Biomedical subjects

R Detels

Publications and source records attributed to R Detels.

At least 37 records · Page 2Linked to original sources

PubMed2000

Antigen-specific production of RANTES, macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta in vitro is a correlate of reduced human immunodeficiency virus burden in vivo.

RANTES (regulated on activation, normal T expressed and secreted), macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta are human immunodeficiency virus (HIV) suppressor factors by virtue of their ability to compete with HIV for access to cell surface R5. Their ability to block HIV infection in vitro is unequivocal; however, their role as HIV suppressor factors in vivo is not firmly established. We therefore conducted a study to test the hypothesis that production of these factors in vitro was a correlate of decreased virus burden in vivo. Moreover, we asked whether higher beta chemokine production could be demonstrated with cells from people who are R5D32 heterozygotes, compared with people who are R5 wild-type homozygotes. Our data support the thesis that RANTES, MIP-1alpha, and MIP-1beta production is associated with decreased in vivo virus load. Moreover, enhanced production of these factors may be explained in part by the genetic background of the host.

CD4 Lymphocyte Count↗

PubMed2000

Association of race and gender with HIV-1 RNA levels and immunologic progression.

CONTEXT: HIV-1 RNA and lymphocyte subset levels are the principal indications for antiretroviral treatment. Past reports have differed with regard to the effect of gender and race on these measures and in measures of disease progression. OBJECTIVE: To assess racial and gender differences in HIV-1 RNA levels and CD4+ lymphocyte decline. DESIGN: A longitudinal study based in the two largest HIV natural history cohort studies conducted in 7 metropolitan areas of the United States. RESULTS: In all, 1256 adult women and 1603 adult men for whom multiple data points were available prior to initiation of antiretroviral therapy were included. Women were more likely to be nonwhite, to have a history of injection drug use, and to have HIV-associated symptoms. After adjustment for differences in measurement method, baseline CD4+ cell count, age, and clinical symptoms, HIV-1 RNA levels were 32% to 50% lower in women than in men at CD4+ counts >200 cells/mm3 (p <.001) but not at CD4+ cell counts <200 cells/mm3. HIV-1 RNA levels were also 41% lower in nonwhites than in whites (p <.001) and 21% lower in persons reporting a prior history of injection drug use (p <.001). Women had more rapid declines in CD4+ cell counts over time than men (difference in slope of 46 cells/year) and nonwhite individuals had slower decline in CD4 cell counts than whites (difference of 39 cells/year). CONCLUSIONS: Both race and gender influence the values of HIV-1 RNA and the rate of HIV-1 disease progression as indicated by decline in CD4 cell counts over time. These effects could provide clues regarding the factors that influence HIV-disease progression and may indicate that guidelines for therapy should be adjusted for demographic characteristics.

Acquired Immunodeficiency Syndrome↗

PubMed2000

Evidence that anoreceptive intercourse with ejaculate exposure is associated with rapid CD4 cell loss.

OBJECTIVE: To determine whether ejaculate exposure through anoreceptive intercourse is associated with rapid CD4 cell loss. DESIGN: Self-reported behavioral, demographic data and blood samples were gathered longitudinally at ten semiannual visits from individuals participating in the Multicenter AIDS Cohort Study (MACS). PATIENTS/PARTICIPANTS: A group of 937 HIV-seropositive men who were continuously followed for four to ten semiannual visits. OUTCOME MEASURES: A loss of 10% or more in CD4 cells between the first two of any three consecutive semiannual visits that was followed by a 10% or greater loss between the second and third visits. RESULTS: A period of rapid CD4 cell loss over three semiannual visits occurred in 389 of the 937 (42%) HIV-seropositive men studied. Men who reported one or more anoreceptive intercourse partners with whom they were exposed to ejaculate (RAI-E) during the 12 months immediately preceding their visits were more than twice as likely to show this rapid CD4 cell loss compared with men with no such partners. CONCLUSIONS: The association between RAI-E partnerships and rapid CD4 cell loss suggests factors associated with ejaculate exposure (e.g., sexually transmitted diseases) may hasten the clinical progression of HIV disease. It is suggested that infectious diseases, which are known to be associated with ejaculate exposure, may be the causal factor underlying the association between RAI-E partnerships and rapid CD4 cell loss in these men, although the presence of these diseases was not ascertained in these data. HIV-infected individuals should be cautioned against unprotected anoreceptive intercourse.

CD4 Lymphocyte Count↗

PubMed2000

Causal pathways for CCR5 genotype and HIV progression.

A homozygous 32-bp deletion in the gene encoding CCR5, a major coreceptor for HIV-1, leads to resistance to infection with HIV-1, and heterozygosity for the deletion is associated with delayed disease progression in persons infected with HIV-1. We investigated the effect of CCR5 heterozygosity on disease progression as measured by both CD4+ T-cell count decline and the occurrence of clinical AIDS symptoms. Using a unified statistical model for CD4 count progression and AIDS development, we examined whether the effect of CCR5 heterozygosity on clinical AIDS is direct or indirect through its effect on CD4 counts. Based on data from the Multicenter AIDS Cohort Study, we noted a protective effect of CCR5 heterozygosity on both CD4 cell count progression and on AIDS occurrence. Furthermore, we found that this protective effect on the occurrence of AIDS was completely mediated through an effect on the CD4 marker. Additional adjustment for the effect of an initial viral load measurement indicate that CCR5 heterozygosity did not have predictive value for either CD4 progression or the development of AIDS beyond its association with early viral load.

Adult↗

PubMed2000

AIDS onset at high CD4+ cell levels is associated with high HIV load.

To identify factors associated with development of AIDS at high CD4+ cell levels a nested case-control study using data from the Multicenter AIDS Cohort Study (MACS) was conducted. HIV-1-infected men who developed AIDS with > or =300/mm3 CD4+ cells (AIDS men) were compared to men who had > or =300/mm3 of CD4+ cells, but remained AIDS free for at least 2 years. The AIDS men had higher plasma HIV-1 RNA levels (mean 10(5.02) vs. 10(4.42), p<0.01) and neopterin levels (mean 18.3 vs. 11.5 units/ml, p<0.05) before the AIDS diagnosis than did the AIDS-free men. A significantly higher proportion of the AIDS men reported genital herpes within the year prior to their initial AIDS diagnosis than did the AIDS-free men (21.9 vs. 4.4%, p<0.05). The higher viral load at relatively high CD4+ cell levels in men who subsequently developed AIDS within 6 months supports the hypothesis that elevated levels of HIV precede CD4+ decline and are the major factor in determining risk of AIDS even at high levels of CD4+ cell levels.

Acquired Immunodeficiency Syndrome↗

PubMed2000

Natural history of human immunodeficiency virus type 1 viremia after seroconversion and proximal to AIDS in a large cohort of homosexual men. Multicenter AIDS Cohort Study.

The natural history of human immunodeficiency virus type 1 (HIV-1) viremia and its association with clinical outcomes after seroconversion was characterized in a cohort of homosexual men. HIV-1 RNA was measured by reverse-transcription polymerase chain reaction (RT-PCR) in stored longitudinal plasma samples from 269 seroconverters. Subjects were generally antiretroviral drug naive for the first 3 years after seroconversion. The decline in CD4 lymphocyte counts was strongly associated with initial HIV RNA measurements. Both initial HIV RNA levels and slopes were associated with AIDS-free times. Median slopes were +0.18, +0.09, and -0.01 log10 copies/mL, respectively, for subjects developing AIDS <3, 3-7, and>7 years after seroconversion. In contrast, HIV RNA slopes in the 3 years preceding AIDS and HIV RNA levels at AIDS diagnosis showed little variation according to total AIDS-free time. HIV RNA load at the first HIV-seropositive visit ( approximately 3 months after seroconversion) was highly predictive of AIDS, and subsequent HIV RNA measurements showed even better prognostic discrimination.

Acquired Immunodeficiency Syndrome↗

PubMed2000

Transmission of HIV from injecting drug users to their wives in India.

We aimed to identify factors associated with transmission of human immunodeficiency virus (HIV) from injecting drug users (IDUs) to their wives in Manipur, northeast India, where the prevalence of HIV among IDUs is 80% via a case-control study. One hundred and sixty-one HIV-infected IDUs and their wives were recruited from September 1996 to August 1997 inclusive. HIV status was determined by enzyme-linked immunosorbent assay (ELISA) plus Western blot, Interviews were administered anonymously. Regression analysis identified factors associated with transmission of HIV from IDU husbands to their non-injecting wives. Seventy-two wives (45%) were HIV-positive. Only 15% of the couples reported regular usage of condoms during intercourse. On multivariate analysis, a sexually transmitted disease (STD) in either member, reported by the husband, estimated duration of HIV in the husband for >8 years, and a history of blood transfusions were associated with infection in the wife. In conclusion, STDs are associated with transmission of HIV from husband to wife. Improved control of STDs, condom promotion, and improved blood screening are urgently needed in Manipur.

Case-Control Studies↗

PubMed2000

Prevalence of HCV & HBV infection amongst HIV seropositive intravenous drug users & their non-injecting wives in Manipur, India.

Hepatitis C virus (HCV) and hepatitis B virus (HBV) infections were evaluated among 77 Manipuri couples of whom all husbands were both intravenous drug users (IDUs) and human immunodeficiency virus (HIV) positive. This study showed for the first time a high prevalence of HCV (92%) and HBV (100%) infection amongst the IDUs in Manipur. Stringent control measures to prevent the transmission of hepatitis viruses (B and C) are urgently required in Manipur.

Coitus↗

PubMed2000

HIV-1 subtypes in injecting drug users & their non-injecting wives in Manipur, India.

The presence of HIV-1 antibodies was determined among the injecting drug users (IDUs) and their non-injecting wives. A total of 233 (72%) were found to be HIV-1 seropositive among the 322 subjects recruited in this study between August, 1996 and September, 1997. The distribution of HIV-1 subtypes among the injecting drug users (IDUs) and their wives was determined using peptide enzyme immunoassay (EIA). Sexual transmission of HIV-1 occurred frequently (45%) from HIV-1 infected IDUs to their spouses. The majority of the subjects (167/233) were infected with subtype C followed by subtype Thai B (29/233). Subtype C was the most common among both IDUs (78%) and their wives (57%), followed by subtype Thai B (12% and 13% respectively). The distribution of subtypes was significantly different between IDUs and their wives with a lower percentage of subtype C and higher percentage of subtype D in the infected wives (P < 0.03). Discordance for subtypes transmitted from IDUs to their wives suggests the occurrence of dual and/or recombinant infection in the IDUs.

Female↗

PubMed1999

Impact of potent antiretroviral therapy on the incidence of Kaposi's sarcoma and non-Hodgkin's lymphomas among HIV-1-infected individuals. Multicenter AIDS Cohort Study.

Effective HIV-1 therapies may directly or indirectly impact the development of AIDS-associated malignancies. Using data from the Multicenter AIDS Cohort Study, a longitudinal cohort study of the natural history of HIV-1 infection among homosexual men, the incidence rates of Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL) over calendar time were determined for the 1813 HIV-1-seropositive men enrolled in 1984 through 1985. Poisson regression models were used to identify statistically significant temporal trends. Nested case control studies were used to assess whether recent cases of these malignancies represented treatment breakthroughs. The incidence of KS as a presenting AIDS illness significantly (p = .003) declined from 25.6 cases per 1000 person-years (95% confidence interval [CI], 21.8-29.9) in the early 1990s to an average incidence of 7.5 per 1000 person-years (95% CI, 3.4-16.7) in 1996 through 1997. In contrast, the incidence of NHL has continued to increase significantly (p < .001) at a rate of 21% per year since 1985, although a possible recent decrease is suggested. None of the recent KS cases and only 1 of 8 NHL cases had used the potent antiretroviral therapies, compared with >70 percent of the HIV-1-seropositive men who were free of malignancies and observed over the same time period. These results may be due to an indirect protection against developing KS by the boosting of the immune system by antiretroviral therapies. However, it is important to clarify the direct therapeutic effect on the pathogenic disease mechanism of human herpesvirus type 8 (HHV-8), the agent postulated to be important in the causal pathway of KS. The absence of a similar effect on NHL may be due to a lack of effect on its pathogenesis or because potent antiretroviral therapies need to be administered early in the disease process and the cases that have occurred represent outcomes following a long latency period. With additional follow-up, an impact on NHL may yet be observed.

AIDS-Related Opportunistic Infections↗

PubMed1999

Prevalence of unprotected sex among men with AIDS in Los Angeles County, California 1995-1997.

OBJECTIVE: To determine the prevalence of unprotected sex among men with AIDS in Los Angeles County. DESIGN: Cross-sectional study. METHODS: All men aged > or = 18 years who were newly reported to the local health department with AIDS and completed a standardized interview between January 1995 and June 1997 were included in the study. Men were classified as having unprotected sex if they reported one or more sex partners during the past year with whom they had vaginal or anal sex and did not always use a condom. RESULTS: Of 617 men interviewed, 29% reported unprotected sex in the past year. The prevalence of unprotected sex was highest among men < 30 years of age (43%) and those who had first learned of their HIV-positive status < 12 months prior to interview (44%). In all, 323 (52%) men reported one or more male sex partners in the past year. Of these, 22% reported unprotected insertive anal sex and 27% unprotected receptive anal sex. One or more female partners in the past year was reported by 131 (21%) men. Of these, 53% reported unprotected vaginal sex and 18% unprotected anal sex. CONCLUSIONS: The findings highlight the importance of early HIV detection efforts, coupled with targeted and sustained HIV prevention services for those who test positive, to prevent ongoing transmission of the virus.

Acquired Immunodeficiency Syndrome↗

PubMed1999

Prognostic value of plasma HIV RNA in the natural history of Pneumocystis carinii pneumonia, cytomegalovirus and Mycobacterium avium complex. Multicenter AIDS Cohort Study.

OBJECTIVES: To use follow-up on untreated HIV-positive men to assess the prognostic information provided by baseline data on plasma HIV RNA, CD4 cell count, age, and HIV-related symptom status, separately for three specific AIDS-defining illnesses: Pneumocystis carinii pneumonia (PCP), cytomegalovirus (CMV), and Mycobacterium avium complex (MAC). METHODS: The study population were 734 HIV-positive homosexual men enrolled in the Multicenter AIDS Cohort Study, with follow-up (1984-1985 through mid-1988) restricted to the antiretroviral treatment-free and prophylaxis-free era. Baseline marker values were categorized and assessed as predictor variables in separate time-to-event analyses for each of the three specific outcomes. RESULTS: A total of 138 cases of PCP, 25 cases of CMV, and 25 cases of MAC were observed. For PCP and CMV, higher categories of HIV RNA and lower categories of CD4 cell count were associated with increased risk relative to the respective reference groups. For MAC, oral candidiasis or fever and elevated HIV RNA at baseline were the primary risk factors. Further analysis highlighted the importance of monitoring HIV RNA levels in addition to CD4 cell counts when evaluating patients' risk of developing PCP. CONCLUSIONS: In the absence of treatment, plasma HIV RNA levels provide prognostic information about the risk of these three specific AIDS-defining illnesses, independently of the CD4 cell count. These data provide a useful reference as researchers investigate changing patterns in the incidence and predictors of opportunistic infections in the era of increasingly active antiretroviral therapies.

AIDS-Related Opportunistic Infections↗

PubMed1999

The prognostic significance in HIV infection of immune activation represented by cell surface antigen and plasma activation marker changes.

One hundred and eighteen HIV-infected homosexual men without AIDS and 40 control seronegative homosexual men were assessed for 23 parameters reflecting immune activation to determine prognostic significance for occurrence of AIDS. Samples cryopreserved in 1987-1989 were analyzed, with AIDS occurrence determined by mid-1992. Cell surface antigens assessed on the major lymphocyte subsets were HLA-DR, CD38, CD71, and CD25. Soluble serum molecules assessed were tumor necrosis factor alpha, soluble TNFalpha receptor II, soluble IL-2 receptor alpha, neopterin, and beta2-microglobulin. Using a proportional hazards model, prognostic markers included decreased CD4 number and percentage; increased sIL-2R, neopterin, and beta2M; increased percentage HLA-DR+ total lymphocytes and CD4+ cells; increased CD38+ total lymphocytes and CD8+ cells; increased CD71+ total lymphocytes and CD4+ cells; and decreased CD25+ total lymphocytes and CD19+ cells. After adjustment for CD4 cell levels, sIL-2R, neopterin, beta2M, and CD25+ CD19 cells remained significant, indicating that additional information about AIDS risk was provided by these markers.

ADP-ribosyl Cyclase↗

PubMed1999

The development of AIDS-associated Burkitt's/small noncleaved cell lymphoma is preceded by elevated serum levels of interleukin 6.

B cell hyperactivation accompanies HIV infection and is believed to contribute to the increased incidence of B cell lymphoma in persons with AIDS. To examine B cell activation which precedes the development of AIDS-associated lymphoma, we measured levels of two B cell stimulatory molecules, soluble CD23 (sCD23) and interleukin 6 (IL6), in the serum of HIV-infected individuals prior to the diagnosis of lymphoma. Serum sCD23 was elevated in those subjects who developed lymphoma, compared to AIDS, HIV+, and HIV- controls (P = 0.001). Serum IL6 was significantly elevated in subjects who developed Burkitt's/small noncleaved cell lymphoma (BL/SNC, P = 0.01), but not in those subjects who developed large cell, immunoblastic, or central nervous system lymphomas, compared to CD4-matched AIDS controls who did not have lymphoma. These results suggest that lymphomagenesis of the BL/SNC subtype of AIDS lymphoma reflects B cell hyperactivation of a different nature from that which precedes other subtypes of AIDS-associated B cell lymphoma.

Biomarkers↗

PubMed1999

Aberrant expression of CD27 and soluble CD27 (sCD27) in HIV infection and in AIDS-associated lymphoma.

CD27 is a member of the tumor necrosis factor receptor superfamily that is expressed primarily on T cells, as well as on subsets of B cells and NK cells. CD70, which is expressed on activated B and T cells, but not on resting lymphocytes, is a ligand for CD27. Cell surface CD27 can be proteolytically cleaved to produce a 32-kDa soluble CD27 (sCD27) molecule. Elevated levels of sCD27 are seen in a number of disease states and malignancies. Although it has been reported that cerebrospinal fluid sCD27 levels were elevated in people who had AIDS dementia, little is known about CD27 expression in HIV disease. To determine if sCD27 levels were elevated in those with HIV infection, and/or in those with AIDS-associated non-Hodgkin's lymphoma (AIDS-NHL), sCD27 levels were measured in HIV-negative and HIV-positive subjects as well as in people who developed AIDS-NHL. Serum sCD27 levels were seen to be elevated in HIV+ subjects. Furthermore, sCD27 levels were particularly elevated in those subjects who went on to develop AIDS-NHL, with serum sCD27 levels in AIDS-NHL subjects being significantly higher than those in HIV+ subjects who did not develop lymphoma. Most AIDS-NHL cell lines and primary AIDS-NHL tumor specimens expressed both CD27 and its ligand, CD70. The proportion of circulating B cells that expressed cell surface CD27 was substantially reduced in those with HIV infection, and B cells from HIV-infected subjects produced decreased levels of sCD27 in culture. Together, these results indicate that CD27/sCD27 expression is abnormal in HIV infection and suggest that this molecule merits further examination as a potential marker for AIDS-NHL.

Antigens, CD↗

PubMed1999

Lack of association between acquisition of TT virus and risk behavior for HIV and HCV infection in Vietnam.

BACKGROUND: The search for the cause of chronic hepatitis among individuals with non-A to G hepatitis has led to the discovery of a post-transfusion hepatitis-related DNA virus, designated TT virus (TTV), which, based on viral sequences, belongs to a new virus family. The principal modes of infection with TTV are poorly understood, and its role in human immunodeficiency virus type 1 (HIV-1) infection is unclear. OBJECTIVE: To determine if injection drug use (IDU) and high-risk heterosexual activity (HRHA), principal modes of acquiring HIV-1 infection, place individuals at greater risk of acquiring TTV. METHODS: The authors analyzed DNA, extracted from sera or filter paper-blotted whole blood, obtained during August 1997 and June 1998 from 324 Vietnamese (148 male; 176 female), for TTV sequences by hot-start, heminested polymerase chain reaction. RESULTS: Prevalence of TTV viremia was similar among individuals engaging in IDU or HRHA (23.4% vs. 20.2%; P > 0.5), with no age- or gender-specific differences. No association was found between TTV viremia and co-infection with HIV-1 or hepatitis C virus (HCV). Phylogenetic analysis of 30 TTV sequences revealed two distinct genotypes and four subtypes that did not segregate according to gender, HIV-1 and HCV risk behaviors, or geographic residence. CONCLUSIONS: Among HIV-1- or HCV-infected Vietnamese, who presumably acquired their infection by either the parenteral or nonparenteral route, the data indicate no clear association between acquisition of TTV infection and risk behavior for HIV-1 or HCV infection, suggesting that the usual route of TTV transmission in Vietnam is other than parenteral or sexual.

Adolescent↗

PubMed1999

Genotype and allele frequency of a 32-base pair deletion mutation in the CCR5 gene in various ethnic groups: absence of mutation among Asians and Pacific Islanders.

BACKGROUND: A 32-base pair (bp) deletion mutation in the beta-chemokine receptor CCR5 gene has been associated with resistance against human immunodeficiency virus type 1 (HIV-1) infection and disease. Large-scale studies conducted among Caucasians indicate that individuals who are homozygous for this deletion mutation (D32/D32) are protected against HIV-1 infection despite multiple high-risk exposures, whereas CCR5/ D32 heterozygotes have a slower progression to acquired immunodeficiency syndrome (AIDS). OBJECTIVE: To determine the genotype and allele frequencies of the CCR5 gene 32-bp deletion mutation among ethnically diverse non-Caucasian populations. METHODS: DNA, extracted from blood collected between 1980 and 1997 from 1912 individuals belonging to various ethnic groups, including 363 Caucasians, 303 Puerto Rican Hispanics, 150 Africans, 606 Asians, and 490 Pacific Islanders, were analyzed for the CCR5 gene 32-bp deletion mutation by a polymerase chain reaction (PCR)-based assay, using an oligonucleotide primer pair designed to discriminate CCR5 alleles without restriction endonuclease analysis. RESULTS: The comparative frequency of CCR5/D32 heterozygosity was 61 of 363 (16. 8%) in Caucasians, 17 of 303 (5.6%) in Puerto Rican Hispanics, 9 of 490 (1.8%) in Pacific Islanders, 0 of 606 (0%) in Asians, and 0 of 150 (0%) in Africans. CONCLUSIONS: The data confirm the high frequency of CCR5/D32 heterozygosity among Caucasians. Intermediate and low-level D32 allele frequencies among Puerto Rican Hispanics and Hawaiians could be attributed to recent European Caucasian gene flow. By contrast, the inability to detect the D32 allele among Asians and other Pacific Islander groups suggests that other mechanisms are responsible for resistance to HIV-1 infection in these populations.

Alleles↗

PubMed1999

AIDS diagnosis and depression in the Multicenter AIDS Cohort Study: the ameliorating impact of pet ownership.

The impact of pet ownership on depression was tested among a sample of gay and bisexual men (n = 1,872). Multivariate analyses, controlling for demographics and baseline depressive symptomatology, showed that neither pet ownership nor the presence of HIV infection was associated with depression. Depression was influenced by the presence of AIDS and by having relatively few confidants. Analyses among HIV-infected men only showed that persons with AIDS who owned pets reported less depression than persons with AIDS who did not own pets. This beneficial effect of pet ownership occurred principally among persons who reported fewer confidants. These results suggest that by enhancing companionship for some HIV-infected persons, pets may buffer the stressful impact of AIDS.

Acquired Immunodeficiency Syndrome↗