Prognostic value of serum beta 2-microglobulin in HIV infection.
Explore the source record for details and available documents.
Biomarkers↗
Biomedical subjects
J J Goedert
Publications and source records attributed to J J Goedert.
Immunologic markers of progression to acquired immunodeficiency syndrome are time-dependent and illness-specific.
Since prevalent cohorts may be biased by the duration of human immunodeficiency virus (HIV) infection (onset bias), it is useful to assess the potential predictive value of markers in incident cohorts of HIV-positive subjects for whom the date of seroconversion is known or can reliably be estimated. Of 131 homosexual men with HIV-1 seroconversion from New York City and Washington, DC, who were evaluated annually beginning in 1982, 60 developed acquired immunodeficiency syndrome (AIDS) by the end of 1989. The prognostic significance of immunologic markers (proportion of CD4+ T-lymphocytes, neopterin, beta 2-microglobulin, serum interferon, and anti-p24 antibody) and of a virologic marker (HIV p24 antigen) was determined using measurements made at defined time intervals after the known or estimated date of HIV seroconversion. When measurements made 3 years after seroconversion were used, all markers except anti-p24 antibody were found to be significant estimators of AIDS risk in univariate analyses. In multivariate Cox regression modeling, the maximum information was obtained by including neopterin, interferon, and the CD4+ T-lymphocyte proportion. The predictive value of markers after HIV seroconversion could change considerably from one interval to another. Elevated levels of beta 2-microglobulin and neopterin significantly predicted the development of Kaposi's sarcoma. These two markers were highly correlated (r = 0.74). The authors conclude that immunologic markers can be important for an HIV staging system for estimating prognosis and facilitating early therapeutic intervention in HIV-positive patients.
Acquired Immunodeficiency Syndrome↗
Patterns and predictors of high-risk sexual behavior in female partners of HIV-infected men with hemophilia.
OBJECTIVE: To characterize and quantify high-risk heterosexual activity in HIV-discordant couples. DESIGN: Analysis of cross-sectional and longitudinal questionnaire data from 217 HIV-negative female sexual partners of HIV-infected hemophilic men. METHODS: Comparison of prevalence rates of anal sex, oral sex, vaginal intercourse with or without condoms, and use of other contraceptives between 1985 and 1991. Logistic regression analysis of demographic, sexual and clinical variables to predict unprotected vaginal sex. Actuarial estimates of semi-annual relapse rates to unsafe sex. RESULTS: The proportion of women at low risk increased from 7 to 69% between 1985 and 1991, mainly because more women were using condoms during all acts of vaginal intercourse. Other contraceptive practices did not change during this time. The proportion engaging in oral or anal sex decreased (from 26 to 13% and 13 to 4%, respectively). Unprotected vaginal sex was more common among women who enrolled earlier, had less education, engaged in oral or anal sex, and among those whose partners had not had AIDS. Unprotected vaginal sex before enrollment was the strongest predictor of this high-risk activity during follow-up. Two-year rates of relapse to high-risk behavior were significantly higher among women who enrolled at high risk compared with those who enrolled at low risk (39 versus 8%, P = 0.005). CONCLUSIONS: Although high-risk sexual behavior became much less prevalent in this population between 1985 and 1991, many continued to have unprotected vaginal sex occasionally. Counseling efforts should target couples who have been the most sexually active or have less education, and should emphasize not only initial risk reduction but also maintenance of low-risk behavior.
Adolescent↗
Vertical transmission of human immunodeficiency virus (HIV) infection. Reactivity of maternal sera with glycoprotein 120 and 41 peptides from HIV type 1.
The observation that approximately 70% of HIV-infected pregnant women do not transmit infection vertically suggests that antibody therapy may be effective in the prevention of transmission of HIV infection from mother to child. Currently, there is an incomplete understanding of the processes involved in vertical transmission of HIV infection. The elucidation of the serological basis of maternal immunity as it relates to protection from vertical transmission is the goal of this study. We have screened 20 maternal sera from HIV+ individuals of known vertical transmission status for reactivity with 31 peptides spanning the entire envelope glycoprotein of HIV-1. Of interest was reactivity to regions outside of the V3 loop of gp120. The findings have been examined in relationship to transmission status, as well as to in vitro anti-HIV-1 biological activity. Our results indicate that lack of vertical transmission is correlated with high viral neutralization activity, but not with antisyncytial activity nor with binding to the V3 peptides examined in this study. Also, the transmission group bound to fewer gp41 peptides when compared with the nontransmission group, suggesting that immune responses to gp41 may be important in preventing transmission. These findings may provide insights into the design of passive immunotherapies.
Adult↗
Clinical utility of HIV-IgA immunoblot assay in the early diagnosis of perinatal HIV infection.
OBJECTIVE: To ascertain the sensitivity, specificity, predictive value, and clinical use of a human immunodeficiency virus (HIV)-IgA immunoblot assay for diagnosing perinatal HIV infection in infants tested at birth to 1 month, 3 months, and 6 months of age. DESIGN: Prospective, longitudinal cohort study of children born to HIV-infected and noninfected women. The HIV-IgA immunoblot assays were performed at birth to 1 month, 3 months, and 6 months of age and compared with the Centers for Disease Control's classification system of HIV infection in the children. Children were followed up for at least 15 months to ensure accuracy of infection status. SETTING: Municipal hospital in central Brooklyn, NY, where the prevalence of HIV infection is high. PATIENTS: Serum samples from 58 children, 22 with documented HIV infection, 18 noninfected children born to seropositive women, and 18 children born to noninfected women, were studied. MAIN OUTCOME MEASURE: Diagnosis of HIV infection using the Centers for Disease Control's classification scheme was compared with diagnosis using the HIV-IgA immunoblot assay for children 6 months of age or younger. RESULTS: The HIV-IgA immunoblot assay yielded negative results at 3 and 6 months of age for all 18 infants born to seronegative women; for the 18 seroreverting, noninfected children born to infected women, the assay yielded negative results at 1 month, 3 months, and 6 months of age. The positive predictive value of the assay was 100%--no false-positive results were identified in the 88 serum samples obtained from noninfected infants. For the HIV-infected children, sensitivity was a function of age: one (5.9%) of 17 infants had an assay that yielded positive results at birth to 1 month of age, 13 (62%) of 21 infants had assays that yielded positive results at 3 months of age, and 17 (77%) of 22 infants had assays that yielded positive results at 6 months of age. The presence or absence of symptoms did not affect the sensitivity. CONCLUSION: The HIV-IgA immunoblot assay can detect a significant proportion of infected children during an early asymptomatic period of their life. This relatively inexpensive, easily standardized assay may allow for institution of therapy before the onset of clinical symptoms.
Female↗
High risk of HIV-1 infection for first-born twins. The International Registry of HIV-exposed Twins.
To examine the epidemiology and natural history of mother-to-infant transmission of human immunodeficiency virus type 1 (HIV-1), especially genetic and intrapartum exposure factors, we obtained data on twins and triplets born to women infected with the virus. 40 investigators in nine countries contributed demographic, clinical, and epidemiological data on 100 sets of twins and 1 set of triplets. Among the 66 evaluable sets, HIV-1 infection was more common in first-born than in second-born twins (p = 0.004). In 22 sets, only one twin was infected (18 first-born, 4 second-born). 50% of first-born twins delivered vaginally and 38% of first-born twins delivered by caesarean were infected, compared with 19% of second-born twins delivered by either route. HIV-1 infection status tended to be concordant in more monozygotic (14 of 17 sets) than dizygotic (26 of 43) sets, but the frequency and clinical signs of HIV-1-related disease were similar in only 3 of the 10 sets with both children infected. These findings suggest that some infants may be infected in utero before labour but that a substantial proportion of HIV-1 transmission occurs as the first twin encounters the cervix and birth canal. Such measures as cleansing of the birth canal and caesarean delivery before membrane rupture might reduce the risk of transmission for infants born to HIV-1-infected women and should be the subjects of controlled clinical trials. Caesarean section should not be regarded as a wholly preventive measure, however, since substantial proportions of both first-born and second-born twins delivered in this way were infected.
Acquired Immunodeficiency Syndrome↗
Heterosexual co-transmission of hepatitis C virus (HCV) and human immunodeficiency virus (HIV).
OBJECTIVES: To determine the prevalence of antibodies to hepatitis C virus (HCV) in female sexual partners of multitransfused men with hemophilia and to compare the frequency of transmission of HCV and human immunodeficiency virus (HIV). STUDY DESIGN: Cross-sectional measurement of HCV and HIV antibodies. SETTING: Ten hemophilia treatment centers. PATIENTS: A total of 234 female sexual partners of 231 multitransfused men with hemophilia. MEASUREMENTS AND MAIN RESULTS: The prevalence of antibodies to HCV (anti-HCV) among female sexual partners of HCV-positive men was 5 of 194 (2.6%). Anti-HIV prevalence among female sexual partners of HIV-positive men was 25 of 196 (12.8%). Five (3%) of the 164 female sexual partners of HIV-positive/HCV-positive men were infected with HCV compared with none of the 30 female sexual partners of HIV-negative/HCV-positive men. Twenty-one (13%) of the 164 female sexual partners of HIV-positive/HCV-positive men were infected with HIV compared with 4 (13%) of 32 female sexual partners of HIV-positive/HCV-indeterminate men. The co-infected men were five times more likely to transmit both viruses than would be expected by chance (P = 0.01). When a single virus was transmitted to a female sexual partner, it was more often HIV than HCV (18 of 164 compared with 2 of 164, P = 0.001; odds ratio, 8.5; 95% Cl, 2.2 to 33.1). CONCLUSIONS: The higher prevalence of HCV in female sexual partners of men with hemophilia than in blood donor and other low-risk groups suggests that there is a low level of sexual transmission. Male to female sexual transmission of HCV is less efficient than that of HIV. The frequency of HCV transmission to sexual partners is five times higher when HIV is also transmitted, suggesting that HIV may be a cofactor for the sexual transmission of HCV.
Adult↗
Projections of the incidence of non-Hodgkin's lymphoma related to acquired immunodeficiency syndrome.
Advances in antiretroviral therapy and treatment or prophylaxis against opportunistic infection have resulted in prolongation of the survival of patients with acquired immunodeficiency syndrome (AIDS). Previous research has demonstrated an association between AIDS and risk of non-Hodgkin's lymphoma (NHL). In addition to the approximately 3% of individuals found to have NHL at the time of AIDS onset, others continue to develop NHL following AIDS diagnosis. Data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute demonstrated a sharply increasing incidence of NHL among men in the age range 20-49 years since 1983 in the United States. Based on new data on the risk of NHL following AIDS diagnosis, on estimates of improved survival following AIDS diagnosis, and on projections of future AIDS incidence, we considered four sets of assumptions and estimated the number of AIDS-related NHL cases in 1992 to be between 2900 and 9800. Three of these projections were higher than the estimate of 4700 cases obtained by linear extrapolation of SEER incidence trends. These projections of AIDS-related NHL incidence suggest that between 8% and 27% of all NHL cases that occur in the United States in 1992 will arise as a consequence of infection with the human immunodeficiency virus (HIV), imposing a substantial health care burden. More research into the pathogenesis of lymphoma and new approaches to antiretroviral and antilymphoma therapy will be necessary to prevent and treat this formidable complication of infection with HIV.
Acquired Immunodeficiency Syndrome↗
Backcalculation of the number with human immunodeficiency virus infection in the United States.
The method of backcalculation was applied to national surveillance data on the acquired immunodeficiency syndrome (AIDS) in order to estimate the cumulative number of adults with human immunodeficiency virus type 1 (HIV-1) infection as of January 1, 1985 and July 1, 1987. A "plausible range" of estimates was constructed which reflected both uncertainty about the AIDS incubation distribution and random variation from selection and fitting of flexible models of the HIV-1 infection curve. The authors estimated that, as of 1985, 411,000 to 756,000 persons were infected. The infected population included 266,000 to 492,000 homosexual men, 69,000 to 136,000 intravenous drug users, 24,000 to 49,000 homosexual intravenous drug users, and 11,000 to 26,000 persons infected through heterosexual contact. The estimated prevalence of infection among persons aged 15-55 years was 0.31% in whites, 0.78% in Hispanics, and 0.81% in blacks. An estimated 32,000 to 66,000 women were infected. Compared with white women aged 15-55 years, the prevalence of infection was 5.3-fold higher in Hispanic women and 10.2-fold higher in black women. Plausible estimates for the total number infected by July 1987 ranged from 707,000 to 1,376,000, with the most likely estimate equal to 992,000. Backcalculation provides an assessment of the magnitude of the HIV-1 epidemic that is independent of estimates based on prevalence surveys in special populations. The estimates obtained from both methods are consistent and emphasize the need for vigorous programs to prevent the spread of HIV-1, especially in minority communities.
Acquired Immunodeficiency Syndrome↗
Neopterin and beta 2-microglobulin as prognostic indices in human immunodeficiency virus type 1 infection.
The great majority of individuals with human immunodeficiency virus type 1 (HIV-1) infection presents with no signs or symptoms, or only lymphadenopathy. To initiate prophylactic measures in time it is necessary to establish risk criteria. CD4+ cell counts are significant predictors. Supplementary methods to improve the predictive information of CD4+ cell counts are still required. In addition, CD4+ cell counting is laborious, expensive, and restricted to specialized laboratories. Thus, there is also a place for more easily performed laboratory tests with similar predictive value as CD4+ cell counts. Neopterin and beta 2-microglobulin levels proved to be significant predictors of AIDS risk in HIV-1 seropositives. The predictive value of both parameters is equal to CD4+ cell counts and both markers are significant joint predictors in addition to CD4+ cell counts. Measurement of the parameters is done in serum (neopterin and beta 2-microglobulin) or urine (neopterin) specimens which reduces the risk of HIV-1 transmission compared to handling of whole-blood samples as it is required for cell counting. Although more studies are needed, especially in developing countries and in persons receiving zidovudine, it can be recommended to use neopterin and beta 2-microglobulin as additional marker to estimate AIDS risk in HIV-1 seropositive individuals. Moreover, both markers may be useful for this purpose without CD4+ cell counts if cell counting is not available.
Acquired Immunodeficiency Syndrome↗
Predicting AIDS onset for individual patients.
Explore the source record for details and available documents.
Acquired Immunodeficiency Syndrome↗
HTLV-I/II seroprevalence and HIV/HTLV coinfection among U.S. intravenous drug users.
Data from a continuing multiyear seroprevalence survey of human T-lymphotropic virus types I or II (HTLV-I/II) among intravenous drug users in seven U.S. locations were analyzed to detect demographic patterns of seropositivity and coinfection with human immunodeficiency virus type 1 (HIV-1). Seropositivity for HTLV-I/II and HIV-1 was detected by whole-virus enzyme immunoassay, with Western blot confirmation. Of 1,800 subjects recruited from methadone maintenance and detoxification clinics, 207 (11.5%) were infected with HTLV-I/II. Seropositivity for HTLV-I/II varied by racial group, age, sex, and geographic location. Blacks had a higher (age- and location-adjusted) infection rate (17.1%) than Hispanics (8.7%) or whites (5.6%), and seropositivity showed a strong gradient with increasing age. Females had a slightly higher rate (14.0%) than males (10.0%), after adjustment for age and location. Among the seven locations, the rate varied from approximately 1% (Miami and Baltimore) to 20% (Los Angeles), although the former rates were based on relatively few subjects (47 and 65, respectively). Overall, the occurrence of coinfection by HIV-1 and HTLV-I/II did not occur more frequently than expected by chance.
Acquired Immunodeficiency Syndrome↗
Interaction of human immunodeficiency and papilloma viruses: association with anal epithelial abnormality in homosexual men.
During the 7th annual follow-up of our cohort of homosexual men in 1989, we tested the hypotheses that infection with human immunodeficiency virus (HIV) may enhance the expression of human papilloma virus (HPV) and that the development of anal epithelial abnormality is related to a biologic interaction between these two viruses. Overall, 41 (39%) of the 105 men had anal swabs positive for one or more genotypes of HPV 6/11, 16/18 or 31/33/35. Twenty-three (53%) of the 43 HIV-positive subjects harbored HPV compared to 18 (29%) of the 64 HIV-negative subjects (p = 0.012), including higher prevalence rates for HPV genotypes 16/18 (p = 0.01), 6/11 (p = 0.007), and 31/33/35 (p = 0.07). Multivariate logistic regression analysis of the HIV-positive subjects showed low CD4+ cell counts to be an independent risk factor for detection of HPV (p = 0.04) and in particular for HPV genotypes 31/33/35 (p = 0.02) and 6/11 (p = 0.07). In contrast, similar analysis of the HIV-negative subset showed that a positive antibody test for syphilis was associated with HPV (p = 0.03). Anal epithelial abnormalities were found in 13 (14%) of 92 technically adequate cytologic smears and were strongly associated with detection of any HPV genotypes by the dot-blot method (p = 0.01), and in particular with HPV genotypes 6/11 (p = 0.001). None of 15 subjects with HPV detected only by PCR had anal epithelial abnormality. We propose a viral interaction model, in which HIV-related immune deficiency allows reactivation of HPV, with a subsequent or concomitant appearance of epithelial abnormality.
Anal Canal↗
Risk of non-Hodgkin lymphoma and Kaposi's sarcoma in homosexual men.
Explore the source record for details and available documents.
Acquired Immunodeficiency Syndrome↗
Markers of risk in HIV-1.
Explore the source record for details and available documents.
Acquired Immunodeficiency Syndrome↗
Infectious and genetic factors in AIDS-associated Kaposi sarcoma.
Explore the source record for details and available documents.
Acquired Immunodeficiency Syndrome↗
Urinary neopterin concentrations and T-cell subset data in HIV-1 infection.
We investigated the ability of urinary neopterin concentrations and T-cell subset data, and their ratios to discriminate between anti-HIV-1 seronegatives, seropositives, and AIDS cases. Using receiver-operated-characteristics curves, neopterin levels were shown to provide the best discrimination. Of the ratios derived from the single variables, neopterin per CD4+ cell counts and neopterin per CD4+/CD8+ cell ratio were superior to the CD4+/CD8+ cell ratio. Multivariate analyses were performed using a generalized likelihood ratio approach as well as linear discriminant analysis. The combination of neopterin concentration and CD4+ T-cell count is well suited to discriminate between various stages of HIV-1 infection and, therefore, we recommend using more than one assay to evaluate disease progression.
Acquired Immunodeficiency Syndrome↗
Serious infections during pregnancy among women with advanced human immunodeficiency virus infection.
Fifty-six human immunodeficiency virus seropositive-women and 76 human immunodeficiency virus seronegative-women had known CD4 cell values and were followed up throughout pregnancy. The women with seronegative results and the 40 with seropositive results and CD4 (helper cell) counts consistently greater than 300 cells/mm3 had no serious infections during pregnancy. Among the 16 with seropositive results and counts that fell below 300 cells/mm3, three developed opportunistic infections, one had pneumonia, and one had a post-cesarean-section abscess. Human immunodeficiency virus seropositive-women with low CD4 counts are at markedly increased risk of serious infections during pregnancy. The consequences of this for fetal health, pregnancy management, maternal well-being, and human immunodeficiency virus testing policies are discussed.
Acquired Immunodeficiency Syndrome↗