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

The seroprevalence of HIV-1 in sub-Saharan African patients with diarrhea in the community remains largely unknown. We present the findings of a 2-month study that we undertook to ascertain the seroprevalence of HIV-1 in Zambian patients presenting with acute diarrhea in a community-based health center. A total of 256 patients with diarrhea and 140 apparently healthy controls was seen. Of the patients with diarrhea, 161 were < 16 years old and 95 were adults. Most children with diarrhea were < 6 years old (147 of 161; 91%). Overall, 81 of 256 (32%) patients with diarrhea were HIV-1-seropositive. When results from children < 18 months old and possibly having maternal anti-HIV-1 antibodies were excluded, 64 of 172 (37%) patients with diarrhea were HIV-seropositive. Rates of HIV-1 seropositivity for patients with diarrhea were significantly higher than were rates for diarrhea-free controls (p < .001 for both the total population; odds ratio [OR], 95% confidence interval [CI], 1.42 < 2.48 < 4.35) and population > 18 months old (OR, 95% CI, 1.54 < 2.90 < 5.49). Among children between 18 months and 5 years old, 14 of 63 (22%) were HIV-1-seropositive compared with 8 of 62 (13%) without diarrhea (p > .05, not significant). Moreover, 49 of 95 (52%) adults with acute diarrhea were HIV-1-seropositive compared with 10 of 44 (23%) healthy adult controls (p < .003; OR, 95% CI, 1.51 < 3.62 < 8.87). No significant differences were found in HIV-1 seroprevalence rates between males and females in all age groups. These data show a close association between acute diarrhea and HIV seropositivity in Zambian adults in the community.

We evaluated factors affecting the feasibility of including young high-risk HIV-negative gay and bisexual men in preventive HIV vaccine trials using data from the U.S. Centers for Disease Control and Prevention Collaborative HIV Seroincidence Study. Of 2189 men enrolled in this study, 17% were <25 years of age. HIV seroincidence was 4.2/100 person-years (95% confidence interval [CI], 2.6-7.0) in young men compared with 2.0/100 person-years (95% CI, 1.4-2.6) for older men. Compared with men 25 and older, young men were more likely to report several high-risk behaviors, to perceive themselves to be at risk for HIV infection, and to report that their risk behavior might be increased by participation in an HIV vaccine trial. The majority of both young men (69%) and older men (74%) expressed willingness in participate in HIV vaccine trials. Young men were less likely to answer questions about vaccine concepts correctly and were more likely to be lost to follow-up. Young gay and bisexual men are important candidates for future HIV vaccine trials, but they may need targeted approaches to recruitment, retention, education about trial concepts prior to enrollment, and behavioral interventions during the trial.

Objective: To characterize the impact of combination antiretroviral therapy on the clinical and laboratory features of mycobacterial lymphadenitis, we conducted a retrospective chart review of HIV-related mycobacterial lymphadenitis at St. Paul's hospital between 1989 and 1997. Among 52 evaluable patients, 12 presented within 12 weeks of initiating combination antiretroviral therapy (group 1, n = 12); the others developed lesions while receiving no antiretrovirals, monotherapy, or a stable combination regimen of >12 weeks duration (group 2, n = 40).

Results: Group 1 patients had higher absolute CD4 lymphocyte counts (median, 150 versus 20 cells/mm3, respectively; p = .001) and hemoglobin levels (median, 113 versus 88 g/L, respectively; p = .002) at the time of mycobacterial diagnosis. Clinical comparison showed that group 1 patients were more likely to develop a draining sinus (50% versus 0%; p < .001), but less often to have weight loss (17% versus 74%; p < .0001) or disease which was disseminated (25% versus 70%; p = .04) or caused by Mycobacterium tuberculosis (0% versus 33%; p = .04).

Conclusions: Mycobacterial lymphadenitis developing within 12 weeks of initiating combination antiretroviral therapy is often localized Mycobacterium avium complex disease, associated with a relatively high CD4 count. The clinical course is often complicated by the development of a draining sinus. The close temporal association suggests that such treatment may unmask subclinical infection by enhancing the immune response to mycobacterial antigens.

We compared the performance of HIV-1 RNA and models based on human leukocyte antigen (HLA) in predicting the rate of HIV-1 disease progression using both linear regression and neural network models across two different cohorts of homosexual men. In all, 139 seroconverters from the Multicenter AIDS Cohort Study were used as the training set and 97 seroconverters from the District of Columbia Gay (DCG) cohort were used for validation to assess the generalizability of trained predictive models. Both viral load and HLA markers were strongly predictive of disease progression (p < .0001 and p = .001, respectively), with viral load superior to HLA (change in -2 log likelihood [-2LL] 26.7 and 10.2, respectively, in proportional hazards models). Consideration of both HLA markers and viral load offered no significant predictive advantage over viral load alone in most cases; however, HLA-based predictions obtained from neural networks modeling improved the discrimination among patients with high viral load (p = .02). Viral load, HLA scores, and rapid disease progression were moderately correlated (p < .01 for all three pairs of these variables). The median viral load was 10(3.70) copies/ml among DCG patients who had more favorable than unfavorable HLA markers and 10(4.66) copies/ml among patients with more unfavorable than favorable HLA markers. Viral load is a simpler, stronger predictor of disease progression than early developed HLA models, but neural network methods and further refined HLA models may offer additional prognostic information, especially for rapid progressors. The correlation between viral load and HLA markers suggests a possible HLA effect on setting viral load levels.

To measure the effect of trimethoprim-sulfamethoxazole (TMP-SMX) in preventing bacterial illness, Pneumocystis carinii pneumonia (PCP), and death in people with AIDS, we conducted a retrospective medical record review of 1078 persons who were observed for 3 years on average who attended nine outpatient facilities in Seattle, Washington between January 1990 and April 1996. We calculated relative risk estimates to measure the protective effect of TMP-SMX on the development of major bacterial illnesses, PCP, and death. Use of TMP-SMX decreased the risk of PCP (relative risk [RR] = 0.23; 95% confidence interval [CI], 0.14-0.36) and deaths not attributable to PCP (RR = 0.59; 95% CI, 0.47-0.73). Prevention of major bacterial illnesses of known etiology was of borderline significance (RR = 0.77; 95% CI, 0.57-1.05) and became statistically significant with the addition of patients with infections of unknown etiology (RR = 0.77; 95% CI 0.61-0.97). Use of TMP-SMX PCP prophylaxis significantly reduced the risks of death and of PCP and was associated with a trend toward reduced risk of major bacterial infections.

From January 1991 through September 1994, we observed people who were infected with HIV to assess the impact of enteric parasite-associated diarrhea. Respondents answered comprehensive questionnaires covering clinical and epidemiologic information and provided stool specimens monthly, which were examined unstained as well as stained with trichrome, chromotrope 2R, and with Kinyoun carbol-fuchsin, and with indirect immunofluorescence for Cryptosporidium. In all, 602 participants, who were interviewed, provided stool specimens at 3254 monthly visits. Parasites were associated with 50 of 354 (14.1%) acute diarrheal episodes (lasting < or = 28 days) and with 97 of 279 (34.8%) chronic episodes (lasting > 28 days). A parasite was associated with 31 of 222 (14.0%) episodes that occurred when CD4+ counts were > or = 200 cells/microl and with 150 of 566 (26.5%) episodes that occurred when CD4+ counts were < 200 cells/microl. The most commonly identified parasite was C. parvum, which was associated with 18 of 354 (5.1%) acute episodes and 36 (12.9%) of the 279 chronic episodes of diarrhea. In this patient population, enteric protozoan parasites were commonly associated with illness, particularly as immunosuppression worsened, and were more likely to be associated with chronic rather than acute diarrhea.

A phase II study was performed to evaluate the feasibility and activity of subcutaneous (SC) interleukin-2 (IL-2) administration plus zidovudine (ZDV) and didanosine (ddI) in patients with early stage HIV infection. Between October 1995 and October 1996, 12 patients completed 6 cycles of the following scheduled therapy: ZDV plus ddI and SC self-administration of 6 mIU of IL-2 at days 1 to 5 and 8 to 12 of a 28-day cycle for a total of 6 cycles (24 weeks). After 6 cycles, patients received only ZDV plus ddI and they were observed up for an additional 24 weeks. Our schedule was well tolerated as an outpatient regimen and led to a significant elevation in CD4 count, which lasted for 24 weeks after the end of IL-2 therapy. Moreover, CD4/CD25, as well as CD4/CD45RO and CD4/CD45RA, cell levels were significantly increased at the end of the therapy and remained significantly elevated after 24 weeks. During the 6 cycles, HIV-associated viremia was significantly decreased and, accordingly, we observed a significant decline of proviral DNA in peripheral blood mononuclear cells (PBMCs). During follow-up, 10 of 12 treated patients continued to show levels of HIV-related viremia <500 copies/ml. Our results demonstrated that IL-2 and ZDV plus ddI is a well tolerated and effective therapy for patients with HIV in early stages of the disease.