摘要:

ObjectivesWe evaluated virologic and immunologic responses to antiretroviral therapy in gut-associated lymphoid tissue (GALT) compared with those found in peripheral blood.MethodsEight HIV-1–infected individuals were treated with three reverse transcriptase inhibitors and one protease inhibitor. Endoscopic biopsies were performed at baseline, and at months 1, 2, and 6. We measured the level of cell–associated multiply spliced and unspliced HIV-1 mRNA in GALT and in peripheral blood mononuclear cells. Immunologic responses were assessed by flow cytometry.ResultsLevels of multiply spliced HIV-1 mRNA declined in parallel fashion both in peripheral blood and GALT. After 6 months of therapy, unspliced HIV-1 mRNA in the GALT was below assay detection although it persisted in peripheral blood mononuclear cells in 4 study subjects. Although the percentage of CD4+lymphocytes increased significantly in peripheral blood, only modest increases occurred in GALT. The percentage of activated CD8+T cells decreased significantly in peripheral blood whereas only modest reductions occurred in GALT.ConclusionsAntiretroviral therapy effectively suppressed HIV-1 replication in GALT. The percentage of CD4+T cells in peripheral blood uniformly increased in all study subjects, whereas it was more variable in the GALT.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Determination of retroviral load is an important tool in the investigation of the success of therapeutic or vaccination trials in patients infected with lentiviruses such as HIV, or with their simian (SIV) or feline (FIV) counterparts.We have developed an one-tube quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay based on the ABI Prism 7700 Sequence Detection System (TaqMan) to quantify the viral load of FIV-infected cats. Two different primer/probe systems were designed to detect a broad range of clade A FIV isolates. Both systems are characterized by excellent reproducibility, high sensitivity, and a wide range of quantification. As a consequence of this improved precision in the quantitative RT-PCR, preassay variations have greater impact on the accuracy of the viral load estimation. To compensate for these variations, we improved the assay and developed a multiplex real-time RT-PCR, which allows simultaneous calculation of the viral copy number and the individual recovery rate in an one-tube reaction. This enables the rapid and accurate calculation of copy number independent of preassay variations. In further studies, two additional real-time RT-PCR assays were designed and used to investigate the influence of sequence variations in the binding regions for either the primers or probe. Sequence mismatches in this region had a significant effect (up to 4 logarithmic decades) on reaction efficiency. In view of the inherent variability of retroviral sequences, these results underline the necessity to check reaction efficiencies before determining viral load.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

AimTo evaluate the safety of BufferGel (ReProtect LLC, Baltimore, MD), a spermicidal microbicide that acidifies semen and maintains the protective acidity of the vagina, in a high-dose tolerance trial.MethodsHIV/STD negative, sexually abstinent, and sexually active women in India, Thailand, Malawi, and Zimbabwe were asked to insert one applicator (∼5 ml) of BufferGel vaginally twice per day for 14 days. Sexually active women agreed to have sex (while using BufferGel and nonlubricated condoms) at least twice per week.ResultsIn total, 98 women (30 sexually abstinent and 68 sexually active) were enrolled. Overall compliance with product use was 93%. Epithelial abnormalities detected by pelvic examination or colposcopy were uncommon (8 cases in 271 examinations). Irritation was reported by approximately one quarter of the women (0.58 events per woman-week) but was generally mild and of short duration. The prevalence of bacterial vaginosis (BV) fell significantly, from 30% at enrollment to 6% at one week, and 7% at two weeks of BufferGel use. Thirty-two women acquired microscopically detectable yeast during BufferGel exposure, but only 3 developed symptomatic vaginitis.ConclusionBufferGel appears to be safe and well tolerated by the cervicovaginal epithelium. Its effect on BV and yeasts merits further study.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Anemia is a common manifestation of HIV infection, occurring in approximately 30% of patients with asymptomatic infection and in as many as 75% to 80% of those with AIDS. Anemia has been associated with decreased quality of life and decreased survival. We performed a cross-sectional study nested within a multicenter prospective cohort study to describe the prevalence of anemia in 2056 HIV-infected and 569 HIV-negative women as well as to define the demographic, clinical, immunologic, and virologic correlates of anemia among HIV-infected women. A total of 37% of HIV-positive women and 17% of HIV-negative women had hemoglobin levels < 12 g/dl (p< .001). Factors associated with anemia in HIV-positive and HIV-negative women included mean corpuscular volume (MCV) < 80 fl (p< .001) and black race (p< .001). Among HIV-infected women, multivariate logistic analyses revealed that African American race (p< .0001), MCV < 80 fl (p< .0001), CD4 count < 200 per microliter (p< .0001), higher HIV RNA in plasma (p= .02), current use of ZDV (p= .01), and history of clinical AIDS (p= .004) were all independent predictors of anemia. These data indicate that worsening parameters of HIV disease are associated with anemia among HIV-infected women. Black women and women with low MCV values are at increased risk for anemia independent of HIV status.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Resistance-mutation patterns in the reverse transcriptase (RT) and protease genes of HIV-1 were analyzed in 22 patients who had been extensively pretreated and who failed to respond to highly active antiretroviral therapy (HAART). The number of mutations ranged from 8 to 19 (median, 13): 4 to 12 (median, 6) mutations in the RT gene, and 4 to 8 (median, 7) mutations in the protease gene. In the RT gene, the most frequent resistance mutations were found at codons 215 (100%), 41 (95%), 67 (91%), and 210 (77%). Multidrug-resistant mutation patterns including Q151M and insertion mutations at codon 69, which confer cross-resistance to the different nucleoside analogue RT inhibitors were detected in 1 and 3 patients, respectively; 1 patient with insertion mutation displayed a NGQCV sequence at codons 67 to 70. In the protease gene, the most frequent mutations were found at codons 63 (95%), 10 (86%), 90(86%), 71(77%), 46 (50%), 36 (45%), and 84 (45%). Genotypic resistance to zidovudine, saquinavir, and indinavir was found in 100% of the patients. All patients showed also resistance or possible resistance to stavudine, abacavir, ritonavir, and nelfinavir. Mutations conferring genotypic resistance to nonnucleoside analogue RT inhibitors (NNRTIs) were found in 12 (80%) of the NNRTI-experienced patients and 1 of 7 NNRTI-naive patients. Our results indicate that failure of HAART in the patients extensively pretreated results from the multiplicity of RT and protease mutations that confer genotypic resistance to almost all available antiretroviral drugs. In these patients, genotypic resistance tests confirm the lack of alternative salvage therapy strategies based on the currently available antiretroviral drugs.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

A pilot study of a combination of highly active antiretroviral therapy (HAART) and cytokines in early HIV-1 infection has been undertaken to test the hypothesis that HIV-1 remission can be reached with this strategy by flushing latently infected viral reservoirs. Ten previously antiretroviral naive patients have received a combination of zidovudine, lamivudine, didanosine, saquinavir, and ritonavir for 72 weeks. Between weeks 12 and 48, three courses of interleukin (IL)-2 (7.5 millions of international units [MUI] twice a day for 5 consecutive days) and 2 courses of &ggr;-interferon (IFN) (100 &mgr;g every other day during 2 weeks) were administered subcutaneously. All patients reached plasma HIV-1 RNA levels < 20 copies/ml within 12 ± 4 weeks. Transient increases in plasma levels (<120 copies/ml) were observed during administration of IL-2, but less frequently during &ggr;-IFN administration. HIV-1 RNA decreased in lymph node cells by ∼ 4 log, then remained stable after week 24. A mean drop of −0.8 log in peripheral blood mononuclear cell (PBMC) proviral DNA was observed during the trial. Isolation of potentially infectious HIV-1 was successful in each case by coculture of CD4+T cells taken at week 72. The 2 patients who stopped therapy at the end of the trial showed rebounding plasma HIV-1 RNA levels within a few weeks. No additional mutations were selected in comparison with those present at baseline in 8 patients. In addition, 2 patients developed new mutations in the reverse transcriptase or protease gene and in 1 case, resistance selection was found in lymphoid tissue HIV-1 RNA but not in latently infected cells. In all cases, a rapid increase in both naive and memory CD4+T cells was observed, with a reduction in activation markers and preservation of the CD8+CD28+subset. Consequently, an aggressive regimen of HAART and cytokines administered in early stage disease is associated with a positive effect in terms of proviral load reduction and immune reconstitution but is unable to induce HIV-1 remission, allowing low levels of viral replication to persist in lymphoid reservoirs.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

BackgroundNew medications for treating HIV/AIDS are effective, but expensive, and funding shortfalls have led many state AIDS Drug Assistance Programs (ADAPs) to ration these drugs. Little is known about the views of those most directly affected by rationing policies. This study explores attitudes of patients with HIV and the general public toward specific rationing strategies.MethodsA Likert-style, self-administered questionnaire about rationing expensive HIV medications in the context of a budget shortfall was administered to patients with HIV and shopping mall patrons in central Pennsylvania. Subjects were asked how much they agreed or disagreed with seven drug rationing policies.ResultsIn all, 100 patients and 101 shoppers completed the survey (response rate = 89%). A majority in both groups “strongly” or “somewhat” disagreed with six of the seven rationing policies described, and patients more strongly disagreed with the policies than did the public. The five policies actually used by state ADAPs (first come first serve, limiting expensive medicines, limiting new patient enrollment, giving the expensive medicines to the sickest, using a spending cap) lacked support in either group.ConclusionsHIV drug rationing policies currently in use do not reflect the preferences of patients and the public. Integrating the views of those affected by the rationing decisions would raise difficult challenges to current programs.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

SummaryThis study examined perceived risks, benefits, and desired information related to willingness to volunteer in preventive HIV vaccine trials.SamplePurposive sampling was used to select 90 participants among injecting drug users (Philadelphia, PA, U.S.A.); gay men (San Francisco, CA, U.S.A.); and black Americans (Durham, NC, U.S.A.).MethodsA qualitative interview guide elicited perceived benefits, risks, and desired information relating to trial participation. Themes were developed from the transcribed texts and from freelists.ResultsStated willingness to volunteer in a preventive HIV vaccine trial was similar across the three communities. Eight perceived benefits were reported, including self-benefits, altruism, and stopping the spread of AIDS. Seven perceived risks were reported, including negative side effects and vaccine safety issues, contracting HIV from the vaccine, and social stigmatization. Participants voiced the desire for eight types of information about issues relating to trust and confidentiality in the research process, health complications and later assistance, and vaccine trial methodology.ConclusionsIn this study, many benefits as well as risks of preventive HIV vaccine trial participation were cited. Scientists conducting preventive HIV vaccine trials need to address community perceptions of risks and provide information about the research if trial enrollment is to be diverse and successful.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID