ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo determine the influences on pediatric AIDS of a heterozygous 32 base pair deletion in the CC-chemokine receptor 5 gene (CCR5 wt/Δ32) and a common polymorphism in the 3′ untranslated region of stromal cell-derived factor-1β gene transcript (SDF1-3′A).DesignThe rate of HIV-1 disease progression and viral burden were compared according to the CCR5 and SDF-1 genotypes in 127 (58 Caucasians, 60 African-Americans and nine Hispanics) perinatally HIV-1-infected children.ResultsRegardless of ethnic background, the CCR5 wt/Δ32 genotype was associated with a delayed onset of AIDS-defining infectious complications during the first 5 years of infection [relative hazard (RH) = 0.22; 95% confidence interval (CI), 0.012–1.02; P = 0.053]. Similarly, CCR5 wt/Δ32 conferred an early protection against severe immune suppression and HIV-1 encephalopathy, but only in those without SDF1-3′A (RH = 0; 95% CI, 0–0.70; P = 0.020, and RH = 0; 95% CI, 0–0.71; P = 0.021, respectively). When examined before 5 years of age (n = 81), the children with CCR5 wt/Δ32 had significantly lower levels of cell-associated HIV-1 DNA than wild-type homozygotes (P = 0.016, adjusted by race), while SDF1-3′A carriers had relatively higher levels (P = 0.047, adjusted by race). Although the disease-retarding effect of CCR5 wt/Δ32 subsequently disappeared, time to death was still significantly delayed in the CCR5 Δ32 heterozygotes without SDF1-3′A (RH = 0; 95% CI, 0–0.53; P = 0.008).ConclusionIn pediatric AIDS, the protective effect of CCR5 wt/Δ32 is more pronounced in early years of infection and appears to be abrogated by the SDF1-3′A genotype.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

BackgroundThe multidrug transporters P-glycoprotein (P-gp) and MRP1 are functionally expressed in several subclasses of lymphocytes. HIV-1 protease inhibitors interact with both; consequently the transporters could reduce the local concentration of HIV-1 protease inhibitors and, thus, influence the selection of viral mutants.ObjectivesTo study the effect of the expression of P-gp and MRP1 on the transport and accumulation of HIV-1 protease inhibitors in human lymphocytes and to study the effects of specific P-gp and MRP1 inhibitors.MethodsThe initial rate and the steady-state intracellular accumulation of radiolabelled ritonavir, indinavir, saquinavir and nelfinavir was measured in three human lymphocyte cell lines: control CEM cells, CEM-MDR cells, which express 30-fold more P-gp than CEM cells, and CEM-MRP cells, which express fivefold more MRP1 protein than CEM cells. The effect of specific inhibitors of P-gp (GF 120918) and MRP1 (MK 571) was also examined.ResultsCompared with CEM cells, the initial rates of uptake and the steady-state intracellular concentrations of all protease inhibitors are significantly reduced in CEM-MDR cells. The intracellular concentrations of the protease inhibitors are increased upon co-administration with GF 120918, in some cases to levels approaching those in CEM cells. The intracellular concentrations of the protease inhibitors are also significantly reduced in CEM-MRP cells. Co-administration with MK -571 can partially overcome these effects.ConclusionsThe overexpression of multidrug transporters significantly reduces the accumulation of protease inhibitors at this major site of virus replication, which, potentially, could accelerate the acquisition of viral resistance. Targeted inhibition of P-gp may represent an important strategy by which this problem can be overcome.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo study the kinetics of HIV-1 RNA and drug-induced mutations after cessation of antiretroviral therapy (ART).Design and methodsSuccessive plasma samples from 26 patients were tested for HIV-1 RNA by PCR and for mutations associated with drug resistance by sequencing of thepolgene.ResultsAfter cessation of ART the phase of undetectable virus (< 50 copies/ml), ranging from 6 to more than 29 days, was followed by a rapid viral increase, which slowed down before a plateau corresponding to pre-treatment levels or higher was reached in most cases (14/19 patients). In one patient virus was still undetectable at 4 weeks. Also, a significantly larger number of primary protease inhibitor (PI)-associated mutations reverted to wild-type, as compared with secondary PI-, and primary reverse transcriptase inhibitor (RTI)-associated mutations. During the rapid viral increase no mutations disappeared, which instead happened during the slower viral increase preceding the viral plateau level.ConclusionAfter discontinuation of ART large individual variations were found for the time period until HIV-1 became detectable in plasma, possibly due to differences in the HIV-1 specific immunity. The more rapid loss of primary PI mutations suggests that they might cause a more impaired viral fitness than primary RTI mutations. However, the persistence of drug mutations during the initial viral load increase indicates that mutated strains may still replicate efficiently.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

AimTo estimate the effectiveness of triple combination therapy in antiretroviral-naive adults.MethodsA systematic overview of results from clinical trials involving triple combination therapy with dual nucleoside reverse transcriptase inhibitors (NRTI) and: a protease inhibitor (PI triple); a non-nucleoside reverse transcriptase inhibitor (NNRTI triple); or a third NRTI (triple NUC). Data from 23 clinical trials involving 31 independent treatment groups, 19 unique antiretroviral regimens, and 3257 enrolled patients were included in this study.ResultsMedian log10baseline plasma HIV RNA and CD4 cell count over all trials averaged 4.69 (49 329 copies/ml) and 375 × 106cells/l, respectively. The overall estimated percentage of patients with plasma HIV RNA ⩽ 400 copies/ml at 24 weeks was 64% [95% confidence interval (CI), 60 to 67%]. The percentages of patients with plasma HIV RNA ⩽ 50 copies/ml at 48 weeks by drug class were: PI triple, 46% (95% CI, 41 to 52%); NNRTI triple, 51% (95% CI, 43 to 59%); triple NUC, 45% (95% CI, 36 to 54%). The CD4 cell count increase over all trials at 24 and 48 weeks averaged +123 × 106cells/l (95% CI, 111 × 106to 135 × 106cells/l) and +160 × 106cells/l (95% CI, 146 × 106to 175 × 106cells/l), respectively and did not differ between drug classes. In multivariable regression analysis, neither baseline plasma HIV RNA level and CD4 cell count nor treatment regimen predicted plasma HIV RNA ⩽ 50 copies/ml at week 48. However, pill count was significantly negatively associated with plasma HIV RNA ⩽ 50 copies/ml at week 48 (P =0.0085).ConclusionsThe results suggest that three drug regimens containing two NRTI with a PI, a NNRTI, or a third NRTI may provide comparable activity, and practical issues such as daily pill burden should be considered when choosing a treatment regimen.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

BackgroundVirologic rebound can result from suboptimal antiviral potency in combination antiretroviral therapy.DesignMulticenter, partially blinded, prospective, randomized study of 202 HIV-infected subjects to determine whether therapy intensification improves long-term rates of virologic suppression.MethodsSubjects had plasma HIV RNA < 200 copies/ml, CD4 cell count of > 200 × 106cells/l, and treatment with indinavir (IDV) + zidovudine (ZDV) + lamivudine (3TC) for at least 6 months before randomization to stay on this regimen or to receive IDV + didanosine (ddI) + stavudine (d4T) plus or minus hydroxyurea (HU) (600 mg twice daily). Treatment failure was defined as either confirmed rebound of HIV RNA level to > 200 copies/ml or a drug toxicity necessitating treatment discontinuation.ResultsTreatment failure occurred more frequently in subjects randomized to the HU-containing arm (32.4%), than in those taking IDV + ddI + d4T (17.6%) or IDV + ZDV + 3TC (7.6%). The time to treatment failure was shorter for the HU-containing arm compared with the IDV + ZDV + 3TC (P< 0.0001) or IDV + ddI + d4T arms (P= 0.032). Dose-limiting toxicities rather than virologic rebound accounted for the differences between treatment failure among the study arms. Pancreatitis led to treatment discontinuation in 4% of subjects in treatment arms containing ddI + d4T. Three subjects with pancreatitis died, all randomized to the HU-containing arm.ConclusionsSwitching to IDV + ddI + d4T + HU in patients treated with IDV + ZDV + 3TC was associated with a worse outcome, principally because of drug toxicity.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo identify clinical factors associated with prevalence of fat atrophy (lipoatrophy) and fat accumulation (lipoaccumulation) in HIV-1 infected patients.DesignEvaluation of HIV-1 infected patients seen for routine care between 1 October and 31 December 1998 in the eight HIV Outpatient Study (HOPS) clinics.SettingEight clinics specializing in the care of HIV-1 infected patients.PatientsA total of 1077 patients were evaluated for signs of fat maldistribution.InterventionsA standardized set of questions and specific clinical signs were assessed. Demographic, clinical and pharmacological data for each patient were also included in the analysis.Main outcome measuresDemographic, immunologic, virologic, clinical, laboratory, and drug treatment factors were assessed in stratified and multivariate analyses for their relationship to the presence and severity of fat accumulation and atrophy.ResultsIndependent factors for moderate/severe lipoatrophy for 171 patients were increasing age, any use of stavudine, use of indinavir for longer than 2 years, body mass index (BMI) loss, and measures of duration and severity of HIV disease. Independent risk factors for moderate/severe fat accumulation for 104 patients were increasing age, BMI gain, measures of amount and duration of immune recovery, and duration of antiretroviral therapy (ART). The number of non-drug risk factors substantially increased the likelihood of lipoatrophy. If non-drug risk factors were absent, lipoatrophy was unusual regardless of the duration of drug use.ConclusionsHIV-associated lipodystrophy is associated with several host, disease, and drug factors. While prevalence of lipoatrophy increased with the use of stavudine and indinavir, and lipoaccumulation was associated with duration of ART, other non-drug factors were strongly associated with both fat atrophy and accumulation.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

BackgroundRates of condom use in sub-Saharan Africa have remained too low to curb HIV/sexually transmitted disease (STD) epidemics. A better understanding of the main determinants of condom use would aid promotion.MethodsCross-sectional population surveys were conducted in four cities in sub-Saharan Africa: Yaoundé, Cameroon; Cotonou, Benin; Ndola, Zambia; and Kisumu, Kenya. In each city, the aim was to interview a random sample of 1000 men and 1000 women aged 15–49 years, including questions on characteristics of non-spousal partnerships in the past 12 months.ResultsData on condom use were available for 4624 non-spousal partnerships. In the four cities, the proportion of partnerships in which condoms were used always or most of the time ranged from 23.8 to 33.5% when reported by men and from 10.7 to 25.9% when reported by women. Based on the reports from men, condom use was associated with higher educational level of the male partner in Yaoundé [adjusted odds ratio (aOR) = 1.76] and Ndola (aOR = 2.94) and with higher educational level of the female partner in Cotonou (aOR = 2.36) and Kisumu (aOR = 2.76). Based on the reports from women, condom use was associated with higher educational level of the female partner in Kisumu (aOR = 2.60) and Ndola (aOR = 4.50) and with higher educational level of the male partner in Yaoundé (aOR = 3.32). Associations with other determinants varied across cities and for men and women.ConclusionsEducation was found to be a key determinant of condom use in all four cities. This suggests that educational level increases response to condom promotion and highlights the need for special efforts to reach men and women with low educational attainment.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo examine the association between seeking sex on the Internet and sexual risk behaviour among gay men in London.MethodsIn January–February 2000, gay men in London gyms were asked to complete self-administered questionnaires concerning use of the Internet, history of sexually transmitted diseases (STD) and recent unprotected anal intercourse (UAI). Internet sex seekers were compared with other men, also with Internet access, who did not seek sex in this way.ResultsOf 743 gay men included in the analysis (121 HIV-positive, 465 HIV-negative, 157 never-tested), 80.9% (601) had access to the Internet. Among those who had access, 34.4% (207) had used the Internet to find a sexual partner; this did not vary significantly by HIV status (P= 0.3). Internet sex seekers were more likely to have had an STD (HIV-negative men, 26.9 versus 17.5%,P= 0.04) or gonorrhoea (HIV-positive men, 22.2 versus 5.8%,P= 0.04) in the previous year than other men with Internet access. HIV-negative Internet sex seekers were also more likely to report non-concordant UAI in the previous 3 months [23.1 versus 11.8%; adjusted odds ratio (aOR), 1.9; 95% confidence interval (CI), 1.2–3.5;P= 0.01]. HIV-positive Internet sex seekers were more likely to report UAI with another positive man (37.8 versus 7.4%; aOR, 7.9; 95% CI, 1.8–34.6;P= 0.006).ConclusionSeeking sex on the Internet was associated with recent STD and high-risk sexual behaviour among HIV-positive and -negative gay men in London. The contribution of seeking sex on the Internet to the recent increase in high-risk behaviour among London gay men merits further investigation.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID