The safety profile and antiviral activity of the combination of stavudine, didanosine, and nelfinavir in patients with HIV infection

We assessed the safety profile, tolerability, and antiviral effect of 12 weeks of triple combination therapy with stavudine (d4T), didanosine (ddI), and nelfinavir in patients who had not previously received therapy with d4T, ddI, or a protease inhibitor. We also assessed the effect of the buffered tablet formulation of ddI on the pharmacokinetics of nelfinavir. The study had a single-arm, open-label design and enrolled patients aged > or =18 years who had HIV infection and > or =10,000 plasma HIV RNA copies/mL. Patients received the full recommended doses of oral d4T, ddI, and nelfinavir. Efficacy was assessed in terms of change from baseline in plasma HIV RNA and CD4+ cell counts, as well as in terms of the proportion of patients achieving HIV RNA levels <400 copies/mL. The first 10 patients enrolled in the study were included in a substudy to determine the effects of the buffered tablet formulation of ddI on the pharmacokinetic profile of nelfinavir. A dose of ddI was given 1 hour before nelfinavir, after which the maximum plasma concentration (Cmax), time to Cmax (Tmax), and area under the concentration-time curve (AUC) of nelfinavir were determined. A total of 22 patients entered the trial, of whom 1 (5%) had AIDS, 12 (55%) had symptomatic HIV infection, and 9 (41%) were asymptomatic. The median baseline CD4+ cell count was 315 cells/microL (range, 70-709 cells/microL), and the median plasma viral load was 4.8 log10 copies/mL (range, 4.0-5.6 log10 copies/mL). ddI had no clinically significant effects on the plasma pharmacokinetics of nelfinavir. At the end of 12 weeks of treatment, the mean (+/- SE) decrease in plasma viral load was 1.36+/-0.24 log10 copies/mL, and 8 of 16 patients (50%) achieved plasma HIV RNA levels <400 copies/mL; the mean (+/- SE) increase in CD4+ cell count was 111.4+/-31.7 cells/microL. Patients who were judged to be compliant with antiretroviral therapy (ie, who missed <7 days of all 3 study drugs during 12 weeks of treatment) experienced mean decreases in viral load exceeding 2.0 log10 copies/mL, and 6 of 7 patients achieved HIV RNA levels <400 copies/mL after 12 weeks of therapy. Although 95% of patients reported an adverse event of grade 1 or higher, only 1 patient experienced a grade 3 or 4 adverse event (maculopapular rash) related to nelfinavir. As reflected in the Cmax, Tmax, and AUC, administration of ddI 1 hour before nelfinavir did not influence the pharmacokinetic profile of the protease inhibitor. Triple drug therapy with d4T, ddI, and nelfinavir was well tolerated and associated with few clinically significant toxicities. This treatment resulted in substantial reductions in viral load and improvements in CD4+ cell count over 12 weeks.     

Oral lactoferrin in HIV-1 vertically infected children: an observational follow-up of plasma viral load and immune parameters

Lactoferrin (LF) is a mammalian iron-binding glycoprotein with antiviral effects. This preliminary study evaluated 6 months' LF (3 g/day, orally) treatment in 22 human immunodeficiency virus type 1 (HIV-1) vertically infected children. Plasma viral load and CD4+ cell counts were assessed every 3 months; before, during and after LF administration. No significant changes were observed during the pre-treatment period. By 6 months, mean (+/- SD) plasma viral load (log10) declined from 4.54 (+/- 0.65) to 4.28 (+/- 0.60); median percentage CD4+ cell count increased from 21.5% to 24.5%. Two months after treatment discontinuation, mean plasma viral load did not differ significantly from baseline or month 6 levels, but the percentage CD4+ cell count remained significantly higher than the baseline value. LF plus antiretroviral (ARV) therapy was more effective at increasing CD4+ cell count than LF alone. None of the patients showed any new HIV-1-related symptoms at follow-up. LF might be a useful addition to ARV therapy, but further large-scale studies are required.     

Antiretroviral therapy of acute HIV-infection

AIM: To study efficacy of a short course of highly active antiretroviral therapy (HAART). MATERIAL AND METHODS: Acute HIV infection was verified in 16 infected subjected basing either on seroconversion (by immunoblotting) or a documented negative result 6-12 months before registration of a positive result for HIV antibodies. RESULTS: HAART was given to 12 patients (combivir + nevirapin). The number of CD+ lymphocytes (by median) 1 month after the treatment increased by 185 cells/mcl, 3 months after the treatment--by 215 cells/mcl. After 1-month therapy viral load (median) diminished by 2.02 log10 copy/ml, after 3 months--by 2.31 log10 copy/ml. 71% patients had HIV RNA under 400 copy/ml. Untreated patients showed changes neither in CD4+ lymphocytes number nor in viral load. The study continues. CONCLUSION: HAART is used at the stage of acute infection in the presence of psychic trauma provoked by establishment of HIV-infection diagnosis. Therefore, it is necessary to consult the patients for preparing them for treatment and to maintain compliance.     

HCV RNA对HIV合并HCV感染者高效抗逆转录病毒治疗的影响

目的 探讨HCV RNA对HIV和HCV合并感染者接受高效抗反转录病毒治疗(highlyactive antiretroviral therapy,HA.ART)后疗效、肝脏功能和血脂的影响.方法 招募我国河南既往有偿供血人群中接受HAART治疗的HIV/HCV合并感染者275例,每6个月随访一次,定期检测HCVRNA、HIV RNA、CD+4T淋巴细胞计数、肝脏功能指标和血脂等实验室指标,采用卡方检验、成组设计秩和检验比较HCV RNA阳性组和HCV RNA阴性组HAART治疗后HIV病毒抑制率、免疫学应答、肝损伤和血脂的差异.结果 HAART治疗6月以上患者中,HCV RNA阳性组和HCV RNA阴性组HIV完全抑制率差异无统计学意义(45.6%vs.38.5%,x2=1.150,P>0.05);HAART治疗前(286个/μ1 vs.209个/μ1,z=0.734,P=0.463)、治疗后6个月(310个/μ1 vs.362个/μ1,z=0.562,P=0.574)、12个月(378个/μl vs.289个/μ1,Z=1.091,P=0.275)、18个月(363个/μ1 vs.288个/μ1,z=1.435,P=0.151)、24个月(413个/μ1 vs.348个/μ1,z=0.939,P=0.348)CD+4;T淋巴细胞计数在HCV RNA阳性组和HCV RNA阴性组间差异无统计学意义.HCV HNA阳性组血清ALT(55.0 U/L vs 29.5 U/L,Z=6.789,P<0.01)、AST(46.0 U/L vs.33.0 U/L,Z=4.890,P<0.01)、TBIL(9.3 mmol/L vs.7.2 mmol/L,z=3.748,P<0.01)水平显著高于HCV RNA阴性组;HCV RNA阳性组HAART治疗后发生肝损伤的风险显著高于HCV RNA阴性组(调整后优势比aOR=3.8,P<0.01).HIV/HCV合并感染者HCV RNA阳性组TG水平显著低于HCV RNA阴性组(1.2 mmol/Lvs.1.4 mol/L,Z=1.936,P=0.043)、而HDL-C水平显著高于HCV RNA阴性组(1.5 mmol/L vs.1.3 mmol/L,z=2.251,P=0.024).结论 HCV RNA对HIV/HCV合并感染者HAART治疗后HIV病毒抑制率无影响,亦不影响HAART治疗后CD+4淋巴细胞的恢复;HCV RNA是HIV/HCV合并感染者HAART治疗后肝损伤的独立危险因素,但可能减轻HAART治疗引起的血脂异常.     

Disease severity and symptoms of depression in Black Americans infected with HIV.

The purpose of this study was to examine depressive symptomatology in a sample of human immunodeficiency virus (HIV) infected Black Americans and to determine the extent to which measures of HIV disease severity were associated with depressive symptoms. Seventy-nine HIV-infected Black men and women (ages 25 to 68 years) participated. Measures included the Center for Epidemiologic Studies Depression Scale (CES-D) and multiple HIV disease severity variables including CD4+ lymphocyte count, CDC HIV stage, and HIV RNA viral load. Levels of self-reported depressive symptoms were high, with 58% (n = 48/79) of study participants exhibiting elevated depressive symptoms (CES-D score of > or =16). No relationship was found between CD4+ count, CDC HIV stage, sociodemographic variables, and depressive symptoms. Viral load, however, was positively correlated with elevated depressive symptoms. Although the level of depressive symptomatology was high, only two participants were receiving antidepressant medication. This study suggests that there is a significant unmet need for identification and treatment of depressive symptoms among Blacks receiving routine care for HIV disease.     

Stavudine plus didanosine and nevirapine in antiretroviral-naive HIV-infected adults: preliminary safety and efficacy results. VIRGO Study Team

The objective of this open-label trial is to evaluate the virological and immunological effects of triple therapy with stavudine (40 mg twice daily if > or = 60 kg, 30 mg twice daily if < 60 kg)/didanosine (400 mg once daily if > or = 60 kg, 300 mg once daily if < 60 kg)/nevirapine (200 mg daily from day 1 to 14, then 200 mg twice daily) in 60 antiretroviral-naive HIV-infected adults with CD4 cell counts > or = 200 cells/mm3 and plasma HIV RNA > or = 5000 copies/ml. At present, 59 patients have begun receiving the trial regimen. Characteristics of patients at baseline were as follows: 46 men/13 women, CDC stage A, 75%; mean CD4 cell count, 429 cells/mm3; mean HIV RNA, 4.6 log10 copies/ml). Mean decrease of viral load was -1.9 log10 at week 4 (n = 39), -1.9 log10 at week 16 (n = 20), with HIV RNA below the detectable level (< 500 copies/ml) in 62% of patients at week 4 and 85% at week 16. Mean CD4 cell count increase was +118 cells/mm3 at week 4. Cutaneous intolerance occurred within the first 4 weeks in 11/59 (19%) patients after a mean of 14 days (range, 3-24 days) and led to nevirapine discontinuation in 3/11 patients. Preliminary results of this ongoing trial show that combination therapy with stavudine/didanosine/nevirapine is a convenient (seven pills in two daily intakes) triple-therapy regimen with rapid immunological and antiviral effects. Rash, frequent in the first weeks of therapy, usually can be managed without stopping nevirapine. Long-term suppression of plasma HIV RNA with this combination needs to be confirmed but may support use of nevirapine as a component of first-line anti-HIV therapy along with two nucleosides.     

The use of highly active antiretroviral therapy (HAART) in patients with advanced HIV infection: impact on medical, palliative care, and quality of life outcomes

The effect of highly active antiretroviral therapy (HAART) in the treatment of HIV infection is usually measured by survival, CD4 lymphocyte counts, HIV-1 RNA viral load testing, and the occurrence of opportunistic infections. This pilot study sought to measure the impact of HAART treatments on a wide range of clinical outcomes and psychological variables in a sample of patients with advanced HIV infection. Seventy patients with advanced AIDS who were protease inhibitor na?ve were started on HAART regimens. Patients were admitted to an AIDS inpatient unit of a long-term care facility that provides treatment and palliative care. All patients were diagnosed with AIDS, had CD4 cell counts below 300/cc(3), and had a projected survival of greater than one month. Patients were started on triple-drug HAART regimens with daily medical supervision and observation. In addition to standard clinical and laboratory markers, a series of observer-rated and self-report instruments were used to measure various physical and psychological factors (e.g., pain and symptom distress, psychological well-being, depression). Data were collected at baseline and after 1 and 3 months of HAART therapy. As expected, the CD4 count increased and viral load levels decreased significantly over the 3-month study period. In addition, patients improved significantly in body weight, and serum albumin and ferritin levels. The only psychosocial measure that improved significantly with treatment was depression. Ratings of pain intensity, physical and psychological symptom distress, and overall quality of life did not change. Of the 70 patients studied, 84.3% were still alive after the 3-month study period. Of these, 6 (8.6%) were discharged to community. However, 17 surviving patients (24.3%) had HAART regimens discontinued due to drug intolerance and 11 patients (15.7%) expired during the study period. While these data are preliminary, HAART regimens appear to have positive effects on CD4 count, HIV viral load, and several other measures of physical well-being in patients with advanced AIDS. Despite these improvements, the benefits of treatment on pain and symptom distress, and psychological well-being were less clear. In addition, treatment failure (mortality and intolerance) were not uncommon in this sample (40%). Further research is clearly necessary to better understand the benefits of HAART therapy in patients with advanced HIV infection.     

HIV/HCV混合感染CD4+细胞计数与HCV病毒载量的相关性研究

目的:通过分析HIV/HCV混合感染的CD4+细胞计数与HCV病毒载量(HCVVL)的相关性,探讨HIV感染时细胞免疫状况对HCV病毒水平的影响。方法:同时测定CD4+细胞计数与HCV-RNA定量,研究两者的相关性。结果:CD4+细胞计数与HCV-RNA定量不相关(r=-0.120,P=0.479)。结论:HIV/HCV混合感染时,细胞免疫状态对HCV病毒载量没有明显影响。     

Interrupting highly active antiretroviral therapy in patients with HIV

Scheduled treatment interruptions are preplanned interruptions of antiretroviral treatment, which may be directed by time (e.g., cycles of 8 weeks on treatment and 8 weeks off treatment); the concentration of CD4+ lymphocytes (the CD4 count); HIV-1 RNA concentration (viral load); or other factors. This review covers the rationale of scheduled treatment interruptions and the different strategies that have been explored. It examines the issue of autovaccination, resistance and other risks and benefits. Scheduled-treatment-interruption studies in three populations are discussed: patients who initiated highly active antiretroviral therapy during acute HIV infection; patients with successfully treated chronic HIV infection; and patients with highly active antiretroviral therapy failure.     

Immunological and virological activity of zalcitabine and zidovudine in combination in HIV-positive people with CD4 cell counts of between 200-500 cells/mm3

We evaluated the effect of combination therapy with zidovudine (AZT) plus zalcitabine (ddC) in human immunodeficiency virus type 1 (HIV-1)-infected patients who had not previously received antiretroviral treatment ('naive' patients). The immunological and virological parameters evaluated were CD4 cell count, syncytium-inducing (SI) viral phenotype and plasma HIV-1 RNA copies/ml (HIV viral load). A total of 75 patients entered the study, with CD4 cell counts between 200 and 500 cells/mm3. All received zidovudine (200 mg) plus zalcitabine (0.75 mg) three times daily for 24 weeks. Treatment was well tolerated. However, four patients presented with anaemia (haemoglobin < 10.0 g/dl) and one patient had both anaemia and neutropenia (0.8 x 10(9) neutrophils/l). Combination therapy with zidovudine plus zalcitabine resulted in a pronounced improvement of virological and immunological markers. Approximately 25% of patients achieved undetectable plasma HIV RNA levels (< 200 copies/ml) at week 24. At the end of the study (24 weeks) a significant reduction (> 0.5 log) of plasma HIV RNA was observed in approximately 70% of patients and in 50% an even greater decrease (> 1 log) was achieved. The most significant decrease in mean plasma HIV RNA levels was observed at week 4, whereas the highest increase in CD4 cell count was found at week 24. Approximately 80% of patients who showed baseline plasma HIV RNA levels below 20000 copies/ml had less than 5000 copies/ml at week 24. The plasma HIV RNA reduction observed at week 4 was significantly maintained at week 24. Therefore, we can rapidly select those who will not respond to therapy and adjust the treatment after a short interval. Our study supports the idea of early therapy because all patients who reached undetectable levels of plasma HIV RNA at week 24 had at baseline a median plasma HIV RNA load of 2560 copies/ml. In conclusion, zidovudine in combination with zalcitabine was well tolerated in the majority of patients and led to a significant reduction in plasma HIV RNA copies in most of the patients with initial viraemia lower than 20000 copies/ml.     

Immunomodulation induced by tucaresol in HIV infection: results of a 16 week pilot Phase I/II trial

OBJECTIVE: Immune reconstitution in highly active antiretroviral therapy (HAART)-treated individuals is incomplete and immunomodulatory compounds are needed to improve the outcome of HIV therapy. In a Phase I/II clinical trial performed on HIV-positive patients we analysed the safety and immunomodulating effects of tucaresol, a novel compound that has previously been described tn enhance cell-mediated immune responses. PATIENTS AND METHODS: Sixteen weeks pulse dose escalation protocol. Four groups of HIV-positive patients were enrolled: group A (n=6): HAART, CD4+ 300-500 cells/microl, HIV RNA <80 copies/ml; group B (n=6): HAART-naive, CD4+ <500 cells/microl, HIV RNA >10 000 copies/ml; group C (n=3): HAART-naive, CD4+ >500 cells/microl, HIV RNA <10000 copies/ml; and group D (n=6): HAART, CD4+ <200cells/microl, HIV RNA <80 copies/ml. Tucaresol was added to HAART in group A and D patients; group B patients started tucaresol with HAART, group C patients received tucaresol alone. Clinical and immunological analyses were performed at different time points. RESULTS: Tucaresol-related serious adverse events were observed in the first week of therapy in 2/21 patients who were viraemic when commencing treatment, but did not occur in patients on stable HAART. Tucaresol did not affect HIV viraemia whereas increases in CD4+ percentages, mainly supported by naive CD4+ cells, were observed. CD8+/28-/45RA+ cells and HIV-specific CD8+ IFNgamma- and perforin-producing cells improved whereas IL-10 mRNA diminished in tucaresol-treated patients. The effects were greater with 25 mg given every other day for 1 week. CONCLUSION: In HAART-receiving patients with proper virus suppression, tucaresol was not associated with serious adverse events and resulted in qualitative and quantitative stimulation of HIV-specific cytotoxic T lymphocyte activity and generation of naive T cells. These data may support further exploration of tucaresol use in reconstitution of immune system parameters in HIV patients with proper virus suppression while on HAART.     

HIV/TB并发感染患者外周血 T淋巴细胞表达及与 HIV RNA载量的相关性研究

目的　探讨人类免疫缺陷病毒 /结核病（ human immunide.ciency virus/tuberculosis,HIV/TB）并发感染患者的外周血 T淋巴细胞亚群的表达及其与 HIV RNA载量的相关性。方法　选取 2018年 6月～ 2020年 6月在南京市公共卫生医疗中心就诊的 HIV/TB并发感染患者 38例作为 HIV/TB组,另选取单纯人类免疫缺陷病毒 /获得性免疫缺陷综合征（human immunode.ciency virus/acquired immune de.ciency syndrome,HIV/AIDS）39例作为 HIV组,单纯 TB患者 35例作为 TB组,体检健康者 35例作为健康对照组。流式细胞术检测各组 CD3+,CD4+,CD8+ T细胞计数和 CD4+/CD8+比值;荧光定量 PCR检测 HIV RNA载量。采用 SPSS17.0统计学软件进行统计分析,并进行 Spearman相关系数分析。结果　CD3+,CD4+和 CD8+ T细胞数, CD4+/CD8+比值在各组中的差异均具有统计学意义（ H=40.758,104.279,9.637和 101.770,均 P＜ 0.05）,组间两两比较结果表明,与健康对照组相比, TB组 CD3+和 CD8+T细胞数明显降低,差异均有统计学意义（ Z=-2.520,-2.972,P=0.012,0.003）;HIV组和 HIV/TB组 CD3+,CD4+ T细胞数以及 CD4+/CD8+比值均明显降低（ Z=-7.391~-4.325,均 P=0.000）。与 TB组相比, HIV组 CD3+, CD4+ T细胞数和 CD4+/CD8+比值均明显降低,差异均有统计学意义（ Z=-2.138,-7.032和 -7.380,P=0.032,0000和 0.003）,但 CD8+ T细胞数明显升高（Z=-2.463,P=0.014）;而 HIV/TB组 CD3+和 CD4+ T细胞数以及 CD4+/CD8+比值均明显降低,差异均有统计学意义（Z=-3.865,-6.907和 -6.759,均 P=0.000）。与 HIV组相比, HIV/TB组的各项流式指标及 HIV RNA载量差异均无统计学意义（均 P >0.05）。HIV RNA载量与 CD3+,CD4+,CD8+ T细胞数以及 CD4+/CD8+比值均呈显著负相关（ r分别为 -0.327,-0.370,-0.296和 -0.327,均 P <0.05）。结论　HIV/TB并发感染患者外周血 CD3+,CD4+ T细胞数和 CD4+/CD8+比值均明显降低。无论有无并发 TB感染,HIV感染者的细胞免疫功能均随着病毒载量的升高而显著降低。     

Restoration of blood total glutathione status and lymphocyte function following alpha-lipoic acid supplementation in patients with HIV infection

OBJECTIVES: To determine whether supplementation with alpha-lipoic acid (ALA), a glutathione-replenishing disulfide, modulates whole blood total glutathione (GSH + GSSG) levels and improves lymphocyte function in human immunodeficiency virus (HIV)-infected subjects with history of unresponsiveness to highly active antiretroviral treatment (HAART). DESIGN AND SETTING: Randomized, double-blinded, placebo-controlled trial conducted at two study sites: an eye clinic at a county hospital in San Jose and a research clinic in San Francisco, California. SUBJECTS: A total of 33 HIV-infected men and women with viral load >10,000 copies/cm(3), despite HAART, aged 44-47 years, approximately 36% nonwhite, were enrolled. INTERVENTION: Patients were randomly assigned to receive either ALA (300 mg three times a day) or matching placebo for 6 months. MAIN OUTCOME MEASURES: The change over 6 months in blood total glutathione status, lymphocyte proliferation response to T-cell mitogens, CD4 cell count, and viral load in patients receiving ALA compared to placebo. RESULTS: The mean blood total glutathione level in ALA-supplemented subjects was significantly elevated after 6 months (1.34+/-0.79 vs. 0.81+/-0.18 mmol/L) compared to insignificant change (0.76+/-0.34 vs. 0.76+/-0.22 mmol/L) in the placebo group (ALA vs. placebo: p=0.04). The lymphocyte proliferation response was significantly enhanced or stabilized after 6 months of ALA supplementation compared to progressive decline in the placebo group (ALA vs. placebo: p<0.001 with phytohemagglutinin; p=0.02 with anti-CD3 monoclonal antibody). A positive correlation was seen between blood total glutathione level and lymphocyte response to anti-CD3 stimulation (R(2)=0.889). There was no significant change in either HIV RNA level or CD4 count over 6 months in the ALA-supplemented compared to the control group. CONCLUSION: Supplementation with alpha-lipoic acid may positively impact patients with HIV and acquired immune deficiency syndrome by restoring blood total glutathione level and improving functional reactivity of lymphocytes to T-cell mitogens.     

Administration of efavirenz (600 mg/day) with rifampicin results in highly variable levels but excellent clinical outcomes in patients treated for tuberculosis and HIV

OBJECTIVES: Pharmacokinetic interactions between rifampicin and antiretroviral therapy (ART), including efavirenz, are problematic and need to be better defined to determine proper dose and to be correlated with short-term and long-term clinical outcomes. PATIENTS AND METHODS: Consenting patients with smear-positive pulmonary TB and HIV received once daily didanosine + lamivudine + efavirenz (600 mg), with rifampicin-containing TB regimen by directly observed therapy and self-administration at TB therapy completion. Trough efavirenz levels were measured by HPLC at 1, 2, 4 and 6 months while on rifampicin and after discontinuation. HIV and TB outcomes were monitored. RESULTS: Twenty African patients were enrolled [15 female, mean age 31 years, baseline weight 59.4 kg (range 45-97), viral load 5.75 log10 copies/mL and CD4 230 cells/mm3]. Seventy-two efavirenz concentrations were available from 19 patients (58 on, 14 after rifampicin). The geometric mean efavirenz concentration was 1730 ng/mL (range 354-27,179) on and 1377 ng/mL (range 572-3975) off rifampicin (P = 0.55). Inter-subject variability in efavirenz concentrations was greater on rifampicin (CV 157% versus 58% off) with relatively consistent intra-subject variation over time (median CV 24%). Over half of patients had efavirenz concentrations above or below the expected therapeutic range (1000-4000 ng/mL). Efavirenz levels were not predicted by weight or gender and were not associated with HIV clinical outcomes. Overall 80% of patients had non-detectable viral loads at 6 months and 65% at 21 months with a cumulative CD4 cell increase of 196 cells/mm3. CONCLUSIONS: In this longitudinal study, despite wide variability in plasma efavirenz concentrations during rifampicin administration, excellent clinical outcomes were obtained. In African patients treated for HIV and TB, our data support the routine use of efavirenz at 600 mg/day when receiving rifampicin.     

Long-term methadone treatment: effect on CD4+ lymphocyte counts and HIV-1 plasma RNA level in patients with HIV infection

The objective was to examine the effect of methadone on CD4+ lymphocyte counts and viral load and to expect to document the safety of methadone maintenance in patients with human immune deficiency syndrome. This is a retrospective chart analysis comparing the trends in CD4+ count and viral load in two populations of 21 human immunodeficiency virus (HIV) infected patients, one on methadone maintenance and a methadone non-using group. Each methadone user was matched with a control methadone non-user that had a similar CD4+ at the beginning of the study. For the CD4+ count we compared the slope of regression for each couple of patients. In 15 patients we also collected the viral load, which was measured at 4-6 monthly intervals. The mean length of follow-up was 811 days for the methadone group and 797 days in the control group. There was no statistical difference in the treatment received by the two groups of patients during the study. The slope of regression of CD4+ count showed a significantly steeper decline in the methadone-using patients compared with the methadone non-users (r= 0.487; p< 0.05). The evolution of the HIV-1 RNA levels was the same during the follow-up of mean 186 months in a few of the patients in each of the two groups. Long-term methadone use was associated with a significantly faster decrease of CD4+ count in HIV-1 affected patients compared with methadone non-users. HIV-1 RNA data were found in too few patients to enable any conclusions about the development of viral load in the two groups.