Search

Objective: The aim of the study was to describe longitudinal changes in serum lipids among HIV-infected men receiving highly active antiretroviral therapy (HAART) with long-term follow-up., Methods: A total of 304 HIV-infected men who initiated HAART and who had serum lipid measurements prior to and for up to 7 years after HAART initiation were identified from the Multicenter AIDS Cohort Study (MACS). Mean levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were examined at biannual time-points., Results: Significant lipid changes were seen within 0.5 years of HAART initiation but increases in TC (+1.09 mmol/L), LDL-C (+0.57 mmol/L), HDL-C (+0.16 mmol/L) and non-HDL-C (+0.91 mmol/L) reached peak levels 2-3 years after HAART initiation. Declines in serum TC, LDL-C and non-HDL-C in subsequent years occurred concurrently with a substantial increase in use of lipid-lowering medications (from 1% usage pre-HAART to 43% 6-7 years after HAART initiation) but the proportion of men who either were treated with cholesterol-lowering medication or had elevated cholesterol levels (>5.18 mmol/L) did not change during the 2-7-year interval after HAART. Mean HDL-C also decreased after 2-3 years and was low (<1.04 mmol/L) in 55% of HIV-infected men 6-7 years after HAART initiation., Conclusions: Atherogenic serum lipids increased early after the initiation of HAART, peaked at 2-3 years and remained high or required treatment thereafter. Low HDL-C levels persisted in the majority of men. The long-term effects of lipid abnormalities on cardiovascular risk and the effectiveness and toxicity of prolonged use of lipid-lowering medications in combination with HAART are not known.

Previous research has demonstrated isolated effects of host genetic factors on the progression of human immunodeficiency virus type 1 (HIV-1) infection. In this paper, the authors present a novel use of multivariable methods for estimating the prevented fraction of acquired immunodeficiency syndrome (AIDS) cases attributable to six restriction genes after accounting for their epidemiologic interactions. The methods presented will never yield a prevented fraction above 1. The study population consisted of a well-characterized cohort of 525 US men with HIV-1 seroconversion documented during follow-up (1984-1996). On the basis of a regression tree approach using a Cox proportional hazards model for times to clinical AIDS, the combinations of genes associated with the greatest protection, relative to the lack of a protective genotype, consisted of: 1) C-C chemokine receptor 5 (CCR5)-Delta 32 and C-C chemokine receptor 2 (CCR2)-64I (relative hazard = 0.44); 2) interleukin 10 (IL10)-+/+ in combination with CCR5-Delta 32 or CCR2-64I (relative hazard = 0.45); and 3) IL10-+/+ in combination with stromal-derived factor (SDF1)-3 'A and CCR5 promoter P1/approximately P1 (relative hazard = 0.37). Overall, 30% of potential AIDS cases were prevented by the observed combinations of restriction genes (95% confidence interval: 7, 47). However, the combined effect was confined to the first 4 years following HIV-1 seroconversion. Additional research is needed to identify AIDS restriction genes with stronger and long-lasting protection to better characterize the genetic epidemiology of HIV-1.

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

Background and Objectives: To predict incident human immunodeficiency virus (HIV)-1 seroconversions among a cohort of gay and bisexual men based on recalled sexual behavior, drug use, partnership status, and an index of sexual adventurism/risk-seeking attitudes., Study Design: A nested case-control design was used in a retrospective study spanning a 9-year period., Results: Sexual adventurism was an important predictor of HIV-1 infection. The partial risk ratio for our 100-point adventurism scale indicated a marginal rate of increase in seroconversion risk of 4% (odds ratio = 1.04; 95% confidence interval = 1.02 to 1.06), with almost 79% of seroconverters scoring above the median on the index. As expected, partner status, drug use, and unprotected receptive anal (RA) intercourse were associated with seroconversion. However, multivariate results indicated that men using condoms consistently in RA sex were also at higher risk for infection (odds ratio = 2.68; 95% confidence interval = 1.04 to 6.95) than men who abstained from RA intercourse., Conclusions: Results are discussed with respect to their implications for HIV prevention intervention and research. Recommendations include the development of new approaches and the adaptation of existing intervention techniques that recognize and treat persons with strong risk-taking predispositions.

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.

Objective: To estimate expected survival time among homosexual men infected with the human immunodeficiency virus type 1 (HIV-1) by (1) the calendar period before (1985-1988) and after (1989-1993) the widespread availability of acquired immunodeficiency syndrome (AIDS) treatments with antiretroviral and prophylactic interventions, and (2) stage of HIV disease., Design: A prospective cohort study. A group of HIV-1-infected homosexual men were followed from July 1985 through June 1993 and evaluated every 6 months for the presence of clinical symptoms and measurement of the CD4 cell count. To measure the effectiveness of AIDS therapies in this nonrandomized study, we used 2 calendar periods as proxy measures of relative intensity of exposure to antiretroviral therapy. Stage of infection was defined by CD4 cell count and presence of HIV-related clinical symptoms or AIDS., Setting and Study Participants: Homosexual men infected with HIV-1 from the Multicenter AIDS Cohort Study., Main Outcome Measure: Survival time based on stage of HIV infection., Results: The percentage of HIV-1-infected individuals free of AIDS and clinical symptoms at baseline who survived 2.5 years according to baseline CD4 cell counts of 0 to 0.100, 0.101 to 0.200, and 0.201 to 0.350 x 10(9)/L was 22%, 53%, and 83%, respectively, for the 1985-1988 calendar period, compared with 54%, 71%, and 91%, respectively, for men in the 1989-1993 calendar period. Among men free of AIDS with CD4 cell counts of greater than 0.350 x 10(9)/L, the relative hazard of mortality was 1.6 to 2.3 times higher for those with clinical symptoms compared with those free of clinical symptoms., Conclusions: Survival of AIDS-free HIV-1-infected individuals with CD4 cell counts of less than 0.350 x 10(9)/L has improved since antiretroviral and HIV prophylactic treatments have become available, but the long-term prognosis remains poor.

This paper focuses on 76 human immunodeficiency virus type 1 (HIV-1) seroconverters who concurrently participated in the Chicago, Illinois, component of the Multicenter AIDS Cohort Study (MACS) and the Coping and Change Study (CCS) of homosexual/bisexual men between 1984 and 1992. A nested case-control analysis was performed to assess the critical behavioral risk factors associated with incident HIV-1 infection and the consistency of these relations in early (1984-1988) versus later (1989-1992) phases of the study. Univariate results revealed strong early period associations between seroconversion and various measures of receptive anal intercourse (RAI) that became considerably weaker in the study's later period. The weaker associations reflected the overall decline in levels of RAI among the cohort during the 9 years of observation. In contrast, univariate results revealed stronger later period associations between seroconversion and measures of receptive oral intercourse and insertive anal intercourse. Subsequent multivariate testing did not support the hypothesis that receptive oral intercourse and/or insertive anal intercourse have replaced unprotected RAI as important risk behaviours in the homosexual transmission of HIV-1. In conditional logistic regression models combining intercourse measures with indices of drug and condom use, only the latter variables were consistently associated with HIV-1 seroconversion in both early and later study periods. Adjusted odds ratios (ORs) for nonuse of condoms during RAI were consistently significant throughout the study (ORs = 3.7-4.8), while adjusted odds ratios for recreational drug use variables rose dramatically during the latter half of the study (e.g., for use of cocaine, OR = 81.3 (95% confidence interval 8-824) [corrected], and for use of nitrite "poppers," OR = 9.1 (95% confidence interval 1.8-45.5)). The behavioral intervention applications of these findings, as well as their relation to data from other recent cohort studies of HIV-1 seroconversion among homosexual/bisexual men, are discussed.

To determine whether the excess prevalence of human immunodeficiency virus type 1 (HIV-1) infection in US black and Hispanic homosexual men relative to white men can be explained by differences in sociodemographic factors, history of sexually transmitted diseases, or sexual and drug-use behaviors, the authors conducted a cross-sectional analysis of baseline HIV-1 seroprevalence and HIV-1 risk factors among 4,475 non-Hispanic white, 234 Hispanic white, and 194 black homosexual men from four centers in the United States (Baltimore/Washington, DC, Pittsburgh, Chicago, and Los Angeles). HIV-1 seroprevalence was significantly higher in Hispanic men (50%; odds ratio (OR) = 1.83, 95% confidence interval (CI) 1.41-2.39) and black men (47%; OR = 1.62, 95% CI 1.21-2.16) compared with white men (35%). Both Hispanic and black men more frequently reported a history of sexually transmitted diseases. Overall, Hispanics had the highest risk profile and blacks the lowest risk profile with respect to certain high-risk sexual behaviors (e.g., receptive anal intercourse and use of anonymous sexual partners) and recreational drug use. After multivariate adjustment, black race remained a significant independent risk factor for HIV-1 seropositivity (OR = 1.60, 95% CI 1.13-2.26), but Hispanic ethnicity was no longer statistically significant (OR = 1.17, 95% CI 0.82-1.69). Most of the excess HIV-1 prevalent infection among Hispanics was explained by their predominant recruitment from Los Angeles--the study center with the highest HIV-1 seroprevalence--and their greater prevalence of a history of sexually transmitted diseases and certain high-risk sexual practices. By contrast, adjustment for these same risk behaviors failed to explain the observed black-white differences in HIV-1 seroprevalence, and further studies are needed to elucidate the reasons for these unexplained racial differences. HIV-1 educational programs for homosexual men should take into account the behavioral differences that exist between white and minority racial/ethnic groups.

We have formulated the problem of determining whether there has been an upturn in HIV-1 seroconversion incidence over the first five years of follow-up in the Multicenter AIDS Cohort Study (MACS) as that of locating the minimum of a quadratic regression or examination of two-knot piecewise spline models. Under a quadratic model, we propose a method to obtain a direct estimate and a bootstrap estimate for the location of the temporal turning point (local minimum) for HIV-1 seroconversion incidence and three methods to estimate confidence intervals for the location of the turning point for HIV seroconversion incidence: (1) Wald confidence interval estimate with or without log transformation assuming the asymptotic normality and applying the Delta method; (2) asymmetric confidence intervals using Fieller's Theorem and its modification; and (3) bootstrapping confidence intervals. Inferences for the temporal turning point based on Wald tests for a single regression term in a non-linear regression model were not reliable compared to inferences based on confidence intervals placed on calendar time. We present results using these different methods applied to the MACS data and we obtain power estimates to illustrate the performances of different methods.

Serum antibody to p24 (anti-p24) and p24 antigen, alone and in combination with CD4+ lymphocyte number, were evaluated as predictors of progression of human immunodeficiency virus type 1 (HIV-1) infection. Two hundred six HIV-1-prevalent seropositive men in the Multi-center AIDS Cohort Study since 1984-1985 were studied cross-sectionally and 84 seroconverters were evaluated longitudinally. Cross-sectional analyses revealed significant associations among titer of anti-p24, CD4+ cell count, disease status (Centers for Disease Control class), and progression to AIDS. A high titer of anti-p24 was associated with lack of p24 antigenemia. Longitudinal studies of seroconverters demonstrated that a low titer of anti-p24, low CD4+ cell count, and detection of HIV-1 p24 antigen are individually strong predictors of AIDS, but only low CD4+ cell count retains its independent predictive value in multivariate analysis of the three markers during the period immediately after infection with HIV-1.