Onset Of Acquired Immunodeficiency Syndrome Research Articles

Dynamics of HIV transmission among men who have sex with men in Taiwan: a mathematical modeling study

BackgroundIn Taiwan, the human immunodeficiency virus (HIV) is primarily transmitted among men who have sex with men (MSM). We believe that the primary source of heterogeneity influencing transmission is from whether the infected individuals engage in behaviors that promote transmission. Therefore, we differentiated and modeled the statuses of infected individuals, estimated parameters, and predicted future infection trends to better understand HIV transmission dynamics among MSM.MethodsWe devised a computational approach to accurately estimate the number of infectious individuals during early surveillance years in Taiwan using monthly data of newly diagnosed patients with HIV from January 2005 to December 2006. Subsequently, using annual incident cases from 2005 to 2019, we estimated the susceptibility rate, transmission rates, and duration of risk and conducted short-term forecasts of HIV infection among MSM through mathematical modeling based on the susceptible-infected-removed model. Parameters and their values, such as HIV and acquired immunodeficiency syndrome (AIDS) transmission rates and removal rates, were also estimated.ResultsA total of 850 infectious individuals with HIV were identified in 2005. From 2005 to 2019, approximately 0.68% (95% confidence interval: 0.64–0.71%) of Taiwan’s male population were estimated to be susceptible to HIV infection via MSM. The transmission rate did not significantly differ between individuals with HIV and AIDS (0.0110 and 0.107 per 10,000 individuals, respectively). The average infection duration between infection and AIDS onset was 4.5 years and between AIDS onset and death was 2.1 years. In 2019, the proportion of infectious infected individuals continuously decreased. By 2026, only 11.85% and 10.21% of individuals with HIV and AIDS, respectively, will be infectious.ConclusionsOur study presents a new dynamic mathematical model for estimating infectious HIV cases among MSM in Taiwan. By accounting for the heterogeneity of infectious HIV/AIDS within the MSM population, we effectively estimated the number of infections during early surveillance years and implement concentrated measures, thereby reducing infectious HIV/AIDS cases, which contributes to the overall reduction in HIV/AIDS cases. With these estimations, identifying target populations and implementing effective intervention measures at appropriate times can be improved.

Impaired Mitochondrial Function in T-Lymphocytes as a Result of Exposure to HIV and ART

Mitochondrial dysfunction is a described phenomenon for a number of chronic and infectious diseases. At the same time, the question remains open: is this condition a consequence or a cause of the progression of the disease? In this review, we consider the role of the development of mitochondrial dysfunction in the progression of HIV (human immunodeficiency viruses) infection and the onset of AIDS (acquired immunodeficiency syndrome), as well as the direct impact of HIV on mitochondria. In addition, we will touch upon such an important issue as the effect of ART (Antiretroviral Therapy) drugs on mitochondria, since ART is currently the only effective way to curb the progression of HIV in infected patients, and because the identification of potential side effects can help to more consciously approach the development of new drugs in the treatment of HIV infection.

Black hairy tongue (Lingua villosa nigra) in a young male precipitated by Lithium

This study carried out to survey the relationship between personality traits and Acquired Immunodeficiency Syndrome (AIDS) in patients with human immunodeficiency virus. This case-control study was conducted on 79 AIDS patients of Triangle Clinic in Arak (case group) and 80 healthy people of Valiasr Hospital in Arak (control group). Demographic information checklist and Cloninger’ Temperament and Character inventory (TCI) were two instruments applied in the study. SPSS software V.19 and tests independent t-tests, Chi squared and Spearman correlation coefficient were used for data analysis with significant level of <0.05. The average of innovativeness variables (M:74.12), harm avoidance (M: 65.17), reward dependence (M:50.030), and self-directedness (M:35.02) in case group in comparison with control group was significantly higher, and there was a significant difference between two groups variables (P-0.000). The novelty seeking had the highest average in the AIDS patients with a history of addiction (M:74.00), and there was statistically significant difference between perseverance variable (P-0.021) and cooperativeness variable (P-0.041) in the two groups of AIDS patients. There was a significant relationship between novelty seeking and age at the onset of AIDS (P-0.038), harm avoidance and age at the onset of addiction (P-0.046), persistence and age at the onset of AIDS (P-0.035) and the time infected with HIV (P-0.033). It is found that two groups are different due to the personalities, so it is essential to consider the personality traits in order to prevent AIDS and also successfully treat patients suffering from AIDS.

The relationship between personality traits and AIDS in patients with human immunodeficiency virus.

This study carried out to survey the relationship between personality traits and Acquired Immunodeficiency Syndrome (AIDS) in patients with human immunodeficiency virus. This case-control study was conducted on 79 AIDS patients of Triangle Clinic in Arak (case group) and 80 healthy people of Valiasr Hospital in Arak (control group). Demographic information checklist and Cloninger' Temperament and Character inventory (TCI) were two instruments applied in the study. SPSS software V.19 and tests independent t-tests, Chi squared and Spearman correlation coefficient were used for data analysis with significant level of <0.05. The average of innovativeness variables (M:74.12), harm avoidance (M: 65.17), reward dependence (M:50.030), and self-directedness (M:35.02) in case group in comparison with control group was significantly higher, and there was a significant difference between two groups variables (P-0.000). The novelty seeking had the highest average in the AIDS patients with a history of addiction (M:74.00), and there was statistically significant difference between perseverance variable (P-0.021) and cooperativeness variable (P-0.041) in the two groups of AIDS patients. There was a significant relationship between novelty seeking and age at the onset of AIDS (P-0.038), harm avoidance and age at the onset of addiction (P-0.046), persistence and age at the onset of AIDS (P-0.035) and the time infected with HIV (P-0.033). It is found that two groups are different due to the personalities, so it is essential to consider the personality traits in order to prevent AIDS and also successfully treat patients suffering from AIDS.

Increased risk of histologically defined cancer subtypes in human immunodeficiency virus–infected individuals

AbstractBACKGROUND:Malignancies that occur in excess among human immunodeficiency virus (HIV)‐infected individuals may be caused by immunosuppression or infections. Because histologically defined cancer subtypes have not been systematically evaluated, their risk was assessed among people with acquired immunodeficiency syndrome (AIDS).METHODS:Analyses included 569,268 people with AIDS from the HIV/AIDS Cancer Match Study, a linkage of 15 US population‐based HIV/AIDS and cancer registries during 1980 to 2007. Standardized incidence ratios (SIRs) were estimated to compare cancer risk in people with AIDS to the general population overall, and stratified by age, calendar period (a proxy of changing HIV therapies), and time since onset of AIDS (a proxy of immunosuppression).RESULTS:Sixteen individual cancer histologies or histology groupings manifested significantly elevated SIRs. Risks were most elevated for adult T cell leukemia/lymphoma (SIR = 11.3), neoplasms of histiocytes and accessory lymphoid cells (SIR = 10.7), giant cell carcinoma (SIR = 7.51), and leukemia not otherwise specified (SIR = 6.69). SIRs ranged from 1.4 to 4.6 for spindle cell carcinoma, bronchioloalveolar adenocarcinoma, adnexal and skin appendage neoplasms, sarcoma not otherwise specified, spindle cell sarcoma, leiomyosarcoma, mesothelioma, germ cell tumors, plasma cell tumors, immunoproliferative diseases, acute lymphocytic leukemia, and myeloid leukemias. For several of these cancer subtypes, significant declines in SIRs were observed across calendar periods (consistent with decreasing risk with improved HIV therapies) or increase in SIRs with time since onset of AIDS (ie, prolonged immunosuppression).CONCLUSIONS:The elevated risk of certain cancer subtypes in people with AIDS may point to an etiologic role of immunosuppression or infection. Future studies are needed to further investigate these associations and evaluate candidate infectious agents. Cancer 2012. © 2012 American Cancer Society.

Cumulative incidence of cancer among individuals with acquired immunodeficiency syndrome in the United States

The overall burden of cancer may increase as individuals with acquired immunodeficiency syndrome (AIDS) live longer because of highly active antiretroviral therapy (HAART), which has been widely available since 1996. A population-based, record-linkage study identified cancers in 472,378 individuals with AIDS from 1980 to 2006. By using nonparametric competing-risk methods, the cumulative incidence of cancer was estimated across 3 calendar periods (AIDS onset in 1980-1989, 1990-1995, and 1996-2006). Measured at 5 years after AIDS onset, the cumulative incidence of AIDS-defining cancer (ADC) declined sharply across the 3 AIDS calendar periods (from 18% in 1980-1989, to 11% in 1990-1995, to 4.2% in 1996-2006 [ie, the HAART era]). The cumulative incidence of Kaposi sarcoma declined from 14.3% during 1980 to 1989, to 6.7% during 1990 to 1995, and to 1.8% during 1996 to 2006. The cumulative incidence of non-Hodgkin lymphoma (NHL) declined from 3.8% during 1990 through 1995 to 2.2% during 1996 through 2006; during the HAART era, NHL was the most common ADC (53%). The cumulative incidence of non-AIDS-defining cancer (NADC) increased from 1.1% to 1.5% with no change thereafter (1%; 1996-2006), in part because of declines in competing mortality. However, cumulative incidence increased steadily over time for specific NADCs (anal cancer, Hodgkin lymphoma, and liver cancer). The cumulative incidence of lung cancer increased from 0.14% during 1980 to 1989 to 0.32% during 1990 to 1995, and no change was observed thereafter. Dramatically declining cumulative incidence was noted in 2 major ADCs (Kaposi sarcoma and NHL), and increases were observed in some NADCs (specifically, cancers of the anus, liver, and lung and Hodgkin lymphoma). As HIV/AIDS is increasingly managed as a chronic disease, greater attention should be focused on cancer screening and prevention.

Effect of Human Immunodeficiency Virus Type 1 (HIV‐1) Subtype on Disease Progression in Persons from Rakai, Uganda, with Incident HIV‐1 Infection

Human immunodeficiency virus type 1 (HIV-1) subtypes differ in biological characteristics that may affect pathogenicity. We determined the HIV-1 subtype-specific rates of disease progression among 350 HIV-1 seroconverters. Subtype, viral load, and CD4(+) cell count were determined. Cox proportional hazards regression modeling was used to estimate adjusted hazard ratios (HRs) of progression to acquired immunodeficiency syndrome (AIDS) (defined as a CD4(+) cell count of < or =250 cells/mm(3)) and to AIDS-associated death. A total of 59.1% of study subjects had subtype D strains, 15.1% had subtype A, 21.1% had intersubtype recombinant subtypes, 4.3% had multiple subtypes, and 0.3% had subtype C. Of the 350 subjects, 129 (37%) progressed to AIDS, and 68 (19.5%) died of AIDS. The median time to AIDS onset was shorter for persons with subtype D (6.5 years), recombinant subtypes (5.6 years), or multiple subtypes (5.8 years), compared with persons with subtype A (8.0 years; P = .022). Relative to subtype A, adjusted HRs of progression to AIDS were 2.13 [95% confidence interval {CI}, 1.10-4.11] for subtype D, 2.16 [95% CI, 1.05-4.45] for recombinant subtypes, and 4.40 [95% CI, 1.71-11.3] for multiple subtypes. The risk of progression to death was significantly higher for subtype D (adjusted HR, 5.65; 95% CI, 1.37-23.4), recombinant subtypes (adjusted HR, 6.70; 95% CI, 1.56-28.8), and multiple subtypes (adjusted HR, 7.67; 95% CI, 1.27-46.3), compared with subtype A. HIV disease progression is affected by HIV-1 subtype. This finding may impact decisions on when to initiate antiretroviral therapy and may have implications for future trials of HIV-1 vaccines aimed at slowing disease progression.

Basic Facts About HIV And AIDS

Basic Facts About HIV And AIDS

HIV-associated Guillain–Barré syndrome

Human immunodeficiency virus-associated Guillain–Barré syndrome (HIV-GBS) has been reported since 1985. Based on previous reports, this neuropathy typically occurs early in HIV infection, even at seroconversion, prior to developing acquired immunodeficiency syndrome (AIDS). Patients with GBS and CD4 counts of <50 have been proposed to have cytomegalovirus (CMV) infection and empiric gancyclovir is recommended. We reviewed medical records of 10 patients with HIV-GBS at five hospitals from 1986 to 1999. The mean CD4 count was 367/mm 3 (range 55–800). GBS was the first symptom of HIV infection in three patients. Four patients had AIDS with CD4 counts ranging from 55 to 190. CSF white blood cell (WBC) was 0 wbc/mm 3 in four patients, 2–10 wbc/mm 3 in three and 11–17 wbc/mm 3 in two. Three had recurrent weakness from 9 weeks to 4 years after the onset of symptoms, which persisted. HIV-GBS occurs in early and late stages of HIV infection, and may follow the onset of AIDS. No patients were seen with severe immunosuppression (CD4<50). A mild cerebrospinal fluid (CSF) pleocytosis in GBS suggests HIV infection, but is frequently absent. Compared to HIV-negative people, HIV-GBS may be associated with more frequent recurrent episodes or the development of CIDP.

Cancers associated with Kaposi's sarcoma (KS) in AIDS: a link between KS herpesvirus and immunoblastic lymphoma.

Kaposi's sarcoma (KS), common among persons with acquired immunodeficiency syndrome (AIDS), is caused by KS herpesvirus (KSHV) but whether KSHV causes other malignancies is uncertain. Using linked United States AIDS and cancer registries, we measured the incidence of specific malignancies in persons with AIDS (4–27 months after AIDS onset). We identified associations with KSHV by calculating a relative risk: cancer incidence in persons with KS (all were KSHV-infected) divided by incidence in persons without KS. Using Poisson regression, relative risks were adjusted for human immunodeficiency virus risk group, gender, age, race, and calendar year. We included 189 159 subjects (26 972 with KS). Immunoblastic lymphoma was significantly associated with KS (506 cases; relative risks: unadjusted 2.44, 95%CI 2.00–2.96, adjusted 1.58, 95%CI 1.29–1.93). Only one immunoblastic lymphoma had pleura as primary site. None of 37 other specified malignancies (other non-Hodgkin lymphomas, haematological malignancies, solid tumours) was significantly associated with KS. In summary, the association of immunoblastic lymphoma with KS was specific among examined malignancies and remained significant after statistical adjustment. Our findings, and the previously demonstrated presence of KSHV in the histologically related primary effusion lymphoma, suggest that KSHV is involved in the pathogenesis of some immunoblastic lymphomas. © 2001 Cancer Research Campaign

Dynamics of HIV infection: a cellular automata approach.

We use a cellular automata model to study the evolution of human immunodeficiency virus (HIV) infection and the onset of acquired immunodeficiency syndrome (AIDS). The model takes into account the global features of the immune response to any pathogen, the fast mutation rate of the HIV, and a fair amount of spatial localization, which may occur in the lymph nodes. Our results reproduce the three-phase pattern observed in T cell and virus counts of infected patients, namely, the primary response, the clinical latency period, and the onset of AIDS. The dynamics of real experimental data is related to the transient behavior of our model and not to its steady state. We have also found that the infected cells organize themselves into spatial structures, which are responsible for the decrease on the concentration of uninfected cells, leading to AIDS.

Human papillomavirus-associated cancers in patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome.

Human papillomavirus (HPV)-associated anogenital malignancies occur frequently in patients with human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS). The purpose of our study was to determine if the high frequency of these cancers is due to lifestyle factors associated with both HPV and HIV infections or to immunosuppression following HIV infection. We studied invasive and in situ HPV-associated cancers among 309 365 U.S. patients with HIV infection/AIDS (257 605 males and 51 760 females) from 5 years before the date of AIDS onset to 5 years after this date. Sex-, race-, and age-standardized ratios of observed-to-expected cancers served as measures of relative risk (RR). Trend tests were used to evaluate changes in the RRs during the 10 years spanning AIDS onset. All statistical tests were two-sided. All HPV-associated cancers in AIDS patients occurred in statistically significant excess compared with the expected numbers of cancers. For in situ cancers, overall risks were significantly increased for cervical (RR = 4.6; 95% confidence interval [CI] = 4.3-5.0), vulvar/vaginal (RR = 3.9; 95% CI = 2.0-7. 0), anal (in females, RR = 7.8 [95% CI = 0.2-43.6]; in males, RR = 60.1 [95% CI = 49.2-72.7]), and penile (RR = 6.9; 95% CI = 4.2-10.6) cancers, and RRs increased during the 10 years spanning AIDS onset for carcinomas in situ of the cervix (P: for trend <.001), vulva/vagina (P: for trend =.04), and penis (P: for trend =.04). For invasive cancers, overall risks were significantly increased for cervical (RR = 5.4; 95% CI = 3.9-7.2), vulvar/vaginal (RR = 5.8; 95% CI = 3.0-10.2), and anal (RR = 6.8; 95% CI = 2.7-14.0) cancers in females and for anal (RR = 37.9; 95% CI = 33.0-43.4), penile (RR = 3. 7; 95% CI = 2.0-6.2), tonsillar (RR = 2.6; 95% CI = 1.8-3.8), and conjunctival (RR = 14.6; 95% CI = 5.8-30.0) cancers in males. However, RRs for invasive cancers changed little during the 10 years spanning AIDS onset. HPV-associated malignancies occur at increased rates in persons with HIV/AIDS. Increasing RRs for in situ cancers to and beyond the time of AIDS onset may reflect the gradual loss of control over HPV-infected keratinocytes with advancing immunosuppression. However, the lack of a similar increase for invasive HPV-associated cancers suggests that late-stage cancer invasion is not greatly influenced by immune status.

Malignancy in HIV/AIDs: A single hospital experience

Background and Objectives Our hospital serves an area with a significant number of patients seropositive for the human immunodeficiency virus (HIV). Intravenous drug abuse and heterosexual exposure are by far the predominant risk factors for HIV and acquired immunodeficiency syndrome (AIDS). Seven percent of these patients develop malignancies. Our aim was to study the types of tumor, their distribution, and to evaluate the patients' outcome. Methods Of 3,578 patients with HIV infection or AIDS treated between 1993 and 1998, 245 had 1 or more malignancies. Information was collected on age, sex, race, predisposing risk factors for AIDS, malignancies, symptoms at presentation, the time of the onset of AIDS, CD4 cell counts, pathology findings, and mortality. Results Although aspects of our patients resembled those of previously studied groups of patients with AIDS, there also were ways in which our patients differed from those other groups. Of our patients, 21.6% had non-AIDS-defining (NAD) invasive malignancies. This was considerably higher than the rate in most studies. Twenty-seven patients with such malignancies died during the study. Forty-two other patients had pre-invasive cancers. Among patients having AIDS-defining (AD) malignancies, 55.9% died, a fact that was related to patients' low CD4 cell counts and late presentation. Our 97 patients with Kaposi sarcoma included 22 women, a relatively high number that may be related to the fact that most of our patients were intravenous drug abusers or had become infected by heterosexual transmission of HIV. Conclusions AIDS is associated with a high risk of malignancy and an unusual spectrum of tumors. Patients with invasive tumors have advanced disease at the time of initial presentation. Those with AD tumors have a worse prognosis than patients with NAD tumors. The impact of highly active antiretroviral therapy on both AD and NAD tumors needs to be further evaluated. J. Surg. Oncol. 2000;75:11–18. © 2000 Wiley-Liss, Inc.

Risk of cancer in children with AIDS. AIDS-Cancer Match Registry Study Group.

Population-based data on cancers associated with acquired immunodeficiency syndrome (AIDS) in children are lacking. To determine risk of pediatric AIDS-associated cancers. Using records from 11 locations in the United States for varying periods between 1978 and 1996, we linked data for children aged 14 years and younger at AIDS diagnosis to local cancer registry data. Cancer frequency and, in the 2-year post-AIDS onset period, cancer incidence and relative risk (RR; measured as standardized incidence ratio), by cancer type. Among 4954 children with AIDS, 124 (2.5%) were identified as having cancer before, at, or after AIDS onset, including 100 cases of non-Hodgkin lymphoma (NHL), 8 of Kaposi sarcoma (KS), 4 of leiomyosarcoma, and 2 of Hodgkin disease; there were 10 other or unspecified cancers. Expected numbers for all cancers identified in the study sample, based on population rates (using area-specific registry data), were less than 1. In the first 2 years after AIDS diagnosis (5485 person-years), NHL incidence was 510 per 100,000 person-years (RR, 651; 95% confidence interval [CI], 432-941). Median time for developing NHL after AIDS diagnosis was 14 months (range, 3-107 months). The most common type of NHL was Burkitt lymphoma. However, the risk of primary brain lymphoma (91 per 100,000 person-years) was especially high (RR, 7143; 95% CI, 2321-16,692), and 4 cases were diagnosed more than 2 years (range, 37-98 months) after AIDS onset. Leiomyosarcomas also tended to occur several years after AIDS onset, with 3 of the 4 cases occurring 33 to 76 months after AIDS diagnosis, whereas KS was reported only at or within 2 years of AIDS diagnosis. Hodgkin disease risk was also significantly increased (RR, 62; 95% CI, 2-342). The spectrum of AIDS-associated pediatric cancers resembled that seen in adults, with the addition of leiomyosarcoma. Both primary brain lymphomas and leiomyosarcomas tended to occur in children surviving several years after AIDS onset. Because the expected numbers of these cancers in this population were less than 1 and because of the small numbers of some types of observed cancers, the RR estimates are imprecise and caution is warranted in their interpretation. JAMA. 2000;284:205-209

Duration of human immunodeficiency virus infection and likelihood of giving birth in a Medicaid population in Maryland.

The objective of this study was to examine the effect of duration of human immunodeficiency virus (HIV) infection on a woman's likelihood of giving birth. Using longitudinal data from the Maryland state Human Immunodeficiency Virus Information System and a retrospective cohort design, the authors compared 1,642 women with acquired immunodeficiency syndrome (AIDS) to 8,443 uninfected women enrolled in the Medicaid program between 1985 and 1995. The decade before AIDS diagnosis was divided into four 2.5-year periods. Proximity to AIDS diagnosis served as a proxy for duration of infection. An extension of the Cox model was used to estimate the relative risk for giving birth, with adjustment for covariates and repeated outcomes. The average number of births per 100 person-years was 6.0 for HIV-infected women and 11.1 for uninfected women (adjusted relative risk = 0.63; 95% confidence interval (CI): 0.57, 0.68). Accounting for duration of infection, the adjusted relative risks for birth among HIV-infected women, as compared with uninfected women, were 0.85 (95% CI: 0.71, 1.03), 0.74 (95% CI: 0.63, 0.86), 0.55 (95% CI: 0.47, 0.64), and 0.45 (95% CI: 0.38, 0.55) for successive 2.5-year periods before AIDS diagnosis. Demographic characteristics, contraception, abortion, fetal loss, or drug use could not fully explain the reductions. These results suggest that HIV-infected women experience a progressive reduction in births years before the onset of AIDS. This may compromise estimation of HIV prevalence and interpretation of time trends from serosurveillance of pregnant women.

Malignancy in HIV/AIDs: a single hospital experience.

Our hospital serves an area with a significant number of patients seropositive for the human immunodeficiency virus (HIV). Intravenous drug abuse and heterosexual exposure are by far the predominant risk factors for HIV and acquired immunodeficiency syndrome (AIDS). Seven percent of these patients develop malignancies. Our aim was to study the types of tumor, their distribution, and to evaluate the patients' outcome. Of 3,578 patients with HIV infection or AIDS treated between 1993 and 1998, 245 had 1 or more malignancies. Information was collected on age, sex, race, predisposing risk factors for AIDS, malignancies, symptoms at presentation, the time of the onset of AIDS, CD4 cell counts, pathology findings, and mortality. Although aspects of our patients resembled those of previously studied groups of patients with AIDS, there also were ways in which our patients differed from those other groups. Of our patients, 21. 6% had non-AIDS-defining (NAD) invasive malignancies. This was considerably higher than the rate in most studies. Twenty-seven patients with such malignancies died during the study. Forty-two other patients had pre-invasive cancers. Among patients having AIDS-defining (AD) malignancies, 55.9% died, a fact that was related to patients' low CD4 cell counts and late presentation. Our 97 patients with Kaposi sarcoma included 22 women, a relatively high number that may be related to the fact that most of our patients were intravenous drug abusers or had become infected by heterosexual transmission of HIV. AIDS is associated with a high risk of malignancy and an unusual spectrum of tumors. Patients with invasive tumors have advanced disease at the time of initial presentation. Those with AD tumors have a worse prognosis than patients with NAD tumors. The impact of highly active antiretroviral therapy on both AD and NAD tumors needs to be further evaluated.

Protective effect of an SDF-1 variant in HIV disease: abstract and commentary.

Stromal-derived factor (SDF-1) is the principal ligand for CXCR4, a coreceptor with CD4 for T lymphocyte cell line–tropic human immunodeficiency virus–type 1 (HIV-1). A common polymorphism, SDF1-3′A, was identified in an evolutionarily conserved segment of the 3′ untranslated region of the SDF-1 structural gene transcript. In the homozygous state, SDF1-3′A/3′A delays the onset of acquired immunodeficiency syndrome (AIDS), according to a genetic association analysis of 2857 patients enrolled in five AIDS cohort studies. The recessive protective effect of SDF1-3′A was increasingly pronounced in individuals infected with HIV-1 for longer periods, was twice as strong as the dominant genetic restriction of AIDS conferred by CCR5 and CCR2 chemokine receptor variants in these populations, and was complementary with these mutations in delaying the onset of AIDS.

Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant. ALIVE Study, Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC)

Stromal-derived factor (SDF-1) is the principal ligand for CXCR4, a coreceptor with CD4 for T lymphocyte cell line-tropic human immunodeficiency virus-type 1 (HIV-1). A common polymorphism, SDF1-3'A, was identified in an evolutionarily conserved segment of the 3' untranslated region of the SDF-1 structural gene transcript. In the homozygous state, SDF1-3'A/3'A delays the onset of acquired immunodeficiency syndrome (AIDS), according to a genetic association analysis of 2857 patients enrolled in five AIDS cohort studies. The recessive protective effect of SDF1-3'A was increasingly pronounced in individuals infected with HIV-1 for longer periods, was twice as strong as the dominant genetic restriction of AIDS conferred by CCR5 and CCR2 chemokine receptor variants in these populations, and was complementary with these mutations in delaying the onset of AIDS.

HLA-DR-positive dendritic cells of the normal human choroid plexus: A potential reservoir of HIV in the central nervous system

In a previous study of choroid plexus (CPx) from patients with the acquired immunodeficiency syndrome (AIDS), we found a population of stromal cells infected with the human immunodeficiency virus (HIV). To determine whether these represented antigen-presenting dendritic cells, we examined the phenotype of normal human choroid plexus by light and electron microscopy (EM) and established the HIV-infected cell type by immunohistochemistry in AIDS cases with HIV-infected CPx. Monoclonal antibodies were used to detect class II major histocompatibility antigens (MHC), S-100 and S-100β protein, lymphocytes, monocytes/macrophages, and HIV glycoprotein. A variable number of stromal cells had slightly elongated nuclei and long branching processes that were strongly immunoreactive for class II MHCs, rarely reactive for S-100 and S-100β and immunonegative for monocyte/macrophage markers. Phagocytic activity was absent by EM and immunomarkers. They were numerous in the subepithelial region, and their processes occasionally extended toward the stromal capillaries or between the CPx epithelial cells. The HIV-infected cells were intensely inununoreactive for class II MHC markers and often displayed a dendritic morphology. These results document the presence of dendritic cells in the normal human CPx whose morphology and immunophenotype closely resemble those of DCs elsewhere in the body. They also show that these immunoreactive MHC class II cells are the cell type infected by HIV. We suggest that the functional activity of the CPx DCs is similar to that of antigen-presenting dendritic cells elsewhere in the body. This includes the potential to harbor HIV during the prolonged period of clinical latency, acting as a central nervous system reservoir of infection before the onset of AIDS.

Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression. Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC), ALIVE Study.

The critical role of chemokine receptors (CCR5 and CXCR4) in human immunodeficiency virus-type 1 (HIV-1) infection and pathogenesis prompted a search for polymorphisms in other chemokine receptor genes that mediate HIV-1 disease progression. A mutation (CCR2-64I) within the first transmembrane region of the CCR2 chemokine and HIV-1 receptor gene is described that occurred at an allele frequency of 10 to 15 percent among Caucasians and African Americans. Genetic association analysis of five acquired immunodeficiency syndrome (AIDS) cohorts (3003 patients) revealed that although CCR2-64I exerts no influence on the incidence of HIV-1 infection, HIV-1-infected individuals carrying the CCR2-64I allele progressed to AIDS 2 to 4 years later than individuals homozygous for the common allele. Because CCR2-64I occurs invariably on a CCR5-+-bearing chromosomal haplotype, the independent effects of CCR5-Delta32 (which also delays AIDS onset) and CCR2-64I were determined. An estimated 38 to 45 percent of AIDS patients whose disease progresses rapidly (less than 3 years until onset of AIDS symptoms after HIV-1 exposure) can be attributed to their CCR2-+/+ or CCR5-+/+ genotype, whereas the survival of 28 to 29 percent of long-term survivors, who avoid AIDS for 16 years or more, can be explained by a mutant genotype for CCR2 or CCR5.