Initiation of antiretroviral therapy at CD4 cell counts >/=350 cells/mm3 does not increase incidence or risk of peripheral neuropathy, anemia, or renal insufficiency

BACKGROUND: US guidelines recommend deferring initiation of highly active antiretroviral therapy (HAART) for most patients with CD4 counts >350 cells/mm in part because of concerns about antiretroviral toxicity. METHODS: Incidence rates of peripheral neuropathy, anemia, and renal insufficiency in a cohort of 2165 patients followed more than 3 years (mean) were analyzed in multivariate Cox proportional hazards models by CD4 cell counts at initiation of HAART. A nested cohort of 895 patients restricted to study participants who did or did not start HAART within a CD4 cell count stratum were also compared. RESULTS: Incidence and risks of all 3 comorbidities decreased with initiation of HAART at CD4 counts >200 cells/mm versus <200 cells/mm. Incidence and risks of renal insufficiency were similar with HAART initiation at CD4 counts >/=350 cells/mm versus 200 to 349 cells/mm, but risk of peripheral neuropathy and anemia were further decreased in persons starting HAART at a CD4 count >/=350 cells/mm. The incidence of these conditions was highest during the first 6 months of treatment at any CD4 cell count and declined up to 19-fold with further therapy. DISCUSSION: Initiating HAART at CD4 cell counts >/=200 cells/mm reduced the incidence and risk of the 3 comorbid conditions and for anemia and peripheral neuropathy as well by starting at CD4 counts >/=350 cells/mm. The incidence of each condition decreased rapidly and remained low with increasing time on HAART.     

HIV diagnosis at CD4 count above 500 cells/mm3 and progression to below 350 cells/mm3 without antiretroviral therapy

A trial to evaluate the risks and benefits of initiation of antiretroviral therapy (ART) in patients with high CD4 count (eg, > or =500 cells/mm3), in comparison with deferral (eg, to <350 cells/mm3), merits consideration. Two issues for consideration in designing such a trial are the proportion of patients seen in clinics who present with high CD4 count and the time it will take for those randomized to deferring ART to reach a level where ART must be initiated. Among 13,572 patients in the UK CHIC Study presenting since 1996, 3631 (27%) had a count > or =500 cells/mm3. Among 4268 ART-naive patients with at least one CD4 count in the 500 to 650 cells/mm3 range, the median time to <350 cells/mm3 (or start of ART) was 2.5 years, with a range of 2.1 to 3.1 years depending on the analysis approach. Viral load at baseline was a strong predictor of the time taken for the CD4 count to reach <350 cells/mm3, with the median ranging from 0.7 years in those with viral load > or =500,000 copies/mL to 4.7 years in those with <1000 copies/mL. This provides timely background data on ART-naive patients seen in clinical practice to support design of a trial to compare immediate with deferred ART in people with high CD4 count.     

Long-term CD4+ T-cell response to highly active antiretroviral therapy according to baseline CD4+ T-cell count

Current treatment guidelines for HIV infection recommend a relatively late initiation of highly active antiretroviral therapy (HAART). Nevertheless, there is still a concern that immune recovery may not be as complete once CD4+ T cells have decreased below a certain threshold. This study addressed the long-term response of CD4+ T-cell counts in patients on HAART and analyzed the influence of baseline CD4+ T-cell counts, baseline viral load, and age. An observational analysis of evolution of CD4+ T cells in 861 antiretroviral therapy-naive chronic HIV-1-infected patients who started treatment consisting of at least 3 drugs in or after 1996 was performed. Patients were classified in 4 groups according to baseline CD4+ T cells: <200 cells/mm3, 200-349 cells/mm3, 350-499 cells/mm3, and >or=500 cells/mm3. The main outcome measures were proportion of patients with CD4+ T cells <200/mm3 and >500/mm3 at last determination and rate of CD4+ T-cell recovery. Patients were followed-up for a median of 173 weeks (interquartile range [IQR], 100-234). There were no differences in follow-up between the 4 groups. CD4+ T cells increased in the whole cohort from a median of 214 cells/mm3 (IQR, 90-355) to 499 cells/mm3 (IQR, 312-733) (P<0.001). Compared with the group with a baseline CD4+ T-cell count of >or=500/mm3, the relative risk of having a last determination of CD4+ T-cell counts >200 cells/mm3 was 0.79 (95% CI, 0.75-0.83), 0.92 (95% CI, 0.89-0.96) and 1 for baseline CD4+ T cells <200 cells/mm3, 200-349 cells/mm3, and 350-499 cells/mm3, respectively. The relative risk of having a last determination of CD4+ T-cell counts >500 cells/mm3 was 0.32 (95% CI, 0.27-0.39, P<0.001), 0.69 (95% CI, 0.60-0.79, P<0.001), and 0.94 (95% CI, 0.83-1.06, P=0.38) for baseline CD4+ T-cell counts <200 cells/mm3, 200-349 cells/mm3, and 350-0499 cells/mm3, respectively, compared with a baseline CD4+ T-cell count of >or=500 cells/mm3. The increase in CD4+ T cells from baseline was statistically significant and was maintained for up to 4 years of follow-up. This increase seemed to slow down after approximately 3 years and reached a plateau after 4-5 years of follow-up even in patients who achieved and maintained viral suppression in plasma. Long-term immune recovery is possible regardless of baseline CD4+ T-cell count. However, patients who start therapy with a CD4+ T-cell count <200 cells/mm3 have poorer immunologic outcome as measured by the proportion of patients with CD4+ T cells <200/mm3 or >500/mm3 at last determination. It seems that the immune recovery slows down after approximately 3 years of HAART and reaches a plateau after 4-5 years of HAART.     

Changes in outcome of persons initiating highly active antiretroviral therapy at a CD4 count less than 50 Cells/mm3

BACKGROUND: Although HIV treatment guidelines recommend highly active antiretroviral therapy (HAART) initiation before reaching a CD4 count of 200 cells/mm3, many people in resource-rich settings, and a substantial proportion in resource-limited settings, present at levels <50 cells/mm3. METHODS: Using UK Collaborative HIV Cohort data, we assessed virologic response to HAART for antiretroviral-naive persons initiating therapy at a CD4 count <50 cells/mm3. We also investigated changes in the probability of having a viral level <400 copies/mL at 48 weeks over calendar time adjusting for gender, age, exposure category, ethnicity, baseline CD4 count and viral load, and whether the regimen contained a protease inhibitor. RESULTS: At 12, 24, 36, and 48 weeks, 80%, 83%, 85%, and 83% of participants, respectively, had a viral level <400 copies/mL. This proportion rose from 1997 to 1998, falling slightly in the most recent calendar period. By far the most important predictor of virologic suppression was calendar year of starting HAART (odds ratio [OR] = 2.49, 4.28, and 3.28 for 1999 to 2000, 2001 to 2002, and 2003 to 2005, respectively, compared with 1997 to 1998). Women were more likely to have a viral level <400 copies/mL at week 48 compared with men (OR = 1.74, 95% confidence interval [CI]: 1.07 to 3.02), as were older individuals (OR = 1.46, 95% CI: 1.11 to 1.96 for every 10 years older). There was marginal or no evidence that other factors were associated with outcome. The estimated corresponding probabilities of achieving a viral level <50 copies/mL at week 48 were 71%, 75%, and 79% for a woman aged 25, 35, and 45 years, respectively, initiating HAART in the most recent calendar period. The respective probabilities for a man at those ages were 68%, 73%, and 78%. CONCLUSIONS: These data, albeit under conditions of good infrastructure for care delivery, are a useful comparator for other populations starting therapy at similar levels of immunodeficiency and may be valuable for evaluating the success of antiretroviral therapy rollout programs.     

Virologic and immunologic response to highly active antiretroviral therapy in indigenous and nonindigenous HIV-1-infected patients in the Netherlands

OBJECTIVE: To compare the results of antiretroviral treatment (highly active antiretroviral therapy [HAART]) in indigenous Dutch (ID) and nonindigenous HIV-1-infected patients in Amsterdam, the Netherlands. We focused on the largest groups of nonindigenous people visiting our outpatient clinic: patients from other industrialized countries (western), from Surinam/Netherlands Antilles (SNA), and from sub-Saharan Africa (SSA). DESIGN: Retrospective cohort analysis of 692 therapy-naive HIV-1-positive individuals who visited our outpatient clinic for the first time between July 1, 1996 and December 31, 2001. METHODS: We compared the groups at the time of their first visit to our clinic; at the start of HAART; and according to the virological, immunologic, and clinical treatment response during the 96 weeks after the start of HAART. RESULTS: Of the patients starting antiretroviral therapy, 362 were ID, 84 were western, 72 were from SNA, and 110 were from SSA. SNA and SSA patients had a lower CD4 cell count at first visit (ID = 330 cells/mm(3), western = 330 cells/mm(3), SNA = 250 cells/mm(3), and SSA = 170 cells/mm(3); P = 0.0002). Treatment in SNA and SSA patients was also started at a lower CD4 cell count, but the plasma HIV-1 RNA level was comparable. After the start of HAART, a similar rise in CD4 cell count was seen in the 4 groups (P = 0.33), but the baseline difference in CD4 cell count remained present during the follow-up period of 96 weeks. After adjusting for variables potentially influencing treatment outcome, the proportion of patients not reaching a plasma HIV-1 RNA level <400 copies/mL was not different for the 4 groups in contrast to the percentage not reaching a plasma HIV-1 RNA level <50 copies/mL (at 48 weeks: ID = 4.8%, western = 27.5%, SNA = 23.1%, and SSA = 24.2%; P = 0.017 over the 96-week time period). After the start of HAART, nonindigenous patients also more often had progression to Centers for Disease Control and Prevention (CDC) stage C or died (P = 0.006). CONCLUSIONS: In nonindigenous patients, treatment with HAART was equally successful in terms of the increase in CD4 cell count but was substantially less effective in achieving a plasma HIV-1 RNA level below 50 copies/mL. Further investigations should explore differences in adherence and pharmacokinetics in these patient groups.     

The impact of adherence on CD4 cell count responses among HIV-infected patients

BACKGROUND: There have been concerns that irreversible immune damage may result if highly active antiretroviral therapy (HAART) is initiated after the CD4 cell count declines to below 350 cells/microL; however, the role of antiretroviral adherence on CD4 cell count responses has not been well evaluated. METHODS: We evaluated CD4 cell count responses of 1522 antiretroviral-naive patients initiating HAART who were stratified by baseline CD4 cell count (<50, 50-199, and >or=200 cells/microL) and adherence. RESULTS: Among patients starting HAART with <50 cells/microL, during the fifth 15-week period after the initiation of HAART, absolute CD4 cell counts were 200 cells/microL (interquartile range [IQR]: 130-290) for adherent patients versus 60 cells/microL (IQR: 10-130) for nonadherent patients. Similarly, among patients starting HAART with 50 to 199 cells/microL, during the fifth 15-week period after the initiation of HAART, absolute CD4 cell counts were 300 cells/microL (IQR: 180-390) versus 125 cells/microL (IQR: 40-210) for nonadherent patients. In Cox regression analyses, adherence was the strongest independent predictor of the time to a gain of >or=50 cells/microL from baseline (relative hazard [RH] = 2.88, 95% confidence interval [CI]: 2.46-3.37). Among patients with baseline CD4 cell counts <200 cells/microL, adherence was the strongest independent predictor of the time to a CD4 cell count >200 cells/microL (RH = 4.85, 95% CI: 3.15-7.47). CONCLUSIONS: These data demonstrate that substantial CD4 gains are possible among highly advanced adherent patients and should contribute to the ongoing debate over the optimal time to initiate HAART.     

Response to highly active antiretroviral therapy at 6 months and long-term disease progression in HIV-1 infection

OBJECTIVE: To compare the long-term prognostic significance of different definitions of immunologic and virologic responses to highly active antiretroviral therapy (HAART) at 6 months. METHODS: This was a prospective study conducted in 68 French hospitals. HAART was initiated in 2236 protease inhibitor-naive patients included in the French Hospital Database on HIV. Multivariate Cox proportional hazard models measuring time from 6 months after starting HAART were used to compare the strength of the association between different definitions of immunologic and virologic responses at 6 months and subsequent progression to AIDS or death. The Akaike's Information Criteria were used to identify the most appropriate model. RESULTS: During a median follow-up of 58 months, 325 patients experienced an AIDS-defining event or died. The model that fitted best was the model in which the CD4 cell count and plasma HIV-1 RNA values attained at 6 months were considered. The risk of clinical progression at 5 years ranged from 7% (95% confidence interval [CI]: 4-10) in patients whose CD4 cell count at 6 months was >or=350 cells/microL and whose HIV-1 RNA concentration was <3 log10 copies/mL to 63% (95% CI: 52-75) in patients whose CD4 cell count at 6 months was <100 cells/microL and whose HIV-1 RNA concentration was >or=5 log10. CONCLUSIONS: Plasma HIV-1 RNA concentration and CD4 cell count should be taken into account independently when evaluating early response to treatment. The persistent impact of early response on clinical progression at 5 years emphasizes the major importance of the success of first-line HAART.     

HIV-infected adults with a CD4 cell count greater than 500 cells/mm3 on long-term combination antiretroviral therapy reach same mortality rates as the general population

OBJECTIVE: To compare mortality rates in combination antiretroviral therapy (cART)-treated HIV-infected adults with mortality in the general population according to the level of CD4 cell count reached and the duration of exposure to cART. METHODS: HIV-infected adults initiating a protease inhibitor-containing treatment between 1997 and 1999 were selected in the Agence Nationale de Recherches sur le Sida et les hepatites virales (ANRS) APROCO and AQUITAINE cohorts. CD4 cell counts were estimated during follow-up using a 2-phase mixed linear model. Standardized mortality ratios (SMRs) were computed in reference to the 2002 French population rates, overall and for the time period spent with a CD4 count >or=500 cells/mm3. To identify if and when mortality rates reached values of the general population, SMRs were computed successively with truncation at each year of follow-up. RESULTS: The 2,435 adults (77% men, baseline median age = 36 years, and baseline median CD4 count = 270 cells/mm3) had a median follow-up of 6.8 years. The SMR was 7.0 (95% confidence interval [CI]: 6.2 to 7.8). During the 5,402 person-years spent with a CD4 count >or=500 cells/mm3, the mortality reached the level of the general population after the sixth year after cART initiation (SMR = 0.5, 95% CI: 0.1 to 1.6). CONCLUSION: Although overall mortality was higher in cART-treated HIV-infected adults, a subgroup with especially good prognosis can be identified, and these characteristics should be targeted for long-term treatment.     

Progression to AIDS or Death as Endpoints in HIV Clinical Trials

Abstract

Purpose: To assess progression to AIDS or death from month 4 after a protease inhibitor-containing regimen is initiated in a cohort of 1,281 patients. Method: We used Kaplan-Meier estimates of probability of clinical progression. RESULT: At month 4, most patients had an HIV-1 RNA plasma value below 500 copies/mL (78%) and a CD4 cell count above 300 cells/mm³ (62%). Starting from month 4, clinical progression at 1 and 2 years of follow-up was low (<3% at 1 year) in patients with HIV RNA <500 copies/mL or 500-10,000 copies/mL and in patients with CD4 between 50 and 300 cells/mm³ or >300 cells/mm³. A higher risk of clinical progression (10% at 1 year) was evidenced only in patients with poor response to antiretroviral therapy, that is, with CD4 <50 cells/mm³ or CD4 between 50-300 cells/mm³ together with an HIV RNA >10,000 copies/mL. Conclusion: In patients currently on antiretroviral therapy, clinical trials with clinical progression as endpoint are almost not feasible, except in patients with a poor immunovirological response to first- or second-line HAART.     

艾滋病患者外周血淋巴细胞计数取代CD4~+T细胞计数监测HAART疗效

评价血友病合并人类免疫缺陷病毒(HIV)和丙型肝炎病毒(HCV)感染的患者接受高效抗逆转录病毒治疗(highly ac-tive anti-retroviral therapy,HAART)时总淋巴细胞计数(total lymphocyte count,TLC)与CD4+T淋巴细胞计数间的相关性。回顾性分析了61例接受HAART的血友病合并HIV和HCV感染的患者共885对TLC与CD4+T淋巴细胞计数间的相关性。TLC用于预测CD4+T淋巴细胞计数的敏感性、特异性和阳性预侧值分别在不同的TLC范围对应于CD4+T淋巴细胞计数<200个/mm3时和CD4+T淋巴细胞计数<350个/mm3时获得。结果885对TLC与CD4+T淋巴细胞计数间存在相关性(r=0.511,P<001)。TLC<1 600个/mm3对应CD4+T淋巴细胞计数<200个/mm3有62.8%的敏感性、68.1%的特异性、43.1%的阳性预测值;TLC<1 800个/mm3对应CD4+T淋巴细胞计数<350个/mm3有79.1%的敏感性、78.0%的特异性、72.5%的阳性预测值。TLC可以作为一种低廉的监测手段在AIDS患者接受HAART时用于估测CD4+T淋巴细胞计数,其敏感性、特异性和阳性预侧值在TLC<1 800个/mm3对应CD4+T淋巴细胞计数<350个/mm3时最为明显。     

Racial and gender disparities in receipt of highly active antiretroviral therapy persist in a multistate sample of HIV patients in 2001

BACKGROUND: National data from the mid-1990s demonstrated that many eligible patients did not receive highly active antiretroviral therapy (HAART) and that racial and gender disparities existed in HAART receipt. We examined whether demographic disparities in the use of HAART persist in 2001 and if outpatient care is associated with HAART utilization. METHODS: Demographic, clinical, and pharmacy utilization data were collected from 10 US HIV primary care sites in the HIV Research Network (HIVRN). Using multivariate logistic regression, we examined demographic and clinical differences associated with receipt of HAART and the association of outpatient utilization with HAART. RESULTS: In our cohort in 2001, 84% of patients received HAART and 66% had 4 or more outpatient visits during calendar year (CY) 2001. Of those with 2 or more CD4 counts below 350 cells/mm in 2001, 91% received HAART; 82% of those with 1 CD4 test result below 350 cells/mm received HAART; and 77% of those with no CD4 counts below 350 cells/mm received HAART. Adjusting for care site in multivariate analyses, age >40 years (adjusted odds ratio [AOR] = 1.13), male gender (AOR = 1.23), Medicaid coverage (AOR = 1.16), Medicare coverage (AOR = 1.73), having 1 or more CD4 counts less than 350 cells/mm (AOR = 1.33), and having 4 or more outpatient visits in a year (OR = 1.34) were significantly associated with an increased likelihood of HAART. African Americans (odds ratio [OR] = 0.84) and those with an injection drug use risk factor (OR = 0.86) were less likely to receive HAART. CONCLUSIONS: Although the overall prevalence of HAART has increased since the mid-1990s, demographic disparities in HAART receipt persist. Our results support attempts to increase access to care and frequency of outpatient visits for underutilizing groups as well as increased efforts to reduce persistent disparities in women, African Americans, and injection drug users (IDUs).     

Risk of non-AIDS-related mortality may exceed risk of AIDS-related mortality among individuals enrolling into care with CD4+ counts greater than 200 cells/mm3

OBJECTIVE: To quantify cause-specific mortality risk attributable to non-AIDS-related and AIDS-related causes before and after the advent of highly active antiretroviral therapy (HAART). METHODS: Competing-risk methods were used to determine the cumulative AIDS-related and non-AIDS-related risk of mortality between 1990 and the end of 2003 in the Johns Hopkins HIV Clinical Cohort, a prospective cohort study. RESULTS: Beginning in 1997 with the introduction of HAART, all-cause mortality declined and has remained stable at approximately 39 deaths per 1000 person-years. AIDS-related mortality continued to decline in this period (P = 0.008), whereas non-AIDS-related mortality increased (P < 0.001). Using competing-risk methods, the risk of dying attributable to AIDS-related causes remains significantly higher than the risk of dying attributable to non-AIDS-related causes for patients with a CD4 count 200 cells/mm, however, non-AIDS-related mortality was greater than AIDS-related mortality, particularly among injection drug users. Other transmission categories had similar AIDS-related and non-AIDS-related cumulative mortalities. CONCLUSIONS: HAART has reduced mortality rates among HIV-infected individuals, but further efforts to reduce mortality in this population require increased attention to conditions that have not traditionally been considered to be HIV related.     

Randomized, open-label study of the impact of two doses of subcutaneous recombinant interleukin-2 on viral burden in patients with HIV-1 infection and CD4+ cell counts of > or = 300/mm3: CPCRA 059

The effect of intermittent courses of recombinant interleukin-2 (rIL-2) on HIV-1 load in patients receiving combination antiretroviral therapy remains uncertain. CPCRA 059 was an open-label, randomized, multicenter trial in which 511 patients with HIV-1 infection and CD4+ cell counts of > or = 300/mm3 who were receiving antiretroviral therapy were assigned to receive no rIL-2 (255 patients [controls]) or subcutaneous rIL-2 in dosages of 4.5 MIU (130) or 7.5 MIU (126) twice daily for 5-day courses every 8 weeks to maintain CD4+ cell counts that were twice the baseline value or > or = 1,000/mm3. The primary objective of this study was to compare the effects of the two doses of rIL-2 and no rIL-2 on viral load and CD4+ cell counts over 12 months. There was no difference in the following viral load measurements between the rIL-2 treatment groups and the control treatment group: percentage of patients with viral loads of <50 copies/mL at 12 months (p =.55), time to viral load of > or = 50 copies/mL for patients who had baseline viral loads of <50 copies/mL (p =.35), and change in viral load from baseline for patients who had viral loads of > or = 50 copies/mL at baseline (p =.63). At each follow-up visit, the change in CD4+ cell count from baseline was significantly greater in the rIL-2 treatment groups than in the control treatment group, with a mean difference of 251/mm3 at month 12 (95% confidence interval, 207-295; p <.0001). No unanticipated adverse experiences were seen in this trial, to our knowledge the largest randomized evaluation of rIL-2 treatment conducted to date.     

Why are baseline HIV RNA levels 100,000 copies/mL or greater associated with mortality after the initiation of antiretroviral therapy?

BACKGROUND: There is conflicting evidence regarding the impact of baseline plasma HIV RNA on virologic responses after the initiation of triple-drug antiretroviral therapy (highly active antiretroviral therapy [HAART]). This has made it difficult to interpret the recently reported association between baseline plasma HIV RNA and mortality. We evaluated whether baseline CD4 cell count and plasma HIV RNA predicted virologic suppression (<500 copies/mL) and rebound (> or =500 copies/mL) among adherent HIV-infected patients. METHODS: Antiretroviral-naive HIV-infected patients were stratified by baseline CD4 cell count, plasma HIV RNA, and adherence level. Cox and logistic regression were used to evaluate the time to suppression and rebound and the odds of ever achieving HIV RNA suppression. RESULTS: A total of 1422 individuals initiated HAART between August 1, 1996 and July 31, 2000 and were followed to March 31, 2002. Adherent patients with HIV RNA levels > or =100,000 copies/mL and 50 to 99,999 copies/mL were slower to suppress HIV RNA than patients with baseline HIV RNA <50,000 copies/mL in Kaplan-Meier analyses. Although the odds of RNA suppression among adherent patients with baseline RNA levels <50,000 copies/mL and 50 to 99,999 copies/mL were similar (P = 0.197), patients with baseline HIV RNA > or =100,000 copies/mL were markedly less likely ever to achieve suppression during follow-up (adjusted odds ratio: 0.27 [95% confidence interval: 0.13-0.54]; P < 0.001). No differences in the rate of virologic rebound were observed between adherent patients in the various baseline HIV RNA strata, and CD4 cell count was not associated with suppression or rebound. CONCLUSIONS: Baseline HIV RNA > or =100,000 copies/mL was associated with a significantly lower likelihood of ever achieving HIV RNA suppression during follow-up. These findings likely explain the association between baseline HIV RNA levels and mortality and have important implications for the development of therapeutic guidelines.     

Normalized CD8+ but not CD4+ lymphocyte IL-2 expression is associated with early treatment with highly active antiretroviral therapy

CD4+ and CD8+ lymphocyte cytokine production in patients with HIV/AIDS and Controls, in response to stimulation with phorbol-12-myristate-13-acetate (PMA) and ionomycin was assessed using single cell flow cytometric methods. Sixty-eight patients with HIV were divided into those on no antiretroviral therapy and those on highly active antiretroviral therapy (HAART). Patients on HAART were analyzed further on the basis of gender, ethnicity, viral load (> or 100 or <100 cells/mm(3)) and CD4 count (>200 or <200 cells/mm(3)). Interferon gamma (IFNgamma) expression by CD4+ and CD8+ lymphocytes was elevated in HIV-infected groups as compared to Controls. This elevation was statistically significant for patients on HAART but not for those not on HAART. The most significant difference was seen when the CD4+ count reached >200 cells/mm(3) (p=0.018 for CD4+ IFNgamma production and p=0.004 for CD8+ IFNgamma production). CD4+ interleukin-2 (IL-2) expression was significantly lower in HIV patients as compared to Controls but did not significantly improve however good the response to HAART. IL-2 expression by CD8+ lymphocytes was also lower in HIV patients as compared to Controls. IL-2 expression by CD8+ lymphocytes significantly improved in all patients on HAART as compared to HIV patients on no HAART. IL-2 expression was not significantly different from that of the Controls when the HIV viral load was less than 50 copies/ml. These results demonstrate improvements in both CD4+ and CD8+ responsiveness with HAART. IFNgamma production was elevated in response to HAART and was maximal only with significant CD4 count recovery. In contrast, normalization of IL-2 production by CD8+ lymphocytes was seen early in patients receiving HAART even when there was only a small increase in CD4+ lymphocyte numbers.     

SEN virus seroprevalence in HIV positive patients: association with immunosuppression and HIV-replication.

BACKGROUND: Patients infected with HIV are often co-infected with other viruses. SEN virus (SENV) was isolated from a HIV positive patient with intravenous drug use and post-transfusion hepatitis. SENV strains D and H seem to be relevant for the development of post-transfusion hepatitis. We compared the prevalence of SENV strains D and H and the viral load of SENV H in HIV-infected patients with healthy blood donors. The results were correlated with clinical markers such as HIV stage, CD4 cell count, HIV-RNA positivity, HAART or the transmission mode in HIV infected individuals. OBJECTIVES: Blood samples of 143 HIV-positive patients were analysed and compared with a control group of 122 healthy blood donors. SENV D and -H was detected by PCR. RESULTS: SENV was detectable in 15.4% (22/143) of HIV-positive patients compared to 10.4% (12/122) in the control group (P=0.18). SENV H DNA-levels were significantly higher in HIV-positive patients (P=0.01). The prevalence in patients with CD4 cells less than 200/mm(3) was 31% (13/42), compared to 12.3% (8/65) in cases with CD4 cells between 200 and 500/mm(3), and 2.8% in cases with CD4 cells above 500/mm(3) (P=0.002 for CD4 cells <200 versus CD4 cells >200, P=0.031 for CD4 cells <500 versus CD4 cells >500). Prevalence of these strains was not significantly influenced by CDC stages. SENV was detected significantly more frequent in patients with detectable HIV-RNA (P=0.005). Patients undergoing HAART were significantly less frequent positive for SENV D or -H (P=0.029) than patients without HAART. In a multivariate analysis using a logistic regression model HIV-RNA positivity and CD4 cell count were identified as independent factors for SENV prevalence. CONCLUSION: SENV (D and H) prevalence is not significantly higher in HIV-positive patients in comparison to healthy blood donors. SENV prevalence depends on CD4 cell count and HIV-RNA.