Search

OBJECTIVE: To examine temporal variation in the effects of CCR5-Delta32 and CCR2-64I chemokine receptor gene polymorphisms on HIV-1 disease progression. DESIGN: Pooled analysis of individual patient data from 10 cohorts of HIV-1 seroconverters from the United States, Europe, and Australia. METHODS: We studied HIV-1 seroconverters of European (n = 1635) or African (n = 215) ancestry who had been genotyped for CCR5-Delta32 and CCR2-64I. We used Cox proportional hazards models with time-varying coefficients to determine whether the genetic protection against AIDS (1987 case definition) and death varied with time since seroconversion. RESULTS: Protection against AIDS conferred by CCR5-Delta32 held constant at a 31% (RH 0.69, 95% CI 0.54, 0.88) reduction in risk over the course of HIV-1 infection, whereas protection against death held constant at a 39% reduction in risk (RH 0.61, 95% CI 0.45, 0.88). When the period from AIDS to death was isolated, the survival benefit of CCR5-Delta32 diminished 2 years after AIDS. Protection against AIDS conferred by CCR2-64I was greatest early in the disease course. Compared with individuals without CCR5-Delta32 or CCR2-64I, individuals with one or two copies of CCR2-64I had a 58% lower risk of AIDS during the first 4 years after seroconversion (RH 0.42, 95% CI 0.23, 0.76), a 19% lower risk during the subsequent 4 years (RH 0.81, 95% CI 0.59, 1.12), and no significant protection thereafter. CONCLUSION: The protection against AIDS provided by CCR5-Delta32 is continuous during the course of infection. In contrast, the protection provided by CCR2-64I is greatest early in the course of infection. AIDS

CD4(+) lymphocyte count and human immunodeficiency virus (HIV) type 1 RNA level are useful for determining when to initiate antiretroviral therapy but are not used widely in developing countries due to the high cost. Heat-denatured protein 24 (p24) antigen is an inexpensive assay that predicts disease progression among persons with advanced disease but has not been assessed among persons with early-stage disease. Plasma levels of heat-denatured p24 antigen were quantified in baseline study-visit specimens obtained from injection drug users enrolled in a longitudinal cohort study of HIV-1 infection. Of the 494 study participants (median initial CD4(+) lymphocyte count, 518 lymphocytes/mm(3)), 90 (18%) progressed to acquired immunodeficiency syndrome within 5 years. p24 antigen level correlated with both CD4(+) lymphocyte count (r=-0.34; P5 pg/mL predicted disease progression, comparable with that of cutoff CD4(+) lymphocyte count 30,000 copies/mL. Heat-denatured p24 antigen level predicted subsequent clinical disease progression in early-stage HIV-1 infection and correlated with both CD4(+) lymphocyte count and HIV-1 RNA level

Background: Studies relating certain chemokine and chemokine receptor gene alleles with the outcome of HIV-1 infection have yielded inconsistent results. Objective: To examine postulated associations of genetic alleles with HIV-1 disease progression. Design: Meta-analysis of individual-patient data. Setting: 19 prospective cohort studies and case-control studies from the United States, Europe, and Australia. Patients: Patients with HIV-1 infection who were of European or African descent. Measurements: Time to AIDS, death, and death after AIDS and HIV-1 RNA level at study entry or soon after seroconversion. Data were combined with fixed-effects and random-effects models. Results: Both the CCR5-Δ32 and CCR2-64I alleles were associated with a decreased risk for progression to AIDS (relative hazard among seroconverters, 0.74 and 0.76, respectively P = 0.01 for both), a decreased risk for death (relative hazard among seroconverters, 0.64 and 0.74 P < 0.05 for both), and lower HIV-1 RNA levels after seroconversion (difference, -0.18 log10 copies/mL and -0.14 log10 copies/mL P < 0.05 for both). Having the CCR5-Δ32 or CCR2-64I allele had no clear protective effect on the risk for death after development of AIDS. The results were consistent between seroconverters and seroprevalent patients. In contrast, SDF-1 3′A homozygotes showed no decreased risk for AIDS (relative hazard for seroconverters and seroprevalent patients, 0.99 and 1.03, respectively), death (relative hazard, 0.97 and 1.00), or death after development of AIDS (relative hazard, 0.81 and 0.97 P < 0.5 for all). Conclusions: The CCR5-Δ32 and CCR2-64I alleles had a strong protective effect on progression of HIV-1 infection, but SDF-1 3′A homozygosity carried no such protection. 135 782 795 Cited By :238

The aim of the study was to compare the signs and symptoms of individuals meeting two different definitions of chronic fatigue syndrome (CFS). Ninety-four patients fitting the eligibility criteria for idiopathic fatigue were enrolled into the study. Of the 94 patients, 48 met the 1988 definition of CFS, 20 the 1994 (but not the 1988) definition of CFS, and 26 met neither definition. The 1994 defined cases were more likely than 1988 defined cases, and non-syndromal individuals to be male, married, and high school educated. The 1994 cases were less likely than 1988 cases to present acute onset, self reported sore throat, mild fever lymphadenopathy, pharyngitis. In conclusion, the 1994 criteria increased the number of patients classified as CFS; however, those who fit only the 1994 criteria were less likely to have an acute symptomatic onset and signs and symptoms suggestive of an infectious process.

Injecting drug users (IDUs) are at high risk for infection by human immunodeficiency virus (HIV) and other blood-borne pathogens. In the United States, IDUs account for nearly one-third of the cases of acquired immunodeficiency syndrome (AIDS), either directly or indirectly (heterosexual and perinatal cases of AIDS where the source of infection was an IDU). IDU also account for a substantial proportion of cases of hepatitis B (HBV) and hepatitis C (HCV) virus infections. The primary mode of transmission of HIV among IDUs is parenteral, through direct needle sharing or multiperson use of syringes. Despite high levels of knowledge about risk, multiperson use of needles and syringes is due primarily to fear of arrest and incarceration for violation of drug paraphernalia laws and ordinances that prohibit manufacture, sale, distribution, or possession of equipment and materials intended to be used with narcotics. It is estimated that in 1997 there were approximately 110 needle exchange programs (NEPs) in North America. In part, because of the ban on the use of Federal funds for the operation of needle exchange, it has been difficult to evaluate the efficacy of these programs. This chapter presents data from the studies that have evaluated the role of NEPs in HIV prevention. Evidence for the efficacy of NEPs comes from three source: (1) studies originally focused on the effectiveness of NEPs in non-HIV blood-borne infections, (2) mathematical modeling of data on needle exchange on HIV seroincidence, and (3) studies that examine the positive and negative impact of NEPs on HIV and AIDS. Case-control studies have provided powerful data on the positive effect of NEPs on reduction of two blood-borne viral infections (HBV and HCV) For example, a case-control study in Tacoma, Washington, showed that a six-fold increase in HBV and a seven-fold increase in HCV infections in IDUs were associated with nonuse of the NEP. The first federally funded study of needle exchange was an evaluation of the New Haven NEP, which is legally operated by the New Haven Health Department. Rather than relying on self-report of reduced risky injection drug use, this study utilized mathematical and statistical modeling, using data from a syringe tracking and testing system. Incidence of HIV infection among needle exchange participants was estimated to have decreased by 33% as a result of the NEP. A series of Government-commissioned reports have reviewed the data on positive and negative outcomes of NEPs. The major reports are from the National Commission on AIDS; the U.S. General Accounting Office; the Centers for Disease Control/University of California; and the National Academy of Sciences. The latter two reports are used in this chapter. The aggregated results support the positive benefit of NEPs and do not support negative outcomes from NEPs. When legal restrictions on both purchase and possession of syringes are removed, IDUs will change their syringe-sharing behaviors in ways that can reduce HIV transmission. NEPs do not result in increased drug use among participants or the recruitment of first-time drug users.

OBJECTIVE: Our first objective was to develop an index of satellite exchange and then determine whether satellite exchangers (SEs) differed demographically or behaviorally from other injecting drug users (IDUs). Our second objective was to determine the degree that SEs contributed to needle exchange program (NEP) effectiveness. METHODS: We collected data from approximately 5000 Baltimore Needle Exchange Program (BNEP) participants on the number of syringes acquired and returned over the two-year period February 1995 to February 1997. We then conducted one-way ANOVAs and logistic regressions to determine if SEs were different from other IDUs. RESULTS: We classified 9.35% of the IDUs and SEs and showed that SEs reported levels of drug use and risk behavior similar to other BNEP participants. Although SEs represented less than 10% of all BNEP clients, they accounted for more than 64% of all needles distributed by the BNEP. We showed that SEs accessed more wide-ranging drug use networks than non-SE IDUs and thus can act as potential bridges for human immunodeficiency virus (HIV) prevention materials and messages to larger numbers of drug injectors. CONCLUSIONS: SEs can be expressly targeted with specific prevention messages and encouraged to be "ambassadors" for HIV prevention messages. Efforts to curtail the activities of SEs may detract from the effectiveness of NEPs.