摘要:

HIV-1 isolated from patients with improved CD4+T-cell counts despite virologic failure on a nucleoside reverse transcriptase inhibitor (NRTI) and protease inhibitor (PI)-containing regimen were characterized. Five paired virus isolates from patients before and after zidovudine, lamivudine, and ritonavir treatment were tested. Human peripheral blood leukocyte-reconstituted severe combined immunodeficient (hu-PBL-SCID) mice were infected with pre-or posttreatment isolates and plasma HIV-1 RNA levels and CD4+T cells were measured. Two of five post-treatment isolates exhibited decreased replication in hu-PBL-SCID mice compared with the paired pretreatment isolate, and both had the V82A mutation in protease associated with resistance to PI. One additional posttreatment isolate with the M184V mutation in reverse transcriptase showed diminished replication. CD4+T-cell depletion was similar following infection with either the pre-or posttreatment isolates. Subtle losses in the replication capacity of PI-or NRTI-resistant viruses may contribute to relative preservation of CD4+T-cell counts in persons who experience virologic failure. Cytopathic effects of viral infection for target T cells vary from patient to patient but appear not to be influenced by mutations associated with failure of therapy in this system.

ISSN:1525-4135    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

SummaryThis research comprised a pilot open prospective clinical study comparing T-cell subset reconstitution in antiretroviral-naive patients, after 12 months of HAART when treatment was initiated in early stages (ES;n= 18) of infection versus advanced stages (AS;n= 20). Control group: 10 healthy HIV-negative individuals. Immunophenotypic markers were evaluated before and after 6-and 12-months' therapy. Functional assays were performed in one subset.ResultsViral load (VL) was < 200 copies/ml in all patients. Median percentages of CD4+pretherapy were 33% and 6%, respectively, in the ES and AS groups, increment after 12 months of therapy was +15% and +13% respectively. Only the ES group achieved normal values. Declines of CD8+percentage were significantly higher in the ES (−18%) than in the AS group (−2%). CD4+memory and naive cells in the ES group were similar to those of controls before treatment and did not change after therapy. In contrast, CD4+memory and naive cells in the AS group did not reach normal levels despite treatment. In the ES group, there was a significant increment in CD8+naive cells (+8%) and a decrement in CD8+CD38+cells (−17%), both populations reached values close to normal, whereas these subsets remained far from normal in the AS group. Improvement of lymphoproliferative response after therapy was observed in both groups. One patient in the ES group showed positive LPR against p24 after treatment.After 12 months' highly active antiretroviral therapy, only those who began such therapy in ES disease reached values within the range of healthy controls. To achieve a more complete immunologic reconstitution, early initiation of potent antiretroviral therapy should be recommended.

ISSN:1525-4135    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ContextDespite the success of highly active antiretroviral therapy, the optimal approach for preventing perinatal HIV-1 transmission is not known.ObjectiveA retrospective survey was conducted at six centers in the United States and Puerto Rico from January 1997 to October 1998 to evaluate the effects of protease inhibitor use during pregnancy on maternal and infant safety, prematurity rate, and frequency of perinatal HIV-1 transmission.ResultsIn the study, 91 live infants, including 3 sets of twins, and 1 neonate who died shortly after birth were born to 89 women. HIV perinatal transmission rate in this series was 0 (95% confidence interval [CI], 0%–3%). Prematurity rate was 19.1%, comparable to rates in earlier reports of HIV-1–infected women. In multiple regression analysis, only cocaine use and premature rupture of membranes were associated with prematurity (p= .03 and .008, respectively). The gestational week during which the protease inhibitors were initiated was not found to be significantly associated with prematurity. Adverse maternal, obstetric, and infant events possibly related to protease inhibitors were uncommon.ConclusionsProtease inhibitors appeared generally safe in mothers and infants in this series. No perinatal HIV-1 transmission occurred. Further prospective, controlled studies are needed to define the optimal management of HIV-1 in pregnancy.

ISSN:1525-4135    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

HIV-lipodystrophy (HIV-LD) is characterized by the loss of body fat from the limbs and face, an increase in truncal fat, insulin resistance, and hyperlipidemia, factors placing affected patients at increased risk for vascular disease. This study evaluated insulin sensitivity and inflammatory status associated with HIV-LD and provides suggestions about its etiology. Insulin sensitivity and immune activation markers were assessed in 12 control subjects and 2 HIV-positive groups, 14 without and 15 with LD syndrome. Peripheral insulin sensitivity (mostly skeletal muscle) was determined with the hyperinsulinemic-euglycemic clamp. Circulating insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) and free fatty acid (FFA) levels, and their response to insulin infusion were indicative of insulin responsiveness of liver and adipose tissue, respectively. Serum levels of soluble type 2 tumor necrosis factor-&agr; (TNF-&agr;) receptor (sTNFR2) were used as an indicator of immune activation. HIV-LD study subjects had significantly reduced (twofold) peripheral insulin sensitivity, but normal levels of FFA and reduced levels of IGFBP-1, relative to the nonlipodystrophy groups, indicating that the loss of insulin sensitivity was more pronounced in skeletal muscle than in liver or fat. The significant loss of peripheral fat in the HIV-LD group (34%;p< .05) closely correlated with the reduced peripheral insulin sensitivity (p= .0001). Levels of sTNFR2 were elevated in all HIV-infected study subjects, but they were significantly higher in those with lipodystrophy than without, and sTNFR2 levels strongly correlated with the reduction in insulin sensitivity (p= .0001). Loss of peripheral fat, normal levels of FFA, and reduced levels of IGFBP-1 indicate that insulin resistance in HIV-LD is distinct from type 2 diabetes and obesity. The relationship between the degree of insulin resistance and sTNFR2 levels suggests an inflammatory stimulus is contributing to the development of HIV-associated lipodystrophy.

ISSN:1525-4135    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo evaluate the safety, tolerability, and anti-HIV activity of ritonavir-nelfinavir (RTV-NFV).DesignSingle-site, open-label, nonrandomized, multiple-dose trial of RTV combined with two doses of NFV in protease inhibitor (PI)-naive, HIV-infected patients.MethodsMean baseline HIV RNA was 39,500 copies/ml; mean baseline CD4 count was 323 cells/mm3. All patients received RTV at a dosage of 400 mg twice daily. Cohorts I (N= 10) and II (N= 10) received NFV at a dosage of 500 mg and 750 mg twice daily, respectively, for the initial 12 weeks of the study before allowing intensification with reverse transcriptase inhibitors.ResultsThe commonest effects of RTV-NFV therapy were study drug-related moderate-to-severe diarrhea (9 patients in cohorts I and II) and drug-related moderate-to-severe nausea (4 patients in cohorts I and II). HIV RNA was suppressed in a biphasic manner. At 48 weeks in cohort I, mean HIV RNA reduction was 2.82 log10copies/ml (standard error [SE] = .61;p= .001;N= 4); mean CD4 cell count increase was 236 cells/mm3(SE = 67.1;p= .006;N= 4). In cohort II, mean HIV RNA reduction at Week 48 was 2.21 log10copies/ml (SE = .430;p= .001;N= 8); mean CD4 cell count increase was 120 cells/mm3(SE = 47.5;p= .03;n= 8). In cohort I patients, 2 of 4 completing Week 48 had HIV RNA <20 copies/ml; and 3 of 4 had HIV RNA <400 copies/ml. In cohort II, 2 of 8 patients completing Week 48 had HIV RNA <20 copies/ml and 4 of 8 had HIV RNA <400 copies/ml. In addition, 3 patients in cohort I withdrew because of virologic failure not thought to be related to poor compliance. Moreover, 15 patients elected to add new reverse-transcriptase inhibitors (RTIs) after week 12.ConclusionsRTV-NFV with concomitant reverse transcriptase inhibitors is a potential dual-PI option for PI-naive patients.

ISSN:1525-4135    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Long-term safety, immunologic effects, and antiretroviral activity of hydroxyurea and didanosine were evaluated in this retrospective study. Some 65 HIV-1–infected patients (39 of whom were antiretroviral naive) were studied (mean baseline CD4 count, 362 cells/mm3; mean plasma HIV-1 RNA viral load, 4.8 log10copies/ml). The mean treatment duration was 20 months. Overall tolerance was good: 15 patients interrupted treatment because of clinical or biologic side effects. Four patients experienced a category B event. Patients had a mean increase of 27 CD4 cell counts after 12 months, of 112 after 24 months and of 59 after 36 months. They had a mean 1.03 log10fall in HIV-1 RNA after 12 months, 1.59 log10after 24 months, and 1.27 log10after 36 months. After 12 months, 35% developed an HIV-1 RNA viral load <200 copies/ml, 53% after 24 months, and 36% after 36 months. Those whose viral load became undetectable after 12 months have significantly lower baseline RNA values (p= .03). Fourteen patients had a viral load <3.4 log10copies/ml after 24 months of the double therapy. A prolonged viral load suppression can be achieved using a simple combination of two drugs that are inexpensive and well tolerated.

ISSN:1525-4135    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

BackgroundPoor health literacy is a prevalent barrier to medical care and people with lower health literacy experience greater illness severity than people with higher health literacy. Health literacy may therefore be an important factor in the health and treatment of people living with HIV-AIDS.MethodsA community-recruited sample of 339 HIV-infected men and women completed surveys and interviews that assessed functional health literacy, health status, AIDS-related disease and treatment knowledge, and health care perceptions and experiences. Medical records were available for chart abstraction of health status for a subsample of participants.ResultsAbout 1 of 4 people living with HIV-AIDS demonstrated difficulty comprehending simple medical instructions and therefore lower health literacy. HIV-infected people with lower health literacy had lower CD4 cell counts, higher viral loads, were less likely to be taking antiretroviral medications, reported a greater number of hospitalizations, and reported poorer health than those with higher health literacy. In addition, after adjusting for years of formal education, lower health literacy was associated with poorer knowledge of one's HIV-related health status, poorer AIDS-related disease and treatment knowledge, and more negative health care perceptions and experiences.ConclusionsHealth literacy is a significant factor in the health and treatment of persons living with HIV-AIDS. Interventions are needed to improve medical care and the health status of people with lower health literacy that are living with HIV-AIDS.

ISSN:1525-4135    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Population HIV prevalence estimates rely heavily on sentinel surveillance in antenatal clinics (ANCs), but because HIV reduces fertility, these estimates are biased. To aid interpretation of such data, we estimated HIV-associated fertility reduction among pregnant women in ANCs in Yaoundé (Cameroon), Kisumu (Kenya), and Ndola (Zambia). Data collection followed existing HIV sentinel surveillance procedures as far as possible. HIV prevalence among the women was 5.5% in Yaoundé, 30.6% in Kisumu, and 27.3% in Ndola. The birth interval was prolonged in HIV-positive multiparous women compared with HIV-negative multiparous women in all three sites: adjusted hazard ratios of pregnancy were 0.84 (95% confidence interval [CI]: 0.62–1.1) in Yaoundé, 0.82 (95% CI: 0.70–0.96) in Kisumu, and 0.74 (95% CI: 0.61–0.90) in Ndola, implying estimated reductions in the risk of pregnancy in HIV-positive women of between 16% and 26%. For primiparous women, the interval between sexual debut and birth was longer in HIV-positive women than in HIV-negative women in all sites, although the association was lost in Ndola after adjusting for age and other factors. Consistent results in different study sites help in the development of standard methods for improving ANC-based surveillance estimates of HIV prevalence. These may be easier to devise for multiparous women than for primiparous women.

ISSN:1525-4135    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:1525-4135    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

To study HIV-1 seroprevalence, risk factors, and preventive behaviors among reproductive-age women in northern Thailand, 804 consenting women who were identified postpartum or who were visiting family planning clinics were interviewed and tested during 1998 to 1999. Almost all women were currently married and had been pregnant more than once. Their median age was 27 years. HIV-1 seroprevalence was 3.1% overall and was higher in women aged between 25 and 29 years (5.9%), having had ≥2 lifetime sex partners (6.5%), or whose current marriage had lasted for ≤1 year (7.0%). No woman reported HIV risk factors other than heterosexual sex. Most (76%) HIV-infected women reported no casual sex partners and, therefore, had likely acquired the infection from their husbands. HIV testing and partner communications were common, but only 2% of couples used condoms consistently in the prior 6 months. Nearly half of these women perceived themselves at no or low risk for HIV infection; these women were less likely to have taken preventive actions. To prevent HIV transmission in stable partnerships in this population, additional efforts are needed to increase HIV testing and condom use, to improve women's negotiation skills, and to develop new methods that do not require partner cooperation such as vaginal microbicides or vaccines.

ISSN:1525-4135    

出版商:OVID    

年代:2000

数据来源: OVID