Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection.

Major histocompatibility complex (MHC) genes (HLA in humans) regulate the immune response to foreign antigens. Molecular and serologic techniques were used to identify products of HLA class I, class II and transporter (TAP) genes (also part of the MHC) in homosexual seroconverters to human immunodeficiency virus type 1 (HIV-1). Comprehensive statistical analysis produced an HLA profile that predicted time from HIV-1 infection to the onset of AIDS. The profile was developed in a cohort of 139 men and evaluated in a second unrelated cohort of 102 men. In the evaluation cohort, the profile discriminated a sixfold difference between groups with the shortest and longest times to AIDS (P = 0.001). These findings support current theory about control of antigen processing by HLA genes and have implications for immunopathogenesis of HIV-1 and other infections.

Efficacy of caspofungin as salvage therapy for invasive aspergillosis compared to standard therapy in a historical cohort.

In a non-comparative study, caspofungin was effective salvage therapy for approximately half of the patients refractory to or intolerant of standard antifungal agents for invasive aspergillosis. To establish a frame of reference for these results, we compared the response to caspofungin with responses to other antifungal agents in a historical cohort of similar patients. The efficacy could be evaluated in 83 patients who received caspofungin 50 mg daily after a 70-mg loading dose. The historical control group, identified through a retrospective review of medical records, included 214 evaluable patients possibly refractory to or intolerant of ≥1 week of standard antifungal therapy. All patients had documented invasive aspergillosis. Favorable response was defined as a complete or partial response to therapy. Underlying diseases, baseline neutropenia, corticosteroid use, and sites of infection were similar in both studies. Most patients had received amphotericin B formulations and/or itraconazole, and were refractory to standard therapy. Favorable response rates were 45% with caspofungin and 16% with standard therapy. The unadjusted odds ratio for a favorable response (caspofungin/standard therapy) was 4.1 (95% confidence interval: 2.2, 7.5). After adjusting for potential imbalances in the frequency of disseminated infection, neutropenia, steroid use, and bone marrow transplantation between groups, the odds ratio remained at 4.1 (2.1, 7.9). Although only tentative conclusions about relative efficacy can be drawn from retrospective comparisons, caspofungin appeared to be at least as efficacious as an amphotericin B formulation and/or itraconazole for the treatment of invasive aspergillosis in patients refractory to or intolerant of their initial antifungal therapy.

Heterozygosity for a defective gene for CC chemokine receptor 5 is not the sole determinant for the immunologic and virologic phenotype of HIV-infected long-term nonprogressors.

HIV-1-infected long-term nonprogressors are a heterogeneous group of individuals with regard to immunologic and virologic markers of HIV-1 disease. CC chemokine receptor 5 (CCR5) has recently been identified as an important coreceptor for HIV-1 entry into CD4+ T cells. A mutant allele of CCR5 confers a high degree of resistance to HIV-1 infection in homozygous individuals and partial protection against HIV disease progression in heterozygotes. The frequency of CCR5 heterozygotes is increased among HIV-1- infected long-term nonprogressors compared with progressors; however, the host defense mechanisms responsible for nonprogression in CCR5 heterozygotes are unknown. We hypothesized that nonprogressors who were heterozygous for the mutant CCR5 gene might define a subgroup of nonprogressors with higher CD4+ T cell counts and lower viral load compared with CCR5 wild-type nonprogressors. However, in a cohort of 33 HIV-1-infected long-term nonprogressors, those who were heterozygous for the mutant CCR5 gene were indistinguishable from CCR5 wild-type nonprogressors with regard to all measured immunologic and virologic parameters. Although epidemiologic data support a role for the mutant CCR5 allele in the determination of the state of long-term nonprogression in some HIV-1- infected individuals, it is not the only determinant. Furthermore, long-term nonprogressors with the wild-type CCR5 genotype are indistinguishable from heterozygotes from an immunologic and virologic standpoint.

Comparison of clinical symptoms of human immunodeficiency virus disease between intravenous drug users and homosexual men.

BACKGROUND: To compare the prevalence of human immunodeficiency virus (HIV)-related clinical symptoms among male intravenous drug users and homosexual men stratified by HIV serostatus and CD4 cell levels. METHODS: A cross-sectional sample using concurrent longitudinal studies of the natural history of HIV-1 infection among intravenous drug users (N = 539) and homosexual men (N = 932) was recruited in Baltimore, Md. Participants were administered a risk behavior interview and physical examination, and had hematologic tests evaluated in a similar calendar period. RESULTS: Both risk groups demonstrated an inverse relationship between frequency of symptoms and CD4 cell count. Fever, night sweats, and lymphadenopathy were not evaluated because pilot data suggested a confounding association with drug injection. Among those with mild to moderate immune suppression, intravenous drug users were significantly more likely than homosexual men to experience fatigue, weight loss, diarrhea, and shortness of breath; to have oral candidiasis, palpable spleen, and lower mean weight on physical examination; and abnormal hematocrit, platelets, and total lymphocyte counts. However, participants in either risk group with CD4 cell levels below 0.2 x 10(9)/L experienced similar frequency of all clinical symptoms. Self-reported oral candidiasis increased fourfold with HIV infection and was as likely in both groups at all CD4 cell levels. Duration and recency of intravenous drug use was not significantly associated with the higher frequency of most clinical symptoms. CONCLUSION: Social factors are an important consideration in evaluating the association between clinical symptoms and HIV immunosuppression. Except for oral candidiasis, there are limitations for the use of clinical symptoms as intermediate outcome measures for HIV infection among intravenous drug users.

Epidemiology of acute respiratory illness during an influenza outbreak in a nursing home. A prospective study.

We observed an influenza epidemic caused by influenza A/Arizona/82 (H3N2) in a nursing home during 1982 to 1983. A survey indicated that 59% of the residents were immunized before the outbreak. The outbreak was observed to begin in November, peak in February, and disappear in April. A significant level of herd immunity may have accounted for the slow progression through the nursing home. In addition, serologic evidence of concurrent infection with respiratory syncytial virus, parainfluenza virus, and Mycoplasma pneumoniae was present in many residents. Epidemics of influenza in a closed, partially immunized population in a nursing home may proceed at a slower rate than in an open, largely unimmunized community. By monitoring for infection with other respiratory agents, the complex nature of the outbreak in this nursing home became evident.

Association of influenza immunization with reduction in mortality in an elderly population. A prospective study.

We prospectively studied the efficacy of influenza vaccine during an influenza A/Arizona/80 (H3N2) outbreak at the Jewish Home and Hospital for the Aged in New York in the winter season of 1982 to 1983. All patients had been offered influenza vaccine before the outbreak; 181 chose to be vaccinated and 124 refused vaccination but agreed to participate in the study. Among those with serologic evidence of influenza infection, respiratory illness was significantly more common in the unvaccinated group (six of 14 vs one of 22). The overall mortality was 13 (7.2%) of 181 in the vaccinated group and 22 (17.7%) of 124 in the control group. The vaccinated and the control groups were examined for comparability. A logistic regression analysis, which controlled for differences in sex and level of nursing care, indicated that the difference in mortality was still significant, with a summary odds ratio of 2.7. The relative risk of death in the unvaccinated group was comparable at 2.18. Influenza vaccine reduced the mortality by 59% in the vaccinated group compared with the control group.

Influenza vaccine and pneumonia mortality in a nursing home population.

The effectiveness of immunization against influenza in elderly persons is uncertain. A retrospective cohort study in a New York City nursing home examined the occurrence of pneumonia and its related mortality over three consecutive influenza seasons (Nov 1 through April 30, 1979 to 1980, 1980 to 1981, and 1981 to 1982). Nearly one half of approximately 450 residents (mean age, 84 years) accepted immunization each year. The vaccinated and unvaccinated groups were similar. The attack rate of pneumonia did not differ significantly between the vaccinated and unvaccinated groups in any of the three influenza seasons. When influenza was occurring in the community (1979 to 1980 and 1980 to 1981), however, the risk of death from pneumonia in the unvaccinated group was three-fold higher than in the vaccinated group (60% vs 18% and 73% vs 25%, respectively). In a year when influenza was specifically sought and not found in the facility (1981 to 1982), however, vaccination did not affect pneumonia-related mortality. This study also suggests that estimates of mortality due to pneumonia should include deaths that occur up to 60 days after onset of pneumonia; shorter follow-up may overestimate the protective effect of vaccination.

Direct comparison of the relationship between clinical outcome and change in CD4+ lymphocytes in human immunodeficiency virus-positive homosexual men and injecting drug users.

BACKGROUND AND METHODS: To compare rates of decline of CD4+ lymphocytes among human immunodeficiency virus-positive homosexual men and injecting drug users, we followed up prevalent human immunodeficiency virus-positive homosexual men and current or former injecting drug users from February 1988 through August 1991. Subjects were free of acquired immunodeficiency syndrome at study entry and had semiannual clinical and laboratory evaluation, including measurement of T-cell subsets, under common protocols. Initial levels and rates of change of CD4+ lymphocyte counts were compared according to cohort membership and clinical progression, defined by the development of thrush or an acquired immunodeficiency syndrome--defining illness. Median follow-up was 30 months for both cohorts. RESULTS: At study entry, homosexual men had lower absolute numbers of circulating CD4+ lymphocytes than did injecting drug users (459/microL [0.46 x 10(9)/L] vs 509/microL, respectively). During follow-up, homosexual men exhibited a faster decline in CD4+ lymphocyte counts as well as more frequent development of HIV-related symptoms (thrush or acquired immunodeficiency syndrome). In both cohorts, initial levels of CD4+ lymphocytes and rates of decline in these cells were strongly associated with progression of disease, defined as remaining asymptomatic, onset of thrush, or onset of acquired immunodeficiency syndrome. Once homosexual men and injecting drug users were stratified by disease progression, their initial levels and rates of decline of CD4+ lymphocyte counts were similar. Thus, crude differences between the two study groups largely resulted from differences in development of clinical symptoms. CONCLUSIONS: In these cohorts of homosexual men and injecting drug users, clinical outcome was much more important than risk group membership in determining changes in CD4+ lymphocyte numbers. The close similarity between the groups also suggests that drug use, ethnicity, and socioeconomic status play a minor role in the progression of human immunodeficiency virus infection.

A survey of occupational blood contact and HIV infection among traditional birth attendants in Rwanda.

OBJECTIVE: To investigate the risk of occupationally acquired HIV infection among traditional birth attendants (TBA) in Rwanda, Africa. DESIGN AND METHODS: A serosurvey was conducted among 219 TBA practicing in a rural but densely populated area in southern Rwanda. Each TBA was interviewed about sociodemographic information, work-related habits and practices, and presence of nonoccupational risk factors for HIV infection. The frequency of skin exposure to HIV-infected blood was estimated for each TBA from HIV seroprevalence data collected previously from pregnant women stratified by the geographic zones in which the TBA practiced. RESULTS: Four TBA (1.8%) tested HIV-1-antibody-positive; all four had reported nonoccupational risk factors for HIV infection. We estimated that the 215 HIV-negative TBA had 2234 potentially infectious blood-skin contacts out of a total of approximately 35,000 deliveries assisted in the past 5 years. However, we found no evidence of HIV infection caused by occupational blood contact (none out of 2234; upper limit of the 95% confidence interval because of one potentially infectious blood-skin contact = 0.2%). CONCLUSION: Although these findings may not be universal to all TBA in Africa, the risk of occupationally acquired HIV infection among TBA appears small. The high frequency of blood-skin contact among TBA in Rwanda highlights the need to include infection control precautions in the training of TBA.

PIP: Samples of blood from 219 traditional birth attendants (TBA) practicing in a rural, densely populated area in southern Rwanda were tested for the presence of antibody against HIV-1 in an investigation of the risk for acquiring HIV infection occupationally. The TBAs were interviewed for sociodemographic data, on work-related habits and practices, and about nonoccupational risk factors for HIV infection. The researchers also estimated the frequency of skin exposure to HIV-infected blood for each TBA from HIV seroprevalence data collected previously from pregnant women stratified by the geographic zones in which each TBA practiced. Four TBAs tested seropositive for HIV-1 antibody; all had reported nonoccupational risk factors for infection. It was also estimated that the 215 HIV-negative TBAs had 2234 potentially infectious blood-skin contacts out of a total of approximately 35,000 deliveries assisted over the previous past five years. No evidence was therefore found of HIV infection caused by occupational blood contact and the risk of occupationally acquired HIV infection among TBAs seems small. The high frequency of blood-skin contact among TBAs in Rwanda, however, highlights the need to include infection control precautions in the training of TBAs.

Association between serum vitamin A and E levels and HIV-1 disease progression.

OBJECTIVE: To examine the associations between serum vitamin A and E levels and risk of progression to three key outcomes in HIV-1 infection: first AIDS diagnosis, CD4+ cell decline to < 200 cells x 10(6)/l, and mortality. DESIGN: Non-concurrent prospective study. METHODS: Serum levels of vitamins A and E were measured at the enrollment visit of 311 HIV-seroprevalent homo-/bisexual men participating in the Baltimore/ Washington DC site of the Multicenter AIDS Cohort Study. Cox proportional hazards models were used to estimate the relative hazard of progression to each outcome over the subsequent 9 years, adjusting for several independent covariates. RESULTS: Men in the highest quartile of serum vitamin E levels (> or = 23.5 mumol/l) showed a 34% decrease in risk of progression to AIDS compared with those in the lowest quartile [relative hazard (RH), 0.66; 95% confidence interval (CI), 0.41-1.06)]. This effect was statistically significant when comparing the highest quartile of serum vitamin E to the remainder of the cohort (RH, 0.67; 95% CI, 0.45-0.98). Associations between serum vitamin A levels and risk of progression to AIDS were less clear, but vitamin A levels were uniformly in the normal to high range (median = 2.44 mumol/l). Similar trends were observed for each vitamin with mortality as the outcome, but neither vitamin was associated with CD4+ cell decline to < 200 cells x 10(6)/l. Men who reported current use of multivitamin or single vitamin E supplements had significantly higher serum tocopherol levels than those who were not taking supplements (P = 0.0001). Serum retinol levels were unrelated to intake of multivitamin or single vitamin A supplements. CONCLUSIONS: These data suggest that high serum levels of vitamin E may be associated with slower HIV-1 disease progression, but no relationship was observed between retinol levels and disease progression in this vitamin A-replete population.

HIV-1 and pregnant women: associated factors, prevalence, estimate of incidence and role in fetal wastage in central Africa.

The major goals of this study were to measure the current prevalence and estimate the annual incidence of HIV-1 infection in young pregnant women from urban Malawi, to identify factors that were associated with HIV-1 infection, and to examine adverse pregnancy outcomes. Four hundred and sixty-one consecutive pregnant women were studied when they presented for prenatal care. The overall seroprevalence for HIV-1 infection in these urban populations was 17.6% (81 out of 461) during early 1989. Based on previous seroprevalence in similar unselected pregnant women, the estimated annual incidence of HIV-1 seroconversion in urban pregnant women ranged from 3 to 4% per annum between 1985 and 1987 and from 7 to 13% between 1987 and 1989. HIV-1 infection was significantly associated with reactive syphilis serology. Reported history of sexually transmitted disease was also correlated with HIV-1 infection but was not statistically significant. Other variables, such as history of transfusion, history of tuberculosis, parity or occupation were not associated with HIV-1 infection. History of spontaneous abortion was significantly associated with reactive syphilis serology, HIV-1 infection and history of sexually transmitted disease. In logistic regression analysis, HIV-1 infection remained the only significant variable that was correlated with spontaneous abortion. This study suggests that HIV-1 infection may play a role in fetal wastage.

Two quick estimates of the HIV prevalence in homosexual men in Los Angeles, New York and San Francisco. The Multicenter AIDS Cohort Study.

Two rough methods are given to estimate the combined HIV prevalence in Los Angeles, New York and San Francisco in homosexual men. Both methods are related to the back calculation technique, and use AIDS surveillance data and information obtained from the Multicenter AIDS Cohort Study. Both methods suggest that the combined HIV prevalence is approximately 100,000, with a possible range of 80,000-140,000.

Traditional vaginal agents: use and association with HIV infection in Malawian women.

OBJECTIVES: To assess the prevalence of traditional vaginal agent use in Malawian women and its association with HIV infection. METHODS: Consenting, consecutive antenatal women were administered a questionnaire and screened for sexually transmitted diseases (STD) including HIV. RESULTS: Of the 6603 consenting women, 886 (13%) reported using intravaginal agents for tightening and 2222 (34%) for self-treatment of vaginal discharge and itching. A higher proportion of HIV-infected than uninfected women (17% versus 14%) reported use of intravaginal agents for treatment (odds ratio, 1.29; 95% confidence interval, 1.05-1.57), but no difference in HIV status was found when these agents were used for tightening. In multivariate analysis, vaginal agent use for treatment was independently associated with HIV seropositivity. CONCLUSIONS: The association of HIV infection with vaginal agents for self-treatment, but not for tightening, suggests that STD may play a role or that vaginal agents are used differently for the two purposes. In addition to a small increased risk of HIV infection associated with vaginal agent use, these agents may interfere with condom effectiveness or acceptability of vaginal microbicides.

PIP: An exploratory study was conducted in Malawi to determine whether a correlation exists between human immunodeficiency virus (HIV) and traditional practices involving the intravaginal application of substances such as herbs and pulverized stone. Included in the survey were 6603 consecutive consenting volunteers who presented at the prenatal clinic of an urban hospital from October 1989-October 1990. The median age of study participants was 24 years. Although only 11% reported having had a sexually transmitted disease (STD) in the three years preceding the interview, laboratory analysis revealed the presence of such an infection in 46%. HIV infection was found in 1502 (23%). A total of 2953 (45%) of these pregnant women reported use of vaginal agents or vaginal incision, either for the treatment of discharge or itching or for the enhancement of sexual pleasure through vaginal tightening. Concerns have been raised that the placement of desiccants, irritants, and astringents in the vagina can induce certain physiological changes that increase the risk of HIV infection. Demonstrated in this survey was a slight association between HIV seropositivity and the use of vaginal agents for self-medication but not for vaginal tightening. In the univariate analysis, this finding persisted only for pregnant women without past or current STD infection. In the multivariate analysis, users of vaginal agents for treatment had a small increased risk of HIV in addition to--and independently of--the risk conferred by an STD history. It is possible, however, that the use of vaginal agents for self-medication is a marker for the presence of genital tract inflammation--a co-factor for HIV transmission. Given the extent of this traditional practice and its potential risk, more research is urged on the type of vaginal agents used and their effects on vaginal tissue.

Racial differences in rate of CD4 decline in HIV-1-infected homosexual men.

OBJECTIVE: To determine whether racial differences exist in the rate of CD4 lymphocyte decline in HIV-1-infected homosexual men. DESIGN: Prospective cohort study. STUDY POPULATION: Non-Hispanic white (n = 321) and black (n = 102) HIV-1-seropositive homosexual and bisexual men were recruited from the Baltimore/Washington, DC metropolitan areas between 1984-1985 and 1987-1990, and evaluated semiannually. MAIN MEASUREMENTS: Changes in CD4 lymphocyte count and CD4 percentage over time were analysed using linear regression methods for the 271 white and 69 black participants who had at least four semiannual CD4 lymphocyte measurements. RESULTS: Rate of decline in CD4 lymphocyte count over 6 months was much slower among black than white seroprevalent men at all levels of baseline CD4 count (baseline 201-400 x 10(6)/l: + 0.24 versus -17.7 x 10(6)/l; 401-600 x 10(6)/l: -11.3 versus -23.9 x 10(6)/l; 601-800 x 10(6)/l: -15.1 versus -35.2 x 10(6)/l; > 800 x 10(6)/l: -4.3 versus -42.7 x 10(6)/l for black versus white, respectively), although this was only statistically significant for the lowest and highest strata of baseline CD4 count. These racial differences persisted after adjustment for recruitment period (1984-1985 or 1987-1990), follow-up duration, age and zidovudine therapy or Pneumocystis carinii pneumonia prophylaxis. Similar findings were observed among the 70 white and 11 black seroconverters. Black participants were also less likely than a subgroup of white participants matched on baseline CD4 lymphocyte count to be HIV-1 p24 antigen-positive. However, after acid dissociation of samples initially p24 antigen-negative, there were no significant differences in the prevalence of p24 antigenemia at enrollment or after 1 year of follow-up. CONCLUSIONS: This analysis suggests a more gradual decline in CD4 lymphocyte count among black than white Americans. The clinical significance of and reasons for this are unclear, but the lower prevalence of p24 antigenemia due to immune complexing among black Americans suggests that racial differences in the immune response to HIV may exist. Additional studies are needed to validate these findings in a larger cohort of non-whites, and to assess their relationship with other measures of cell-mediated immune function.

Solar ultraviolet radiation exposure does not appear to exacerbate HIV infection in homosexual men. The Multicenter AIDS Cohort Study.

OBJECTIVE: To determine the effect of sun exposure on HIV progression. DESIGN: Cross-sectional survey nested within a longitudinal cohort study. SETTING: The Multicenter AIDS Cohort Study. PARTICIPANTS: A total of 1155 white HIV-seronegative and 496 white HIV-seropositive homosexual men, of whom 142 seroconverted during the study. MAIN OUTCOME MEASURES: T-helper lymphocyte decline and AIDS. RESULTS: No positive correlation was found between the development of AIDS or loss of T-helper lymphocytes and (i) phenotypic characteristics associated with enhanced ultraviolet radiation (UVR) sensitivity (hair or eye color, skin type), or (ii) reported UVR exposure (sun lamp/tanning bed use, frequency of beach vacations, sunscreen use), or (iii) composite score of UVR sensitivity and exposure history. The composite scores and individual measures of risk were not correlated with rate of T-helper lymphocyte decline (slope) based upon rank correlation (correlation coefficient, 0.04; P = 0.32). In fact, individuals purposefully seeking the sun had slower T-helper lymphocyte declines. Sensitivity to UVR was also not significantly associated with AIDS [odds ratio (OR), 1.11 per unit of higher composite score; 95% confidence interval (CI), 0.66-1.88; P = 0.63]. Among individuals who were HIV-infected at baseline, those who have been purposely seeking sun exposure were less likely to have AIDS (OR, 0.67; 95% CI, 0.39-1.11; P = 0.12). CONCLUSIONS: These data suggest that phenotypic characteristics of high UVR sensitivity and exposure are not highly correlated with decline in T-helper lymphocyte count or with progression to AIDS.

Association of HLA profiles with early plasma viral load, CD4+ cell count and rate of progression to AIDS following acute HIV-1 infection. Multicenter AIDS Cohort Study.

BACKGROUND: Host genetic factors, such as HLA alleles, play an important role in mediating the course of HIV-1 disease progression through largely undefined mechanisms. OBJECTIVES: To examine the association of HLA markers with HIV-1 RNA plasma viral load and other factors associated with course of disease progression in HIV-1 infection. DESIGN AND METHODS: A group of 139 HIV-1 seroconverters from the Multicenter AIDS Cohort Study had been typed for a variety of HLA markers. HIV-1 RNA plasma viral load was measured from frozen plasma specimens obtained approximately 9 months following seroconversion. CD4+ cell counts were available from the same study visit. Statistical analysis was performed using survival techniques and linear regression models to quantify the relative associations of an HLA score profile, HIV-1 RNA plasma viral load, CD4+ cell count and age with each other and with rate of progression to AIDS and death. RESULTS: Cox proportional hazards models showed statistically significant differences in time to AIDS by HLA score profile category per unit increase [relative hazard (RH), 0.64; P < 0.0001], HIV-1 RNA plasma viral load per 10-fold increase (RH, 2.04; P = 0.0003), and CD4+ cell count per 100 cell (x 10(6)/l) increase (RH, 0.90; P = 0.02). Multivariate linear regression showed that viral load was 39% lower (P = 0.0001) for each unit increase in HLA score profile and 13% lower (P = 0.002) for each 100 cell (x 10(6)/l) increase in CD4+ cell count. CONCLUSION: The means by which the HLA score profile influences the time to AIDS is probably through immunologic responses that affect the rate of HIV-1 replication, as manifested by the HIV-1 RNA plasma viral load during the first 6-12 months following acute infection.

Factors influencing survival after AIDS: report from the Multicenter AIDS Cohort Study (MACS).

The objective of this study was to determine if clinical signs, symptoms, laboratory variables, and use of therapeutic or prophylactic agents have prognostic associations with survival after diagnosis of clinical AIDS. A total of 2,168 homosexual men, seropositive for human immunodeficiency virus type 1 (HIV-1) participated in a longitudinal cohort study of the greater metropolitan areas of Baltimore, Maryland, Washington, D.C., Chicago, Illinois, Pittsburgh, Pennsylvania, and Los Angeles, California, U.S.A.--the Multicenter AIDS Cohort Study (MACS). Variables within 6 months prior to AIDS diagnosis included age, CD4+ lymphocyte counts, hemoglobin, and self-reported thrush, fever, anti-retroviral therapy (ART) beginning prior to AIDS onset, and ART beginning after AIDS (as a time-dependent covariate) were analyzed as mutually exclusive categories, as was prophylaxis for Pneumocystis carinii pneumonia (PCP). Univariate and multivariate survival models of time from AIDS to death were fit. In univariate analysis, younger age, higher counts of CD4+ lymphocytes, hemoglobin, and absence of thrush or fever prior to AIDS onset were associated with longer survival after AIDS. Those who began ART within 3 months after AIDS onset had longer median survival (1.75 years), from 3 months after AIDS, when compared with those who began ART prior to AIDS (1.18 years). This comparison is not influenced by the bias that those who survive longer have a greater likelihood to subsequently receive ART. Prophylaxis for PCP beginning after AIDS onset was also associated with longer post-AIDS survival when compared with beginning prophylaxis prior to AIDS or never using prophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibody to human T-lymphotropic virus type I/II (HTLV-I/II) among male inmates entering Maryland prisons.

Serum specimens that had been obtained for routine operational procedures from consecutive entering male inmates during Spring 1987 and the same calendar period in 1988 were tested to identify prevalence and risk groups for antibody to HTLV-I/II. Specimens were assayed for antibody to HTLV-I/II using ELISA, RIPA, and Western blot techniques. Demographics were compared by serostatus using chi 2 and Fisher's exact tests. Of the 1,932 inmates entering prison, 49.3% were 25 years of age or older, 70.1% were black, 62.4% were committed from the Baltimore metropolitan area, 34.1% were intravenous drug users, and 7.0% demonstrated antibody to HIV-1. Among 1,932 inmates, 18 (0.9%) were HTLV-I/II seropositive. All seropositives were black; age greater than 25 years old was significantly (p less than 0.01) associated with seropositivity. Reactivity to HTLV-I/II did not vary significantly by year of entry, HIV-1 serostatus, jurisdiction, offense category, or sentence. Prevalence of HTLV-I/II among incoming male inmates was elevated compared to available local population comparisons. Additional blinded epidemiological serosurveys of antibody to HTLV-I/II are indicated for prison populations in order to monitor the extent and scope of infection in this population.

Changes in T and non-T lymphocyte subsets following seroconversion to HIV-1: stable CD3+ and declining CD3- populations suggest regulatory responses linked to loss of CD4 lymphocytes. The Multicenter AIDS Cohort Study.

We investigated changes in lymphocyte subsets (total, CD4+ and CD8+ T cells, as well as non-T cells) associated with human immunodeficiency virus type I (HIV-1) seroconversion in 321 homosexual or bisexual men in the Multicenter AIDS Cohort Study (MACS). These subjects had serial lymphocyte characterizations for up to 4 years before and 5 years after seroconversion. CD4+ lymphocyte levels declined rapidly in the first 18 months following seroconversion and less rapidly thereafter, while CD8 lymphocytes increased with similar kinetics. In contrast, total T (CD3+) lymphocytes declined only slightly in the first 18 months following seroconversion, and then remained stable. These results support the hypothesis of physiologic regulation of the total number of circulating T cells, such that lost CD4+ lymphocytes are replaced by newly generated CD4+ and CD8+ lymphocytes; over time, continued loss of CD4+ lymphocytes due to HIV-1 infection would result in net replacement of lost CD4+ lymphocytes with CD8+ lymphocytes. Non-T (CD3-) lymphocytes also declined after seroconversion, and this decline paralleled that of CD4+ lymphocytes. Thus, changes in both T and non-T lymphocytes after HIV-1 seroconversion may reflect the operation of homeostatic or regulatory mechanisms. Whether these mechanisms contribute to the development of immune deficiency requires further study.

Relationship of serum copper and zinc levels to HIV-1 seropositivity and progression to AIDS.

Dietary, serum, and tissue levels of copper and zinc were determined at baseline in a cohort of homosexual men to investigate the relationship of these factors to human immunodeficiency virus type 1 (HIV-1) seropositivity and subsequent progression to AIDS. Using a nested case control design, 54 asymptomatic HIV-1 seropositives who later progressed to AIDS were compared with 54 HIV-1 seropositives who did not progress and 54 seronegatives (mean follow-up time 2.5 years). Serum levels of copper and zinc were estimated from frozen serum samples, tissue levels from stored toenail samples, and dietary intakes from a semiquantitative food frequency questionnaire administered at baseline. Neither dietary copper and zinc nor their levels in toenails were associated with HIV-1 seropositivity or progression to AIDS. However, serum copper levels were higher (p = 0.002) in HIV-1-seropositive progressors (mean = 115.6 micrograms/dl; SD = 17.1) than the seropositive nonprogressors (mean = 109.0 micrograms/dl; SD = 15.8) and the seronegatives (mean = 101.9 micrograms/dl; SD = 16.7). Conversely, serum zinc levels were lower (p = 0.016) in the seropositive progressors (mean = 85.2 micrograms/dl; SD = 11.5) than the seropositive nonprogressors (mean = 90.7 micrograms/dl; SD = 12.0) and the seronegatives (mean = 92.0 micrograms/dl; SD = 14.7). Furthermore, in a logistic regression, higher serum copper (odds ratio per 20-micrograms/dl increase = 2.23; 95% confidence interval = 1.02-4.87) and lower serum zinc (odds ratio per 20-micrograms/dl increase = 0.30; 95% confidence interval = 0.14-0.66) predicted progression to AIDS independently of baseline CD4+ lymphocyte level, age, and calorie-adjusted dietary intakes of both nutrients.(ABSTRACT TRUNCATED AT 250 WORDS)