DEPIVIH 2: Use of three HIV testing methods in French primary care settings - ELISA laboratory screening versus two rapid point-of-care HIV tests.

OBJECTIVE: The primary endpoint was to evaluate the use of HIV testing methods by French primary care providers: Elisa laboratory screening, instant result HIV diagnostic test and rapid result HIV diagnostic test. The secondary endpoints were the population screening rate of unknown HIV status consulting during the study period, reasons for screening and for choosing the specific screening method, the investigators' satisfaction with the rapid diagnostic test (RDT) and problems encountered. PATIENTS AND METHODS: National prospective interventional study with French family physicians (FP) from December 2013 to December 2014. FPs enrolled all consenting adults consulting for an HIV screening test during a 6-month period: the choice was an Elisa laboratory test or one of the two RDTs. RESULTS: During the study period, 43 FPs included 981 patients. HIV screening was performed for the first time for 31.6% of patients; 767 (78.2%) Elisa laboratory test prescriptions and 214 (21.8%) RDTs were performed, leading to a screening rate of 1.3%. For 120 (15.7%) of the Elisa laboratory tests, the result was not reported and six RDTs were not valid. Nine patients were diagnosed as HIV-infected (0.9%): five with Elisa laboratory test and four with RDT. Almost 90% of FPs were willing to keep on using RDTs in their daily practice. CONCLUSION: In general practice, RDTs may be an important additional tool to traditional HIV screening. They could account for one in five tests prescribed in this context.

Feasibility and acceptability of rapid HIV test screening (DEPIVIH) by French family physicians.

BACKGROUND: In France, around 50,000 people were unaware of their HIV positivity at the end of 2008. The latest guidelines recommend routine screening of all adults. Family physicians have been identified as key persons for this new policy. Rapid HIV tests (RHT) have been proposed as an alternative to conventional blood tests. OBJECTIVES: The authors assessed the feasibility and acceptability of RHT test based screening in French community practice. METHOD: We made a prospective interventional study of the BioMerieux VIKIA(®) HIV 1/2 RHT among French family physicians. Data on the RHT was posted in the physician's waiting room. RESULTS: Sixty-two French physicians, mostly family practitioners, included 383 patients with a mean age of 36.2 years, from June to October 2010. Twenty-two percent (83) of these patients had never been tested for HIV. The RHT was proposed and 382 tests were accepted and performed (acceptability rate of 99.7%). Sixty-five percent of the tests were made on the patient's request. The tested population represented 1.5% of consulting patients during the study period (feasibility rate). Patients were quite satisfied but physicians less so. Test steps and capillary blood sampling were the main source of difficulty mentioned. At the end of the study, 59% of physicians were ready to continue using RHT in their daily practice. CONCLUSION: Routine RHT screening in community practice is feasible and well accepted by patients. It was the first screening test for 22% of our patients. Its feasibility was limited by capillary blood sampling technique and time constraints during consultation.

Longer prior exposure to zidovudine/lamivudine-containing combination antiretroviral therapy, age, and male gender are each associated with reduced subcutaneous adipose tissue.

OBJECTIVES: Whether zidovudine (AZT)-associated lipoatrophy occurrence differs by concomitant exposure to protease (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) remains unclear. Baseline body composition data from a randomized trial in subjects stable on first-line AZT-based therapy were used to explore this issue. METHODS: In this substudy of the PREPARE trial, centrally read baseline whole-body dual energy x-ray aborptiometry (DXA) and single-slice abdominal CT scans were analyzed with respect to duration and type of prior AZT/lamivudine (3TC) combination antiretroviral therapy (cART), including by multivariate linear regression adjusted for age, gender, ethnicity, body mass index (BMI), and nadir CD4. RESULTS: DXA and CT, from 134 and 136 patients, respectively [87% male; 82% Caucasian; mean (SD) age, 45.6 years (10); BMI, 24.3 kg/m² (3.2)], were analyzed. Prior AZT/3TC cART exposure was 5.5 (2.2) years. Seventy-eight and 27 patients had concomitantly and exclusively used NNRTIs and PIs, respectively. AZT/3TC cART, AZT/3TC/NNRTI, and AZT/3TC/PI, respectively, were associated with the presence of a mean (95% CI) of 247 g (-438 to -56; P = .012), 267 g (-467 to -66; P = .010), and 216 g (-430 to -1.7; P = .048) less baseline limb fat per additional year of prior exposure. Although abdominal subcutaneous (SAT) adipose tissue was likewise less with longer AZT/3TC cART, this was only significant for AZT/3TC/ NNRTI but not AZT/3TC/PI. Visceral adipose tissue (VAT) amount was not clearly associated to prior treatment. Increased age and male gender were independently associated with lower limb fat and SAT, but more VAT. CONCLUSIONS: Longer exposure to AZT/3TC, regardless of whether in combination with PI or NNRTI, as well as increased age and male gender are independently associated with lower limb fat mass.

Twenty-four-week efficacy and safety of switching virologically suppressed HIV-1-infected patients from nevirapine immediate release 200 mg twice daily to nevirapine extended release 400 mg once daily (TRANxITION).

OBJECTIVES: Once-daily (qd) antiretroviral therapies improve convenience and adherence. If found to be effective, nevirapine extended release (NVP XR) will confer this benefit. The TRANxITION trial examined the efficacy and safety of switching virologically suppressed patients from NVP immediate release (NVP IR) 200 mg twice daily to NVP XR 400 mg qd. METHODS: An open-label, parallel-group, noninferiority, randomized (2:1 NVP XR:NVP IR) study was performed. Adult HIV-1-infected patients receiving NVP IR plus a fixed-dose nucleoside reverse transcriptase inhibitor (NRTI) combination of lamivudine (3TC)/abacavir (ABC), tenofovir (TDF)/emtricitabine (FTC) or 3TC/zidovudine (ZDV) with undetectable viral load (VL) were enrolled in the study. The primary endpoint was continued virological suppression with VL < 50 HIV-1 RNA copies/mL up to week 24 (calculated using a time to loss of virological response algorithm). Cochran's statistic (background regimen adjusted) was used to test noninferiority. Adverse events (AEs) were recorded. RESULTS: Among 443 randomized patients, continued virological suppression was observed in 93.6% (276 of 295) of NVP XR- and 92.6% (137 of 148) of NVP IR-treated patients, an observed difference of 1% [95% confidence interval (CI) -4.3, 6.0] at 24 weeks of follow-up. Noninferiority (adjusted margin of -10%) of NVP XR to NVP IR was robust and further supported by SNAPSHOT analysis. Division of Acquired Immunodeficiency Syndrome (DAIDS) grade 3 and 4 events were similar for the NVP XR and NVP IR groups (3.7 vs. 4.1%, respectively), although overall AEs were higher in the NVP XR group (75.6 vs. 60.1% for the NVP-IR group). CONCLUSIONS: NVP XR administered once daily resulted in continued virological suppression at week 24 that was noninferior to that provided by NVP IR, with similar rates of moderate and severe AEs. The higher frequency of overall AEs with NVP XR may be a consequence of the open-label design.

Effect of early initiation of highly active antiretroviral therapy on CD4 cell count and HIV-RNA viral load trends within 24 months of the onset of acute retroviral syndrome.

OBJECTIVES: The effect of starting highly active antiretroviral therapy (HAART) early after the onset of acute retroviral syndrome (ARS) on CD4 and HIV-RNA trends was studied over a 2-year follow-up period. METHODS: Four groups of HIV-infected patients stratified according to the time interval from ARS onset to HAART initiation and a control group of untreated patients were compared. RESULTS: The results indicated that the earlier the start of HAART, the faster was the rate of CD4 increase and HIV-RNA decrease. However, this difference did not seem to persist at 24 months. CONCLUSIONS: The optimal treatment strategy for HIV-infected patients needs to be explored further.

Pneumococcal pneumonia in HIV-infected patients by antiretroviral therapy periods.

OBJECTIVE: To ascertain the relationship between periods of various antiretroviral therapies and the incidence of first community-acquired pneumococcal pneumonia (CAPP) among HIV-1 infected patients. METHODS: We analysed 4075 patients enrolled prospectively in the Lyon section of the French Hospital Database on HIV between 1993 and 2004, stratified into three groups. The first group (G1) included patients for whom enrolment and last follow-up were before the highly active antiretroviral therapy (HAART) period (beginning 1 July 1996); the second group (G2) comprised patients who were enrolled before HAART but had last follow-up in the HAART period; the third group (G3) included patients for whom both enrolment and last follow-up took place in the HAART period. RESULTS: Fifty-five CAPP episodes were identified. The incidence of CAPP per 1000 patient-years declined over time, from 10.6 to 1.5 and 2.5 in calendar periods G1, G2 and G3, respectively (P=0.004 for linear trend). Factors associated with a decreased risk of CAPP were lower age, baseline CD4 count >or=200 cells/microL and more recent years of enrolment, when HAART use became extensive (P<0.001). The use of intravenous drugs increased the risk of CAPP (P<0.001). CONCLUSIONS: There has been a significant reduction in the incidence of CAPP in HIV-1 infected patients since the advent of HAART.

Characteristics and survival of HIV-infected patients not screened for hepatitis C virus infection in a hospital-based cohort.

The rate of human immunodeficiency virus (HIV) disease progression or death of individuals coinfected with hepatitis C virus (HCV) is conflicting. The complete-case analysis systematically used, excludes patients unscreened for HCV. Our objective was to assess if rate of survival differed between HIV-infected patients screened and unscreened for HCV in a hospital-based prospective cohort study. Patients were enrolled in the Lyon section of the French Hospital Database on HIV between 1 July 1992 and 31 May 2005. A multivariate Cox regression model was used to analyse the association of HCV screening with survival. Of 3244 patients, 299 (9.2%) were not screened for HCV. The populations screened and unscreened differed by the proportion of acquired immune deficiency syndrome at baseline, presumed route of infection, CD4 cell count category at baseline, mean duration of follow-up, mean number of visits per year, type of antiretroviral therapy and survival. The rate of progression to death was higher for non-HCV-screened vs HCV-screened patients: the incidence rate among HCV-screened patients was 22.9/1000 patient-years; the incidence rate among HCV-unscreened patients was 52.4/1000 patient-years. The adjusted hazards ratio of death was 2.48 [95% confidence interval (1.83-3.35); P < 0.001] for patients with unknown HCV status compared with others. In conclusion, unscreened or unknown HCV status was associated with an increased risk of death in our hospital cohort. Important prognostic factors are related to, or confounded by the practice of HCV screening.

Pharmacokinetic parameters of nevirapine and efavirenz in relation to antiretroviral efficacy.

Optimal adherence is essential for successful antiretroviral therapy. We analyzed the relation between minimum plasma drug concentration (Cmin) and total drug exposure over 24 hr (AUC24) with virologic failure for therapy-adherent patients in the nevirapine (NVP) and efavirenz (EFV) groups of the double nonnucleoside study (2NN), which compared the efficacy of NVP and/or EFV together with stavudine and lamivudine. The objective was to find cutoff values of the Cmin and AUC24 below which the risk of virologic failure increased. The relation between Cmin and AUC24 with virologic failure (never a plasma viral load [pVL] < 50 copies/ml or a rebound to two consecutive pVL > 50 copies/ml) was analyzed with proportional hazard analyses. Data were censored at end of study or change of allocated treatment. The risk of virologic failure with NVP (n = 511) started to increase at a Cmin < 3.1 mg/L (hazard ratio [HR], 1.33; 95% confidence interval [CI], 0.89-1.97), but there was no cutoff value below which a statistically significant increased risk occurred. Neither was such a cutoff point identified for the AUC24. The risk of virologic failure with EFV (n = 312) was significantly increased at a Cmin < 1.1 mg/L (HR, 1.95; 95% CI, 1.08-3.54) and an AUC24 < 40 mg x hr x L1 (HR, 1.95; 95% CI, 1.07-3.54). Both cutoff values represent the median values for adherent patients. These associations were driven by patients from Thailand. Adjusting for geographical region made the association between Cmin and AUC24 with virologic failure statistically nonsignificant. The sensitivity of the Cmin values was too low (29% for NVP, 64% for EFV) to be an adequate predictor for virologic failure. We conclude that identifying the Cmin value for the sole purpose of predicting virologic failure in patients who report to be adherent to NVP or EFV is questionable because of the absence of a concentration-response relation (NVP) or the low sensitivity for such a cutoff value (NVP and EFV).

A recent increase in AIDS at Lyon University Hospitals: patient characteristics and comparisons with previous years.

BACKGROUND: A 36% increase in the incidence of AIDS was observed in 2002/2003 compared with 2000/2001 at Lyon University Hospitals. OBJECTIVES: We compared the characteristics of these patients with the characteristics of those diagnosed previously with AIDS. METHODS: Data for all patients with AIDS diagnosed at Lyon University Hospitals were analyzed. The data were collected prospectively. Multiple logistic regression was used for analysis. RESULTS: The variables independently associated with an AIDS diagnosis in 2002/2003 compared with the 1985-1989 period were: homosexual exposure [odds ratio (OR) 0.4; 95% confidence interval (CI) 0.2-0.8]; heterosexual exposure in an endemic area (OR 22.5; 95% CI 6.8-74.8), compared with other exposure to HIV; lymphoma as initial AIDS event (OR 10.3; 95% CI 2.7-39.1) compared with Pneumocystis carinii pneumonia; and age at first AIDS event aged 34-38 years (OR 2.5; 95% CI 1.0-6.4), aged 39-46 years (OR 5.1; 95% CI 2.2-11.8), and aged 47-84 years (OR 10.6; 95% CI 4.5-25.1) compared with aged <30 years. The variables independently associated with an AIDS diagnosis in 2002/2003 compared with the 1997/2001 period were age at first AIDS event aged 34-38 years (OR 0.4; 95% CI 0.2-0.9) compared with aged <30 years. CONCLUSION: Recently diagnosed AIDS patients differed from those diagnosed previously, showing an epidemic switch in different populations. The characteristics of the AIDS population in 2002/2003 might reflect public health messages disseminated around 10 years ago or more for the prevention of HIV transmission. Anticipation of populations affected by the AIDS epidemic is difficult.

[Redox status in HIV+ patients under HAART]. / Statut oxydatif de patients VIH positifs sous trithérapie.

Oxidative stress decreases immune defences and is also suggested to participate in the activation of HIV virus replication. That is why we decided to explore some biomarkers of oxidative stress (reduced glutathione, lipoperoxides, true malondialdehyde and vitamin C) in 20 HIV positive patients whose HIV replication was determined by measurement of RNA viral load. Reduced glutathione is decreased in HIV positive patients, without correlation with the viral load. The patients mean content of lipoperoxides is twice that of controls but with such a large range that there is no statistical difference.

Survival in HIV-infected patients is associated with hepatitis C virus infection and injecting drug use since the use of highly active antiretroviral therapy in the Lyon observational database.

Highly active antiretroviral therapy (HAART) has reduced the incidence of death in HIV-infected patients but various rates of survival have been reported due to the infection with hepatitis C virus (HCV) and the use of injecting drugs (IDU). A survival analysis was performed to estimate and compare the death rates in HIV-positive patients infected by IDU and/or positive for HCV antibodies in the pre-HAART and HAART periods in Lyon (France) between 1992 and 2002. Patients were stratified into four groups (G): HCV-/IDU-(G1), HCV+/IDU-(G2), HCV+/IDU-(G3), HCV+/IDU+ (G4) and adjusted death rates in the pre-HAART era (< 1996) and the HAART era (> or = 1996) were compared. The aHR of progression to death was 1.05 (95% CI 0.75-1.47, P = 0.75) for G2, 1.09 (95% CI 0.54-2.22, P = 0.81) for G3 and 0.90 (95% CI 0.65-1.24, P =0.51) for G4 compared with G1 in the pre-HAART era. The aHR of progression to death was 0.76 (95% CI 0.28-2.08, P = 0.59) for G2, 1.23 (95% CI 0.17-8.86, P = 0.84) for G3 and 2.90 (95% CI 1.62-5.20, P < 0.001) for G4, compared with G1 in the HAART era. HAART management of HCV+/IDU+ patients needs to be optimized for them to achieve a similar benefit as observed among other individuals.

Characteristics of patients diagnosed with AIDS shortly after first detection of HIV antibodies in Lyon University hospitals from 1985 to 2001.

A diagnosis of AIDS shortly after the detection of HIV antibodies suggests a long-lasting course of the disease without care. The factors associated with a short delay between the initial HIV-1-positive test and the first AIDS-defining event were identified in 1901 patients from 1985 to 2001 in Lyon University hospitals. A total of 576 individuals (30.3%) had an interval of /=60 years (OR 4.5; 95% CI 2.5-8.1), compared to those<30 years old; heterosexuality (OR 2.4; 95% CI 1.6-3.4); injection drug use (OR 2.1; 95% CI 1.5-2.7); and other exposures (OR 2.4; 95% CI 1.6-3.4), compared to homosexual exposure; two opportunistic infections at AIDS (OR 1.8; 95% CI 1.4-2.4) compared to one; and Pneumocystis carinii pneumonia as initial AIDS event (OR 2.6; 95% CI 1.8-3.7), compared to Kaposi's sarcoma. These results provide opportunities to refocus local public health interventions to reduce delayed access to care.

The AIDS epidemic in Lyon: patient characteristics and defining illnesses between 1985 and 2000.

OBJECTIVES: To define the characteristics of 1899 patients diagnosed with AIDS at Lyon University Hospitals (LUH) across four time periods corresponding to different antiretroviral eras, and to analyse the evolution of specific AIDS-defining illnesses (ADIs) with time. METHODS: All AIDS patients at LUH between 1 January 1985 and 31 December 2000 were included in the study. The data were compared using the chi(2) test and one-way analysis of variance. RESULTS: The absolute number of new AIDS cases increased by 30.3% between 1985 and 1995 but decreased by 26.5% between 1996 and 2000. The proportion of women with AIDS increased significantly (P<0.001) and mean age at diagnosis also increased significantly over time (P<0.001). The proportion of infection through heterosexual contact increased dramatically, while that through homo/bisexual intercourse or injection drug use (IDU) decreased significantly (P<0.001). The absolute number of ADIs declined with the introduction of highly active antiretroviral therapies (HAART) (P<10(-6)). Pneumocystis carinii pneumonia remained the leading ADI in 1996-2000 (23.3%). A significant increase in the proportion of non-Hodgkin's lymphoma (NHL) was observed over time (P<10(-5)) but the number of new NHL cases decreased during HIV infection after 1996. CONCLUSIONS: The decline in the incidence of AIDS with the advent of HAART was confirmed in our hospital cohort. The gradual increase in the proportion of NHL among ADIs underscores the long latency period between infection with HIV and the achievement of an effect of HAART on HIV-associated lymphomagenesis.

Early control of HIV replication in primary HIV-1 infection treated with antiretroviral drugs and pegylated IFN alpha: results from the Primoferon A (ANRS 086) Study.

IFN alpha has both antiviral and immunostimulating properties. The ANRS086 Primoferon A Study evaluated in 12 patients with primary HIV infection the tolerance and efficacy of an early and transient administration of pegylated IFN alpha, in addition to highly active antiretroviral therapy. Tolerance was good, and this regimen allowed the early control of HIV replication and rapid decay of the viral reservoir. These results support the initiation of comparative studies with pegylated INF alpha in primary HIV infection.

Decreased production of local immunoglobulin A to Pneumocystis carinii in bronchoalveolar lavage fluid from human immunodeficiency virus-positive patients.

An enzyme-linked immunosorbent assay and a Western blot analysis were developed to study the antibody response to Pneumocystis carinii in serum and bronchoalveolar lavage fluid from 27 human immunodeficiency virus 27 (HIV)-infected patients with P. carinii pneumonia (Pcp), 32 patients without Pcp, and 51 HIV-negative controls. Urea was used for the correct dilution of epithelial lining fluid, and albumin was used to evaluate transudation from plasma for the assessment of local production of antibodies to P. carinii. By contrast with those of immunoglobulin G (IgG), IgA responses to P. carinii were increased in serum from HIV-positive patients compared to negative controls. Local production of antibodies to P. carinii, especially IgA, was decreased in patients with Pcp. In a study of 10 patients of each group, IgG and IgA responses to gp116 from P. carinii were lower in patients with Pcp than in other groups. These results suggest that, in addition to alveolar macrophages, local antibodies may play a role in host defense against P. carinii.

Multiple eruptive dermatofibromas in a patient with HIV infection: case report and literature review.

Multiple eruptive dermatofibromas have been reported in the setting of autoimmune diseases treated with immunosuppressive drugs and more recently in the course of human immunodeficiency virus (HIV) infection. We report herein the ninth case of multiple eruptive dermato fibromas associated with HIV infection. The relevant literature is reviewed and the differences of these lesions from "ordinary" dermatofibromas are discussed.

[Intrathecal synthesis of anti-Toxoplasma gondii antibodies during cerebral toxoplasmosis associated with African AIDS]. / Synthèse intrathécale d'anticorps anti-Toxoplasma gondii au cours de la toxoplasmose cérébrale associée au sida africain.

Thirty-four HIV-1-infected in-patients of the Hôpital Central des Forces Armées Congolaises, Brazzaville, Congo, hospitalized for suspected cerebral toxoplasmosis, have been evaluated for integrity of the blood-brain barrier, intrathecal synthesis of total IgG, toxoplasmic serology in blood and cerebrospinal fluid, and for intrathecal synthesis of IgG to Toxoplasma gondii. An empiric scale to gauge the possibility of clinical cerebral toxoplasmosis was used to classify the patients (+, +2, +3). Only an intrathecal synthesis of IgG to Toxoplasma gondii was found to be associated with suspected cerebral toxoplamosis: it was found in about 80% of patients, and more frequently in patients with a higher probability of disease. In contrast, alteration of the blood-brain barrier, intrathecal synthesis of total IgG and toxoplasmic serology in blood as well as in cerebrospinal fluid were not associated with suspected cerebral toxoplamosis. Taken together, these findings confirm that intrathecal synthesis of antitoxoplasmic antibodies of IgG isotype occurs in cerebral toxoplasmosis. Demonstration of intrathecal synthesis of antitoxoplasmic IgG antibodies could be used to confirm clinical diagnosis of cerebral toxoplamosis, especially in an African context, where sophisticated laboratory facilities are often lacking.

Humoral immune response within the lung in HIV-1 infection.

In order to study the humoral immune defences in the respiratory tract during HIV-1 infection, we measured the levels, local productions and anti-HIV and antibacterial activities of IgG and IgA in the bronchoalveolar lavage fluid (BALF) and serum of 61 adult patients with severe HIV infection and of 56 HIV- controls. Albumin was used as the serum transudation factor. The increase of immunoglobulin levels in the serum of HIV-infected patients was confirmed. The IgG level was also increased in epithelial lining fluid (ELF), whereas the total IgA level was unchanged and secretory IgA (SIgA) level was decreased. The ELF/serum immunoglobulin ratios suggested that the IgG present in ELF resulted mainly from transudation, in contrast to SIgA, which was synthesized locally in controls but greatly diminished in HIV-infected patients. IgG to HIV-1 could be detected in BALF of all the patients, but IgA to HIV-1 only in 30% of patients. BAL IgG reacted more consistently and with a broader array of HIV-1 antigens than did IgA. BAL IgA, when present in samples, reacted primarily with viral envelope antigens. Because IgA specificities to some HIV-1 antigens were detected more intensively by BAL than by serum immunoglobulins, we conclude that the mucosal immune response is distinct from that in serum. IgG antibody activity to Streptococcus pneumoniae was decreased in HIV-infected patients' sera, and IgA antibody activities to S. pneumoniae and to Pseudomonas aeruginosa were decreased in ELF in HIV-infected patients.

Interleukin (IL)-2 deficiency aggravates the defect of natural killer cell activity in AIDS patients.

A decrease in natural killer (NK) cell activity is a common feature of the immune dysfunction found in patients with human immunodeficiency virus (HIV)-induced acquired immune deficiency syndrome (AIDS). The present study was aimed at exploring the NK and the lymphokine-activated killer (LAK) cell activities of lymphocytes from HIV-seropositive subjects. The in vitro production of interleukins (IL-2 and IL-10) in response to mitogens was also studied. Two groups of HIV-seropositive subjects were studied: asymptomatic and AIDS patients. Controls were normal blood donors. The NK cell activity in peripheral blood mononuclear cells (PBMC) from AIDS patients was significantly lower than that in PBMC from both HIV-seronegative subjects and asymptomatic patients. There was no significant difference between asymptomatic patients and controls. Exposure of PBMC from all three groups of individuals to an optimal dose of IL-2 in vitro enhanced LAK cell activity. At all three effector: target cell ratios, the LAK activity in AIDS patients remained below that in normal subjects. However, the proportional increase of lytic activity with IL-2 was slightly higher in AIDS patients than in HIV-seronegative subjects. The mitogen-induced production of IL-2 was especially reduced in AIDS patients. In contrast, very high levels of mitogen-induced production of IL-10 were found in the AIDS group, as compared to asymptomatic subjects or to controls. We therefore conclude that the alteration of NK cell activity occurs at an advanced stage of HIV infection, that the reduction of cytotoxic activity is partially restored by exogenous IL-2, and that decreased production of IL-2 and increased production of IL-10 may account for part of this reduction in cytotoxicity.