摘要:

BackgroundImmune reconstitution following the introduction of highly active antiretroviral therapies (HAART) has lead to a remarkable reduction in the incidence of opportunistic infections (OI) in subjects with advanced HIV disease. Moreover, discontinuation of primary prophylaxis for some OI can be attempted without risk in patients experiencing a favourable response to treatment. However, data on the feasibility of discontinuing secondary prophylaxis are much more scarce, and restricted mainly to the withdrawal of maintenance treatment for cytomegalovirus (CMV) retinitis.Patients and methodsRetrospective review of the clinical outcome at 18 months in HIV-infected patients in whom discontinuation of secondary prophylaxis, for different OI, was recommended 3 months after the introduction of HAART, if both CD4 counts > 100 × 106CD4 lymphocytes/l and plasma HIV-RNA < 500 copies/ml had been achieved.ResultsFifty-three subjects were analysed. Secondary chemoprophylaxis was discontinued for the following OI:Pneumocystis cariniipneumonia (PCP) (n = 29), cerebral toxoplasmosis (n = 9), disseminatedMycobacterium aviumcomplex infection (n = 7), CMV retinitis (n = 5), recurrent oroesophageal candidiasis (n = 5), Visceral leishmaniasis (n = 2), recurrent herpes zoster (n = 2), and chronic mucocutaneous herpes simplex infection (n = 1). In six individuals, OI prophylaxis was discontinued for two or more entities. Only two episodes of OI were recorded in these individuals during 18 months of follow-up. One developed tuberculous lymphadenitis despite having a good response to treatment, and another suffered a new episode of PCP after voluntary treatment interruption for 6 weeks.ConclusionSecondary prophylaxis for OI can be attempted without major risk in HIV-infected patients experiencing a favourable response to HAART. The benefit of this intervention should reduce costs, drug side-effects and pharmacologic interactions, and indirectly will improve patient's quality of life and adherence to antiretroviral treatment.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo evaluate the effect of adjuvant granulocyte-macrophage colony-stimulating factor (GM-CSF) (sargramostim, yeast-derived recombinant human GM-CSF) on incidence and time to opportunistic infection or death, plasma HIV-RNA, and CD4 cell count in patients with advanced HIV disease.MethodsThis Phase III randomized, double-blind, placebo-controlled trial enrolled subjects with CD4 cell counts ⩽ 50 × 106/l or ⩽ 100 × 106/l with a prior AIDS-defining illness on stable antiretroviral therapy. Subjects were stratified by baseline HIV-RNA level (⩾ or < 30 000 copies/ml) and randomized to receive subcutaneous injections of GM-CSF 250 μg or placebo three times per week for 24 weeks. Subjects were permitted to continue on blinded drug for up to 20 months. Subjects were evaluated for infections, plasma HIV-RNA, lymphocyte counts, changes in antiretroviral therapy, toxicity, and survival.ResultsThree-hundred and nine subjects received at least one dose of study drug, 70% completed 24 weeks of therapy. Groups were well matched at baseline. Significant increases in CD4 cell and neutrophil counts were observed at 1, 3, and 6 months in the GM-CSF group. GM-CSF significantly reduced the incidence of overall infections (78% placebo versus 67% GM-CSF;P= 0.03) and delayed time to first infection (56 days placebo versus 97 days GM-CSF;P= 0.04). No statistical difference in cumulative opportunistic infections was observed between groups; however, among subjects without an opportunistic infection prior to study, the GM-CSF group demonstrated a trend towards fewer subjects with an opportunistic infection on study (26% placebo versus 8% GM-CSF;P= 0.08). Change in HIV-RNA was not significantly different between groups, but significantly fewer GM-CSF subjects with baseline viral load < 30 000 copies/ml had changes in antiretroviral therapy for increased viral load (42% placebo versus 21% GM-CSF;P= 0.01). In patients with HIV-RNA levels below the limit of detection at baseline, more GM-CSF patients maintained an undetectable viral load at 24 weeks (54% placebo versus 83% GM-CSF;P= 0.02). GM-CSF was well tolerated.ConclusionsGM-CSF significantly increased CD4 cell count and decreased virological breakthrough and overall infection rate in subjects with advanced HIV disease.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo investigate the virological and immunological impact of a structured treatment interruption (STI) in a cohort of HIV-1 chronically infected patients with a further long-lasting effective virus suppression.MethodsTwelve HIV-1 chronically infected adults who had maintained viral suppression (< 20 copies/ml) for more than 2 years, as well as a CD4 : CD8 ratio > 1 for a median time of 22 months, were included in the study. Participants interrupted their antiretroviral treatment during a maximum period of 30 days or until a viral load rebound > 3000 copies/ml was detected. The same prior antiretroviral regimen was resumed after STI. Kinetics of plasma viral rebound was evaluated every 2 days during the treatment interruption period. Flow cytometry and cell proliferation assays were performed before and after STI. Genotypic resistance was assessed at the time of treatment resumption.ResultsNo adverse events occurred during the interruption period. In two patients no viral rebound was detected after 30 days of treatment interruption. In the remaining 10 patients, viral load became detectable (> 20 copies/ml) at a median time of 14 days after treatment interruption. Afterwards, viral load increased exponentially with a mean t1/2of 1.6 days. Treatment was successfully resumed in all patients. No resistance-conferring mutations associated with the pre-interruption antiretroviral regimen were detected. The percentage of CD4 and CD8 lymphocytes did not vary during the STI period; however, the level of expression of T-cell activation antigen CD38 on CD8 T cells increased significantly in response to viral rebound. Four patients gained T-helper cell responses to recall antigens (tuberculin and tetanus toxoid), two of who developed an HIV-specific response to p24.ConclusionsSTI in chronically HIV-1-infected patients is not associated with reductions in CD4 T lymphocytes or to clinical complications in this group of patients after 2 years of effective plasma viral suppression. Viral load rebounds in most but not all patients, without evidence of selection of resistance-conferring mutations. Thereafter, viraemia can be effectively controlled by antiretroviral agent reintroduction. HIV-specific T-helper cell responses may be achieved after one cycle of treatment interruption suggesting some degree of immune-stimulation. These data do not discard consecutive cycles of STI as a therapeutic strategy to boost HIV-specific immunity in order to maintain viral replication under effective control.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo evaluate the effect of treatment with ritonavir (RTV)/saquinavir (SQV)/stavudine (D4T) or RTV/SQV alone, with treatment intensification if needed, in protease inhibitor- and D4T-naïve HIV-1-infected individuals.DesignMulticentre, open-label, randomized controlled trial. Two-hundred and eight patients were randomized to receive treatment with RTV 400 mg/SQV 400 mg twice daily or RTV 400 mg/SQV 400 mg/D4T 40 mg twice daily. Intensification of study medication with reverse transcriptase inhibitors was permitted if serum HIV-RNA remained > 400 copies/ml after 12 weeks of treatment. Follow-up of this study was 48 weeks.ResultsIn a strict intention-to-treat analysis, counting all dropouts as virological failures, 63% [95% confidence interval (CI), 54–73%] of subjects in the RTV/SQV group (n = 104) reached a serum HIV-RNA < 400 copies/ml at week 48, as compared with 69% (95% CI, 60–78%) in the RTV/SQV/D4T group (n = 104;P =0.379). In the on-treatment analysis these percentages were 88 and 91% respectively. Thirty-one patients intensified their study medication according to the protocol (28 in the RTV/SQV group, three in the RTV/SQV/D4T group). Thirty out of 31 (97%) patients had a serum HIV-RNA < 400 copies/ml at their last follow-up visit. Ten per cent of patients discontinued study medication due to adverse events.ConclusionThe concept of starting with a simple, potent regimen, that could be intensified if necessary, showed good virological results after 48 weeks in this study, comparable to starting with more drugs from the beginning. Longer follow-up is needed to determine the long-term efficacy of this treatment strategy.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectivesTo determine the frequency of cervicovaginal lavage and plasma HIV-1 RNA levels that are below detectable levels (< 400 copies/ml) among women on highly active antiretroviral therapy (HAART), non-HAART and on no therapy. To compare the effect of initiating HAART on the timing of HIV-1 RNA suppression in the blood plasma and genital tract among antiretroviral-naïve women.MethodsData were obtained from 205 HIV-infected women with paired plasma and cervicovaginal lavage viral load measurements. Seven antiretroviral-naïve women starting HAART had viral load measurements performed daily for one week, at 2 weeks and at 1 month after initiating therapy. Viral load quantification was carried out by nucleic acid sequence-based amplification assay. The lower limit of detection was 400 copies/ml.ResultsPlasma and cervicovaginal HIV-1 RNA was detectable in 71 and 26% of the women, respectively. Among women with plasma viral loads less than 400, 400–9999, and 10 000 copies/ml or over, genital tract HIV-1 RNA was detected in 3, 17 and 48%, respectively (P< 0.001). Fifty-one per cent of the women with CD4 cell counts of less than 200/mm3had detectable cervicovaginal viral loads compared with 18% among women with CD4 cell counts of 200/mm3or over (P< 0.001). Cervicovaginal HIV-1 RNA was less than 400 copies/ml in 85% of those on HAART, 69% of those on non-HAART and 69% of those on no therapy (P< 0.045). In seven antiretroviral-naïve women initiating HAART, cervicovaginal HIV-1 RNA decreased by 0.7–2.1 log10within 1–14 days of starting therapy.ConclusionThe cervicovaginal HIV-1 RNA level was positively correlated with plasma HIV-1 RNA and negatively with the CD4 cell count. The use of HAART was significantly associated with below-detectable levels of HIV-1 RNA in both plasma and the genital tract. HIV-1 RNA suppression in the genital tract may occur rapidly after initiating therapy.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo examine possible formation of new social contacts at the Baltimore Syringe Exchange Program (SEP).DesignSystematic sub-sample of new SEP participants recruited into evaluation cohort for biannual interviews. This analysis used 6-month interview data.MethodsParticipants were interviewed for behavioral and network characteristics, and number of new social contacts formed at the SEP. Variables were cross-tabulated using χ2statistics.ResultsOf 413 participants interviewed, 32 (8%) said they had made at least one social contact at the SEP. These 32 individuals were more likely to have engaged in commercial sex (16 versus 3%,P= 0.005) and, among active injectors, were more likely to have used syringes obtained from other drug users (22 versus 8%,P= 0.026).ConclusionsFindings argue against the formation of new social networks (and therefore new disease transmission networks) in the context of syringe exchange participation.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo assess trends in HIV-1 infection rates and changes in sexual behaviour over 7 years in rural Uganda.MethodsAn adult cohort followed through eight medical–serological annual surveys since 1989–1990. All consenting participants gave a blood sample and were interviewed on sexual behaviour.ResultsOn average, 65% of residents gave a blood sample at each round. Overall HIV-1 prevalence declined from 8.2% at round 1 to 6.9% at round 8 (P =0.008). Decline was most evident among men aged 20–24 years (11.7 to 3.6%;P< 0.001) and women aged 13–19 (4.4% to 1.4%;P =0.003) and 20–24 (20.9% to 13.8%;P =0.003). However, prevalence increased significantly among women aged 25–34 (13.1% to 16.6%;P =0.04). Although overall incidence declined from 7.7/1000 person-years (PY) in 1990 to 4.6/1000 PY in 1996, neither this nor the age-sex specific rates changed significantly (P> 0.2). Age-standardized death rates for HIV-negative individuals were 6.5/1000 PY in 1990 and 8.2/1000 PY in 1996; corresponding rates for HIV-positive individuals were 129.7 and 102.7/1000 PY, respectively. There were no significant trends in age-adjusted death rates during follow-up for either group. There was evidence of behaviour change towards increase in condom use in males and females, marriage at later age for girls, later sexual debut for boys and a fall in fertility especially among unmarried teenagers.ConclusionsThis is the first general population cohort study showing overall long-term significant reduction in HIV prevalence and parallel evidence of sexual behaviour change. There are however no significant reductions in either HIV incidence or mortality.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo compare the survival of children born to HIV-1 or HIV-2 seropositive mothers with that of children born to HIV-seronegative mothers and to evaluate risk factors for mortality.DesignPhysician-blinded prospective study.MethodsOne hundred and one HIV-1-seropositive, 243 HIV-2-seropositive pregnant women, and 468 HIV-seronegative women (control group) matched by age, parity, and health centre, were followed up in a study of mother-to-child transmission of HIV. Mothers and children were seen at 2 and 6 months of age and subsequently followed at 3-monthly intervals up to 18 months of age. HIV infection in children was diagnosed by polymerase chain reaction at 2, 9 or 18 months and by antibody assays at 18 months.ResultsFifteen per cent of children born to HIV-1-infected mothers died compared with 7% of children born to HIV-2-infected mothers [hazard ratio, 2.3; 95% confidence interval (CI), 1.1–4.7;P= 0.02], and 6% of HIV-seronegative mothers (hazard ratio, 2.6; 95% CI, 1.4–5.0;P= 0.003). Six of the 17 children known to be HIV-1 infected died compared with none among the eight HIV-2-infected children (P= 0.13). High proviral load in the babies, high antenatal maternal RNA plasma viral load, and maternal death increased child mortality significantly.ConclusionsMore children born to HIV-1-infected mothers died in comparison with those born to HIV-2-infected mothers or to mothers from the control group. This effect was due to excess death in HIV-1-infected infants which was associated with a high viral load in the affected mother and child.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectivesTo determine the rates of, and risk factors for, mother-to-child transmission (MCT) of HIV-1 and HIV-2 infection in The Gambia.DesignA blinded, prospective, community-based cohort study of 29 549 pregnant women attending the eight largest antenatal clinics in The Gambia.MethodsWomen were tested for HIV-1 and HIV-2 infection. Infected subjects and a group of HIV-seronegative women were followed with their babies until 18 months after delivery. Maternal CD4 cell count percentages were measured before and 18 months after delivery, and the antenatal plasma viral load was determined. Babies were tested for HIV by the polymerase chain reaction and/or serology at 2, 9 and 18 months of age.ResultsThe study enrolled 144 women positive for HIV-1 and 294 for HIV-2 plus 565 seronegative pregnant women: the mean antenatal percentage CD4 cell counts of 96 HIV-1-positive, 223 HIV-2-positive and 125 HIV-seronegative mothers were 31% [95% confidence interval (CI) 28–33], 41% (95% CI 39–42) and 47% (95% CI 45–49), respectively. The geometric mean antenatal plasma viral load of 94 HIV-1-infected women was 15 100 copies×103ml (95% CI 10 400–19 000) which was much higher than that of 60 randomly selected HIV-2-infected women, which was 410 copies×103ml (95% CI 150–910) (P< 0.001). The estimated transmission rate of HIV-1 was 24.4% (95% CI 14.6–33.9) and that of HIV-2 was 4.0% (95% CI 1.9–7.4). Five of 17 HIV-1-positive and three of eight HIV-2-positive babies were infected after 2 months of age. Birth in the rainy season [odds ratio (OR) 2.9; 95% CI 1.2–7.2], a low postnatal CD4 cell percentage (OR for a 10% fall 2.4; 95% CI 1.1–5.1) and a high maternal plasma viral load (OR for a 10-fold increase 2.9; 95% CI 1.1–7.8) were risk factors for transmission that applied equally to both viruses.ConclusionLow maternal HIV-2 RNA levels, which on average are 37-fold less than in HIV-1 infection, relate to the low MCT rate of HIV-2.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectivesLimited information is available on the prevalence in African populations of host genetic polymorphisms conferring resistance to HIV-1 infection and disease. The objective of this study was to determine the allelic frequencies in South African populations of the chemokine receptor gene variants CCR5Δ32, CCR5m303 and CCR2b-64I and the CXCR4 ligand gene variant SDF1-3′A.MethodCross-sectional study to determine the prevalence of these gene variants in South African subjects of African and European descent.ResultsThe CCR5Δ32 genetic variant is rare in individuals of African origin, having an allelic frequency of 0.1% (n = 1247) compared with 9.8 % (n = 144) in Caucasians. The CCR5m303 mutation was not detected in Africans (n = 687), whereas an allelic frequency of 0.9% (n = 145) was identified in Caucasians. The frequency of CCR2b-64I allele was 13.1% (n = 180) in Africans, which was significantly higher that the 7.2% (n = 146) detected in Caucasians. Finally the allelic frequency of the SDF1-3′A gene variant was only 1.0% (n = 198) in Africans compared with 19.8% (n = 145) in Caucasians.ConclusionsThese results indicate that genetic polymorphisms conferring resistance to HIV-1 infection are rare in the South African Black population. Except for the CCR2b-64I gene variant, individuals of African origin also had a much lower prevalence of genetic variants associated with prolonged disease progression.

ISSN:0269-9370    

出版商:OVID    

年代:2000

数据来源: OVID