摘要:

Tenofovir has been shown to cross the placenta in quantities sufficient to sustain reductions in viral load in simian immunodeficiency virus (SIV)–infected fetal monkeys. With chronic exposure (30 mg/kg), however, significant bone-related toxicity has been shown in ∼25% of infants studied. Further investigations were conducted to determine whether the bone-related toxicity observed was initiated during fetal life. Gravid rhesus monkeys (n= 4) were administered tenofovir subcutaneously once daily from 20 to 150 days of gestation (30 mg/kg; term: 165 ± 10 days). Fetuses were monitored sonographically, and maternal and fetal blood and urine samples were collected to assess hematologic parameters, clinical chemistry, insulin-like growth factor (IGF) levels, and bone biomarkers. Fetuses were delivered by hysterotomy near term for necropsy and evaluation of bone-related mechanical properties. Results of these studies have shown 1) normal fetal development, although overall body weights and crown-rump lengths were less than those for age-matched controls (p≤ .03); 2) a significant reduction in circulating IGF-I (p< .001); 3) a small reduction in fetal bone porosity (p≤ .03); and 4) transient alterations in maternal body weights and bone-related biomarkers during the treatment period. The results of these studies suggest that chronic fetal exposure to tenofovir at the maternal dose of 30 mg/kg throughout gestation can alter select fetal parameters and transiently affect maternal bone biomarkers.

ISSN:1525-4135    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The effect of intermittent courses of recombinant interleukin-2 (rIL-2) on HIV-1 load in patients receiving combination antiretroviral therapy remains uncertain. CPCRA 059 was an open-label, randomized, multicenter trial in which 511 patients with HIV-1 infection and CD4+cell counts of ≥300/mm3who were receiving antiretroviral therapy were assigned to receive no rIL-2 (255 patients [controls]) or subcutaneous rIL-2 in dosages of 4.5 MIU (130) or 7.5 MIU (126) twice daily for 5-day courses every 8 weeks to maintain CD4+cell counts that were twice the baseline value or ≥1,000/mm3. The primary objective of this study was to compare the effects of the two doses of rIL-2 and no rIL-2 on viral load and CD4+cell counts over 12 months. There was no difference in the following viral load measurements between the rIL-2 treatment groups and the control treatment group: percentage of patients with viral loads of <50 copies/mL at 12 months (p= .55), time to viral load of ≥50 copies/mL for patients who had baseline viral loads of <50 copies/mL (p= .35), and change in viral load from baseline for patients who had viral loads of ≥50 copies/mL at baseline (p= .63). At each follow-up visit, the change in CD4+cell count from baseline was significantly greater in the rIL-2 treatment groups than in the control treatment group, with a mean difference of 251/mm3at month 12 (95% confidence interval, 207–295;p< .0001). No unanticipated adverse experiences were seen in this trial, to our knowledge the largest randomized evaluation of rIL-2 treatment conducted to date.

ISSN:1525-4135    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Most HIV-1 transmission studies use self-reported history to define the source contact. To evaluate the reliability of epidemiologic source partner reporting, heteroduplex mobility assays (HMAs) were performed comparing the different viral strains present in the partners. Partners were typed for human leukocyte antigen (HLA) to evaluate the degree of shared alleles. Of 11 couples evaluated, HMA analysis confirmed nine transmissions (including 1 oral-genital transmission), indicated probable transmission in 1 couple, and suggested an alternative source partner in another. Nine source partners transmitted a major variant. Four source partners knew their HIV status. Previous HIV monitoring was reported by 5 of the 6 confirmed source partners who were unaware of their HIV status at the time of transmission. We also evaluated potential “sharing of HLA alleles” as a risk factor for HIV-1 acquisition; partners were not found to have a higher degree of shared HLA alleles. Lack of awareness about infection status as a consequence of infrequent testing plays a major role in the secondary transmission of HIV. These findings re-emphasize the importance of using safe sex practices at all times.

ISSN:1525-4135    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

We assessed the impact of an efavirenz-containing regimen versus a protease inhibitor–containing regimen on quality of life, emotional status, and adherence of HIV-1–infected patients. In addition, we sought to define the adverse events associated with these treatments, with a special focus on central nervous system disorders in the efavirenz treatment group. This prospective, randomized, two-arm, controlled study included 100 patients for whom initial treatment with a protease inhibitor–containing regimen failed. Patients were randomized to start treatment with two nucleoside retrotranscriptase inhibitors plus efavirenz (group 1; 51 patients) or two nucleoside retrotranscriptase inhibitors plus one or more new protease inhibitors (group 2; 49 patients). Quality of life was assessed by a five-point item adapted from the HIV questionnaire of the Medical Outcomes Study, emotional status was evaluated by the Profile of Mood State questionnaire, and patients self-reported adherence. Data were analyzed by both an as-treated method and an intention-to-treat–last observation carried forward method. Patients in group 1 reported the following findings at week 4: dizziness (66%), abnormal dreaming (48%), light-headedness (37%), and difficulty sleeping (35%). At week 24, dizziness (13%;p< .001), abnormal dreaming (18%;p= .002), light-headedness (13%;p= .01), difficulty sleeping (7%;p= .001), and nervousness (13%;p= .01) decreased in these patients. Irritability, abnormal dreaming, and nervousness persisted at week 48 in 13%, 10%, and 8% of group 1 patients, respectively. Patients in group 2 reported the following findings at week 4: light-headedness (8%), dizziness (5%), difficulty sleeping (4%), nervousness (4%), and headaches (3%). Patients in group 2 reported the following findings at week 48: difficulty sleeping (4%), nervousness (3%), headaches (3%), and light-headedness (2%). In group 1, quality of life (p< .001) and emotional status (week 48;p= .004) improved, both of which were better than those in group 2 (p= .001). Both groups maintained high levels of medication adherence, and no significant differences in the number of patients who had viral loads of <200 copies/mL at week 48 were found (78% of group 1 patients vs. 85% of group 2 patients;p= not significant). At week 48, the mean CD4 cell count ± SD was 497 ± 224/mm3in group 1 and 539 ± 298/mm3in group 2 (p= not significant). Despite similar immunologic and virologic outcomes, a second-line efavirenz-containing regimen improved quality of life of HIV-1–infected patients compared with a second-line protease inhibitor–containing regimen. However, close follow-up of patients receiving treatment with efavirenz-based regimens is recommended, especially for those with previous emotional disturbances due to central nervous system disorders in the short term and those with persistence of a low percentage of these disorders in the long term.

ISSN:1525-4135    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

To test the safety and immunogenicity of a high-titered preparation of ALVAC-HIV vCP205 in both high-risk and low-risk persons and to evaluate variations in dosing schedule, we conducted a multicenter, randomized, double-blind trial of this vector in combination with recombinant subunit gp120 in 150 HIV-1–seronegative volunteers. The high-titered ALVAC vaccine was well tolerated; adverse events were minimal and not influenced by dosing. At day 728, the cumulative probability of a cytotoxic T-lymphocyte (CTL) response was 76% (95% confidence interval [CI]: 64%–89%) among volunteers receiving vaccine, and the net amount attributable to vaccination was 50% (CI: 16%; 74%). The net probability of a repeated positive CTL response by day 728 was 50% (CI: 21%; 64%). There was a significant difference in CTL response at day 182 between volunteers who had received four doses versus three doses of vCP205 (42% vs. 24%,p= .052). The CTL response was similar in high-risk volunteers and vaccinia-naive volunteers compared with vaccinia-immune volunteers. Neutralizing antibody responses were detected in 95% of vaccinees at day 287, with higher geometric mean titers in recipients of sequential versus simultaneous dosing of the two vaccines and in vaccinia-naive volunteers. This high-titered preparation of ALVAC-HIV vCP205 in combination with gp120 was safe and immunogenic in a diverse group of HIV-1–seronegative volunteers.

ISSN:1525-4135    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The effect of placental membrane inflammation on mother-to-child transmission (MTCT) of HIV-1 is reported. Placentas from HIV-1–infected women were examined as part of a perinatal HIV-1 project in Mombasa, Kenya. Polymerase chain reaction analysis was used to test for HIV-1 in the infants at birth and at 6 weeks. The maternal HIV-1 seroprevalence was 13.3% (298 of 2,235). The overall rate of MTCT of HIV-1 was 25.4%; polymerase chain reaction analysis revealed that of the 201 infants 6.0% (12) were already HIV-1–positive at birth (intrauterine transmission) and 19.4% (39) were infected during the peripartum period or in early neonatal life (perinatal transmission). The prevalence of acute chorioamnionitis was 8.8%, that of deciduitis was 10.8%, and that of villitis was 1.6%. Acute chorioamnionitis was independently associated with peripartum HIV-1 transmission but not with in utero MTCT (17.9% vs. 6.7%, respectively; adjusted odds ratio, 3.9; 95% confidence interval, 1.2–12.5;p= .025). Other correlates of perinatal MTCT were presence of HIV in the genital tract and in the baby's oral cavity and a high maternal viral load in peripheral blood. The adjusted population attributable fraction of 12.8% (95% confidence interval, 1.5%–22.8%) indicated that approximately 3% of MTCT could be prevented if acute chorioamnionitis was eliminated. We suggest that further research on the role of antimicrobial treatment in the prevention of chorioamnionitis and the reduction of peripartum MTCT needs to be performed.

ISSN:1525-4135    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

HIV-1 viral load (VL) testing is a standard component of HIV care. We examined the use and predictors of VL testing in drug users, a group at risk for problematic care. Using 1996 to 1998 New York State (NYS) Medicaid files, we studied drug users who had been enrolled >10 months, had been prescribed antiretroviral agents in 1997 and 1998, and who had undergone any VL testing in 1997. Our outcome was regular VL testing shown by two or more paid claims for this test in 1998. Patterns of care in 1997 were defined as: regular source of medical care (>35% of visits to one provider), and/or regular drug treatment of >6 months, or neither. We counted visits in 1997 to a provider offering HIV-focused care. Adjusted odds ratios (AORs) of VL testing were assessed. Of 3131 drug users, 73.9% had at least one VL test, whereas 56.2% had two or more VL tests in 1998. The AORs of two or more VL tests were increased for those with regular drug abuse care alone (AOR, 1.50; 95% confidence interval [CI], 1.21–1.84) or with regular medical care (AOR, 1.27; 95% CI, 1.03–1.57) versus those with neither. HIV-focused care was positively associated with two or more VL tests (AOR, 1.38; 95% CI, 1.05–1.81 for 1–3 visits; AOR, 1.94; 95% CI, 1.50–2.51 for four or more visits). We found that nearly half this cohort of drug users did not have regular VL testing. Drug users with HIV-focused care or with regular drug treatment are more likely to have regular VL testing.

ISSN:1525-4135    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

We evaluated the association between HIV-1 RNA copies/mL in men and heterosexual transmission to their female partners among 493 couples in Thailand. Husbands were identified as HIV-positive when they were screened as blood donors; nearly all were infected with HIV subtype E. Wives had no known risks for HIV infection other than sex with their husbands. In multivariate analysis, each log10increment of HIV RNA in the man was associated with an 81% increased rate of HIV transmission to his wife (odds ratio = 1.81, 95% confidence interval: 1.33–2.48). No transmission occurred at viral loads below 1094 copies/mL, and a dose-response effect was seen with increasing viral load in the man. In multivariate analysis, a history of a sexually transmitted disease in the man or woman, longer duration of hormonal contraceptive use, and the woman's onset of sexual activity at less than 20 years of age were also associated with increased seropositivity of the wife.

ISSN:1525-4135    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

To determine the incidence of and risk factors for HIV-1 infection among married women in northern Thailand, we enrolled 779 seronegative women from family planning clinics and a postpartum ward in Chiang Rai, Thailand, from 1998 through 1999. Women were tested for HIV antibodies at 6 and 12 months after enrollment. They received HIV prevention counseling at enrollment and at each follow-up visit. Counseling covered partner communication, partner HIV testing, and condom use by steady partners. Effects of counseling were measured using standardized questionnaires. Follow-up rates were 94% at 6 months and 92% at 12 months. Only 1 woman seroconverted during the follow-up period, yielding an overall HIV incidence of 0.14 per 100 person-years. After receiving counseling, women reported significantly increased communication with husbands concerning HIV risk, HIV testing, and condom use during the first 6 months after enrollment; communication remained high for 6 to 12 months. Women reported a modest increase in HIV testing and consistent condom use by husbands. The risk for HIV transmission to women in steady relationships is low in northern Thailand. Although HIV prevention counseling promoted partner communication, its effects on HIV preventive behaviors were limited.

ISSN:1525-4135    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

High-risk sexual behavior by HIV-positive individuals is an important factor contributing to the spread of the HIV epidemic. We conducted a retrospective chart review to compare self-reported sexually transmitted disease (STD) risk behavior and clinic diagnoses of known HIV-positive clients attending Miami-Dade County STD clinics with those of uninfected controls. One hundred ninety-one HIV-positive clients and 191 HIV-negative controls, 130 (68.1%) men and 61 (31.9%) women, were included in the analysis. HIV-positive clients were more likely than controls to report no sexual activity in the last 2 months (odds ratio [OR] = 2.6, 95% confidence interval [CI]: 1.5–4.5) or, if active, to report condom use at last sexual intercourse (OR = 3.1, CI: 1.9–5.3). However, HIV-positive clients were more likely to be diagnosed with infectious syphilis (OR = 13.0, CI: 1.6–99.4) and/or gonorrhea (OR = 2.1, CI: 1.1–4.2) than controls. This may be a result of overreporting of condom use or sexual activity in high-risk sexual networks with inefficient use of condoms. Ongoing sexual risk behavior and access to HIV primary care are important issues in this population.

ISSN:1525-4135    

出版商:OVID    

年代:2002

数据来源: OVID