Clinical predictors for the aetiology of peripheral lymphadenopathy in HIV-infected adults.

OBJECTIVES: The aim of the study was to determine the aetiology and clinical predictors of peripheral lymphadenopathy in HIV-infected individuals during the antiretroviral (ARV) era in a nontuberculosis endemic setting. METHODS: A multicentred, retrospective cohort study of peripheral lymph node biopsies in HIV-positive adults was carried out. A total of 107 charts were identified and reviewed for clinical features, lymphadenopathy size, and ARV use and duration. Biopsy results were categorized, and multivariate logistic regression determined independent predictors of lymphadenopathy aetiology. RESULTS: Evaluation of 107 peripheral lymph node biopsies revealed that 42.9% of peripheral lymphadenopathy was attributable to malignancy, 49.5% to reactive changes, and 7.5% to infections, with only 2.8% of all cases secondary to tuberculosis. Fevers, weight loss, ARV use, and lower viral loads are significantly associated with nonreactive lymphadenopathy. CONCLUSIONS: Lymphadenopathy is likely to be reactive or malignant in nontuberculosis endemic regions. Readily available clinical features can aid clinicians in predicting the underlying aetiology, those at risk for malignancy, and who to biopsy.

[Prevalence of neurological complications in Japanese patients with AIDS after the introduction of HAART].

We investigated trends in neurological complications of infection with human immunodeficiency virus (HIV) in Japan after the introduction of highly active antiretroviral therapy (HAART). Two questionnaire surveys were performed in hospitals treating acquired immunodeficiency syndrome (AIDS) to compare two periods: immediately after the introduction of HAART (1999-2001); and a few years later (2002-3). Neurological complications accompanied 15.9% in 1999-2001 and 9.8% in 2002-3. Neurological complications developed without HAART in about 80% of cases. Neurological complications developed as the first AIDS-defining disease for 8.3% of AIDS patients in 1999-2001 and for 5.4% in 2002-3. Prevalences of HIV encephalopathy and myelopathy decreased markedly over the study period, as reported in other developed nations. However, prevalences of cytomegalovirus encephalitis, PML and primary brain lymphoma did not decrease. PML and primary brain lymphoma occurred in patients who received HAART and whose CD4 counts were relatively high during the study period. This is probably related to the extended survival of HIV-infected individuals after the introduction of HAART as a worldwide therapy, and the reactivation of viremia or latent infection persisting within the central nervous system.

Immune thrombocytopenic purpura might be an early hematologic manifestation of undiagnosed human immunodeficiency virus infection.

Little research focuses on the association between immune thrombocytopenic purpura and human immunodeficiency virus infection in Taiwan. This study investigated whether immune thrombocytopenic purpura might be an early hematologic manifestation of undiagnosed human immunodeficiency virus infection in Taiwan. We conducted a retrospective population-based cohort study using data of individuals enrolled in Taiwan National Health Insurance Program. There were 5472 subjects aged 1-84 years with a new diagnosis of immune thrombocytopenic purpura as the purpura group since 1998-2010 and 21,887 sex-matched and age-matched, randomly selected subjects without immune thrombocytopenic purpura as the non-purpura group. The incidence of human immunodeficiency virus infection at the end of 2011 was measured in both groups. We used the multivariable Cox proportional hazards regression model to measure the hazard ratio and 95 % confidence interval (CI) for the association between immune thrombocytopenic purpura and human immunodeficiency virus infection. The overall incidence of human immunodeficiency virus infection was 6.47-fold higher in the purpura group than that in the non-purpura group (3.78 vs. 0.58 per 10,000 person-years, 95 % CI 5.83-7.18). After controlling for potential confounding factors, the adjusted HR of human immunodeficiency virus infection was 6.3 (95 % CI 2.58-15.4) for the purpura group, as compared with the non-purpura group. We conclude that individuals with immune thrombocytopenic purpura are 6.47-fold more likely to have human immunodeficiency virus infection than those without immune thrombocytopenic purpura. We suggest not all patients, but only those who have risk factors for human immunodeficiency virus infection should receive testing for undiagnosed human immunodeficiency virus infection when they develop immune thrombocytopenic purpura.

[Clinical and laboratory characteristics of HIV-infection in servicemen].

HIV-infection in Russia and its Armed Forces is a serious threat to the national health and country's safety. Study of peculiarities of disease spread in the military collectives and HIV-infection manifestation is an actual problem. HIV-infection is diagnosed during the latent stage in all categories of servicemen and characterized by unchanged function of cellular and humoral immunity. In most servicemen with HIV-infection the disease course has a form of co-infection with parenteral hepatitis B and C.

Late manifestations of HIV in Asia and the Pacific.

PIP: Late-stage HIV infection is characterized by profound immunodeficiency with a progressive and irreversible decline in the CD4 count, functional impairment of cellular and humoral immunity, and evidence of increased viral replication, with the appearance of p24 antigenemia and increasing levels of beta(2)-microglobulin and neopterin. These changes are associated with increased susceptibility to many infections, the emergence of malignancies, and neurological complications due to the direct infection of neural tissue with HIV. In Australia, opportunistic infections and malignancies account for 75% and 18% of AIDS diagnoses, respectively. Opportunistic infections and neurological involvement usually occur late in the illness and may be associated with disturbances of function of each part of the neuraxis. The detailed clinical nature of the involvement has been described in several recent reviews and is probably not different in the Asia-Pacific region. The most common opportunistic infections in Australia are Pneumocystis carinii pneumonia (PCP), esophageal candidiasis, toxoplasmosis, CMV infection, atypical mycobacteriosis, and cryptococcal meningitis. There are few data from Asian countries, but it seems that the most common opportunistic infections are tuberculosis, PCP, systemic Penicillium marneffei infection, and cryptococcal meningitis. There is little information from Asia on neurological conditions. Tuberculosis is probably the most significant threat to public health in Asia and the Pacific. Its management and prevention require ongoing planning and resources. To that end, a collaborative effort is called for to help resource-poor countries. Mycobacterial, fungal, viral, and protozoal infections are discussed, along with consideration of neurological complications, malignant disease, and late manifestations of HIV infection in children.^ieng

Natural history of advanced HIV disease in patients treated with zidovudine. The Zidovudine Epidemiology Study Group.

OBJECTIVE: To describe the natural history of advanced HIV disease in patients treated with zidovudine. DESIGN: Longitudinal, observational study. SETTING: Twelve academic and community-based sites. PATIENTS, PARTICIPANTS: Eight hundred and sixty-three patients with AIDS or AIDS-related complex (ARC) with a CD4+ lymphocyte count less than 250 x 10(6)/l, who first received zidovudine between 15 April 1987 and 14 April 1988. MAIN OUTCOME MEASURES: Survival, progression to AIDS and first development of specific opportunistic illness. RESULTS: Median survival after initiation of zidovudine therapy ranged from greater than 900 days in patients with a baseline CD4+ lymphocyte count greater than or equal to 150 x 10(6)/l to 560 days in patients with a CD4+ lymphocyte count less than 50 x 10(6)/1. Other factors associated significantly with poorer survival were diagnosis of AIDS (versus ARC), baseline age greater than or equal to 40 years, hematocrit less than 35%, and diminished functional status. In patients with ARC at enrollment, median time of progression to AIDS ranged from 810 days in patients with a CD4+ lymphocyte count greater than or equal to 150 x 10(6)/l to 310 days in patients with a CD4+ lymphocyte count less than 50 x 10(6)/l. Rates of development of specific opportunistic infections or neoplasms and HIV encephalopathy were determined for different baseline CD4+ lymphocyte count ranges. Myelosuppression was significantly more common in patients with CD4+ lymphocyte counts greater than or equal to 100 x 10(6)/l. Sixty-five per cent of patients with a CD4+ lymphocyte count greater than or equal to 100 x 10(6)/l and 51% with a CD4+ lymphocyte count less than 100 x 10(6)/l continued to receive zidovudine 2 years after starting therapy. CONCLUSIONS: We describe the natural history of a cohort of patients treated with zidovudine for advanced HIV disease. These CD4+ lymphocyte count-stratified estimates of disease progression should provide prognostic information useful in the clinical management of advanced disease and the design of future studies.

Clinical and epidemiological features of HIV infection at a referral clinic in Zambia.

Among 1,350 patients with serologically confirmed HIV-1 infection evaluated at the Dermatovenerealogy Clinic, University Teaching Hospital. Lusaka, through March 1987, 125 (9.3%) had AIDS, 1,178 (87.3%) had AIDS-related complex, and 46 (3.5%) were asymptomatic. The male to female ratio of cases was 1.5:1 and women were younger (mean age of 26.2 years) than were men (mean age of 31.2 years). HIV-infected persons had significantly more lifetime sex partners than uninfected persons; other risk factors were a prior history of venereal disease, blood transfusion, travel abroad, and a positive syphilis serology. Clinical features in decreasing order of frequency were weight loss, persistent generalized lymphadenopathy, chronic cough, multidermatomal herpes zoster, diarrhea, recurrent fevers, tuberculosis, and oropharyngeal candidiasis. The WHO clinical case definition for the diagnosis of AIDS had a low positive predictive value for the 125 Zambians with AIDS, but among all those infected with HIV, the positive predictive value was 76.4%. Thirty (35.3%) of 85 patients who were HIV seronegative when first examined acquired HIV infections during a 12- to 39-month (means = 21.8 months) period of observation. Heterosexual intercourse unrelated to prostitution appears to be the major mode of HIV transmission in Lusaka.

PIP: The clinical and epidemiologic characteristics of the 1st 1350 individuals diagnosed at Zambia's Dermatovenerealogy Clinic in Lusaka between August 1985-December 1986 as a positive for human immunodeficiency virus (HIV) infection were evaluated. 125 (9.3%) of these seropositive individuals presented with aggressive Kaposi's sarcoma or an opportunistic infection and were thus diagnosed with acquired immunodeficiency syndrome (AIDS), 1178 (87.3%) had AIDS-related complex (ARC), and a further 47 (3.5%) were asymptomatic. The male to female ratio of HIV-positive cases was 1.5 to 1. Female patients were younger (mean age 26.1 years) than male patients (mean age, 31.2 years). The only sexual practice acknowledged by the vast majority of cases was heterosexual vaginal intercourse, although infected men and women had significantly more lifetime sexual partners than uninfected controls. Other significant risk factors for HIV seropositivity were (for men) blood transfusion, travel outside of Zambia, and a history of syphilis; for women, these risk factors were blood transfusion and a history of venereal disease. The most common clinical features in AIDS and ARC patients were, in decreasing order of frequency, weight loss greater than 10%, generalized lymphadenopathy, chronic cough, multidermatomal herpes zoster, recurrent diarrhea, recurrent fever, tuberculosis, and oropharyngeal candidiasis. The provisional WHO clinical case definition of AIDS in Africa has a positive predictive value of 82.1 for the sample as a whole, but only 46.3 for the 125 patients diagnosed with AIDS. 17 of the HIV-positive patients had died by the 18-month follow-up.

Epidemiology of human immunodeficiency virus in families in Lusaka, Zambia.

Persons living in the same household as index patients with AIDS or ARC in Lusaka, Zambia were clinically and serologically evaluated for HIV-1 infection. In the 150 households of male index cases, 92 (61.3%) of their spouses were infected, compared with 57 (73.1%) of the spouses of the 78 female index cases. The more advanced the clinical stage of illness in the index cases, the greater the probability of HIV infection in the spouse (RR = 4.44), and the more likely the spouse was symptomatic. Four of the 11 spouses who seroconverted to HIV had also had sexual intercourse at a time when their HIV-infected partner had genital ulcers (RR = 7.45). Of 144 children under 5 years of age, 36 (25.0%) were infected, all had infected mothers and were the last to be borne in all but one household. Three of 120 children 5 to 10 years of age were also infected, presumably through perinatal transmission. Forty-six of 52 discordantly infected couples followed for 1 year continued to have unprotected vaginal intercourse, and 11 (21.2%) of these seroconverted to HIV. There were no HIV infections that could be attributed to transmission by other means than heterosexual intercourse between spouses or by perinatal infection in children borne of infected mothers. The study suggests that there is an increasing risk of HIV heterosexual transmission as infection progresses in the infected partner, and that more effective counseling is needed to prevent it.

PIP: An investigation of members of households of patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) in Lusaka, Zambia, revealed a high rate of human immunodeficiency virus (HIV) infection in marital partners, regardless of the sex of the index case. The study, conducted in August 1985-June 1987, involved individuals in 244 households of index patients diagnosed with AIDS or ARC. 92 (61.3%) of the 150 male index cases and 57 (73.1%) of the 71 female index cases had an HIV-infected marital partner, and the severity of HIV disease (AIDS or ARC) in the index partner was linearly associated with the severity of HIV disease in the spouse. 10 (25.6%) of 39 uninfected wives of HIV-positive men compared with only 1 (7.7%) of 13 uninfected husbands seroconverted during the 1st year of follow- up. 4 of the 11 spouses who seroconverted during this period reported sexual intercourse at a time when their HIV-infected partner had genital ulcers. Of the 264 children under 10 years of age from 154 households with an HIV-positive adult who were also evaluated as part of this study, 39 (14.8%) were infected--26 had ARC and 13 had asymptomatic infection. Only 3 of the infected children were older than 5 years of age; the mean was 24.9 months. In all cases, transmission in children was attributable to HIV infection in the mother. These findings suggest a need for more aggressive counseling to reduce the sexual transmission of HIV infection to uninfected partners. 46 of 52 discordantly infected couples followed for 1 year continued to have unprotected vaginal intercourse--a factor that certainly contributed to the high concordance of HIV infection among the couples in this study.

Hospital use by HIV patients in Italy: a retrospective longitudinal study. National Study Group on HIV-Related Hospital Use.

Hospital-based treatment for HIV patients consumes considerable health care resources, and for planning purposes it is important to know the hospital needs for each stage of infection. In this paper, we report the results of a national study in Italy on hospital stay for cohorts of patients hospitalized for the first time with HIV-related illnesses during the years 1984-86 and 1987-88. Using the Kaplan-Meier survival methods, we demonstrate a substantial decrease in the proportion of time spent in the hospital by patients newly diagnosed with AIDS (from 49% to 25%) in the latter study period. Treatment with zidovudine (ZDV), estimated only for 1988, emphasizes this trend even more. A reduction in hospital use also occurred for AIDS-related complex (ARC) and persistent general lymphadenopathy (PGL) patients. Possible reasons for this decrease in proportion of time spent in the hospital include longer life span of patients and expansion of outpatient care, as has already been reported in the United States.

Comparison of three HIV antigen detection kits in sequential sera from a cohort of homosexual men.

HIV antigen detection kits are available from a number of commercial sources. Abbott, Coulter, and Du Pont antigen kits were used to test 661 sera collected sequentially from 65 members of the Toronto Sexual Contact Study (TSCS). The sera had been collected at 3-month intervals over 4 years from nine persistently HIV-seronegative men, 14 seroconverters, and 42 seroprevalent participants. Antigen was not detected in any seronegative men. Two of 14 seroconverters were antigen positive in the specimen immediately preceding seroconversion (by all kits). Antigen was detected in 22 of 56 seropositive participants; of these, 16 of 22 demonstrated the emergence of antigen during observation. Discrepancies were noted in the time of detection of antigen (ranging from 3 months to more than 3 years) in nine participants. Although overall concordance among all kits for all specimens appears high (95.4%), when the bias introduced by testing multiple specimens from the same patient is removed, the lower bound of concordance among all three kits is estimated to be 80%. Similarly, after correction, the upper and lower bound of estimates of sensitivity are Abbott 96, 92%; Coulter 88, 63%; and Du Pont 88, 58%. There are significant differences in the performance characteristics of these commercial products for the detection of HIV antigen in serum.

Projecting the medical costs of AIDS and ARC in the United States.

We projected the direct medical costs of acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC) for the United States during the period 1987-1991, by applying current epidemiologic projections to state-of-the-art medical decision algorithms for diagnosis and treatment of AIDS-related illnesses. We included the cost of azidothymidine (AZT) therapy, as well as other therapeutic innovations likely to be approved by the FDA, and estimated average ARC patient treatment costs. By combining prospective study data on rates of progression to AIDS with current AIDS incidence data, we arrived at human immunodeficiency virus (HIV) seroprevalence and AIDS incidence projection that were considerably lower than those of the Public Health Service. We estimated the average total medical costs per patient for AIDS in the 1990s at $27,950-$40,455 and for ARC at $3,621-$4,913 per year (1987 U.S. dollars). We projected the medical costs of AIDS and ARC at $2-4 billion annually by 1991, substantially lower than previous estimates. We projected that Pneumocystis carinii pneumonia and other pulmonary complications would account for the largest share (over 40%) of AIDS medical costs, and that AZT therapy and medication would account for more than 25% of total ARC/AIDS treatment costs by 1991. In our estimates, the total medical costs of treating ARC patients could approach one-half of the costs of treating AIDS patients by 1991, primarily due to costs associated with AZT.

Ten-year follow-up of HIV-infected homosexual men with lymphadenopathy syndrome: evidence for continuing risk of developing AIDS.

Seventy-five homosexual men with lymphadenopathy syndrome (LAS), subsequently shown to be seropositive for the human immunodeficiency virus (HIV), were enrolled in a prospective study in Atlanta in 1982 and 1983. Subjects have been followed up at 3- to 6-month intervals with clinical and immunologic evaluations, including analysis of T-cell subsets. As of February 28, 1991, AIDS had developed in 36 (48%) of the 75 men. The AIDS cases continued to occur through the 10th year after onset of LAS; the 10-year cumulative incidence of AIDS was 56.6% (Kaplan-Meier survival analysis). Six-year incidence rates following the first observation of a T-helper cell count greater than or equal to 500/mm3, 400-499/mm3, 300-399/mm3, 200-299/mm3, and less than 200/mm3 were 29, 35, 50, 58, and 88%, respectively. Among individual symptoms and signs, only thrush conferred a poorer prognosis (odds ratio = 5.80; 95% confidence interval, 2.93, 11.39, p less than 0.001, Mantel-Byar analysis). The risk of AIDS persists 10 years after the onset of LAS. The AIDS incidence is related directly to T-helper cell depletion; with the exception of thrush, the presence or absence of symptoms and signs appears to be of lesser prognostic significance.

Influence of host genotype on progression to AIDS among HIV-infected men.

To evaluate whether host genotype influences disease progression among persons infected with human immunodeficiency virus type 1 (HIV-1), molecular techniques were used to determine genotypes at immune response loci for 114 HIV-1-infected homosexual/bisexual white men in the San Francisco Men's Health Study. Candidate genes evaluated were HLA-DQA1 and -DRB1, complement C4A and C4B, alpha- and beta-interferons, and the heavy chain of immunoglobulin gamma 1. Of the 114 men, 29 were asymptomatic, 21 were symptomatic men and AIDS patients (p = 0.02). Specifically, the HLA haplotype DRB1*0702-DQA1*0201 was associated with absence of symptoms (p = 0.003). Conversely, the frequency of the complement C4B-L allele was higher among patients with symptoms or with AIDS than among asymptomatic subjects (p = 0.02). These results suggest that genes in or near the major histocompatibility complex may influence the rate of disease progression among HIV-1-infected men.

Results of a one year longitudinal study of HIV antibody test notification from the San Francisco General Hospital cohort.

We examined the psychological impact of HIV antibody testing in 107 homosexual men in San Francisco. Seventy-eight percent of the seropositives but only 43% of the seronegatives correctly anticipated their results. Twelve months after notification (but not earlier), notified seropositives reported significantly greater increases in total distress than nonnotified controls. However, notified seronegatives demonstrated significantly lower levels of hopelessness than nonnotified controls at every follow-up assessment. Thus, knowledge of HIV antibody status appears to dispel a sense of gloom in persons who incorrectly believe themselves to be infected with HIV, but does not appear to induce significant distress in those whose expectation of a positive result is confirmed. Both groups reported lower distress than men with ARC or AIDS, suggesting that distress was related more to symptomatology than knowing antibody status. These results suggest the benefits of HIV testing for the considerable proportion of seronegative subjects believing themselves to be seropositive and should be weighted against the more limited induction of distress in seropositives who receive confirmation of their test result expectation. The benefits of testing are also supported by increasing knowledge of the usefulness of early intervention in HIV disease.

High risk of acquired immune deficiency syndrome (AIDS) and of AIDS related complex (ARC) in hemophiliacs seropositive for more than 5 years.

A group of 90 hemophiliacs who had been regularly treated with non virus-inactivated factor VIII or IX concentrates were studied in 1983. At that time 50 patients were HIV-1-antibody positive, 6 additional seroconversions occurred until 1985. 26 of the 50 patients seropositive in 1983 are currently asymptomatic. 4 patients have developed the lymphadenopathy syndrome, 9 patients AIDS and 11 patients ARC (CDC IV C 2). 6/9 cases of AIDS and 10/11 cases of ARC have occurred only after 1985. Patients, who subsequently became symptomatic, had significantly higher IgG levels in 1983, otherwise no predictive laboratory tests were identified. Patients with T4 counts above 500/microliters became symptomatic later, but after 5 years the incidence of AIDS was comparable in patients with original T4 counts of more than or below 500/microliters.

Human immunodeficiency virus-associated disorders in Pakistan.

We have documented evidence of the human immunodeficiency virus (HIV) infection in four individuals including a blood donor and three members of a family (husband, wife, and a child) in Karachi, Pakistan. Our data indicate that HIV has been transmitted to the wife of the seropositive male, a drug abuser, in the recent past and that she has passed the virus to her newborn child perinatally/transplacentally. The two seropositive males (blood donor and drug abuser) were diagnosed clinically as having persistent generalized lymphadenopathy, an AIDS-related condition (ARC), and the child presented with developmental disorders and neurologic manifestations. This is the first report of AIDS/ARC cases from Pakistan that can be directly related to HIV infection and its heterosexual transmission.

Serological, virological, and polymerase chain reaction studies of HIV type 1 and HIV type 2 infections in Ghanaian patients with AIDS and AIDS-related complex.

We have used a particle agglutination (PA) test, Western blot (WB) test, polymerase chain reaction (PCR) test, and virus isolation to define the human immunodeficiency virus (HIV) status of 17 acquired immunodeficiency syndrome (AIDS), 6 AIDS-related complex (ARC), and 2 asymptomatic Ghanaians. HIV-1 antibodies were more frequently detected. The PCR detected 66.7% HIV-1, 11.1% HIV-2, and 5.6% of both HIV-1 and HIV-2 proviral DNA in peripheral blood mononuclear cell (PBMCs) and PBMC-Molt 4 coculture samples tested. Of the 12 viruses isolated from the 25 Ghanaians, 9 were HIV-1, 2 were HIV-2, and both HIV-1 and HIV-2 were isolated from 1 individual. Two of the HIV-1 isolates were from ARC patients who have been PA negative and either HIV-1 or HIV-2 WB indeterminate for more than 1 year without developing antibodies to HIV envelope proteins. Our results indicate that HIV-1 is now predominant in Ghanaian AIDS and ARC patients and that dual infection can occur.

PIP: While HIV is believed to be the causative agent for AIDS, many clinically diagnosed AIDS and AIDS-related complex (ARC) cases in Ghana have been reported to be negative or indeterminate for HIV antibodies. Dual seropositive reactions have also been common among AIDS and ARC cases in the country. A particle agglutination (PA) test, Western blot (WB), polymerase chain reaction (PCR), and virus isolation were used to define the HIV status of 17 AIDS, 6 ARC, and 2 asymptomatic Ghanaians. The PA test detected HIV-1 antibodies in 72% of the plasma samples, 94.4% of which were also positive according to WB. 1 sample was indeterminate by WB and 2 HIV-1 negative samples were determined to be positive by WB. HIV-2 was detected by PA in 32% of all samples, of which 87.5% were confirmed by WB. PCR detected 66.7% of HIV-1 cases, 11.1% of HIV-2, and 5.6% of both HIV-1 and HIV-2 proviral DNA in peripheral blood mononuclear cells (PBMCs) and PBMC-Molt 4 coculture samples tested. 12 viruses were isolated from the 25 subjects; 9 were identified as HIV-1, 2 as HIV-2, and 1 person was infected with both HIV-1 and HIV-2. 2 of the HIV-1 isolates were from ARC patients who had been PA-negative and either HIV-1 or HIV-2 WB indeterminate for more than 1 year without developing antibodies to HIV envelope proteins.

Genetic subtypes of HIV type 1 in Republic of Congo.

To assess the molecular epidemiology of HIV-1 in Republic of Congo (Congo), we investigated 29 HIV-1s obtained from 82 Congolese AIDS and ARC patients in 1996 and 1997. Part of the env region including the V3 loop was phylogenetically analyzed. The genotypes observed were varied: of 29 specimens, 12 (41 %) were subtype A, 1 (3%) was subtype D, 6 (21%) were subtype G, 6 (21%) were subtype H, 2 (7%) were subtype J, and 2 (7%) could not be classified as any known subtypes (U, unclassified). The heterogeneous profile of HIV-1 infection was different from the profiles of neighboring Central African countries. These data show that subtypes G and H as well as subtype A were circulating with high prevalence. The fact that new genetic subtypes (J and U) are circulating indicates a need for a greater surveillance for these subtypes both in Congo as well as in other parts of the world.

Serum IgG and IgA antibodies specific to Epstein-Barr virus capsid antigen in a longitudinal study of human immunodeficiency virus infection and disease progression in homosexual men.

A longitudinal study of serum IgG and IgA antibody titers to Epstein-Barr virus (EBV) viral capsid antigen (VCA) was carried out in 218 homosexual men at various stages of human immunodeficiency virus (HIV) infection. The serum samples tested were obtained from the following groups: 24 HIV seroconverters, 41 persistently HIV-seropositive asymptomatic individuals, 22 seropositives who developed AIDS-related complex (ARC), 29 HIV seropositives who developed lymphadenopathy syndrome (LAS), 35 HIV seronegatives with LAS, 36 asymptomatic HIV seronegatives, and 31 AIDS patients. Blind-tested samples were titrated for IgG and IgA EBV-VCA antibodies by immunoperoxidase assay (IPA). Cross-sectional analysis indicated that all HIV-seropositive subjects exhibited significantly elevated EBV IgG and IgA antibody titers compared with HIV-seronegative subjects. The proportions with EBV-VCA IgA antibodies at a titer of greater than or equal to 128 rose during the course of HIV infection and progression of the disease: 8% in HIV seronegatives, 11% in HIV seronegatives with LAS, 25% in HIV seronegatives prior to HIV seroconversion, 44% in asymptomatic HIV seropositives, 34% in LAS, 50% in ARC, and 58% in AIDS patients. An increase in EBV-VCA IgG and IgA titers was detected following HIV seroconversion and in samples obtained 6 months before disease progression to LAS. These data suggest the possible involvement of EBV in the natural history of HIV infection and disease progression. The possibility that EBV-VCA IgA antibody levels would be of value in prediction of progression of HIV-related illness is discussed.

Antibodies to HIV in Israeli hemophiliacs: relationship between serological profile and disease development.

We studied 66 Israeli hemophiliacs for antibodies to HIV in blood samples collected between 1978 and 1985. By May 1985, 2 had AIDS, 2 had ARC, 4 had lymphadenopathy with some immunologic dysfunction, and 58 were asymptomatic. Antibodies to HIV were detected in 40 (60.6%) patients, including all 8 with disease. Presence of HIV antibodies was significantly associated with receipt of non-heat-treated commercial factor VIII concentrates (NHT fac VIII) between 1980 and 1983. Thirty-eight of 45 (84.44%) patients treated with NHT fac VIII developed antibodies to HIV, compared to 1 of 16 (6.25%) treated with cryoprecipitates and fresh plasma only. Of 40 seropositive patients, 1 (2.5%) had antibodies by 1980, 4 (10%) by 1982, 14 (35%) by 1983, 10 (25.0%) by 1984, and 11 (27.5%) by May 1985. The decline in the rate of seroconversion can be attributed to the replacement of NHT fac VIII concentrate with heat-inactivated factor VIII (HT fac VIII) concentrate by November 1983. As of January 1984 only HT fac VIII was administered. Twenty-nine multitransfused thalassemia patients as well as 20 healthy Israeli blood donors were seronegative to HIV. All 40 (100%) seropositive hemophiliacs had antibodies to viral env gene encoded gp120/gp160 antigens. Twenty-four (60.05%) also had antibodies to viral gag gene encoded p24 and/or p55 antigens. While antibodies to gp120/160 persisted during the follow-up time, a loss of antibodies to p24/55 was observed in 5 of 16 (31.25%) seropositive patients from whom multiple samples were available. gp120/160 positive, p24/55 negative hemophiliacs had significantly lower absolute T-helper cell counts and reversed Th/Ts ratios when compared to gp120/160 p24/55 seropositive patients. Four of the 16 (25.0%) asymptomatic gp120/160 positive, p24/55 negative patients developed overt disease within 15 months of the last blood collection. The data suggest that exposure to HIV antigens is widespread among hemophiliacs in Israel, and can be attributed to receipt of NHT fac VIII concentrates prior to 1984. Antibodies to gp120/160 are of the most important diagnostic value while loss of antibodies to p24/p55 may be of prognostic value.