Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association最新文献

The ability of cyclophilin to bind a panel of recombinant HIV-gag proteins was assessed using sensitive, quantitative, sandwich enzyme-linked immunosorbant assays (ELISAs). Significantly higher binding to cyclophilin was observed when recombinants contained at least 12 carboxy-terminal amino acids of p17 in addition to p24 sequences. These results indicate that the carboxy-terminus of p17 is important for optimal binding of cyclophilin to p24 and support the theory that cyclophilin acts on the uncleaved HIV-1 gag (p17-p24) precursor.

Objective: To study the stability of cutaneous anergy in women with or at risk for HIV infection.

Design: Prospective multicenter cohort study

Methods: Interviews, CD4+ lymphocyte counts, and intradermal skin testing with mumps, Candida, and tetanus toxoid antigens were performed on two occasions at a median interval of 74 weeks in 436 HIV-seropositive and 252 seronegative at-risk women; only 10 (2%) HIV-seropositive women were taking highly active antiretroviral therapy at the time of delayed-type hypersensitivity (DTH) testing. Anergy was defined as induration <2 mm to all three antigens.

Results: Skin test reactivity at repeat testing was seen in 202 of 233 (87%) HIV-seronegative women who were not anergic at baseline, compared with 10 (53%) of 19 seronegative women who were anergic at baseline (relative risk [RR], 1.7; 95% confidence interval [CI], 1.07-2.5). Anergy at retesting was seen in 108 of 169 (64%) HIV-seropositive women who were previously anergic, compared with 77 of 267 (29%) who were not previously anergic (RR, 2.2; 95% CI, 1.8-2.8). Among initially anergic seropositive women, CD4+ lymphocyte counts were lower at both initial and follow-up testing in those who remained anergic than in those who reacted at follow-up (p < .001). The relative risks for anergy at retesting of initially anergic seropositive women, compared with initially reactive seropositive women, were related to CD4+ level; 2.5 (95% CI, 1.4-4.3) for CD4+ counts < 200 cells/mm3, 2.0 (95% CI, 1.5-1.7) for CD4+ counts 200-500 cells/mm3, and 1.6 (95% CI, 0.9-2.8) for CD4+ counts >500 cells/mm3.

Conclusions: Although anergic HIV-seropositive women may become reactive, cutaneous anergy predicts a higher likelihood of anergy at retesting as well as lower CD4+ counts. Stability of anergy is greatest in HIV-seropositive women with low CD4+ counts.

Objectives: This study assessed the relation between year of recruitment into an AIDS prevention project and likelihood of engaging (yes/no) in injection risk behaviors.

Methods: In total, 834 injection drug users were recruited over a 44-month period (January 1992-August 1995) in New York City. Logistic regression was used to examine trends in three behaviors, across four successive annual cohorts: using needles/syringes that were previously used by another person, using injection supplies (e.g., cookers, cotton, rinse water) that had been previously used, and giving or lending of used needles/syringes to another person.

Results: Significant (p < .0001) decreasing trends occurred in two behaviors: giving or lending of used needles/syringes to another person and use of injection supplies that had been used by another person. Sample characteristics were generally consistent over time and did not obviate significant injection risk trends.

Conclusions: Decreasing trends in injection risk behaviors could not be explained by changing sample characteristics. Even though some injectors report engaging in risky injection practices, the confluence of numerous AIDS prevention efforts in the 1990s has contributed to an overall reduction in the likelihood of such behaviors.

Behavioral and social issues were investigated in phase I/II preventive HIV vaccine trial volunteers in Thailand. These included risk behavior, HIV knowledge, distress, and social experiences associated with trial participation. Data were collected at baseline and at 4- and 8-month follow-up visits. Volunteers reported relatively low levels of risk behaviors at baseline and at the follow-up visits. About one fifth reported overtly negative reactions from family or friends. No problems with discrimination in employment, health care, or insurance were reported. Findings add to the evidence suggesting the feasibility of phase I/II prophylactic HIV vaccine trials with low-risk volunteers in Thailand.

Antiviral agents are the primary therapy for patients infected with HIV-1. However, supportive therapies are often necessary in addition to antiviral drugs because of the devastating wasting process associated with HIV-1 infection and AIDS. Oxandrolone, an anabolic steroid, is used in promoting weight gain and, most important lean body mass (LBM), in patients with HIV-1 disease. We investigated whether oxandrolone interferes with the antiviral activity of zidovudine (ZDV), dideoxyinosine (ddI), and dideoxycytidine (ddC) on HIV-1 replication in peripheral blood lymphocytes and macrophage-monocytes. The nucleoside analogues had nanomolar 50% inhibitory concentrations (IC50) in peripheral lymphocytes. Combinations of nucleoside analogues and oxandrolone did not result in increased IC50 values. Oxandrolone used alone exhibited micromolar IC50 values in peripheral blood lymphocytes. Lack of interference was consistent for nucleoside concentrations up to 5 microM and for oxandrolone concentrations up to 100 microM in several combinations of drugs, viral strains, and peripheral lymphocytes and macrophages. We conclude that oxandrolone can be used for the promotion of weight gain in patients with AIDS-related wasting without interference with the antiviral effects of ZDV, ddI, or ddC.

Background: A growing proportion of AIDS cases in the United States are due to heterosexual transmission of HIV, particularly in women. The risk of heterosexually acquired HIV was prospectively studied in a cohort of inner-city women with no history of parenteral drug use.

Methods: Study participants were evaluated at 6-month intervals for the presence of HIV antibody, sexually transmitted diseases, self-reported sexual behavior, and drug use by self-report and urine screening.

Results: Of 449 initially HIV-negative women who were seen at least once in follow-up, 4 seroconverted to HIV, with a cumulative incidence of 2.4% at 30 months. Risk factors for HIV seroconversion included nonparenteral drug use (p < .02) and anal intercourse (p < .01). Sexually transmitted diseases were not associated with HIV, although the power to detect such an association was limited. In addition, 3 of 4 seroconverters became pregnant, yielding a rate of 55.5 pregnancies/100 person-years of follow-up compared with a rate of 11.1 pregnancies/100 person-years of follow-up in nonseroconverters (p < .03).

Conclusion: The incident rate of heterosexually acquired HIV in this inner-city U.S. cohort of women who were not using parenteral drugs is comparable with that reported in some developing countries where heterosexually acquired HIV is endemic. Most seroconversions appeared related to risk behavior seen in association with nonparenteral drug use. The previously unreported association of incident HIV infection with pregnancy in this cohort may be related to either behavioral or biologic factors.

Hepatitis C virus (HCV) has been associated with various lymphoproliferative disorders, and a high prevalence (9%-32%) of chronic HCV infection has been demonstrated among patients with lymphoma. Dual coinfection by HIV and HCV has been demonstrated in approximately 40% of certain populations of HIV-infected individuals. Because of this high prevalence of coinfection by HIV and HCV, the known relations between HCV and lymphoproliferative disorders, and the association of HIV and B cell lymphoma, the potential association between chronic HCV and the development of AIDS-related lymphoma was examined. The prevalence of HCV infection in HIV-infected patients with lymphoma was compared with that in patients with AIDS, diagnosed on the basis of an illness other than lymphoma. Risk factors for HCV infection, overall, were also evaluated. Evidence of HCV infection was ascertained by assessing anti-HCV antibodies, and HCV RNA in serum. The study consisted of 99 homosexual/bisexual men with AIDS-related lymphoma, and 43 other AIDS patients. HCV infection was detected in 11 of 99 (11.1 %) men with lymphoma, and in 5 of 43 (11.6%) other AIDS patients. Further, in patients with AIDS-related lymphoma, no relation was found between HCV infection and lymphoma histology or site. History of use of injected illicit drugs was associated with a significantly elevated risk of HCV infection in the combined group of lymphoma and other AIDS patients. The current study demonstrates no relation between dual infection by HIV and HCV and subsequent increased risk of lymphoma.

Objective: To assess the association of squamous intraepithelial lesions (SIL) on cervicovaginal Papanicolaou (Pap) smear among women infected with HIV-1 and their pregnancy status, and historical and clinical factors.

Methods: Study enrollment Pap smears of 452 pregnant and 126 nonpregnant HIV-infected women had cytologic evaluation. The rates of SIL were compared with pregnancy status, immunosuppression, presence of sexually transmitted diseases (STDs) and demographic features.

Results: Rates of low grade SIL were similar for pregnant and nonpregnant HIV-1-infected women (17% and 23.8%, respectively; p = .09). Of them, 12 women, 9 pregnant and 3 nonpregnant, had high grade SIL. None had invasive cervical cancer. Low CD4 percentage (odds ratio, [OR] = 3.8; 95% confidence interval [CI], 2.0-7.3) and inflammation (OR = 2.8; 95% CI, 1.8-4.3) were associated with SIL. An association between herpes simplex and SIL (OR = 3.3; 95% CI, 1.1-9.5) was less certain due to clinical diagnosis and low prevalence of herpes simplex (17 of 456 women).

Conclusions: Pap smears for a cohort of HIV-infected pregnant and nonpregnant women revealed a high prevalence of LGSIL but a low prevalence of HGSIL and no cases of cervical cancer. Although pregnancy may not affect the rate of Pap smear abnormalities, SIL is associated with immunosuppression, cervical inflammation, and herpes simplex. Closer surveillance of HIV-1-infected women with these risk factors may be warranted.

Early in the history of the AIDS epidemic there was clear evidence of differences in the outcomes of HIV infection between injecting drug users and men who have sex with men. There were also some indications that high levels of nonsterile drug injection may increase the progression of HIV infection. Recent epidemiologic studies indicate no differences in rates of progression to AIDS among drug injectors, men who have sex with men, or persons infected through heterosexual contact. In vitro and animal studies suggest that the effects of different psychoactive drugs on HIV infection may be negative, positive, or mixed, and that the effects of a psychoactive drug on immune functioning may differ among acute administration, chronic administration, or cessation of chronic administration. Although the current epidemiologic data do not provide support for the hypothesis that psychoactive drug use will have any important effects on the course of HIV infection, possible interactions between psychoactive drugs and antiviral medications and medication adherence issues among drug users are important areas for AIDS research. Relations between psychoactive drug use, the nervous system, and the immune system are a promising area for basic research.