Nadir CD4+ T-cell count and numbers of CD28+ CD4+ T-cells predict functional responses to immunizations in chronic HIV-1 infection

OBJECTIVE: To ascertain whether delaying the initiation of highly active antiretroviral therapy (HAART) compromises functional immune reconstitution in HIV-1 infection in persons who regain 'normal' CD4 T-cell counts after suppressive antiretroviral therapies. DESIGN: Prospective open-label study carried out at two University-affiliated HIV-outpatient clinics in the USA. SUBJECTS AND METHODS: Response to immunization was used as a model for in vivo functional immune competence in 29 HIV-1 infected patients with CD4 T-cell counts > 450 x 106 cells/l and HIV-RNA < 400 copies/ml for > 12 months after HAART and nine HIV-1 seronegative controls. After immunization with tetanus toxoid, diphtheria-toxoid, and keyhole limpet hemocyanin, immune response scores (IRS) were calculated using postimmunization antibody concentrations, lymphocyte proliferation, and delayed-type hypersensitivity responses to vaccine antigens. RESULTS: Despite normal numbers of circulating CD4 T-cells, the CD4 T-cell nadir before HAART initiation predicted the immune response to immunization (rho = 0.5; P < 0.005) while current CD4 T-cell count did not. Likewise, CD4 T-lymphocyte expression of the co-stimulatory molecule CD28 was also an independent predictor of response to immunization (rho = 0.5; P < 0.005). CONCLUSIONS: Even among persons who controlled HIV replication and normalized CD4 T-cell counts with HAART, pretreatment CD4 T-cell count and numbers of circulating CD4+CD28+ T-cells at immunization, but not current CD4 T-cell count, predict the ability to respond to vaccination. Delaying the initiation of HAART in chronic HIV-1 infection results in impaired functional immune restoration despite normalization of circulating CD4 T-cell numbers.     

Oral candidosis as a clinical marker of immune failure in patients with HIV/AIDS on HAART

Oral candidosis (OC) has been proposed as a clinical marker of highly active antiretroviral therapy (HAART) success or failure. The principal objective of this work was to assess whether the presence OC is associated with immunologic or virologic failure in patients with HIV/AIDS undergoing HAART. One hundred fifty-one patients with HIV/AIDS from Regional Hospital "Carlos Haya," Malaga, Spain, were examined orally. All patients had been undergoing HAART for a minimum of 6 months prior to oral examination. OC diagnosis was in accordance with World Health Organization-Centers for Disease Control (WHO-CDC) criteria. Age, gender, route of HIV infection, CD4 lymphocyte counts, and viral load were taken from the medical records. In regard to HAART response the patients were classified as: virologic- responders (viral load < 50 copies per milliliter), virologic nonresponders (viral load >50 copies per milliliter); immunologic responders (CD4 cells counts > 500 per milliliter), and immunologic nonresponders (CD4 cells counts < 500 per milliliter). Prevalence of OC was determined for each group. The presence of OC was closely related to immune failure (p 0.006; odds ratio [OR] 3.38 95% confidence interval [CI] 1.262-12.046) in patients with HIV/AIDS undergoing HAART. The probability of immune failure in the presence of OC was 91% for men who have sex with men, 95.5% for heterosexuals, and 96% for intravenous drug users. In conclusion, OC should be considered a clinical marker of immune failure in patients with HIV/AIDS undergoing HAART.     

Alleles of the gene encoding IL-1alpha may predict control of plasma viraemia in HIV-1 patients on highly active antiretroviral therapy

OBJECTIVE: Some HIV patients treated with highly active antiretroviral therapy (HAART) do not resolve their plasma viraemia or HIV RNA can reappear after a period of virological control. We investigate whether polymorphisms in cytokine genes affect the control of plasma HIV RNA over 5 years on HAART. DESIGN: The study utilized adult HIV-infected patients in Western Australia. Plasma HIV-RNA levels were assessed from commencement of HAART in patients who had a CD4 T-cell count less than 100 cells/microl before HAART and achieved immune reconstitution assessed by CD4 T-cell counts. RESULTS: Control of plasma viraemia could be predicted from carriage of allele 2 at position -889 in the IL1A gene (IL1A-889*2). This was significant when assessed by the proportion of patients with a plasma HIV-RNA level of 400 copies/ml or less (P = 0.002). At 48 months post-HAART, proportions were approximately 0.76, 0.51 and 0.32 for IL1A (1,1), (1,2) and (2,2) patients, respectively. The outcome was independent of the patients' CD4 T-cell counts before or on therapy, drug regimen or age. Polymorphisms in IL6, TNFA, IL1B or IL12B had less significant effects, which became marginal when IL1A was included in the statistical model. IL1A-889 was in linkage disequilibrium with a non-synonymous polymorphism at IL1A+4845. CONCLUSION: Alleles carried at IL1A-889 or IL1A+4845 may predict the control of HIV replication in previously immunodeficient patients responding to HAART.     

The prevalence and incidence of neurocognitive impairment in the HAART era

OBJECTIVES: HAART suppresses HIV viral replication and restores immune function. The effects of HAART on neurological disease are less well understood. The aim of this study was to assess the prevalence and incidence of neurocognitive impairment in individuals who initiated HAART as part of an AIDS clinical trial. DESIGN: A prospective cohort study of HIV-positive patients enrolled in randomized antiretroviral trials, the AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trials (ALLRT) study. METHODS: We examined the association between baseline and demographic characteristics and neurocognitive impairment among 1160 subjects enrolled in the ALLRT study. RESULTS: A history of immunosuppression (nadir CD4 cell count < 200 cells/microl) was associated with an increase in prevalent neurocognitive impairment. There were no significant virological and immunological predictors of incident neurocognitive impairment. Current immune status (low CD4 cell count) was associated with sustained prevalent impairment. CONCLUSION: The association of previous advanced immunosuppression with prevalent and sustained impairment suggests that there is a non-reversible component of neural injury that tracks with a history of disease progression. The association of sustained impairment with worse current immune status (low CD4 cell count) suggests that restoring immunocompetence increases the likelihood of neurocognitive recovery. Finally, the lack of association between incident neurocognitive impairment and virological and immunological indicators implies that neural injury continues in some patients regardless of the success of antiretroviral therapy on these laboratory measures.     

哈尔滨市艾滋病病人高效抗反转录病毒治疗效果评价

目的探讨哈尔滨市艾滋病（AIDS）病人的高效抗反转录病毒治疗（HAART）效果与不良反应。方法应用国家免费提供的抗病毒治疗药品,对符合治疗条件的HIV/AIDS病人进行规范抗病毒治疗,并检测病人的CD4＋T淋巴细胞计数与病毒载量。结果 HAART开始12个月后,病人CD4＋T淋巴细胞计数平均增长（241.61±148.02）个/μl,病毒载量均低于检测下限。结论抗病毒治疗效果显著,能够实现部分免疫重建,但也存在较多的不良反应。     

AIDS diagnoses at higher CD4 counts in Australia following the introduction of highly active antiretroviral treatment

OBJECTIVES: To assess whether AIDS cases in Australia have been diagnosed at higher CD4 counts since the widespread availability of highly active antiretroviral treatment (HAART) in mid-1996. METHODS: Data on the CD4 count at AIDS diagnosis for AIDS cases diagnosed between 1 January 1992 and 31 December 1997, and reported to the National AIDS Registry in Australia by 31 March 1998, were analysed. The median CD4 count at AIDS diagnosis, and the proportions of AIDS diagnoses with a CD4 count above 100 cells/microl, and above 200 cells/microl, were calculated by the year of diagnosis, both for all AIDS-defining illnesses, and for each illness separately. Analyses were also stratified by the time interval between HIV and AIDS diagnoses (less than or equal to, or more than, 3 months) because people diagnosed with HIV close to the diagnosis of AIDS would generally not have received any antiretroviral treatment before the diagnosis of AIDS, and so no trends in CD4 counts at the diagnosis of AIDS would be expected in this group. RESULTS: There was an increase in CD4 count at AIDS diagnosis in 1996 and 1997, although this increase was only apparent for AIDS-defining illnesses other than Pneumocystis carinii pneumonia (PCP), and was limited to AIDS cases diagnosed with HIV more than 3 months before AIDS. In cases of AIDS other than PCP, and diagnosed with HIV more than 3 months before AIDS, the median CD4 count increased from 50 cells/microl in 1995 to 80 cells/microl in 1996 and 134 cells/microl in 1997. CONCLUSIONS: There has been an increase in the CD4 count at AIDS diagnosis for most AIDS-defining illnesses in Australia coincident with the widespread availability of HAART.     

Impact of baseline viral load and adherence on survival of HIV-infected adults with baseline CD4 cell counts > or = 200 cells/microl

BACKGROUND: Baseline plasma HIV RNA levels > 100 000 copies/ml have been associated with elevated mortality rates after the initiation of HAART. There is uncertainty regarding the optimal strategy for patients with high plasma HIV RNA but CD4 cell count > or = 200 cells/microl. OBJECTIVE: To evaluate the impact of baseline plasma HIV RNA on survival among patients with CD4 cell counts > or = 200 cells/microl. METHODS: Patients were stratified by plasma HIV RNA, CD4 cell count and adherence level. Mortality rates were evaluated using Kaplan-Meier methods and Cox regression. RESULTS: Among 1166 patients initiating HAART with a CD4 cell count > or = 200 cells/microl, a baseline HIV RNA > or = 100 000 copies/ml was statistically associated with elevated mortality among non-adherent patients (log-rank P = 0.032), but not for adherent patients (log-rank P = 0.690). In a multivariate Cox model comparing patients with a baseline CD4 cell count > or = 200 cells/microl and a baseline plasma HIV RNA < 100 000 copies/ml, the mortality rate was statistically similar among patients with a baseline CD4 cell count > or = 200 cells/microl and a baseline plasma HIV RNA > or = 100 000 copies/ml (relative hazard, 1.21; 95% confidence interval, 0.89-1.65; P = 0.232). CONCLUSION: HIV RNA > or = 100 000 copies/ml was only associated with mortality among HIV-infected patients initiating HAART with CD4 cell counts > or= 200 cells/microl if the patients were non-adherent.     

Response to highly active antiretroviral therapy among severely immuno-compromised HIV-infected patients in Cambodia

BACKGROUND: HAART efficacy was evaluated in a real-life setting in Phnom Penh (Médecins Sans Frontières programme) among severely immuno-compromised patients. METHODS: Factors associated with mortality and immune reconstitution were identified using Cox proportional hazards and logistic regression models, respectively. RESULTS: From July 2001 to April 2005, 1735 patients initiated HAART, with median CD4 cell count of 20 (inter-quartile range, 6-78) cells/microl. Mortality at 2 years increased as the CD4 cell count at HAART initiation decreased, (4.4, 4.5, 7.5 and 24.7% in patients with CD4 cell count > 100, 51-100, 21-50 and < or = 20 cells/microl, respectively; P < 10). Cotrimoxazole and fluconazole prophylaxis were protective against mortality as long as CD4 cell counts remained < or = 200 and < or = 100 cells/microl, respectively. The proportion of patients with successful immune reconstitution (CD4 cell gain > 100 cells/microl at 6 months) was 46.3%; it was lower in patients with previous ART exposure [odds ratio (OR), 0.16; 95% confidence interval (CI), 0.05-0.45] and patients developing a new opportunistic infection/immune reconstitution infection syndromes (OR, 0.71; 95% CI, 0.52-0.98). Similar efficacy was found between the stavudine-lamivudine-nevirapine fixed dose combination and the combination stavudine-lamivudine-efavirenz in terms of mortality and successful immune reconstitution. No surrogate markers for CD4 cell change could be identified among total lymphocyte count, haemoglobin, weight and body mass index. CONCLUSION: Although CD4 cell count-stratified mortality rates were similar to those observed in industrialized countries for patients with CD4 cell count > 50 cells/microl, patients with CD4 cell count < or = 20 cells/microl posed a real challenge to clinicians. Widespread voluntary HIV testing and counselling should be encouraged to allow HAART initiation before the development of severe immuno-suppression.     

Do gender differences in CD4 cell counts matter?

OBJECTIVE: To examine the effect of gender on disease progression and whether gender differences in CD4 lymphocyte counts persisted for the entire course from HIV seroconversion until (death from) AIDS. METHODS: CD4 lymphocyte counts were modelled in 221 female and 443 male seroconverters following seroconversion, backwards from AIDS and backwards from death using regression analysis for repeated measurements. RESULTS: In the period before use of highly active antiretroviral therapy (HAART), progression to AIDS and to death were marginally slower in women than in men as assessed by proportional hazards analysis. Women seroconverted for HIV, developed AIDS and died at higher CD4 cell counts than men (women: 815, 146 and 44 x 10(6) cells/l, respectively; men: 727, 49 and 22 x 10(6) cells/l, respectively), although differences were only statistically significant at AIDS onset. Declines in CD4 lymphocyte counts were not significantly affected by gender and absolute differences between men and women were stable, with exception for the trajectory close to AIDS when the decline became steeper for men than women. CONCLUSION: These gender differences in CD4 lymphocyte counts suggest a delay of initiation of therapy in women compared with men (our model predicted that women reach the threshold of starting HAART at about 12 months later than men). If this delay unfavourably influences progression, treatment guidelines should be revised so that women can benefit equally from HAART.     

Rate,causes, and clinical implications of presenting with low CD4+ cell counts in the era of highly active antiretroviral therapy

Of patients attending HIV clinics, neither the proportion with CD4(+) cell counts below 200 cells/microl, and therefore at risk for developing opportunistic infections (OIs), nor the reasons for the persistence of low CD4(+) cell counts are well known in the era of highly active antiretroviral therapy (HAART). In an effort to gather data concerning this issue, the charts of all outpatients who attended two reference HIV clinics in Spain throughout the year 2001 were retrospectively reviewed. Of 1897 subjects, 213 (11%) had at least one CD4(+) cell count determination below 200 cells/microl during 2001. The main reasons for presenting with low CD4(+) cell counts were as follows: (1) poor treatment adherence, 64 (30%); (2) poor immune recovery despite complete virus suppression for longer than 1 year on HAART, 47 (22%); (3) virologic failure under HAART, 33 (15%); (4) no antiretroviral therapy, 23 (11%); (5) initiation of HAART within the current year in subjects with very low CD4(+) cell counts, 17 (8%); (6) impediment in using HAART due to toxicity, 17 (8%); and (7) drug-induced myelotoxicity, 12 (6%). During the period under review, one or more OIs developed in 52 of the 213 (24%) patients with low CD4(+) cell counts. They occurred more frequently in subjects who were naive for antiretroviral drugs or who initiated therapy recently (RR, 6.45; 95% CI, 2.43-17.12; p < 0.001), and conversely tended to be less frequent among subjects with poor immune reconstitution despite complete virologic suppression while on HAART (RR 0.86; 95% CI, 0.28-2.62; p = 0.79). A lower lifetime CD4(+) cell count nadir was associated with a greater risk of developing an OI (RR, 0.98; 95% CI, 0.97-0.99; p < 0.001). We conclude that, despite the availability of HAART, more than 10% of patients currently attending HIV clinics have CD4(+) cell counts <200 cells/microl, and continue to be at risk for developing OIs. Poor treatment adherence and lack of immune recovery despite complete virus suppression while on HAART account for more than half of cases.     

Graves' disease during immune reconstitution after highly active antiretroviral therapy for HIV infection: evidence of thymic dysfunction

A patient with HIV infection who experienced immune reconstitution after highly active antiretroviral therapy (HAART) [increase in CD4 T cell count from <1/microl to >600/microl] presented with severe Graves' disease 32 months after commencing HAART. A comprehensive clinical and laboratory study demonstrated pronounced regional lymphadenopathy and thymic enlargement at presentation, and that the onset of thyrotropin receptor antibody production was associated with increased production of soluble CD30 (a marker of type 2 immune responses). Blood naive CD8 T cell counts and TREC levels in both CD4 and CD8 T cells were increased at multiple time points compared with carefully selected controls. We conclude that the Graves' disease in this patient was associated with abnormally high blood counts of thymus-derived T cells, and propose that Graves' disease after HAART in this and other HIV patients may result from failure to delete autoreactive T cell clones in the regenerating thymus.     

Disease progression in patients with virological suppression in response to HAART is associated with the degree of immunological response

OBJECTIVE: To determine if immunological response is associated with disease progression in patients with virological suppression after initiating HAART. DESIGN: A cohort study of 1084 treatment-naive participants in the British Columbia HIV/AIDS Drug Treatment Program who had achieved viral loads < 500 copies/ml at 3-9 months after initiating triple-drug therapy. METHODS: Cox proportional hazards was used to model the association with disease progression of baseline variables, change in CD4 cell counts and CD4 cell count strata at 6 months. Logistic regression analysis was used to examine associations with two definitions of poor immunological response. RESULTS: Patients were followed for a median of 51.4 months. In univariate analyses, increases in CD4 cell counts of < 25 cells/microl and absolute CD4 cell counts of < 200 cells/microl were associated with an increased risk of death or new AIDS events. Two mulitivariate models, one including baseline CD4 cell count and change in CD4 cell count from baseline and the other including only absolute CD4 cell counts at 6 months, were found to predict disease progression in this setting. Increases in CD4 cell count of < 25 cells/microl were associated with increasing age and inversely associated with low baseline CD4 cell counts, high baseline viral loads and good adherence to therapy. CD4 cell counts of < 200 cells/microl at 6 months were associated with low baseline CD4 cell counts and having AIDS at baseline. CONCLUSION: Patients with virological suppression are still at risk for HIV disease progression if adequate immunological responses are not achieved.     

Alcohol Consumption and HIV Disease Progression: Are They Related?

BACKGROUND: The relationship between alcohol consumption and HIV disease progression has received limited attention in the era of highly active antiretroviral therapy (HAART). METHODS: We assessed CD4 cell count, HIV RNA levels, and alcohol consumption in the past month, defined as none, moderate, and at risk, in 349 HIV-infected people with a history of alcohol problems. We investigated the relationship between alcohol consumption and HIV disease markers CD4 cell count and HIV RNA level, stratified by HAART use, using multivariable regression. RESULTS: No significant differences in CD4 cell count or HIV RNA level were found across the categories of alcohol consumption for patients who were not receiving HAART. However, among patients who were receiving HAART, log HIV RNA levels were significantly higher in those with moderate (2.17 copies/ml) and at-risk (2.73 copies/ml) alcohol use compared with none (1.73 copies/ml; p = 0.006). CD4 cell counts in those with moderate (368 cells/microl) and at-risk (360 cells/microl) alcohol use were lower than for subjects who reported none (426 cells/microl; p = 0.07). CONCLUSION: Among patients who have a history of alcohol problems and are receiving antiretroviral treatment, alcohol consumption was associated with higher HIV RNA levels and lower CD4 counts. No comparable association was found for similar patients who were not receiving HAART. Addressing alcohol use in HIV-infected patients, especially those who are receiving HAART, may have a substantial impact on HIV disease progression.     

182例HIV/AIDS实施高效抗反转录病毒治疗的疗效评价

目的分析182例HIV/AIDS实施高效抗反转录病毒治疗(highly active antiretroviral therapy,HAART)的效果及其影响因素,为进一步有效治疗提供依据。方法采用回顾性调查方法,对我院接受规范HAART的182例HIV/AIDS患者的CD4+T淋巴细胞绝对计数和病毒载量进行分析。结果 182例中,157例治疗后CD4+T淋巴细胞计数增加,且在治疗后前6个月内增加速度最快,随着治疗时间延长则较为缓慢。病毒载量在治疗后的6个月内下降最快,大部分降至血浆检测不到的水平,6个月后比较稳定;但随着治疗时间延长,部分患者的病毒载量出现反弹,可能与患者服药依从性差和病毒耐药性的出现有关。治疗前后CD4+T淋巴细胞计数差异有统计学意义(P0.05)。多因素logistic回归分析表明年龄和病毒载量是影响HAART疗效的危险因素,基线CD4+T淋巴细胞计数和按时服药是保护因素。结论 HAART能明显增加CD4+T淋巴细胞计数,降低病毒载量,有效控制机会感染,治疗效果显著。影响HAART疗效的因素是多方面的,在治疗过程中应综合考虑各种可能影响因素以提高疗效,对符合条件的患者应尽早进行规范的抗病毒治疗。     

AIDS events among individuals initiating HAART: do some patients experience a greater benefit from HAART than others?

OBJECTIVE: To describe the rate of new AIDS events over the first year of HAART in patients with different characteristics and to describe the decrease in incidence of AIDS between the first and second 6 months of the year in these patients. DESIGN: Collaboration of cohort studies from Europe and North America. METHODS: AIDS rates in the first year of HAART were calculated for 22 217 antiretroviral-naive individuals. Event rates were compared in the periods 0-6 and 7-12 months after starting HAART. RESULTS: The number of events and person-years of follow-up (PYFU) in the two time periods were 1185 (9601) and 336 (8690), respectively (event rates: 12.3 and 3.9 per 100 PYFU, relative decline in incidence: 68%). Whereas rates decreased in all groups, tests for interaction suggested that relative declines in incidence were more rapid in homosexual men (P = 0.002), in those starting HAART from 2001 in comparison with earlier years (P = 0.03), in those with lower CD4 cell counts (P-values of 0.001, 0.002 and 0.11 for those with cell counts < 50, 50-199 and 200-349 cells/microl compared to those with cell counts >or= 350 cells/microl) and HIV RNA levels >or= 5 log10 copies/ml (P = 0.0008). Those with AIDS at the time of starting HAART had a less rapid relative decline in incidence (P = 0.0007). CONCLUSIONS: Our results suggest that some groups may experience less rapid relative declines in AIDS incidence than others over the first year on HAART.     

Prognostic value of plasma HIV RNA among highly active antiretroviral therapy users

BACKGROUND: The study objective was to compare the prognostic value of plasma HIV RNA and CD4 cell count at baseline and as time-updated variables in highly active antiretroviral therapy (HAART) users for two outcomes: development of AIDS and change in CD4 cell count. METHODS: The study population comprised 387 men enrolled in the Multicenter AIDS Cohort Study who were AIDS-free and initiated HAART between 1996 and 2001. Follow-up until AIDS diagnosis (n=36, 9%) or the last AIDS-free visit was included. To determine the predictive value of combining HIV RNA and CD4 cell count, regression tree methods using recursive partitioning at pre-specified cut points for both variables were used. RESULTS: Low CD4 cell count was a strong predictor of AIDS among HAART users. However, HIV RNA showed strong prognostic value for AIDS development among those with CD4 cell counts > 250 x 10(6) cells/l, in whom an HIV RNA level > 1000 copies/ml carried a 4.6-fold greater risk of developing AIDS. HIV RNA < 5000 copies/ml was also predictive of subsequent increase in CD4 cell count with significantly higher increases among those with initial CD4 counts > 300 x 10(6) cells/l. CONCLUSION: Although, in HAART users, CD4 cell count was the primordial prognostic marker, an HIV RNA > 1000 copies/ml attained after HAART initiation was a strong predictor of the rate of subsequent CD4 cell count increase and of developing AIDS in patients whose CD4 cell counts were > 250 x 10(6) cells/l.     

Neutropenia in human immunodeficiency virus infection: data from the women's interagency HIV study

BACKGROUND: Neutropenia is well described in individuals infected with human immunodeficiency virus (HIV) and occurs in approximately 10% to 50% of cases. Neither the effect of highly active antiretroviral therapy (HAART) on neutrophil counts nor the significance of neutropenia in terms of survival has previously been evaluated. METHODS: The prevalence of neutropenia among 1729 HIV-infected women, followed up as part of the Women's Interagency HIV Study, was evaluated. The CD4 lymphocyte counts, HIV-1 RNA levels, and complete blood cell counts, including absolute neutrophil counts, were obtained at 6-month intervals. RESULTS: Neutropenia was common among HIV-infected women; at baseline, 44% had neutrophil counts less than 2000/microL, whereas 7% had counts less than 1000/microL. During 7.5 years of follow-up, neutrophil counts less than 2000/microL occurred on at least 1 occasion in 79%, whereas absolute neutrophil counts less than 1000/microL were documented in 31%. Worsening HIV disease parameters, such as lower CD4 cell counts (P<.001) and higher HIV-1 RNA levels (P<.001), were associated with development of neutropenia. Resolution of neutropenia was associated with higher CD4 cell counts (P<.001) and use of HAART (P=.007). We found that HAART, without zidovudine, was associated with protection against development of neutropenia. On multivariate analysis, neutropenia was not found to be associated with decreased survival among HIV-infected women. CONCLUSIONS: Worsening HIV disease parameters are associated with neutropenia in HIV-infected women. Treatment with HAART, without zidovudine in the regimen, protects against development of neutropenia, whereas HAART use and higher CD4 cell counts are associated with resolution of neutropenia. Neutropenia is not associated with decreased survival in HIV-infected women.     

Positive outcomes of HAART at 24 months in HIV-infected patients in Cambodia

OBJECTIVES: African and Asian cohort studies have demonstrated the feasibility and efficacy of HAART in resource-poor settings. The long-term virological outcome and clinico-immunological criteria of success remain important questions. We report the outcomes at 24 months of antiretroviral therapy (ART) in patients treated in a Médecins Sans Frontières/Ministry of Health programme in Cambodia. METHODS: Adults who started HAART 24 +/- 2 months ago were included. Plasma HIV-RNA levels were assessed by real-time polymerase chain reaction. Factors associated with virological failure were analysed using logistic regression. RESULTS: Of 416 patients, 59.2% were men; the median age was 33.6 years. At baseline, 95.2% were ART naive, 48.9% were at WHO stage IV, and 41.6% had a body mass index less than 18 kg/m. The median CD4 cell count was 11 cells/microl. A stavudine-lamivudine-efavirenz-containing regimen was initiated predominantly (81.0%). At follow-up (median 23.8 months), 350 (84.1%) were still on HAART, 53 (12.7%) had died, six (1.4%) were transferred, and seven (1.7%) were lost to follow-up. Estimates of survival were 85.5% at 24 months. Of 346 tested patients, 259 (74.1%) had CD4 cell counts greater than 200 cells/microl and 306 (88.4%) had viral loads of less than 400 copies/ml. Factors associated with virological failure at 24 months were non-antiretroviral naive, an insufficient CD4 cell gain of less than 350 cells/microl or a low trough plasma ART concentration. In an intention-to-treat analysis, 73.6% of patients were successfully treated. CONCLUSION: Positive results after 2 years of advanced HIV further demonstrate the efficacy of HAART in the medium term in resource-limited settings.     

Virological outcome of chronic hepatitis B virus infection in HIV-coinfected patients receiving anti-HBV active antiretroviral therapy

The immune suppression caused by HIV infection accelerates the course of liver disease caused by chronic hepatitis B virus (HBV) infection. We assessed the outcome of HIV/HBV-coinfected patients exposed to highly active antiretroviral therapy (HAART) including anti-HBV active drugs. Baseline and follow-up plasma HBVDNA and HIV-RNA levels, HBV serological markers, and CD4 counts were longitudinally evaluated in all HBsAg(+) individuals with HIV infection on regular follow-up at an urban HIV reference clinic. Out of 79 HBsAg(+) chronic carriers identified, 39 (50%) were HBeAg(+). Lamivudine (3TC) alone had been received by 37% of patients, while 3TC plus tenofovir (concomitantly or consecutively) had been taken by 58% of them. The median follow-up was of 52 months. Loss of HBeAg or HBsAg occurred in 28% (10/36) and 13% (10/75) of patients, respectively. In multivariate analysis, only undetectable plasma HIV-RNA levels [OR 4.58 (95% CI 1.25-16.78); p = 0.02] and greater CD4 gains on HAART [OR 1.003 (95% CI 1.000-1.006); p = 0.03] were associated with undetectable serum HBV-DNA at the end of follow-up. Anti-HBV active HAART makes it possible to achieve HBsAg clearance, anti-HBe seroconversion, and suppression of HBV replication in a substantial proportion of HBV/HIV-coinfected patients, particularly in those with complete HIV suppression and greater immune recovery. Thus, HBV/HIV-coinfected patients might benefit from an earlier introduction of HAART.     

The relationship between non-injection drug use behaviors on progression to AIDS and death in a cohort of HIV seropositive women in the era of highly active antiretroviral therapy use

AIMS: To evaluate the effects of longitudinal patterns and types of non-injection drug use (NIDU) on HIV progression in the highly active antiretroviral therapy (HAART) era. DESIGN: Women's Interagency HIV Study (WIHS), a prospective cohort study conducted at six US sites. METHODS: Data were collected semi-annually from 1994 to 2002 on 1046 HIV(+) women. Multivariate Cox proportional hazards modeling was used to estimate relative hazards for developing AIDS and for death by pattern and type of NIDU. FINDINGS: During follow-up, 285 AIDS events and 287 deaths, of which 177 were AIDS-related, were reported. At baseline, consistent and former NIDU was associated with CD4(+) counts of < 200 cells/microl (43% and 46%, respectively) and viral load > 40,000 copies/ml (53% and 55%, respectively). Consistent NIDU reported less HAART use (53%) compared with other NIDU patterns. Stimulant use was associated with CD4(+) cell counts of < 200 cells/microl (53%) and lower HAART initiation (63%) compared with other NIDU types. In multivariate analyses, progression to AIDS was significantly higher among consistent (RH = 2.52), inconsistent (RH = 1.63) and former (RH = 1.56) users compared with never users; and for stimulant (RH = 2.04) and polydrug (RH = 1.65) users compared with non-users. Progression to all-cause death was higher only among former users (RH = 1.48) compared with never users in multivariate analysis. NIDU behaviors were not associated with progression to AIDS-related death. CONCLUSIONS: In this study, pattern and type of NIDU were associated with HIV progression to AIDS and all-cause mortality. These differences were associated with lower HAART utilization among consistent NIDU and use of stimulants, and poor baseline immunological and virological status among former users.