From biology to sexual behaviour--towards the prevention of mother-to-child transmission of HIV.
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Cohort Studies↗
Biomedical subjects
J J Goedert
Publications and source records attributed to J J Goedert.
Determination of T-lymphocyte subsets on site in rural Tanzania: results in HIV-1 infected and non-infected individuals.
With the FACSCount flow cytometer, counts of CD4, CD8 and CD3 lymphocytes and CD4/CD8 ratios were performed in a rural hospital in Tanzania. A total of 168 subjects (21 HIV-1 seropositive and 147 HIV-1 seronegative) were tested as part of a population-based serosurvey and AIDS education programme; 134 other subjects were hospitalized patients who had signs and symptoms suggestive of AIDS (69 HIV-1 seropositive and 65 HIV-seronegative). Mean values for the 147 HIV-1 seronegative subjects from the local population were 980 CD4 cells (95% CI 930, 1031), 598 CD8 cells (560, 635) and CD4/CD8 ratio 1.78 (1.68, 1.89). Seropositive subjects from the local population had significantly lower CD4 cell counts, higher CD8 counts and a lower CD4/CD8 ratio. CD4 cells were significantly lower and CD8 cells significantly higher in HIV-1 seropositive hospital patients compared to HIV-1 seronegative patients. However, 23 (35%) seronegative hospital patients had CD4 counts lower than 600. These results establish baseline values for the lymphocyte subsets in this population and indicate that this technique can be used in remote areas to monitor progress of HIV-infected individuals.
Acquired Immunodeficiency Syndrome↗
Simian virus 40 and pleural mesothelioma in humans.
It has been reported that DNA of SV40, a virus of Asian macaques that is tumorigenic for rodents and can transform human cells in vitro, is present in pleural mesotheliomas and in several other cancers. To verify these observations, we tested paraffin sections from mesothelioma tissues of 50 patients for SV40 DNA using PCR with two separate sets of primers. The analytic sensitivity for detection of SV40 DNA was 1-10 genome copies. We also tested the specimens for beta-globin by PCR to assess the suitability of the specimen DNAs for amplification. beta-Globin amplification was detected in 48 of the 50 specimens, but SV40 DNA was not detected in any tumors, with either of two SV40 primer sets. Furthermore, sera from 34 additional patients with mesothelioma, 33 patients with osteosarcoma (another cancer reported to be SV40-related) and 35 controls were tested for SV40 antibodies by a plaque neutralization assay. The serological data, like the DNA results, did not support an association of SV40 with mesothelioma or with osteosarcoma; antibodies to SV40 were detected in three mesothelioma patients, in one osteosarcoma patient, and in one control. These findings call into question the association of SV40 with mesothelioma.
Adult↗
Neurologic status of human immunodeficiency virus 1-infected infants and their controls: a prospective study from birth to 2 years. Mothers and Infants Cohort Study.
OBJECTIVE: To determine the timing, extent, severity, and persistence of neurologic abnormalities in children with perinatally acquired human immunodeficiency virus 1 (HIV-1) infection compared with similar uninfected children of HIV-1-infected women and control children. METHODS: Serial neurologic examinations and head circumference measurements were performed on a cohort of HIV-1-infected children born to HIV-1-infected women, seroreverting children born to HIV-1-infected women, and control children born to uninfected women. Examination data from 32 HIV-1-infected children, 99 reverters, and 116 control children were summarized by eight neurologic domains. Data were analyzed by longitudinal analysis. RESULTS: Reverter children were not different from control children in neurologic function for any of the eight domains or head circumference. HIV-1-infected children had significantly more neurologic problems than the control and reverter children for seven of the eight domains. The HIV-1-infected children were further classified by whether they had acquired immunodeficiency syndrome (AIDS)-defining clinical conditions (other than lymphoid interstitial pneumonitis) in the first 24 months of life (the AIDS-opportunistic infection group) or did not (the infected-other group). Neurologic abnormalities were early, severe, pervasive, and persistent in the AIDS-opportunistic infection group, and nearly all in this group had head circumference measurements below the 10th percentile. The infected-other group had no statistically significant differences from the uninfected children, although individual children in the infected-other group had some abnormalities. CONCLUSIONS: In utero exposure to HIV-1 without infection seems to have no negative impact on neurologic function in children in the first 2 years of life. Among children with perinatally acquired HIV-1 infection, the most severe and pervasive neurologic problems occur in those children who have early serious HIV-1 clinical disease. Most children without serious AIDS-defining clinical conditions in the first 2 years of life are also free from serious neurologic problems during that period.
AIDS-Related Opportunistic Infections↗
Mortality and haemophilia.
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Acquired Immunodeficiency Syndrome↗
Causes of death in haemophilia.
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Cause of Death↗
Natural history of HIV-1 cell-free viremia.
OBJECTIVE: To characterize the natural history of viremia with human immunodeficiency virus type 1 (HIV-1) and its association with disease progression from infection to acquired immunodeficiency syndrome (AIDS). DESIGN: Prospective cohort study. Annual specimens were tested for quantitative virion-associated HIV-1 RNA, p24 antigen, and CD4+ lymphocyte levels. PARTICIPANTS: A total of 42 homosexual men who seroconverted to HIV-1 between 1982 and 1985. MAIN OUTCOME MEASURES: Trends over time in serum HIV-1 RNA level, correlations between serum HIV-1 RNA and other markers, and prediction of AIDS using these markers. RESULTS: HIV-1 RNA levels were stable over time, increasing by 10-fold or more in only six (14%) of the 42 subjects during 3 to 11 years of follow-up. Mean HIV-1 RNA levels were 10(3.8) copies/mL if AIDS occurred in less than 4 years, 10(3.07) copies/mL if AIDS developed within 4 through 9 years, and 10(2.27) copies/mL if AIDS did not develop within 6 through 11 years. In both univariate and multivariate models, initial and subsequent HIV-1 RNA levels, p24 antigenemia, and percentage of CD4+ lymphocytes were independently predictive of AIDS. CONCLUSIONS: The stability of virion-associated HIV-1 RNA levels suggests that an equilibrium between HIV-1 replication rate and efficacy of immunologic response is established shortly after infection and persists throughout the asymptomatic period of the disease. Thus, defective immunologic control of HIV-1 infection may be as important as the viral replication rate for determining AIDS-free survival. Because individual steady-state levels of viremia were established soon after infection, HIV-1 RNA levels may be useful markers for predicting clinical outcome.
Acquired Immunodeficiency Syndrome↗
Prognostic factors for all-cause mortality among hemophiliacs infected with human immunodeficiency virus.
To identify the prognostic significance of hemophilia- and virus-related factors, the authors undertook a survival analysis among 644 human immunodeficiency virus (HIV)-infected subjects enrolled in the Multicenter Hemophilia Cohort Study between 1985 and 1993. Acquired immunodeficiency syndrome (AIDS) was the leading cause of death, followed by hemorrhage and hepatic disease. Adverse prognostic factors included older age and CD4-positive lymphocyte values below 14 percent either at entry (age-adjusted mortality rate ratio (RR) = 6.4, 95% confidence interval (CI) 3.4-12.1) or after entry (time-dependent RR = 4.2, 95% CI 2.6-6.7); indeterminate antibody responses to hepatitis C virus (RR = 3.0, 95% CI 1.8-5.0); and inhibitory antibodies to factor VIII concentrates (RR = 1.8, 95% CI 1.1-3.1). Indeterminate hepatitis C virus status was associated with mortality from hepatic disease but not with AIDS mortality. Factors that were not prognostic included duration of HIV infection, hepatitis B virus infection, and other hemophilia variables. These findings suggest that fatal liver disease among coinfected subjects with an indeterminate hepatitis C virus status is probably related to an insufficient humoral response secondary to HIV immune dysfunction and that the risk of death among HIV-infected subjects is best evaluated with age and duration of low CD4 percentage.
Acquired Immunodeficiency Syndrome↗
Conjunctival malignant disease with AIDS in USA.
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Acquired Immunodeficiency Syndrome↗
Persistence of immunoglobulin heavy chain/c-myc recombination-positive lymphocyte clones in the blood of human immunodeficiency virus-infected homosexual men.
We studied blood lymphocytes of human immunodeficiency virus (HIV)-seropositive and -negative homosexual men for the presence of T(8;14) translocations that recombine c-myc and immunoglobulin heavy-chain (IgH) mu/IgH alpha switch regions. Clones with T(8;14) translocations were detected in 10.5% (12/114) of the HIV-positive and in 2.0% of the 99 uninfected patients. The majority of recombinations were found at a single time point only. Four patients, however, harbored multiple (up to four) and persistent (up to 9 years) translocation-positive cell clones. No correlation between the presence of these aberrant lymphocytes and a later lymphoma could be established. The exon 1/intron 1 region of the recombined c-myc was investigated for the presence of point mutations and these were found in the nonpersistent clones. Additional alterations detected in these clones included duplications and a deletion in the c-myc gene. The pattern of base substitution indicates that they were introduced after the translocation event.
Base Sequence↗
Idiopathic CD4+ T-lymphocytopenia in HIV seronegative men with hemophilia and sex partners of HIV seropositive men. Multicenter Hemophilia Cohort Study.
Persons with hemophilia or other HIV-1 risk factors may be more likely to have idiopathic CD4+ T-lymphocytopenia (ICL). We determined the frequency of ICL in prospectively followed cohorts of HIV-1 seronegative hemophilic men and seronegative female sex partners of HIV-1 infected hemophilic men, and examined factors potentially associated with ICL. Seven of 304 (2.3%) seronegative hemophilic men and one of 160 (0.6%) female partners met the ICL definition, but the condition resolved for two of the men and for the sole female partner. All five men with persistent ICL had lymphocytopenia (< 1,200 total lymphocytes/microliters) and < 300 total CD4+ lymphocytes/microliters; only one had a low CD4+ percentage. On the most recent measurement, 14.5% of the 304 seronegative hemophilic men had lymphocytopenia. Compared with matched hemophilic controls, men with persistent ICL more often had a history of liver disease (3/5 cases, 0/21 controls, P = 0.007) or splenomegaly (3/5 cases, 4/21 controls; P = 0.04), but not severe hemophilia, greater clotting factor concentrate exposure, high alanine aminotransferase levels, hepatitis B virus antigenemia, or detectable hepatitis C virus RNA in plasma. All five cases and 20/21 controls had antibodies to hepatitis C virus present in their serum. In this cohort of hemophilic men, ICL was related to lymphocytopenia associated with liver disease rather than selective loss of CD4+ lymphocytes.
Acquired Immunodeficiency Syndrome↗
The relationship of the duration of ruptured membranes to vertical transmission of human immunodeficiency virus.
OBJECTIVE: Intrapartum events may play a role in determining the likelihood of vertical transmission of human immunodeficiency virus-1. Timing and duration of rupture of membranes have been shown to modify transmission risk of other organisms but have not been examined for human immunodeficiency virus. This study was undertaken to assess the relationship between duration of rupture of membranes, maternal immune status, and transmission of human immunodeficiency virus. METHODS: The Mothers' and Infants' Cohort Study enrolled 207 human immunodeficiency virus-positive women and their infants at five study sites in Brooklyn and the Bronx, New York between January 1986 and January 1991. One hundred twenty-seven woman-infant sets for whom antepartum CD4+ levels were available, the infant's human immunodeficiency virus infection outcome was known, and the duration of ruptured membranes could be determined were included in this analysis. RESULTS: Thirty of the 127 evaluable infants (24%) were infected. Women with low CD4+ levels (< 20%) were significantly more likely to transmit the virus if rupture of membranes was > or = 4 hours (relative risk 4.53, 95% confidence interval 1.14 to 1.81, p = 0.02). The same association was not observed among women with higher CD4+ levels (relative risk 1.11, 95% confidence interval 0.52 to 2.69, p = 0.69). No association with the duration of labor or mode of delivery was seen. CONCLUSIONS: In this urban North American cohort women with low CD4+ levels were significantly more likely to transmit human immunodeficiency virus to their offspring if the duration of rupture of membranes was > or = 4 hours.
Acquired Immunodeficiency Syndrome↗
Birth order, delivery route, and concordance in the transmission of human immunodeficiency virus type 1 from mothers to twins. International Registry of HIV-Exposed Twins.
BACKGROUND: We evaluated data from prospectively identified twins to understand better the mechanisms and covariates of mother-to-infant transmission of human immunodeficiency virus (HIV). METHODS: Using data obtained from an international collaboration and multivariate quasilikelihood modeling, we assessed concordance, birth order, route of delivery, and other factors for HIV infection in 115 prospectively studied twin pairs born to HIV-infected women. Actuarial methods were used to evaluate overall survival and survival free of acquired immunodeficiency syndrome for HIV-infected twins. RESULTS: Infection with HIV occurred in 35% of vaginally delivered firstborn (A) twins, 16% of cesarean-delivered A twins, 15% of vaginally delivered second-born (B) twins, and 8% of cesarean-delivered B twins. In a multivariate model, the adjusted odds ratios for HIV infection were 11.8 (confidence interval: 3.1 to 45.3) for concordance of infection with the co-twin, 2.8 (confidence interval: 1.6 to 5.0) for A versus B twins, and 2.7 (confidence interval: 1.1 to 6.6) for vaginally delivered versus cesarean-delivered twins. Among A twins, 52% (lower confidence limit: 6%) of the transmission risk was related to vaginal delivery. Comparing vaginally delivered A twins (infants most exposed to vaginal mucus and blood) to cesarean-delivered B twins (infants least exposed), 76% (lower confidence limit: 48%) of the transmission risk was related to vaginal exposure. Infected B twins had slightly reduced Quetelet indexes and more rapid development of illnesses related to acquired immunodeficiency syndrome. CONCLUSIONS: These results indicate that HIV infection of B twins occurs predominantly in utero, whereas infection of A twins (and, by implication, singletons) occurs predominantly intrapartum. We propose that intrapartum transmission is responsible for the majority of pediatric HIV infections and that reducing exposure to HIV in the birth canal may reduce transmission of the virus from mother to infant.
Birth Order↗
Mortality among drug users in the AIDS era.
BACKGROUND: Infection with human immunodeficiency virus type 1 (HIV-1) causes progressive immune deficiency, the acquired immunodeficiency syndrome (AIDS), and death. Mortality, however, particularly with causes other than AIDS, deserves further study. A retrospective cohort study among drug users in Italy was performed to estimated absolute and proportional mortality rates due to AIDS and other causes, with or without HIV-1 infection. METHODS: All subjects who enrolled between January 1980 and July 1990 in the drug treatment programme in the Province of Bologna, Italy, were included in the cohort. Each subject was categorized for HIV-1 antibody status (positive, negative, untested), vital status (in 1990 by national surveillance), and causes of death (by death certificate). Data were analysed with actuarial and time-dependent covariate methods. RESULTS: There were 332 deaths among 4962 drug users who were followed for 21,130 person-years. This mortality rate (1.57 per 100 person-years) was increased 18-fold compared to the general population. Actuarial 10-year mortality estimates were 28.2% for the 2040 HIV-1 positive subjects, 12.1% for the 1859 HIV-1 untested subjects, and 2.5% for the 1063 HIV-1 negative subjects. AIDS contributed to 150 deaths, followed by drug overdose (64 deaths) and trauma (39 deaths). Compared to others in the cohort, mortality with AIDS and non-AIDS causes was reduced for HIV-1 negative subjects. In contrast, mortality for HIV-1 positive subjects was increased with AIDS, trauma, overdose, various bacterial infections, hepatitis, and cirrhosis. CONCLUSIONS: Mortality with HIV-1 infection was associated not only with opportunistic infections and malignancies but also with competing causes of death, particularly hepatic disease. Further investigation is needed to clarify whether alcohol, analgesics, hepatitis viruses, or other agents have enhanced hepatotoxicity for HIV-1 infected patients.
Acquired Immunodeficiency Syndrome↗
Seroprevalence of human T cell lymphotropic virus type II infection, with or without human immunodeficiency virus type 1 coinfection, among US intravenous drug users.
Seroprevalence of human T lymphotropic virus (HTLV) and human immunodeficiency virus type 1 (HIV-1) was determined among 7841 intravenous drug users (IVDUs) from drug treatment centers in Baltimore, Chicago, Los Angeles, New Jersey (Asbury Park and Trenton), New York City (Brooklyn and Harlem), Philadelphia, and San Antonio, Texas; 20.9% had evidence of HTLV infection, as determined using a p21e EIA for screening and p21e blot for confirmation. With a type-specific EIA and blot used in combination, HTLV-II was identified in 97.6% of HTLV-positive IVDUs whose sera could be subtyped. HIV-1 seroprevalence was 13.2%. HTLV-II without HIV-1 was most common in Los Angeles and San Antonio. HIV-1 without HTLV-II was most common in New York, New Jersey, and Baltimore. Dual infection was most common in New York and New Jersey. Logistic regression analysis revealed that seroprevalence of HTLV-II was significantly greater with HIV-1 infection and increasing age and among women, blacks, and Mexican-Americans. In conclusion, it appears that among US IVDUs, nearly all HTLV infection is attributable to HTLV-II, and HTLV-II infection is associated with HIV-1 and sociodemographic background.
Acquired Immunodeficiency Syndrome↗
Concordance of human leukocyte antigen haplotype-sharing, CD4 decline and AIDS in hemophilic siblings. Multicenter Hemophilia Cohort and Hemophilia Growth and Development Studies.
OBJECTIVE: To assess the association between human leukocyte antigen (HLA) haplotypes and the incidence rates of CD4 decline to < 20% and to AIDS. DESIGN: Retrospective cohort study of 95 HIV-1-infected hemophilic sibling pairs. METHODS: HLA haplotype-sharing between siblings was assigned on the basis of serologic typing of HLA class I alleles and molecular typing of HLA class II alleles. Concordance of time to CD4 decline to < 20% and to AIDS within and between sibling pairs was assessed by analysis of variance models and calculations of intraclass correlation coefficients. The age-adjusted relative risks of these two endpoints for unique class II haplotypes were determined from proportional hazards models. RESULTS: Sibling pairs sharing one or two haplotypes were significantly concordant in CD4 decline and AIDS status within 5 years of seroconversion. No concordance was found in pairs sharing zero haplotypes. At 6-10 years after seroconversion, significant concordance of these two endpoints was also observed in the pairs sharing one haplotype. The concordant results were not explained by the use of zidovudine within the pairs. Among the individuals in this cohort, the relative hazards for CD4 decline to < 20% and for AIDS were significantly elevated for one class II haplotype (DQB1*0501, DQA1*0101, DRB1*0101). In addition, the risk for AIDS was significantly increased for two other class II haplotypes (DQB1*0603, DQA1*0103, DRB1*1300, DRB3*0202 and DQB1*0301, DQA1*0501, DRB1*1400, DRB3*0202) and significantly decreased for one haplotype (DQB1*0302, DQA1*0301, DRB1*0401, DRB4*0101). CONCLUSIONS: These data demonstrate that HIV-1 disease progression is associated with the genes in the major histocompatibility complex that regulate the host's immune response.
Acquired Immunodeficiency Syndrome↗
Risks of immunodeficiency, AIDS, and death related to purity of factor VIII concentrate. Multicenter Hemophilia Cohort Study.
In HIV-infected subjects with haemophilia, CD4 counts seem to fall more slowly in those on high-purity factor VIII (FVIII) than on intermediate-purity product. We evaluated whether risks for AIDS or death were associated with either product among 411 HIV-infected individuals. The relative hazard of AIDS was slightly elevated for both current (1.34) [corrected] and cumulative (1.01 per month) use of high-purity products (neither significant). The corresponding hazards for death were 1.49 and 1.03 (neither significant). Thus we found no evidence that high-purity FVIII concentrates retard the development of AIDS.
Acquired Immunodeficiency Syndrome↗
Increasing hepatitis C virus RNA levels in hemophiliacs: relationship to human immunodeficiency virus infection and liver disease. Multicenter Hemophilia Cohort Study.
We have previously observed an increased frequency of liver failure in human immunodeficiency virus (HIV)-infected hemophiliacs. The purpose of this study was to quantitate hepatitis C virus (HCV) RNA levels in serial samples from HIV-seropositive (HIV+) and HIV-seronegative (HIV-) hemophiliacs before and after HIV seroconversion, and to examine the relationship of HCV RNA levels to CD4 cell counts and to hepatic dysfunction over time. HCV RNA levels were measured on serial samples of serum stored frozen from 17 HCV+/HIV+ and 17 HCV+/HIV- subjects matched within 5 years of their birth dates. All were HCV+ before study entry. HCV RNA levels were quantitated by a branched DNA-enhanced label amplification (bDNA) assay. For samples less than the cut off, HCV RNA was measured by the nested polymerase chain reaction. Individual changes over time, clinical groups, and mean values within predetermined time windows were compared with Wilcoxon rank sum tests. Mean HCV RNA levels increased from 2.76 (standard error [SE] 1.33) x 10(5) to 2.84 (SE 1.39) x 10(6) eq/mL during the first 2 years after HIV seroconversion (P = .006). Baseline HCV RNA levels in the pre-HIV seroconversion group were not significantly different from the baseline levels in those who remained HIV (P = .79). Over the entire period of study, HCV RNA levels increased nearly threefold in those who remained HIV- (mean 9.47 [SE 4.78] x 10(5) to 2.81 [SE 1.13] x 10(6)/mL; P = .02). Among those who became HIV+, HCV RNA levels increased 58-fold (mean 2.85 [SE 1.26] x 10(5) to 1.66 [SE 0.57] x 10(7) eq/mL; P = .0001). The rate of increase in HCV RNA levels was eightfold faster for HIV+ subjects than for subjects who remained HIV- (P = .009). HCV RNA levels increased twofold higher in 5 subjects who developed liver failure compared with the 12 who did not (P = .43). HCV RNA levels correlated significantly with CD4 counts (R = -.33, P = .01) and serum aspartate aminotransferase levels (AST) (R = .36, P = .007). We conclude that HCV RNA levels are significantly higher in HIV+ than in HIV- multitransfused hemophiliacs. HCV load increases over time, is enhanced by HIV, and further increases as immune deficiency progresses. HCV RNA levels are directly associated with high AST levels. These findings suggest that HIV-induced immune deficiency may promote increased HCV replication.
Adolescent↗