass surgery was performed to connect the gastric corpus to the jejunum (20 cm distal from the ligament of Treitz). HAART, including lopinavir–ritonavir (oral liquid), abacavir, and tenofovir, was restarted, and measurement of serum lopinavir concentration 18 weeks later demonstrated adequate absorption of the medication, with HIV viral suppression (to 52 copies/mL). Darunavir is an HIV-1 protease inhibitor recommended for combination HAART regimens for both treatment-naive and treatment-experienced patients. This antiretroviral agent must be administered with ritonavir and food to enhance its pharmacokinetic profile and to ensure adequate antiretroviral activity. The absolute bioavailability of darunavir without ritonavir is only 37%; however, when darunavir is adminstered concurrently with ritonavir, systemic exposure to darunavir increases 14-fold. Limited data suggest adequate absorption of crushed darunavir tablets, both when swallowed and when administered via various enteral tubes. This report describes a case in which crushed darunavir tablets were administered to a critically ill patient through an orogastric feeding tube.

Boosted protease inhibitor monotherapy in HIV-infected adults: outputs from a pan-European expert panel meeting.

While the introduction of combination highly active antiretroviral therapy (HAART) regimens represents an important advance in the management of human immunodeficiency virus (HIV)-infected patients, tolerability can be an issue and the use of several different agents may produce problems. The switch of combination HAART to ritonavir-boosted protease inhibitor (PI) monotherapy may offer the opportunity to maintain antiviral efficacy while reducing treatment complexity and the risks of toxicity. Current European AIDS Clinical Society (EACS) guidelines recognise ritonavir-boosted PI monotherapy with twice-daily lopinavir/ritonavir or once-daily darunavir/ritonavir as a possible option in patients who have intolerance to nucleoside reverse transcriptase inhibitors, or for treatment simplification. Clinical trials data for PI boosted monotherapy are encouraging, showing substantial efficacy in the majority of patients; however, further data are required before this approach can be recommended as a routine treatment. Available data indicate that the most suitable candidates for the use of boosted PI monotherapy are long-term virologically suppressed patients who have demonstrated good adherence to antiretroviral therapy, who do not have chronic hepatitis B, have no history of treatment failure on PIs and are able to tolerate low-dose ritonavir.

HIV patients treated with low-dose prednisolone exhibit lower immune activation than untreated patients

BackgroundHIV-associated general immune activation is a strong predictor for HIV disease progression, suggesting that chronic immune activation may drive HIV pathogenesis. Consequently, immunomodulating agents may decelerate HIV disease progression.MethodsIn an observational study, we determined immune activation in HIV patients receiving low-dose (5 mg/day) prednisolone with or without highly-active antiretroviral therapy (HAART) compared to patients without prednisolone treatment. Lymphocyte activation was determined by flow cytometry detecting expression of CD38 on CD8(+) T cells. The monocyte activation markers sCD14 and LPS binding protein (LBP) as well as inflammation markers soluble urokinase plasminogen activated receptor (suPAR) and sCD40L were determined from plasma by ELISA.ResultsCD38-expression on CD8+ T lymphocytes was significantly lower in prednisolone-treated patients compared to untreated patients (median 55.40% [percentile range 48.76-67.70] versus 73.34% [65.21-78.92], p = 0.0011, Mann-Whitney test). Similarly, we detected lower levels of sCD14 (3.6 μg/ml [2.78-5.12] vs. 6.11 μg/ml [4.58-7.70]; p = 0.0048), LBP (2.18 ng/ml [1.59-2.87] vs. 3.45 ng/ml [1.84-5.03]; p = 0.0386), suPAR antigen (2.17 μg/ml [1.65-2.81] vs. 2.56 μg/ml [2.24-4.26]; p = 0.0351) and a trend towards lower levels of sCD40L (2.70 pg/ml [1.90-4.00] vs. 3.60 pg/ml [2.95-5.30]; p = 0.0782). Viral load in both groups was similar (0.8 × 105 ng/ml [0.2-42.4 × 105] vs. 1.1 × 105 [0.5-12.2 × 105]; p = 0.3806). No effects attributable to prednisolone were observed when patients receiving HAART in combination with prednisolone were compared to patients who received HAART alone.ConclusionsPatients treated with low-dose prednisolone display significantly lower general immune activation than untreated patients. Further longitudinal studies are required to assess whether treatment with low-dose prednisolone translates into differences in HIV disease progression.

Prevalence of Anaemia in HIV-Infected Children at the University of Abuja Teaching Hospital, Gwagwalada

Use of highly active antiretroviral therapy (HAART) has remained the only regimen potent enough to reduce viral replication in HIV-infected individuals. Its combination with cotrimoxazole has also been recommended in those with CD4% of less than 15%. The use of HAART containing zidovudine (ZDV) in combination with co-trimoxazole carries the risk of anaemia in already anaemic predisposed individuals from HIV infections, opportunistic infections, parasitic infestations, sickle cell anaemia, and malnutrition. The aim of the study is to document the effect of use of combination of HAART containing ZDV with cotrimoxazole in haemoglobin profile of HIV-infected children after one year of its administration at the University of Abuja Teaching Hospital (UATH), Gwagwalada. It is also aimed at comparing the result obtained with those on stavudine containing HAART with co-trimoxazole. A two year prospective study of HIV-infected children on treatment with HAART in combination with co-trimoxazole, and attending the paediatric outpatient special treatment clinic (POSTC) for HIV infected children at the UATH, Gwagwalada from November 2006 to October 2008, was carried out to determine effect of these drug combinations in the haemoglobin profile of infected children. Three monthly PCV level was carried out using haematocrit centrifuge and reader. A total of 173 patients were started on HAART during the first year recruitment period, 90 (52.0%) were males, while 83 (48.0%) females, giving a male to female ratio of 1.1:1. One hundred and seventeen (67.7%) of patients were on ZDV containing HAART, while 56 (32.3%) were on stavudine containing combination. All patients were started on co-trimoxazole prophylaxis with the exception of 6 (3.5%) patients because of drug reaction. The mean PCV of patients on ZDV containing combination with cotrimoxazole decreased from 30.2 +/- 5.5% to 29.0 +/- 2.3%, with a net decrease of 1.2% after one year treatment, those on stavudine containing combination with co-trimoxazole instead showed an increased from initial PCVof 28.3 +/- 4.2% to 34.2 +/- 3.0% with a net increase of 5.9% after the same duration of treatment, (p > 0.05). While patients on ZDV combination alone without co-trimoxazole prophylaxis had a minimal decrease of 0.9% in their PCV level after one year treatment, those on stavudine combination alone without any prophylaxis instead showed an increase of 6.8% in their PCV after the same duration of treatment. A combination of HAART containing ZDV plus co-trimoxazole carries risk of anaemia than that of stavudine containing combination with co-trimoxazole. Such combination should therefore not be given to anaemic patients. Regular check in PCV of patients on HAART combination with ZDV and additional cotrimoxazole prophylaxis is required for early detection of significant drop in PCV level.

Idiopathic AIDS Enteropathy and Treatment of Gastrointestinal Opportunistic Pathogens

Diarrhea in patients with acquired immune deficiency syndrome (AIDS) has proven to be both a diagnostic and treatment challenge since the discovery of the human immunodeficiency virus (HIV) virus more than 30 years ago. Among the main etiologies of diarrhea in this group of patients are infectious agents that span the array of viruses, bacteria, protozoa, parasites, and fungal organisms. In many instances, highly active antiretroviral therapy remains the cornerstone of therapy for both AIDS and AIDS-related diarrhea, but other targeted therapies have been developed as new pathogens are identified; however, some infections remain treatment challenges. Once identifiable infections as well as other causes of diarrhea are investigated and excluded, a unique entity known as AIDS enteropathy can be diagnosed. Known as an idiopathic, pathogen-negative diarrhea, this disease has been investigated extensively. Atypical viral pathogens, including HIV itself, as well as inflammatory and immunologic responses are potential leading causes of it. Although AIDS enteropathy can pose a diagnostic challenge so too does the treatment of it. Highly active antiretroviral therapy, nutritional supplementation, electrolyte replacements, targeted therapy for infection if indicated, and medications for symptom control all are key elements in the treatment regimen. Importantly, a multidisciplinary approach among the gastroenterologist, infectious disease physician, HIV specialists, oncology, and surgery is necessary for many patients.

Thymic 18F-fluorodeoxyglucose uptake on positron emission tomography scanning after doxorubicin, bleomycin, vincristin and dacarbazine chemotherapy and highly-active antiretroviral therapy in HIV-associated Hodgkin's disease in an adult

Positron emission tomography (PET) scanning is being increasing used to stage disease and monitor response to therapy in lymphoma patients [1]. More recently, it has been used as a prognostic tool to predict disease recurrence after chemotherapy [2,3]. PET-positive residual mass with standardized uptake value (SUV) > 3 after chemotherapy is associated with recurrence rate of 60–80% [4,5] PET imaging has a high sensitivity and specificity of 86% and 96%, respectively, and, in many centres, treatment recommendations were made solely on the basis of PET results for diagnosis of recurrence without confirmatory tissue diagnosis. This is the first report of a patient in whom anterior mediastinal PET positivity was due to thymic reconstitution after successful chemotherapy for HIV-related Hodgkin's disease and highly-active antiretroviral therapy (HAART) rather than disease relapse. A 26-year-old HIV-infected man presented with a 3-month history of night sweats, fevers and generalised lymphadenopathy. He had been diagnosed with HIV infection 2 years previously. His CD4 count was 330 cells/μl and his HIV RNA load was 12 000 copies/ml. A computed tomography (CT) scan showed a large anterior mediastinal mass measuring 10 × 6 cm with further enlarged nodes seen in the right para-tracheal, sub-carinal, right hilar, retroperitoneal and inguinal regions. Biopsy of the mediastinal mass was performed and the histological examination showed large cells with Reed–Sternberg morphology and expressing both CD30 and CD15, establishing the diagnosis of classical Hodgkin's lymphoma, nodular sclerosis subtype. Bone marrow aspirate and trephine showed no evidence of bone marrow involvement. The patient was staged as stage IIIb. Treatment with doxorubicin, bleomycin, vincristin, and dacarbazine (ABVD) was started. He was also treated with HAART using efavirenz 600 mg daily, emtricitabine 200 mg daily, and tenofovir 245 mg daily in an attempt to maintain and/or improve his immune status while undergoing chemotherapy treatment. His HIV RNA became undetectable (<50 copies/ml) and the CD4 cell counts remained reasonably stable during the chemotherapy treatments. A CT scan after six cycles of chemotherapy showed a residual anterior mediastinal mass measuring 7 × 4 cm but this was shown not to take up fluorodeoxyglucose (FDG) on PET scanning (Fig. 1a).Fig. 1: Positron emission tomography (PET)–computed tomography (CT) scan performed 1 month after the completion of chemotherapy showed residual anterior mediastinal mass which was, however, not fluorodeoxyglucose (FDG)-avid (a). Another CT–PET scan was performed 16 months after the completion of chemotherapy and it showed increased FDG uptake with an SUV of 3.2 (arrow) in the anterior mediastinum, consistent with disease relapse (b). Biopsy of the mediastinal mass that was positive on FDG–PET 16 months after the completion of chemotherapy was performed but the histological examination showed regenerated thymus with a lobular architecture and containing morphologically normal cortex, medulla, and Hassall's corpuscles (c); original magnification × 45).The patient continued to receive HAART and maintained good virological control. Sixteen months later, he presented with enlarged 1.0 cm axillary lymph node and a CT–PET scan was requested to exclude disease recurrence. His CD4 count was 600 cells/μl and HIV RNA remained undetectable. On this CT–PET scan, there was now an increased uptake detected in the anterior mediastinum with an SUV of 3.2, suggesting disease relapse (Fig. 1b; arrow). Mediastinoscopic biopsy was requested to confirm disease progression with the view of high-dose chemotherapy and peripheral blood stem cell transplantation. To our surprise, the histology revealed normal regenerating thymic tissue with no evidence of lymphoma (Fig. 1c). In our patient, the PET positivity in the mediastinum after chemotherapy in a HAART patient with HIV-associated Hodgkin's lymphoma is the result of T-cell immune reconstitution in a functional thymus gland. Initiation of HAART in HIV-infected patients is associated with immune reconstitution of T cells and this is correlated with thymus volume increase and generally occurs in patients with initial low CD4 counts and/or rising CD4 counts [6–8]. The thymic reconstitution is also associated with increased thymic metabolism, which is reflected by increased FDG uptake detected by PET [9]. Interestingly, in our patient, the number of CD4 cell was high prior to treatment. It is possible that HAART in combination with transient lymphopenia induced by chemotherapy could have triggered the thymic reconstitution. In conclusion, this is the first case to report on the occurrence of FDG-avid uptake in functional thymic tissue in a HAART patient with HIV-associated Hodgkin's lymphoma previously treated with chemotherapy. Our case illustrates the importance of verification of PET findings by a biopsy. It is also important to consider this differential diagnosis in HIV-infected patients treated with HAART and chemotherapy if a post-treatment PET scan shows increased mediastinal uptake.

Stopping HAART temporarily in the absence of virus rebound: exploring new HIV treatment options

To examine the literature in search of data supporting (stopping highly active antiretroviral therapy (HAART) temporarily in the absence of virus rebound) to expand HIV treatment options. We proposed investigating HAART interruptions after the 'Berlin patient' had discontinued HAART while keeping HIV suppressed. The idea of inducing immune control of HIV by treatment interruptions has been largely abandoned and with clinicians have mainly investigated whether treatment withdrawal can reduce toxicity, improve the quality of patients' lives, and save costs. Some data suggest that treatment interruptions remain a feasible strategy and the benefits outweigh the costs; others warn against several pitfalls: onset of resistance, HIV transmission and increased toxicity. Researchers have also found, however, that the viral set point can be lowered by treatment interruptions during chronic infection, similar to (but to a lesser extent than) acute infection. Preliminary studies suggest that immunomodulators and therapeutic vaccines may further improve immune control of HIV replication. Exposure to HIV leads to excessive immune activation and exhaustion. Viral rebounds should be contained to obtain therapeutic benefits and decrease virus transmission. Temporary interruptions of HAART in combination with therapeutic vaccinations and immune modulators, such as antiproliferative drugs, may suppress HIV for extended periods of time.

Body Fat Changes and Lipodystrophy in HIV-infected Children

Body Fat Changes and Lipodystrophy in HIV-infected Children

Immunosuppressive drugs as an adjuvant to HIV treatment.

Although highly active antiretroviral therapy (HAART) has dramatically changed the epidemiological impact of HIV infection, many problems with currently used antiretroviral therapy have underscored the urgent need for additional therapeutic approaches. Structured treatment interruption trials, which can be considered an immune-based therapy with an autologous virus, have failed to control viral replication in most chronically HIV-1-infected patients. Alternative approaches could be the use of immunosuppressive drugs to enhance the control of viral replication mediated by their immune and antiviral properties. The use of immunosuppressive drugs may reduce the number of activated CD4 cells that support massive virus production and may prevent sequestration of CD4 T cells into lymphoid tissue, which is the place of antigen presentation and productive HIV infection. The strategy of using drugs that interfere with the HIV life-cycle, acting on the target cells of HIV rather than on viral enzymes, offers the advantage of avoiding the development of antiretroviral drug-resistant HIV mutants. However, it is not known if these approaches will clinically benefit long-term infection, by establishing a new immunological set-point that may affect the rate of disease progression. Caution is required when using HAART in combination with cytostatic drugs in HIV-1 infection until their impact and long-term safety have been investigated further in larger clinical trials.

Impact of Highly Active Antiretroviral Therapy in the Treatment of HIV–Infected Patients with Systemic Non-Hodgkin‘s Lymphoma

Twenty cases of systemic non-Hodgkin‘s lymphoma (NHL) in HIV-infected patients were reviewed over a 10-year-period, divided into Group A, including 13 NHL cases treated before the highly active antiretroviral therapy (HAART) era, and Group B, including 7 patients who received HAART. A Kaplan-Meier survival curve was performed and log-rank was applied to assess statistical differences between the groups. In group A, the median CD4 count was 36 cells/mm 3 . No complete remission was found. In group B, the median CD4 count was 137 cells/mm 3 . Four patients (57.0%) are still alive and in complete remission. Group A had a median survival of 5 months and group B 31 months (p=0.0032). Our results are in agreement with recent reports in that a higher CD4 count and better immune status achieved with HAART is predictive of a better outcome. We found that HAART in combination with chemotherapy improves overall survival of NHL patients without increasing adverse effects.

Better response to chemotherapy and prolonged survival in AIDS-related lymphomas responding to highly active antiretroviral therapy.

To evaluate the impact of response to highly active antiretroviral therapy (HAART) on the natural history of AIDS non-Hodgkin's lymphoma (NHL) and to analyse the feasibility, efficacy and toxicity of HAART in combination with chemotherapy. Prospective observational study in two AIDS clinical centres in Italy. All consecutive HIV-infected patients with NHL were included (n = 44; 48% high-risk group) and prospectively followed for 27 months. HAART was administered concomitantly with chemotherapy. The association between response to HAART and clinical presentation, response to chemotherapy and toxicity was analysed by univariate and multivariate models. Survival analysis was performed by Kaplan-Meier estimates and the Cox proportional hazards regression model. A complete response (CR) to chemotherapy was achieved in 71% of HAART responders and 30% of non-responders. Virological response to HAART was the only variable associated with tumour response on multivariate analysis. A higher relative dose intensity (RDI) of chemotherapy was administered in patients with virological response compared with those without. The probability of 1 year survival was higher in patients with virological or immunological response. At Cox regression analysis, immunological response, a higher RDI and a CR to chemotherapy were all associated with a reduced risk of death. In HIV-infected patients with NHL, response to HAART was strongly associated with a better response to chemotherapy and prolonged survival. Concurrent treatments were well tolerated, and HAART-responder patients could receive a higher RDI of chemotherapy. In patients with AIDS lymphomas, combining HAART with chemotherapy could be a feasible and effective approach.

Management of AIDS-related non-Hodgkin's lymphomas.

The incidence of non-Hodgkin's lymphoma in individuals infected with HIV is approximately 60- to 100-fold increased over the general population. The majority of patients with AIDS-related lymphoma (ARL) present with stage III-IV disease and with B-symptoms. They often have multiple extranodal localisations, with a high incidence of central nervous system involvement. Histologically, most tumours are either diffuse large cell lymphomas or Burkitt lymphomas. Several factors, such as disrupted immune surveillance, Epstein-Barr virus infection, chronic antigenic stimulation, cytokine dysregulation and the acquisition of genetic lesions, are thought to contribute to the pathogenesis. Patients with ARL have a poor prognosis: overall survival ranges from 1.5 to 18 months. The most important adverse prognostic factors are poor performance status, a low CD4+ cell count and a history of opportunistic infections. Results of treatment with polychemotherapy compare unfavourably to results in patients without HIV infection. Since the advent of highly active antiretroviral therapy (HAART), there appears to be a decrease in the incidence of ARL. In addition, the use of HAART in combination with chemotherapy and the use of new treatment modalities may improve the outcome of this disease.