Infection with multiple human immunodeficiency virus type 1 variants is associated with faster disease progression

Human immunodeficiency virus type 1 (HIV-1)-infected individuals develop a genetically diverse virus population over time, but often only a limited number of viral variants are transmitted from a chronic carrier to a newly infected person. Interestingly, many women but few men are infected by multiple HIV-1 variants from a single partner. To determine whether the complexity of the infecting virus population influences clinical outcome, we examined viral diversity in the HIV-1 envelope sequences present at primary infection in 156 women from Kenya for whom we had follow-up data on viral RNA levels and CD4 T-cell counts. Eighty-nine women had multiple viral genotypes, while 67 women had a single genotype at primary infection. Women who acquired multiple viral genotypes had a significantly higher viral load (median, 4.84 versus 4.64 log(10) copies/ml, P = 0.04) and a significantly lower CD4(+)-T-cell count (median, 416 versus 617 cells/mm(3), P = 0.01) 4 to 24 months after infection compared to women who were infected with a single viral genotype. These studies suggest that early HIV-1 genetic diversity is linked to faster disease progression.     

HIV-1 subtype B epidemic and transmission patterns in Slovenia

In the present study the epidemic of human immunodeficiency virus type 1 (HIV-1) subtype B in Slovenia during the 10-year period was investigated using phylogenetic analysis of pol gene sequences. 119 pol sequences generated on samples dated from January 1996 to December 2005 were retrieved from the database of Slovenian HIV/AIDS Reference Laboratory. The phylogenetic analysis revealed 14 potentially significant transmission clusters (bootstrap value > or = 98%), comprising 34 HIV-1 strains. The vast majority of clustered individuals were men (91%), and of them, 79% were men who have sex with men. Factors significantly associated with clustering were: recent infection (HIV-1 infection during or after year 2003), diagnosis of primary HIV-1 infection, higher CD4 cell count and acquiring HIV-1 infection in Slovenia. Recent subtype B HIV-1 infections are the important driving force of current HIV-1 epidemic in Slovenia.     

Changes in the level of apoptosis-related proteins in Jurkat cells infected with HIV-1 versus HIV-2

Human immunodeficiency virus (HIV) infection-induced apoptosis of infected CD4 T cells as well as uninfected (bystander) CD4 T cells and other types of cells is a major factor in the pathogenesis of AIDS. Clinically, HIV-2 patients have a higher CD4 cell count at the time of an AIDS diagnosis, and generally have longer survival after development of symptoms. The mortality after an AIDS diagnosis has been reported to be more influenced by CD4 cell count than HIV type. Previous studies have shown significant variations in cytopathic effects following in vitro infection with primary isolates of HIV-1 or HIV-2 subtypes; however, the relative contributions of HIV-1 and HIV-2 infection leading to cell death remain unclear. Using a human cell line, Jurkat, we examined differences in key molecules involved in apoptotic signaling pathways during infection with either HIV-1 or HIV-2. HIV-1 infection generated more reactive oxygen species (ROS), increased the expression of a larger number of molecules involved in cell signaling such as p47, p38α, JNK, c-Yes, total PKC, and decreased the expression of molecules such as p38β, ERK1/2, and XIAP relative to HIV-2 infection. HIV-1 induced a higher degree of cell death through stronger activation of both apoptotic pathways. HIV-1 infection downregulated both Bcl-X_L and FLIP expressions at later time points postinfection, while HIV-2 infection dramatically upregulated both Bcl-X_L and FLIP expression. We also found that the expression of Bcl-X_L or FLIP resulted in significant inhibition of HIV replication in Jurkat cells. These findings suggest that HIV-1 infection with high levels of cytotoxicity results in a higher level of cell death through apoptosis during a short time postinfection. The longer period of infection observed with HIV-2 with a lower degree of cytotoxicity was accompanied by increased Bcl-X_L and FLIP expression. High protein levels of Bcl-X_L or FLIP inhibit HIV replication and may be one explanation for the clinical observation that HIV-2 infected patients generally tend to be long-term nonprogressors with high CD4 lymphocyte counts compared with HIV-1 infected persons.     

Characteristics of HIV-2 and HIV-1/HIV-2 Dually Seropositive Adults in West Africa Presenting for Care and Antiretroviral Therapy: The IeDEA-West Africa HIV-2 Cohort Study

Background

HIV-2 is endemic in West Africa. There is a lack of evidence-based guidelines on the diagnosis, management and antiretroviral therapy (ART) for HIV-2 or HIV-1/HIV-2 dual infections. Because of these issues, we designed a West African collaborative cohort for HIV-2 infection within the framework of the International epidemiological Databases to Evaluate AIDS (IeDEA).

Methods

We collected data on all HIV-2 and HIV-1/HIV-2 dually seropositive patients (both ARV-naive and starting ART) and followed-up in clinical centres in the IeDEA-WA network including a total of 13 clinics in five countries: Benin, Burkina-Faso Côte d’Ivoire, Mali, and Senegal, in the West Africa region.

Results

Data was merged for 1,754 patients (56% female), including 1,021 HIV-2 infected patients (551 on ART) and 733 dually seropositive for both HIV-1 and HIV 2 (463 on ART). At ART initiation, the median age of HIV-2 patients was 45.3 years, IQR: (38.3–51.7) and 42.4 years, IQR (37.0–47.3) for dually seropositive patients (p = 0.048). Overall, 16.7% of HIV-2 patients on ART had an advanced clinical stage (WHO IV or CDC-C). The median CD4 count at the ART initiation is 166 cells/mm³, IQR (83–247) among HIV-2 infected patients and 146 cells/mm³, IQR (55–249) among dually seropositive patients. Overall, in ART-treated patients, the CD4 count increased 126 cells/mm³ after 24 months on ART for HIV-2 patients and 169 cells/mm³ for dually seropositive patients. Of 551 HIV-2 patients on ART, 5.8% died and 10.2% were lost to follow-up during the median time on ART of 2.4 years, IQR (0.7–4.3).

Conclusions

This large multi-country study of HIV-2 and HIV-1/HIV-2 dual infection in West Africa suggests that routine clinical care is less than optimal and that management and treatment of HIV-2 could be further informed by ongoing studies and randomized clinical trials in this population.     

Increase in CD3+ CD4- T lymphocytes in patients with AIDS and disseminated Mycobacterium avium-intracellulare complex infection: a prospective study. GECSA. Groupe d'Epidemiologie Clinique du SIDA en Aquitaine

In a retrospective study, an increase in double-negative (CD3+ CD4- CD8-) (DN) T lymphocytes has been shown to be an independent predictor of disseminated Mycobacterium avium complex (D.MAC) infection in patients with less than 100 CD4+ T cells per mm3. To better characterize this cell expansion, a prospective study was designed. From July 1995 to April 1997, 206 HIV-infected patients with less than 100 CD4+ T cells per mm3 were prospectively followed up and immunophenotyped. The median followup was 1.1 year (+/-0.5 year), and 14 new D.MAC infections were diagnosed among 84 first AIDS-defining events. In univariate and multivariate analyses, D.MAC infections were the only opportunistic infection with a significant increase in DN T-cell percentage (median = 6.6; range = 1.7 to 24.5, P = 0.004) compared with patients without any opportunistic infection. This alteration in T-lymphocyte count could constitute a predictor for D.MAC infection in clinical practice.     

The IgM antibody level against ganglioside GM2 correlates to the disease status of HIV-1-infected patients

HIV-1 infection induces the expression of high level of GM2 ganglioside on infected cells and IgM antibody (Ab) against GM2 can cause complement (C)-mediated cytolysis of HIV-1-infected cells. Since GM2 is immunogenic in human, we proposed that an anti-GM2 IgM Ab may be produced by some HIV-1-infected patients and the titer of this Ab might provide some insight into the progress of the disease. On this premise, the amount of IgM Ab against GM2 was determined in 124 HIV-1-infected patients and 111 seronegative donors. As expected, the anti-GM2 IgM Ab titers of the patients was significantly higher than that of the seronegative donors while the total IgM levels remained unchanged. In addition, we determined the CD4+ cell count and the HIV-RNA load in the HIV-1-infected patients. The results showed a positive correlation between the anti-GM2 IgM Ab titer and CD4+ cell count but a negative correlation between the anti-GM2 IgM Ab titer and HIV-RNA load. These suggest that anti-GM2 IgM Ab induced and/or enhanced by HIV-1 infection causes C-mediated cytolysis of HIV-1-infected cells in vivo to a certain extent, and may help lower the plateau level of the HIV-RNA load. Therefore, the amount of IgM Ab against GM2 may be related to the prognosis of HIV-1 infected patients.     

Herpes simplex virus type 2, genital ulcers and HIV-1 disease progression in postpartum women

Background

Co-infection with herpes simplex virus type 2 (HSV-2) has been associated with increased HIV-1 RNA levels and immune activation, two predictors of HIV-1 progression. The impact of HSV-2 on clinical outcomes among HIV-1 infected pregnant women is unclear.

Methods

HIV-1 infected pregnant women in Nairobi were enrolled antenatally and HSV-2 serology was obtained. HIV-1 RNA and CD4 count were serially measured for 12–24 months postpartum. Survival analysis using endpoints of death, opportunistic infection (OI), and CD4<200 cells µL, and linear mixed models estimating rate of change of HIV-1 RNA and CD4, were used to determine associations between HSV-2 serostatus and HIV-1 progression.

Results

Among 296 women, 254 (86%) were HSV-2-seropositive. Only 30 (10%) women had prior or current genital ulcer disease (GUD); median baseline CD4 count was 422 cells µL. Adjusting for baseline CD4, women with GUD were significantly more likely to have incident OIs (adjusted hazard ratio (aHR) 2.79, 95% CI: 1.33–5.85), and there was a trend for association between HSV-2-seropositivity and incident OIs (aHR 3.83, 95% CI: 0.93–15.83). Rate of change in CD4 count and HIV-1 RNA did not differ by HSV-2 status or GUD, despite a trend toward higher baseline HIV-1 RNA in HSV-2-seropositive women (4.73 log10 copies/ml vs. 4.47 log10 copies/ml, P = 0.07).

Conclusions

HSV-2 was highly prevalent and pregnant HIV-1 infected women with GUD were significantly more likely to have incident OIs than women without GUD, suggesting that clinically evident HSV-2 is a more important predictor of HIV-1 disease progression than asymptomatic HSV-2.     

Residual Viral Replication during Antiretroviral Therapy Boosts Human Immunodeficiency Virus Type 1-Specific CD8+ T-Cell Responses in Subjects Treated Early after Infection

Human immunodeficiency virus type 1 (HIV-1)-infected subjects treated early after infection have preserved HIV-1-specific CD4+ T-cell function. We studied the effect of highly active antiretroviral therapy (HAART) on the frequency of HIV-1-specific CD8+ T cells in patients treated during early (n = 31) or chronic (n = 23) infection. The degree of viral suppression and time of initiation of treatment influenced the magnitude of the CD8+ T-cell response. HIV-1-specific CD8+ T cells can increase in number after HAART in subjects treated early after infection who have episodes of transient viremia.     

Differential susceptibility to human immunodeficiency virus type 1 infection of myeloid and plasmacytoid dendritic cells

Human immunodeficiency virus type 1 (HIV-1) infection of dendritic cells (DCs) plays an important role in HIV-1 transmission and pathogenesis. Here, we studied the susceptibility of ex vivo-isolated CD11c+ myeloid DCs (MDCs) and CD123+ plasmacytoid DCs (PDCs) to HIV-1 infection and the function of these cells early after infection. Both DC subsets were susceptible to CCR5- and CXCR4-using HIV-1 isolates (BaL and IIIB, respectively). However, MDCs were more susceptible to HIV-1(BaL) infection than donor-matched PDCs. In addition, HIV-1(BaL) infected MDCs more efficiently than HIV-1(IIIB), whereas PDCs were equally susceptible to both isolates. While exposure to HIV-1 alone resulted in only weak maturation of DCs, Toll-like receptor 7/8 ligation induced full maturation in both infected and uninfected DCs. Maturation did not increase HIV-1 replication in infected DCs, and infected DCs retained their ability to produce tumor necrosis factor alpha after stimulation. Both HIV-1 isolates induced alpha interferon production exclusively in PDCs, irrespective of productive infection. In conclusion, PDCs and MDCs were susceptible to HIV-1 infection, but neither displayed functional defects as a consequence of infection. The difference in susceptibility of PDCs and MDCs to HIV-1 may have implications for HIV-1 transmission and DC-mediated transfer of HIV-1 to T cells.     

The Clinical and Immune Characteristics of Patients with Hepatitis-Associated Aplastic Anemia in China

Hepatitis-associated aplastic anemia (HAAA) is a variant of severe aplastic anemia (SAA) in which bone marrow failure follows an acute attack of hepatitis. Its pathogenesis is poorly understood. We investigated the prevalence of HAAA among cases of newly diagnosed SAA presenting to our hospital between January 1998 and February 2013, and analyzed the clinical and immune characteristics of HAAA and non-hepatitis-associated SAA (non-HASAA) patients. The prevalence of HAAA among cases of SAA was 3.8% (36/949), and the majority of patients (33/36) were seronegative for a known hepatitis virus. Compared with non-HASAA patients, HAAA patients had a larger proportion of CD8+ T cells, a lower ratio of CD4+/CD8+ T cells, and a smaller proportion of CD4+CD25+ regulatory T cells. There was no significant difference in peripheral blood count, bone marrow cellularity, or the number of blood transfusions received between HAAA and non-HASAA patients. HAAA patients had a higher early infection rate and more infection-related mortality in the first 2 years after diagnosis than non-HASAA patients, and their 2-year survival rate was lower. The results demonstrate that HAAA patients have a more severe T cell imbalance and a poorer prognosis than non-HASAA patients.     

Acute Plasma Biomarkers of T Cell Activation Set-Point Levels and of Disease Progression in HIV-1 Infection

T cell activation levels, viral load and CD4⁺ T cell counts at early stages of HIV-1 infection are predictive of the rate of progression towards AIDS. We evaluated whether the inflammatory profile during primary HIV-1 infection is predictive of the virological and immunological set-points and of disease progression. We quantified 28 plasma proteins during acute and post-acute HIV-1 infection in individuals with known disease progression profiles. Forty-six untreated patients, enrolled during primary HIV-1 infection, were categorized into rapid progressors, progressors and slow progressors according to their spontaneous progression profile over 42 months of follow-up. Already during primary infection, rapid progressors showed a higher number of increased plasma proteins than progressors or slow progressors. The plasma levels of TGF-β1 and IL-18 in primary HIV-1 infection were both positively associated with T cell activation level at set-point (6 months after acute infection) and together able to predict 74% of the T cell activation variation at set-point. Plasma IP-10 was positively and negatively associated with, respectively, T cell activation and CD4⁺ T cell counts at set-point and capable to predict 30% of the CD4⁺ T cell count variation at set-point. Moreover, plasma IP-10 levels during primary infection were predictive of rapid progression. In primary infection, IP-10 was an even better predictor of rapid disease progression than viremia or CD4⁺ T cell levels at this time point. The superior predictive capacity of IP-10 was confirmed in an independent group of 88 HIV-1 infected individuals. Altogether, this study shows that the inflammatory profile in primary HIV-1 infection is associated with T cell activation levels and CD4⁺ T cell counts at set-point. Plasma IP-10 levels were of strong predictive value for rapid disease progression. The data suggest IP-10 being an earlier marker of disease progression than CD4⁺ T cell counts or viremia levels.     

Dynamics of intermittent viremia during highly active antiretroviral therapy in patients who initiate therapy during chronic versus acute and early human immunodeficiency virus type 1 infection

The meaning of viral blips in human immunodeficiency virus type 1 (HIV-1)-infected patients treated with seemingly effective highly active antiretroviral therapy (HAART) is still controversial and under investigation. Blips might represent low-level ongoing viral replication in the presence of drug or simply release of virions from the latent reservoir. Patients treated early during HIV-1 infection are more likely to have a lower total body viral burden, a homogenous viral population, and preserved HIV-1-specific immune responses. Consequently, viral blips may be less frequent in them than in patients treated during chronic infection. To test this hypothesis, we compared the occurrence of viral blips in 76 acutely infected patients (primary HIV infection [PHI] group) who started therapy within 6 months of the onset of symptoms with that in 47 patients who started HAART therapy during chronic infection (chronic HIV infection [CHI] group). Viral blip frequency was approximately twofold higher in CHI patients (0.122 +/- 0.12/viral load [VL] sample, mean +/- standard deviation) than in PHI patients (0.066 +/- 0.09/VL sample). However, in both groups, viral blip frequency did not increase with longer periods of observation. Also, no difference in viral blip frequency was observed between treatment subgroups, and the occurrence of a blip was not associated with a recent change in CD4(+) T-cell count. Finally, in PHI patients the VL set point was a significant predictor of blip frequency during treatment.     

Rate of increase in circulating IL-7 and loss of IL-7Ralpha expression differ in HIV-1 and HIV-2 infections: two lymphopenic diseases with similar hyperimmune activation but distinct outcomes

IL-7 is a nonredundant cytokine for T cell homeostasis. Circulating IL-7 levels increase in lymphopenic clinical settings, including HIV-1 infection. HIV-2 infection is considered a "natural" model of attenuated HIV disease given its much slower rate of CD4 decline than HIV-1 and limited impact on the survival of the majority of infected adults. We compared untreated HIV-1- and HIV-2-infected patients and found that the HIV-2 cohort demonstrated a delayed increase in IL-7 levels during the progressive depletion of circulating CD4 T cells as well as a dissociation between the acquisition of markers of T cell effector differentiation and the loss of IL-7Ralpha expression. This comparison of two persistent infections associated with progressive CD4 depletion and immune activation demonstrates that a better prognosis is not necessarily associated with higher levels of IL-7. Moreover, the delayed increase in IL-7 coupled with sustained expression of IL-7Ralpha suggests a maximization of available resources in HIV-2. The observation that increased IL-7 levels early in HIV-1 infection were unable to reduce the rate of CD4 loss and the impaired expression of the IL-7Ralpha irrespective of the state of cell differentiation raises concerns regarding the use of IL-7 therapy in HIV-1 infection.     

Slower evolution of human immunodeficiency virus type 1 quasispecies during progression to AIDS.

The evolution of human immunodeficiency virus type 1 (HIV-1) quasispecies at the envelope gene was studied from the time of infection in 11 men who experienced different rates of CD4+ cell count decline and 6 men with unknown dates of infection by using DNA heteroduplex mobility assays. Quasispecies were genetically homogeneous near the time of seroconversion. Subsequently, slower proviral genetic diversification and higher plasma viremia correlated with rapid CD4+ cell count decline. Except for the fastest progressors to AIDS, highly diverse quasispecies developed in all subjects within 3 to 4 years. High quasispecies diversity was then maintained for years until again becoming more homogeneous in a subset of late-stage AIDS patients. Individuals who maintained high CD4+ cell counts showed continuous genetic turnover of their complex proviral quasispecies, while more closely related sets of variants were found in longitudinal samples of severely immunocompromised patients. The limited number of variants that grew out in short-term PBMC cocultures were rare in the uncultured proviral quasispecies of healthy, long-term infected individuals but more common in vivo in patients with low CD4+ cell counts. The slower evolution of HIV-1 observed during rapid progression to AIDS and in advanced patients may reflect ineffective host-mediated selection pressures on replicating quasispecies.     

HIV-1 Genetic Diversity and Its Impact on Baseline CD4+T Cells and Viral Loads among Recently Infected Men Who Have Sex with Men in Shanghai,China

The HIV-1 epidemic among men who have sex with men (MSM) has been spreading throughout China. Shanghai, a central gathering place for MSM, is facing a continuously increasing incidence of HIV-1 infection. In order to better understand the dynamics of HIV-1 diversity and its influence on patient’s immune status at baseline on diagnosis, 1265 newly HIV-1-infected MSM collected from January 2009 to December 2013 in Shanghai were retrospectively analyzed for genetic subtyping, CD4+T cell counts, and viral loads. HIV-1 phylogenetic analysis revealed a broad viral diversity including CRF01_AE (62.13%), CRF07_BC (24.51%), subtype B (8.06%), CRF55_01B (3.24%), CER67_01B (0.95%), CRF68_01B (0.4%), CRF08_BC (0.08%) and CRF59_01B (0.08%). Twenty-four unique recombination forms (URFs) (1.98%) were identified as well. Bayesian inference analysis indicated that the introduction of CRF01_AE strain (1997) was earlier than CRF07_BC strain (2001) into MSM population in Shanghai based on the time of the most recent common ancestor (tMRCA). Three epidemic clusters and five sub-clusters were found in CRF01_AE. Significantly lower CD4+T cell count was found in individuals infected with CRF01_AE than in those infected with CRF07_BC infection (P<0.01), whereas viral load was significantly higher those infected with CRF01_AE than with CRF07_BC (P<0.01). In addition, the patients with >45 years of age were found to have lower CD4+T cell counts and higher viral loads than the patients with <25 years of age (P<0.05). This study reveals the presence of HIV-1 subtype diversity in Shanghai and its remarkable influence on clinical outcome. A real-time surveillance of HIV-1 viral diversity and phylodynamics of epidemic cluster, patient’s baseline CD4+T cell count and viral load would be of great value to monitoring of disease progression, intervention for transmission, improvement of antiretroviral therapy strategy and design of vaccines.     

Suppression of human immunodeficiency virus replication by CD8+ cells from infected and uninfected chimpanzees.

Over a 4-year period, infectious human immunodeficiency virus type 1 (HIV-1) has been recovered from cultured peripheral blood mononuclear cells (PBMC) of virus-infected animals only intermittently and at relatively low titers. In examining the possible mechanism for this observation, CD4+ cells or CD8+ cells were removed by panning from the PMBC before culture. A dramatic increase in frequency of HIV-1 recovery as well as in the level of virus replication was observed in the CD4+ cell-enriched or CD8+ cell-depleted cultures of PBMC from 3/3 infected animals. Moreover, addition of purified CD8+ effector cells from all 6 HIV-infected and 5/10 uninfected animals to an equal number of HIV-1 acutely infected purified CD4+ target cells resulted in 75-100% suppression of virus production. CD8+ cells from 3 additional uninfected animals caused delayed replication kinetics and moderate to low suppression of peak virus production. These findings contrast with the previously recognized absence of this HIV-1-suppressing activity of CD8+ cells from seronegative humans. This CD8+ cell-mediated suppression of viral replication could help explain the natural resistance of chimpanzees to HIV-induced disease.     

Transient mobilization of human immunodeficiency virus (HIV)-specific CD4 T-helper cells fails to control virus rebounds during intermittent antiretroviral therapy in chronic HIV type 1 infection

Immune control of human immunodeficiency virus (HIV) is not restored by highly active antiretroviral therapies (HAART) during chronic infection. We examined the capacity of repeated structured therapeutic interruptions (STI) to restore HIV-specific CD4 and CD8 T-cell responses that controlled virus production. Eleven STI (median duration, 7 days; ranges, 4 to 24 days) were performed in three chronically HIV-infected patients with CD4 counts above 400/mm(3) and less than 200 HIV RNA copies/ml after 18 to 21 months of HAART; treatment resumed after 1 week or when virus became detectable. HIV-specific T-cell responses were analyzed by proliferation, gamma interferon (IFN-gamma) production, and enzyme-linked immunospot assays. Seven virus rebounds were observed (median, 4,712 HIV-1 RNA copies/ml) with a median of 7 days during which CD4 and CD8 counts did not significantly change. After treatment resumed, the viral load returned below 200 copies/ml within 3 weeks. Significant CD4 T-cell proliferation and IFN-gamma production against HIV p24 appeared simultaneously with or even before the virus rebounds in all patients. These CD4 responses lasted for less than 3 weeks and disappeared before therapeutic control of the virus had occurred. Increases in the numbers of HIV-specific CD8 T cells were delayed compared to changes in HIV-specific CD4 T-cell responses. No delay or increase in virus doubling time was observed after repeated STI. Iterative reexposure to HIV during short STI in chronically infected patients only transiently mobilized HIV-specific CD4 T1-helper cells, which might be rapidly altered by virus replication. Such kinetics might explain the failure at delaying subsequent virus rebounds and raises concerns about strategies based on STI to restore durable HIV-specific T-cell responses in chronic HIV infection.     

Frequency of HLA-A*03 associates with HIV-1 infection in a Chinese cohort

During the early mid-1990s, a number of rural farmers across central China were employed to the unregulated plasmaselling-activity and many of them were infected by HIV-1. However, AIDS progression in the former blood donors (FBDs) is various. The aim of this study is to assess human leukocyte antigen (HLA) class I allele distribution in FBDs and evaluate its association with HIV-1 infection and disease progression. A total of 353 FBDs were enrolled in the cohort including 294 ART naïve HIV-1 seropositive and 59 HIV-1 seronegative age-matched subjects. The viral load and CD4/CD8 T cell counts were assessed in all subjects. Compared with HIV-seropositive group, the frequency of HLA-A*03 in control was significantly higher. After classifying the HLA-B alleles of the subjects according to the presence of Bw4/Bw6 serological epitopes, detrimental effect of HLA Bw6/ Bw6 homozygosity was also confirmed in the HIV-seropositive subjects. This study provides novel evidence on HLA class I allele distribution and association of HLA-A*03 frequency with HIV-1 infection and viremia in the HIV-1 infected FBDs, which may throw light on intervention strategy for the HIV-1 infection and our understanding how host immunity and genetic background affect HIV infection and AIDS progression.