摘要:

ObjectiveTo compare the effectiveness of initial highly active antiretroviral therapy with either: a single protease inhibitor (PI); ritonavir (RTV)/saquinavir (SQV); or efavirenz (EFV) plus nucleoside reverse transcriptase inhibitors.DesignCohort study.SettingUrban HIV clinic.PatientsFive-hundred and forty-five HIV-1-infected individuals with minimal antiretroviral exposure who started combination therapy with ⩾ 3 antiretroviral drugs and ⩾ 1 NRTI to which they had not previously been exposed (single PI, 416; RTV/SQV, 68; EFV, 61).Main outcome measuresHIV-1 RNA < 400 copies/ml within 8 months of starting therapy; time to HIV-1 RNA rebound to > 1000 copies/ml in the subset of patients achieving initial viral suppression; change in CD4 cell count from baseline within 12 months of starting therapy.ResultsBy intent-to-treat analysis, initial viral suppression was achieved by 72% of patients in the EFV group, compared to 49% in the single PI group (P= 0.001) and 51% in the RTV/SQV group (P= 0.019). Among patients who achieved initial viral suppression, time to viral rebound was similar in the three groups. Durable viral suppression (⩾ 3 consecutive HIV-1 RNA levels < 400 copies/ml for > 6 months) was achieved by 53% of patients in the EFV group, 26% in the single PI group, and 29% in the RTV/SQV group (P< 0.05 for both comparisons with EFV). The median CD4 cell count increase was 139 × 106cells/l, and was similar in the three groups.ConclusionsIn agreement with a recent clinical trial, use of initial EFV-based combination antiretroviral therapy was associated with higher rates of viral suppression than PI-based therapy in a clinical cohort.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesMitochondrial toxicity is a serious side-effect of antiretroviral drugs, especially nucleoside reverse transcriptase inhibitors (NRTI). Anin vitroassay to predict mithocondrial toxicity of in-use and developmental NRTI would be invaluable. To test the ability of a cytofluorimetric technique to predict the mitochondrial-dependent pancreatic and hepatic toxicity we used didanosine (ddI) alone or in combination with hydroxyurea (HU).MethodsThe technique is based on the ability of the lipophilic cation JC-1 to enter selectively into mitochondria and change its colour as the membrane potential changes due to toxicity. Mitochondrial toxicity by HU and ddI was evaluated in pancreatic and hepatic human cell lines. The results were expressed as mitochondrial toxicity index (MTI), ranging from 0 to 100: the negative control was 0, and 100 indicating maximal toxicity.ResultsDose-dependent pancreatic toxicity of ddI was evident after 14 days of culture (MTI 34 ± 4 at 100 μM, 10 ± 4 at 10 μM, 2 ± 3 at 1 μM ddI). HU alone was not toxic (MTI 7 ± 10 at 100 μM, 2 ± 2 at 50 μM and 2 ± 4 at 10 μM HU); however, HU increased the toxicity of high, but not low, concentrations of ddI. For example, the MTI of 10 μM ddI plus 50 μM HU was 54 ± 9. Negligible mitochondrial toxicity was observed in the hepatic cell line exposed to ddI alone or in combination with HU.ConclusionsThisin vitroassay might havein vivorelevance. First, ddI-related pancreatitis is dose dependent, and is reported more frequently than hepatic failure, consistent with ourin vitroresults. Second, patients who developed pancreatitis during randomized, controlled trials were treated with HU in combination with 400 mg ddI once daily (high peak concentration of ddI in the blood). In contrast, no pancreatitis was observed when HU was combined with 200 mg ddI twice daily (low peak concentration of ddI). Thesein vivoresults are consistent with ourin vitroobservation that HU increases pancreatic cell toxicity in the presence of high concentrations of ddI. Thein vitroassay described here might be used to predict the mitochondrial toxicity of other NRTI, alone or in combination.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveEfficacy and safety of adefovir dipivoxil (adefovir) added to background antiretroviral therapy in advanced HIV disease.DesignRandomized, double-blind, placebo-controlled multicenter trial.SettingFifteen clinical trial units providing HIV primary care.ParticipantsAdults with CD4 cell count ⩽ 100 × 106/l, or 101–200 × 106/l with prior nadir ⩽ 50 × 106/l.InterventionsOral adefovir or placebo 120 mg once daily.Main outcome measuresSurvival, cytomegalovirus (CMV) disease, plasma HIV-RNA, CD4 cell count, grade 4 drug toxicity, permanent drug discontinuation due to toxicity.ResultsAmong the 253 patients assigned adefovir and the 252 assigned placebo, respectively, 17 and 16 died (P= 0.88), and four and eight experienced CMV disease (P= 0.25). Mean change in log10plasma HIV-RNA in the adefovir and placebo groups, respectively, was 0.09 and −0.03 copies/ml at 6 months (P= 0.22) and 0.06 and −0.02 at 12 months (P= 0.87). Changes in CD4 cell counts were not different between groups. At 12 months the cumulative percent with proximal renal tubular dysfunction (PRTD) was 17% in the adefovir group and 0.4% in the placebo group (P< 0.0001, log rank test). Median time to resolution of PRTD was 15 weeks among patients assigned adefovir, and 16% of patients did not resolve completely 41 weeks after onset. More drug discontinuations occurred in the adefovir group than in the placebo group.ConclusionsNo virologic or immunologic benefit was observed when adefovir was added to background antiretroviral therapy in advanced HIV disease, and adefovir was associated with considerable nephrotoxicity. This study does not support the use of adefovir for treatment of advanced HIV disease in pretreated patients.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo assess the pattern of drug resistance mutations selected in HIV-1-infected patients failing a first line triple combination therapy including indinavir.Patients and methodsPlasma samples from 87 patients collected at the time of the first virological rebound (> 50 HIV-RNA copies/ml) were examined for the presence of drug-resistant genotypes.ResultsThe mean level of plasma viraemia at rebound was 7824 HIV-1 RNA copies/ml in 73 subjects with good compliance, whereas it was 359 460 HIV-1 RNA copies/ml in 14 patients who admitted to poor adherence. Genetic sequence analysis yielded results for 51 (70%) of the patients having good adherence. More than half of them (26/51, 51%) carried primary mutations associated with resistance to nucleoside analogues. In contrast, primary protease inhibitor resistance mutations were recognized less frequently (14/51, 27%;P< 0.05). Moreover, in 23 (45%) patients there was no evidence of drug-resistant viruses at all. The most frequent drug-resistant genotypes in the reverse transcriptase gene were at codons 184 (n = 19), 215 (n = 14) and 41 (n = 8), whereas for the protease they were at codons 46 (n = 10), 82 (n = 9) and 90 (n = 7). No resistance genotypes were found among non-compliant patients.ConclusionThe overall rate of drug-resistant HIV genotypes was 38% (28/73) in patients with good adherence and who were experiencing a first virological failure under a triple combination regimen including indinavir; resistance to nucleoside analogues was more frequent than resistance to indinavir. Therefore, treatment intensification in those patients without resistance, or a selective substitution of nucleosides in those with resistance limited to these compounds, might be justified.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveStudies have shown that HIV-infected injection drug users (IDUs) are less likely to receive antiretroviral therapy than non-drug users. We assess factors associated with initiating highly active antiretroviral therapy (HAART) in HIV-infected IDUs.MethodsA cohort study of IDUs carried out between 1 January 1996 and 30 June 1999 at a community-based study clinic affiliated to the Johns Hopkins University, Baltimore, Maryland. The participants were a total of 528 HIV-infected IDUs eligible for HAART based on CD4+ cell count. The main outcome measure was the time from treatment eligibility to first self-reported HAART use, as defined by the International AIDS Society–USA panel (IAS–USA) guidelines.ResultsBy 30 June 1999, 58.5% of participants had initiated HAART, most of whom switched from mono- or dual-combination therapy to a HAART regimen. Nearly one-third of treatment-eligible IDUs never received antiretroviral therapy. Cox proportional hazards regression showed that initiating HAART was independently associated with not injecting drugs, methadone treatment among men, having health insurance and a regular source of care, lower CD4+ cell count and a history of antiretroviral therapy.ConclusionsSelf-reported initiation of HAART is steadily increasing among IDUs who are eligible for treatment; however, a large proportion continues to use non-HAART regimens and many remain treatment-naive. Although both groups appear to have lower health care access and utilization, IDUs without a history of antiretroviral therapy use would have more treatment options available to them once they become engaged in HIV care.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo compare HIV prevalence in antenatal clinics (ANC) and the general population, and to identify factors determining the differences that were found.DesignCross-sectional surveys in the general population and in ANC in three cities.MethodsHIV prevalence measured in adults in the community was compared with that measured by sentinel surveillance in ANC in Yaoundé, Cameroon, Kisumu, Kenya, and Ndola, Zambia.ResultsIn Yaoundé and Ndola, the HIV prevalence in ANC attenders was lower than that in women in the population overall, and for age groups over 20 years. In Kisumu, the HIV prevalence in ANC attenders was similar to that in women in the population at all ages. The only factors identified that influenced the results were age, marital status, parity, schooling, and contraceptive use. The HIV prevalence in women in ANC was similar to that in the combined male and female population aged 15–40 years in Yaoundé and Ndola, but overestimated it in Kisumu. In Yaoundé and Ndola, the overall HIV prevalence in men was approximated by using the age of the father of the child reported by ANC attenders, but this method overestimated the HIV prevalence in Kisumu, and did not give good age-specific estimates.ConclusionFew factors influenced the difference in HIV prevalence between ANC and the population, which could aid the development of adjustment procedures to estimate population HIV prevalence. However, the differences between cities were considerable, making standard adjustments difficult. The method of estimating male HIV prevalence should be tested in other sites.

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

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

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID