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1.
True long-term nonprogressors (LTNPs)/elite controllers (ECs) maintain durable control over HIV replication without antiretroviral therapy. Herein we describe 4 unique persons who were distinct from conventional LTNPs/ECs in that they had extraordinarily low HIV burdens and comparatively weak immune responses. As a group, typical LTNPs/ECs have unequivocally reactive HIV-1 Western blots, viral loads below the lower threshold of clinical assays, low levels of persistent viral reservoirs, an over-representation of protective HLA alleles, and robust HIV-specific CD8(+) T-cell responses. The 4 unique cases were distinguished from typical LTNPs/ECs based on weakly reactive Western blots, undetectable plasma viremia by a single copy assay, extremely low to undetectable HIV DNA levels, and difficult to isolate replication-competent virus. All 4 had at least one protective HLA allele and CD8(+) T-cell responses that were disproportionately high for the low antigen levels but comparatively lower than those of typical LTNPs/ECs. These unique persons exhibit extraordinary suppression over HIV replication, therefore, higher-level control than has been demonstrated in previous studies of LTNPs/ECs. Additional insight into the full spectrum of immune-mediated suppression over HIV replication may enhance our understanding of the associated mechanisms, which should inform the design of efficacious HIV vaccines and immunotherapies.  相似文献   

2.
Seven long-term nonprogressors (LTNPs) have been identified in a cohort of 128 human immunodeficiency virus (HIV)-1 infected individuals with hemophilia. Studies included quantitation of virus by polymerase chain reaction, characterization of primary virus isolates in vitro, analysis of lymphocyte surface markers, and measurement of virus-specific cytotoxic T lymphocytes (CTLs). Viruses of LTNPs exhibited slow growth in vivo and in vitro. LTNPs had expansion of CD8 T cells with increased expression of HLA-DR. Intermittent HIV-1-specific CTL effector activity was detected in freshly isolated peripheral blood mononuclear cells of most LTNPs. CTL precursor frequencies were higher in LTNPs than in patients with progressive disease. Virus antigen-specific lymphoproliferation was vigorous in some LTNPs. Thus, LTNPs in this cohort have maintained remarkably low virus burdens and vigorous HIV-1-specific cell-mediated immunity over a 15-year period. The presence of expanded, activated CD8 T cells with cytotoxic effector function in the peripheral blood suggests ongoing viral replication.  相似文献   

3.
BACKGROUND: Specific mutations in VPR and V2 potentially restrict HIV-1 replication in macrophages. Such restriction could potentially limit HIV replication in long-term non-progressors (LTNP), thus accounting for low viral load and delayed progression to AIDS. OBJECTIVE: To examine whether a specific VPR phenotype (truncated versus non-truncated) correlates with disease progression and whether elongated V2 restricts viral replication in macrophages or alters viral tropism. METHODS: Sequence analysis was carried for VPR and V1-V3 env from four rapid progressors (RPs), six late progressors (LPs), and three LTNPs in cohort of HIV-1-infected homosexual men. The replication kinetics of sequential isolates was examined in primary CD4 cells and macrophages and coreceptor usage was determined by GHOST infection assays. RESULTS: No differences were found in the VPR protein from RP and LTNP isolates. Analysis of the V2 region revealed that all RPs maintained similar V2 lengths (40 aa), whereas LPs and LTNPs acquired additional amino acids (2-13 aa) in the V2 region. Coreceptor specificity revealed that RP switch from CCR5 to multiple coreceptor usage, whereas LTNPs maintained R5 viruses. Sequential isolates from each group revealed comparable replication efficiencies in both T-cells and macrophages, regardless of the V2 length or coreceptor utilization. In addition, cross-section analysis of six LTNPs from Australia revealed extended V2 with consistent usage of CCR5 coreceptor. CONCLUSION: The present results suggest that acquisition of a V2 extension over time in HIV-1-infected LPs/LTNPs appears to correlate with maintenance of CCR5 usage among LTNPs. These findings may be important for a better understanding of the host interactions and disease progression.  相似文献   

4.
Twenty patients with human immunodeficiency virus type 1 (HIV-1) infection for >7 years, no HIV-1-related symptoms, no treatment, and CD4+ cell counts >500/microL were included in a prospective study in 1993. Four years later, 12 patients had progressed (SPs), while 8 had not (long-term nonprogressors [LTNPs]). At inclusion, HIV-1 RNA, but not DNA, levels were higher in SPs. During follow-up, a consistent increase in HIV-1 RNA was seen in only 1 LTNP. In 2 LTNPs, plasma viremia was persistently undetectable or <110 copies/mL. Infectious virus was isolated from only 1 LTNP and from 11 SPs. In 4 LTNPs, HIV-1 DNA levels decreased spontaneously with time. The restricted viral replication and the declining HIV-1 DNA levels suggest that the HIV-1 infection can be controlled efficiently in a few LTNPs, leading to a decrease in the total virus burden with time.  相似文献   

5.
Leukocytes of persons coinfected with HTLV-2 and HIV-1 secrete chemokines that prevent CCR5-dependent (R5) HIV-1 infection of CD4+ T cells and macrophages, with HTLV-2-induced MIP-1alpha as dominant HIV-1 inhibitory molecule. Two nonallelic genes code for CCL3 and CCL3L1 isoforms of MIP-1alpha, and the population-specific copy number of CCL3L1 exerts a profound effect on HIV-1 susceptibility and disease progression. Here, we demonstrate that CCL3L1 is secreted spontaneously by leukocytes of HTLV-2-infected persons and superinduced when cells of HTLV-2/HIV-1 multiply exposed-uninfected seronegative (MEU) persons were stimulated with HIV-1 Env peptides. The CCL3L1 median copy number in MEU, HTLV-2/HIV-1-coinfected long-term nonprogressors (LTNPs) and HIV-1-monoinfected LTNPs were 1, 2, and 3, respectively. An increased CCL3L1/CCL3 mRNA ratio versus PHA-activated healthy leukocytes was observed in both HIV-1-monoinfected LTNPs and in HTLV-2/HIV-1(MEU) subjects. An additional potential correlate of HTLV-2 infection was a rapid and persistent leukocyte secretion of GM-CSF and IFN-gamma, 2 cytokines endowed with CCR5 down-regulation capacity. This study confirms a crucial protective role of CCL3L1 from both HIV infection and disease progression, highlighting a previously not described functional up-regulation of this chemokine variant in both HIV-positive and -negative persons infected with HTLV-2.  相似文献   

6.
Exposure to HIV-1 does not necessarily result in infection and progression toward disease, thus suggesting that the control of viral infection may be achieved. Antibodies to CCR5 have been detected in HIV-exposed but uninfected subjects (ESNs); thus, these antibodies could be involved in HIV protection. To assess whether anti-CCR5 antibodies may also contribute to slow HIV disease progression, we searched for anti-CCR5 antibodies in 497 subjects, including 85 long-term nonprogressors (LTNPs), 70 progressors, 135 HIV(+) patients treated with highly active antiretroviral therapy (HAART), and 207 seronegative donors. We found anti-CCR5 antibodies in a fraction of the LTNPs(23.5%) but not in the other populations studied (P < .001). These antibodies recognized a conformational epitope within the first extramembrane loop of CCR5, and they induced a stable and long-lasting downregulation of CCR5 on the surface of T lymphocytes, which inhibited HIV entry. In addition, CD4(+) lymphocytes from LTNPs having anti-CCR5 antibodies are resistance to R5 strains of HIV-1. Follow-up studies showed that the loss of anti-CCR5 antibodies occurred in some subjects, and this loss was significantly associated with a progression toward disease, whereas subjects who retained anti-CCR5 Abs maintained their LTNP status. Induction of anti-CCR5 Abs could be relevant to vaccine design and therapeutics.  相似文献   

7.
To establish immunologic correlates of progression to AIDS in long-term survivors of HIV-1 infection, HIV-1-specific T cell-mediated responses, together with T cell reactivity to recall antigens, were studied in frozen samples collected after 5 and 8 years of documented HIV-1 infection. Eight of 21 homosexual men, who remained asymptomatic and maintained CD4+ T cell numbers >400 cells/microl for 9 years of HIV-1 infection, progressed to AIDS (CDC 1993 definition) within 12.5 years of infection (late progressors, LPs). The remainders showed minimal deterioration of immune parameters (long-term nonprogressors, LTNPs). CD4+ T cell numbers and T cell function measured at years 5 and 8 of follow-up were comparable in the two groups. At both time points responses to recall antigens did not significantly differ between the two groups, although a significant decline of lymphoproliferative responses to Candida and tetanus toxoid was observed in LPs. Circulating HIV-1-specific cytotoxic T lymphocyte precursors were found in broad frequency ranges in both LPs and LTNPs and, similarly, no significant differences were found in comparing the breadth of serum neutralizing activity against heterologous HIV-1 primary isolates. In contrast, lymphoproliferative responses to p24gag, but not p17gag or gp160env, were detected only in LTNPs and were totally absent in LPs at both time points (p < 0.01). Our data suggest that the presence of circulating p24-specific CD4+ T cells may reflect effective viral control and be predictive of subsequent favorable clinical course in long-term asymptomatic individuals.  相似文献   

8.
Linear conserved B cell epitopes in envelope glycoprotein of long-term nonprogressors (LTNPs) HIV-1 CRF01_AE were determined. The envelope sequences of HIV-1 subtype E from Thailand were aligned to define consensus sequences. Then the peptides corresponding to these predicted regions were synthesized as peptides represent C1, C2, C3, C5, V2, V3, and gp41 regions. After that, the neutralizing B cell epitopes were determined by neutralized competitive assay with pool sera of typical progressor and LTNP HIV-1 CRF01_AE patients against HIV-1 CRF01_AE 24 primary isolates (PI) and laboratory strains (TCLA). We found that the strength and breadth of neutralization were greater for sera from LTNPs compared with sera from typical progressors. Peptides C1E and C2E could inhibit primary isolates but not the TCLA strain in LTNP sera. The new B cell epitopes, which were located in the C1 and C2 regions of CRF01_AE against primary HIV-1 isolates, were identified in HIV-1 CRF01_AE LTNPs. This may be important in HIV-1 vaccine development and trial.  相似文献   

9.
AIMS: To determine the HIV-1 seroprevalence, risk behaviors and demographic characteristics associated with HIV-1 infection among injection drug users (IDU) in rural Guangxi, China. DESIGN AND SETTING: Between July and November 2002, 702 IDU were screened for HIV-1 antibody through community outreach in rural Guangxi, China for enrollment in an HIV sero-incidence study. PARTICIPANTS: A total of 702 active high-risk IDU were screened. High-risk injection was defined as anyone who reported injecting drugs at least three times per week in the last month or injected drugs with shared equipment on at least three occasions in the last 3 months. MEASUREMENTS: HIV-1 antibody testing with confirmation by Western blot was performed on all subjects. Demographic and risk assessment survey data were collected at screening from everyone whose baseline HIV antibody status was known. FINDINGS: HIV-1 antibody prevalence among 702 IDU at baseline was 25% with a median age of 26.7 years (18.2-43.2). Based on a multivariate logistic regression model using risk factors identified in univariate analyses, the following risk factors were associated significantly with an increase in risk for HIV seropositivity: age > 26 years (OR 1.50; 95% CI 1.04, 2.17), sharing of rinse water (OR = 1.24; 95% CI 1.09, 1.40), not having sex in the last 6 months (OR = 1.62; 95% CI 1.08, 2.43). CONCLUSIONS: HIV infection among IDU in Guangxi, one of China's major HIV epidemic regions, is high and the infection occurs predominantly among older IDU males who share rinse water.  相似文献   

10.
In this study which was carried over a period of 4 years, from 2001 to 2004, 600 adult patients with active TB disease attending the OPD of TBDTC, Agra, were screened for HIV-1/2 antibodies. Of these, 26 were found to be HIV-positive. Seroprevalence of HIV infection among adult TB patients in Agra is 4.3% (26/600). The HIV infection was found to be more in females, i.e. 7.95% (7/88) than in males, 3.71% (19/512). HIV-positivity of 5% was observed in the age groups, 15-24 and 25-34 years, i.e. 3/60 and 13/260, respectively. Among HIV-positive TB patients, 4.2% (22/524) were of pulmonary and 5.3% (4/76) were of extra-pulmonary type. A total of 3.04% (6/197) of HIV-positive TB patients were PPD positive and 4.96% (20/403) were PPD negative and bacillary positivity was 4.4% (15/340) and bacillary negativity was 4.2% (11/260). A total of 3.5% (18/515) of TB patients had a history of positive contact, i.e. spouse or one of the family members was HIV-infected. The difference in signs and symptoms among the HIV positive and HIV negative TB patients was found to be statistically significant.  相似文献   

11.
Liver transplantation (LT) has become an accepted therapy for end-stage liver disease in human immunodeficiency virus-positive (HIV+) patients, but the specific results of LT for hepatocellular carcinoma (HCC) are unknown. Between 2003 and 2008, 21 HIV+ patients and 65 HIV- patients with HCC were listed for LT at a single institution. Patient characteristics and pathological features were analyzed. Univariate analysis for overall survival (OS) and recurrence-free survival (RFS) after LT was applied to identify the impact of HIV infection. HIV+ patients were younger than HIV- patients [median age: 48 (range = 41-63 years) versus 57 years (range = 37-72 years), P < 0.001] and had a higher alpha-fetoprotein (AFP) level [median AFP level: 16 (range = 3-7154 μg/L] versus 13 μg/L (range = 1-552 μg/L), P = 0.04]. There was a trend toward a higher dropout rate among HIV+ patients (5/21, 23%) versus HIV- patients (7/65, 10%, P = 0.08). Sixteen HIV+ patients and 58 HIV- patients underwent transplantation after median waiting times of 3.5 (range = 0.5-26 months) and 2.0 months (range = 0.5-24 months, P = 0.18), respectively. No significant difference was observed in the pathological features of HCC. With median follow-up times of 27 (range = 5-74 months) and 36 months (range = 3-82 months, P = 0.40), OS after LT at 1 and 3 years reached 81% and 74% in HIV+ patients and 93% and 85% in HIV- patients, respectively (P = 0.08). RFS rates at 1 and 3 years were 69% and 69% in HIV+ patients and 89% and 84% in HIV- patients, respectively (P = 0.09). In univariate analysis, HIV status did not emerge as a prognostic factor for OS or RFS. CONCLUSION: Because of a higher dropout rate among HIV+ patients, HIV infection impaired the results of LT for HCC on an intent-to-treat basis but had no significant impact on OS and RFS after LT.  相似文献   

12.
目的 了解长期不进展HIV-1感染者HIV-1准种膜蛋白V3环氨基酸序列特征及变异特点.方法 应用终点有限稀释套式PCR方法,对5例长期不进展HIV-1感染者不同时间点单个HIV-1前病毒env基因c2-v3-c3区域进行扩增和序列测定,用序列确证分析技术分析env基因区V3环氨基酸序列特征.结果 5例患者不同随访时间点获得的准种序列中,V3环35个氨基酸中出现多样性的位点分别有1~10个不等,同一患者不同随访时间点准种优势株序列完全一致或仅有1~2个位点不同;4例患者V3环顶端四肽为GPGR,1例患者为GPGK,同一患者不同随访时间点V3环顶端四肽一致;根据V3环11和25位氨基酸及V3环的电荷推测HIV-1辅助受体均为趋化因子受体(CCR)5.结论 长期不进展HIV-1感染者V3环序列存在不同程度变异,顶端四肽稳定性高,感染的HIV-1毒株可能为非合胞体诱导型毒株.  相似文献   

13.
Members of the Sydney Blood Bank Cohort (SBBC) have been infected with an attenuated strain of HIV-1 with a natural nef/LTR mutation and have maintained relatively stable CD4+ T lymphocyte counts for 14-18 years. Flow cytometric analysis was used to examine the phenotype of CD4+ and CD8+ T lymphocytes in these subjects, including the immunologically important naive (CD45RA+CD62L+), primed (CD45RO+), and activated (CD38+HLA-DR+ and CD28-) subsets. The median values were compared between the SBBC and control groups, comprising age-, sex-, and transfusion-matched HIV-1-uninfected subjects; transfusion-acquired HIV-1-positive LTNPs; and sexually acquired HIV-1-positive LTNPs. Members of the SBBC not only had normal levels of naive CD4+ and CD8+ T lymphocytes, but had primed CD45RO+ CD4+ T lymphocytes at or above normal levels. Furthermore, these primed cells expressed markers suggesting recent exposure to specific antigen. SBBC members exhibited variable activation of CD8+ T lymphocytes. In particular, SBBC members with undetectable plasma HIV-1 RNA had normal levels of activated CD8+ T lymphocytes. Therefore, the result of long-term infection with natural nef/LTR mutant HIV-1 in these subjects suggests a decreased cytopathic effect of attenuated HIV-1 on susceptible activated CD4+ T lymphocyte subsets in vivo, and minimal activation of CD8+ T lymphocytes.  相似文献   

14.
15.
目的 了解长期不进展HIV-1感染者HIV-1准种膜蛋白V3环氨基酸序列特征及变异特点.方法 应用终点有限稀释套式PCR方法,对5例长期不进展HIV-1感染者不同时间点单个HIV-1前病毒env基因c2-v3-c3区域进行扩增和序列测定,用序列确证分析技术分析env基因区V3环氨基酸序列特征.结果 5例患者不同随访时间点获得的准种序列中,V3环35个氨基酸中出现多样性的位点分别有1~10个不等,同一患者不同随访时间点准种优势株序列完全一致或仅有1~2个位点不同;4例患者V3环顶端四肽为GPGR,1例患者为GPGK,同一患者不同随访时间点V3环顶端四肽一致;根据V3环11和25位氨基酸及V3环的电荷推测HIV-1辅助受体均为趋化因子受体(CCR)5.结论 长期不进展HIV-1感染者V3环序列存在不同程度变异,顶端四肽稳定性高,感染的HIV-1毒株可能为非合胞体诱导型毒株.  相似文献   

16.
The replicative potential of HIV-1 strains in a well-characterized group of eight HIV controllers was investigated. Replication-competent viruses were detected in CD4 T-cell co-culture supernatants from all HIV controllers. The phylogenetic analysis of C2V4 suggested viral evolution or co-infection or superinfection in two out of the four patients analysed. The vif and vpr genes were normal. Infection with HIV-1 variants with attenuated replicative capacity cannot be a general factor accounting for undetectable viraemia in HIV controllers.  相似文献   

17.
目的 了解长期不进展HIV-1感染者HIV-1准种膜蛋白V3环氨基酸序列特征及变异特点.方法 应用终点有限稀释套式PCR方法,对5例长期不进展HIV-1感染者不同时间点单个HIV-1前病毒env基因c2-v3-c3区域进行扩增和序列测定,用序列确证分析技术分析env基因区V3环氨基酸序列特征.结果 5例患者不同随访时间点获得的准种序列中,V3环35个氨基酸中出现多样性的位点分别有1~10个不等,同一患者不同随访时间点准种优势株序列完全一致或仅有1~2个位点不同;4例患者V3环顶端四肽为GPGR,1例患者为GPGK,同一患者不同随访时间点V3环顶端四肽一致;根据V3环11和25位氨基酸及V3环的电荷推测HIV-1辅助受体均为趋化因子受体(CCR)5.结论 长期不进展HIV-1感染者V3环序列存在不同程度变异,顶端四肽稳定性高,感染的HIV-1毒株可能为非合胞体诱导型毒株.  相似文献   

18.
Ojukwu JU  Ogbu CN 《AIDS care》2007,19(3):330-336
The increasing prevalence of HIV infection in Nigeria, its similar manifestations with endemic diseases and limited facilities for screening calls for judicious HIV testing. Children aged one month to 15 years admitted into the paediatric ward of the Ebonyi State University Teaching Hospital between January 2000 and September 2001 for various endemic diseases were reviewed retrospectively. Eight clinical risk factors commonly associated with HIV infection and endemic diseases present either singly or in combination, were reviewed to determine whether they could help to predict HIV infection and at what level and finally help formulate criteria for selective screening of HIV infection. Children above 18 months of age were diagnosed as being infected with HIV if they tested positive by two different HIV enzyme-linked immunosorbent assay (ELISA) tests. In children less than 18 months of age the diagnosis of HIV infection was made if they were ELISA positive and also fulfilled the WHO criteria for symptomatic HIV infection. Of the 282 children reviewed 31 (11.0%) were HIV positive giving a sero-prevalence rate of 4.1% of total admission. The HIV seropositive rate was highest in oral candidiasis (OC) (38.2%), followed by severe malnutrition (SM) (33.8%) then generalized lymphadenopathy (GLN) (31.4%).The presence of SM, GLN, OC and chronic dermatitis were highly significant independent risk factors for predicting HIV seropositivity (p<0.05). A marked shift towards the likelihood of HIV sero-positivity in the presence of at least two of the eight risk factors was documented. Children with two risk factors present had a 9.1 times more risk of being HIV sero-positive compared with those who had only one risk factor present (chi(2)=11.6, p=0.0007, OR = 9.1, 95% Cl = 2.5-32.8). Thirteen children (41.9%) representing a vast majority of HIV-positive children showed evidence of at least two of the eight clinical risk factors. As the number of risk factors concomitantly present increased, the chances of the child being infected with HIV also increase significantly (p<0.0001). Our study shows that clinically-directed selective screening in the presence of at least two risk factors should be carried out which does have a practical role in early diagnosis of HIV infection in a resource-poor setting.  相似文献   

19.
We have examined the occurrence of HIV-1 superinfection in 14 HIV-seroconcordant couples (i.e., partners were independently infected with different HIV-1 strains) with high risk of reexposure to the virus. Phylogenetic analyses based on pol and env global sequences obtained from more than 100 longitudinal plasma samples (corresponding to a period of 1-4 years) failed to detect HIV-1 superinfection in this cohort of patients. Our results suggest that despite recent reports of HIV-1 reinfection, chronic HIV infection seems to confer protection against superinfection with a second HIV-1 strain.  相似文献   

20.
BACKGROUND: In sub-Saharan Africa, tuberculosis (TB) is the most frequently diagnosed opportunistic infection and cause of death among HIV-infected patients. HIV-2 has been associated with less immune suppression, slower disease progression and longer survival. OBJECTIVE: To examine whether the incidence of TB and survival after TB are associated with CD4 cell count rather than HIV type. METHODS: Clinical and immunological data were retrospectively evaluated among an open clinic-based cohort of HIV-1- and HIV-2-infected patients to determine incidence of TB (first diagnosis > 28 days after HIV diagnosis) and subsequent mortality. Patients were grouped by CD4 cell count into those with < 200, 200-500 and > 500 x 10 cells/l. RESULTS: Incident TB was diagnosed among 159 of 2012 patients, with 4973 person-years of observation time. In 105/159 (66.0%), the diagnosis was confirmed by direct microscopy or culture. Incidence of TB was highest in the group with < 200 x 10 cells/l (9.1/100 and 8.8/100 person-years in HIV-1 and HIV-2, respectively). Adjusted for CD4 cell count, there was no significant difference in incidence or mortality following TB between HIV-1- and HIV-2-infected patients. Mortality rate was higher in those with incident TB and HIV infection, most markedly in the group with the highest CD4 cell count (hazard ratio, 10.0; 95% confidence interval, 5.1-19.7). CONCLUSION: Adjusted for CD4 cell count, incidence of TB was similar among HIV-1- and HIV-2-infected patients. Mortality rates after TB diagnosis were similar in both groups and high compared with those without TB.  相似文献   

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