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

Condom failure (slippage or breakage) has been shown to be associated with HIV seroconversion among men who have sex with men (MSM), but predictors of failure have been poorly elucidated. Of 2592 HIV-seronegative MSM participants in the HIV Network for Prevention Trials (HIVNET) multisite Vaccine Preparedness Study who reported condom use for anal sex in the 6 months before enrollment, condom failure was reported by 16.6%, with failure rates of 2.1/100 episodes of condom usage (2.5 failures/100 episodes for receptive anal sex and 1.9/100 episodes for insertive anal sex). In separate multivariate models evaluating predictors of condom failure reported by the insertive and receptive partners, more frequent condom use was associated with a decreased per-condom failure rate and amphetamine and heavy alcohol use with increased rates in both models. Being employed, having private medical insurance, and using lubricants for >80% of anal sex acts were significantly associated with decreased failure rates in the insertive model. Safer sex counseling should particularly target men of lower socioeconomic status, promote proper and consistent use of condoms with appropriate lubricants, and address the impact of drug use, especially amphetamines and alcohol, on condom failure.

Persons attending sexually transmitted disease clinics at three sites in Thailand were recruited to participate in a 1-year study of HIV-1 incidence. Between September 1995 and February 1996, 31% (371 of 1205) of eligible men and 24% (161 of 659) of eligible women agreed to participate. At enrollment, HIV-1 seropositivity was 3.8% among men and 2.5% among women. Follow-up of the 514 participants who were seronegative at baseline was 78% at the 12-month visit. During the study period, 53% of men reported 2 or more sexual partners, 31% reported sex with a commercial sex worker (CSW), and 33% with a casual partner. Of those visiting CSWs, 72% reported consistent condom use. Among women, 11% reported 2 or more sexual partners. Decreased HIV risk behaviors among men were observed during the study. Four incident infections occurred in men (1.4/100 person-years, 95% confidence interval [CI] = 0.4-3.6) and none among women. Based on the observed HIV-1 incidence, HIV vaccine efficacy trials in such populations would have to be larger than previously planned or more selective of high risk subgroups for recruitment.

Objective: To determine the independent contribution of specific nutritional factors on disease progression and survival in HIV-1-infected children.

Population: HIV-infected children (N = 24), who were perinatally exposed to the virus and symptomatic, were recruited between October and December of 1990 from the Jackson Memorial Pediatric Immunology Clinic, Miami, Florida, and observed for 5 years.

Methods: Immune status was measured by CD4 cell count; nutritional status was determined using serum albumin and plasma trace elements including iron, zinc, and selenium. Cox proportional hazards regression models were used to evaluate the relationship of these parameters to survival. Use of antiretroviral treatment was considered in the statistical model, and age at death was considered a parameter of disease progression.

Results: Over the course of the study, 12 children died of HIV-related causes. The final Cox multivariate analysis indicated that, of the variables evaluated, only CD4 cell count below 200 (risk ratio [RR] = 7.05; 95% confidence interval [CI], 1.87-26.5); p = .004], and low levels of plasma selenium (RR = 5.96; 95% CI, 1.32-26.81; p = .02) were significantly and independently related to mortality. Among the children who died, those with low selenium levels (< or =85 microg/L), died at a younger age, suggesting more rapid disease progression.

Conclusions: In pediatric HIV-infection, low plasma level of selenium is an independent predictor of mortality, and appears to be associated with faster disease progression.

Immune cell death or dysfunction is induced by HIV infection and results in an immunocompromised state. Newer treatments are able to control viral replication to prevent massive cytoreduction. Attention must now focus on therapies that will rapidly reconstitute the immune system to provide defense against future HIV attacks as well as opportunistic infections. In addition to increasing the rate of differentiation of myeloid and lymphoid precursors from marrow stem cells, ideal therapies should improve thymic function as well. Growth hormone (GH), a member of the hematopoietic cytokine superfamily and its receptors, is expressed in multiple sites within the immune system. GH has been shown to have a stimulatory effect on the function of thymic cells, as well as other immune cell types. In this paper, we consider the use of GH to reconstitute the immune system following cytoreduction due to HIV infection.

To investigate the genetic and biologic features of HIV-1 strains circulating in Cambodia, viruses from 95 HIV-1-seropositive individuals were subtyped by heteroduplex mobility assay (HMA) and 23 were further analyzed for their biologic characteristics. Eighty-nine individuals were clearly infected by HIV-1 subtype E. The other six samples were sequenced, together with 17 HMA subtype E samples. All but one of the 23 Cambodian env sequences clustered with previously described Thai and Vietnamese subtype E sequences, bearing a GPGQ motif at the tip of the V3 loop; the last had a GPGR motif and was phylogenetically equidistant from Asian and African subtype E viruses. Nonsyncytium-inducing, CCR5-dependent viruses predominated in patients of clinical stage B even in some with a high viral load and were detected in about 50% of the patients of stage C. All syncytium-inducing strains, mostly from AIDS patients, used both CCR5 and CXCR4. The presence of syncytium-inducing viruses did not correlate with the plasma viral load. These data show that CCR5-dependent HIV-1 subtype E is currently predominant in Cambodia. The analysis of clinical and virologic markers strongly supports the idea that dynamics of the viral population during subtype E infection in Southeast Asia is similar to that of subtype B infection in Europe and the United States.

HIV-1-infected children have higher plasma viral loads and progress to disease more quickly than infected adults. To gain insight into the accelerated pathogenesis of HIV-1 in children, viral dynamics were measured following the initiation of highly active antiretroviral therapy (HAART) and compared with those reported for adults. A biphasic decline in plasma HIV-1 RNA was observed, with a rapid decrease during the first 1 to 2 weeks of therapy (phase I) followed by a slower decline (phase II). The phase I and II decay rates were not significantly different among children of different ages, pretherapy plasma HIV-1 RNA levels, or CD4 cell counts. Estimated phase I decay rates were similar to those previously reported in adults with a mean of 0.43 days(-1) and a half-life of 1.6 days. The phase II decay rates were slower in children compared with adults with a mean of 0.016 days(-1) versus 0.066 days(-1), and a half-life of 43.3 versus 14.1 days, respectively (p < .05). The mean time required to reach viral levels below detection thresholds was also longer in these children compared with that in adults. These data suggest that HIV-1 dynamics may be different in children, and that these differences may necessitate different treatment strategies.

Objective: To describe the epidemiologic and clinical features of AIDS-associated Kaposi's sarcoma (KS) in women compared with men.

Methods: In a retrospective study, within the Italian Cooperative Group on AIDS and Tumors (GICAT), we compared selected characteristics of 54 women and 108 men with AIDS-associated KS, matched by date of KS diagnosis and referral hospital. The chi2 test was used to test differences among proportions; the Kaplan-Meier method to estimate the survival time, and the Cox proportional hazard model was used to assess the role of gender, age, and CD4 cell count on death's risk.

Results: KS occurred at an earlier age (p = .001), was associated with a more severe immunodeficiency (p = .03), more advanced stages of HIV disease (p = .05), and had more aggressive presentation and course in women than in men. At KS diagnosis, women had a significantly increased proportion of visceral disease (p = .009), in particular pulmonary involvement (p = .002) and atypical sites of involvement (p = .008). The number of deaths due to KS was significantly higher (p = .01) in female patients. Both the higher proportion of visceral disease and of KS-related deaths observed in women did not change after adjusting for CD4 cell count and age. Women showed a decreased overall survival compared with men (8.9 and 14.4 months, respectively; p = .07), and the CD4 cell count at diagnosis significantly influenced survival.

Conclusions: This study suggests that KS is more aggressive and life threatening in female than in male patients. This peculiar clinical behavior may reflect an inherently more aggressive biology of KS in women, possibly mediated by the level of immunodeficiency.

Background: Foscarnet is an antiviral agent commonly used for managing patients with cytomegalovirus infection. Despite its clinical usefulness, foscarnet is associated with substantial adverse effects including nephrotoxicity. Moreover, foscarnet is primarily eliminated unchanged through the kidneys, thus requiring aggressive dose adjustment during kidney failure. To develop specific dosage guidelines, information on the disposition of this compound in patients with varying degrees of renal function and those requiring dialysis is essential.

Design: Twenty-six subjects were enrolled in this study and divided into five groups depending on their degree of renal dysfunction. Group 1 included subjects with normal renal function; group 5 included subjects requiring maintenance hemodialysis. Nondialysis study subjects received a single 60-mg/kg intravenous dose of foscarnet whereas hemodialysis subjects received two intravenous doses, separated by 1 week, to compare the effects of conventional and high-flux dialysis methods.

Results: Mean plasma clearance in control subjects averaged 2.1+/-0.7 ml/minute/kg and declined proportionally with changing renal function as indicated by the regression equation: Clp (ml/minute/kg) = 1.48 [CrCl (ml/minute/kg)]-0.08 (r2 = 0.82). Mean half-life averaged 1.9+/-0.1 hours in normal subjects and increased to a mean of 25+/-19 hours in study subjects with severe impairment not on dialysis. Foscarnet dialysis clearance (based on dialysate recovery) averaged 183 ml/minute with conventional dialysis methods and 253 ml/minute during high-flux procedures, which resulted in removal of 37% and 38% of a dose for the two methods, respectively.

Conclusions: These data indicate that substantial dosage adjustments must be made in renal failure patients. Therefore, a patient-specific dosage nomogram has been developed.

We examined sexual behavior as a risk factor for Kaposi's sarcoma-associated herpesvirus (KSHV) infection and examined the relation between KSHV seropositivity and development of KS in cross-sectional and cohort studies of 130 homosexual men diagnosed with AIDS in Sydney, Australia during the period from 1991 to 1993. KSHV serology was measured using antibody tests to latency-associated nuclear antigen (LANA) and lytically expressed open reading frame (ORF) 65.2. In the cross-sectional analysis, 52% (68) of study subjects were KSHV-seropositive by either assay. KSHV-seropositive men were significantly more likely to be seropositive to both herpes simplex type 2 (odds ratio [OR] 3.0; 95% confidence interval [CI], 1.2-7.5 for LANA and OR 2.8; 95% CI, 1.3-6.0 for ORF 65) and hepatitis A virus (OR 2.2; 95% CI, 1.1-4.5 for ORF 65). KSHV-seropositive men reported nonsignificantly more casual sexual partners and were nonsignificantly more likely to report insertive oroanal contact with casual partners. These data suggest that KSHV might be sexually transmitted among homosexual men. Men were observed until October 1996 for development of KS. Those seropositive to either KSHV assay at baseline were more likely than the seronegative to develop KS during follow-up (rate ratio [RR] 4.4; 95% CI, 1.9-10.2). Of those seropositive for KSHV, 53% developed KS.