摘要:

IntroductionIn a large number of patients on HAART who achieved plasma HIV RNA levels below the limit of detection (50 copies/ml), transient relapses of HIV RNA levels (“blips”) are observed.ObjectiveTo determine whether relapses of plasma HIV RNA during HAART are associated with development of drug resistance.MethodsPlasma samples from 15 patients with a transient viral load relapse during HAART were studied. All regimens contained lamivudine (3TC). We used an ultrasensitive sequence approach to analyze the presence of drug resistance mutations during the relapse.ResultsThe median plasma HIV RNA load of the relapse was 76 copies/ml (range 50–1239). In 11 of 15 cases, a genotype of HIV could be obtained. Mutations in the RT and protease gene conferring resistance to one or more drugs were observed in 8 of 11 patients, 6 of whom had the M184V substitution. During a median follow-up of 27 months after the relapse, plasma HIV RNA levels remained undetectable in 13 of 15 patients.ConclusionsPlasma HIV RNA blips during HAART can be associated with selection of drug-resistant HIV. This indicates that viral replication may occur during HAART, probably caused by a temporary decrease in active drug concentrations. A blip containing only wild-type virus is not necessarily caused by viral replication. In this situation the raise of HIV RNA could also originate from release of wild-type viruses, caused by activation of the latent virus reservoir. Independent of the mechanism, blips did not preclude successful inhibition of viral replication during 2-year follow-up in the majority of these cases.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

BackgroundHighly active antiretroviral therapy (HAART) is strongly effective in reducing morbidity and mortality in HIV-1–positive individuals. Its main drawback is the potential toxicity. Data on the frequency and determinants of severe hepatotoxicity in a clinical setting are still sparse.MethodsThis is a prospective study of HIV-1–positive individuals with known HBsAg and HCV-Ab serology. The study end point was progression to alanine aminotransferase (ALT) levels ≥200 IU/L after HAART initiation. Cumulative probability of progression to this end point was estimated by the Kaplan-Meier method. Crude and adjusted hazard ratios (HR) were estimated by proportional hazards regression model.ResultsOne thousand two hundred fifty-five patients were included. HBsAg was found in 91 (7.2%), HCV-Ab in 578 (46.5%) patients; almost all injection drug users (451 of 482; 93.6%) were HCV-Ab positive. Sixty-one individuals progressed to the end point with a probability of 7.9% (95% confidence interval [CI], 5.6–10.0) of progression at 24 months from starting. Independent factors predicting progression to the end point were baseline ALT levels (HR, 5.29; 95% CI, 3.24–8.65; every 10 IU/L higher), HCV-Ab positivity (HR, 4.01; 95% CI, 1.48–10.85) or both HBsAg and HCV Ab positivity (HR, 3.85, 95% CI, 1.01–14.61), and previous non-HAART therapy (HR, 1.84, 95% CI, 1.04–3.42). Patients receiving stavudine-containing regimens had a lower risk than those receiving zidovudine-containing regimens (HR, 0.30, 95% CI, 0.12–0.71).ConclusionsThere was a low risk of ALT ≥200 IU/L in our cohort. Hepatitis C coinfection and elevated ALT levels at HAART initiation are important predictors of progression to ALT ≥200 IU/L; stavudine-containing regimens were associated with a lower risk compared with zidovudine-containing regimens.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

BackgroundResearch regarding treatment adherence in chronic diseases, such as hypertension, suggests that increasing complexity in the medication regimen is associated with decreasing patient adherence. However, less is known about the relationship between regimen complexity and adherence in the treatment of HIV/AIDS.ObjectiveTo examine the relationship between antiretroviral (ART) regimen complexity and patient understanding of correct regimen dosing to adherence (missing doses in the past 1 and 3 days).MethodsCross-sectional survey of a cohort of women living with HIV/AIDS and enrolled in the HER (HIV Epidemiologic Research) Study.ResultsSeventy-five percent of patients correctly understood the dosing frequency of their ART medications, 80% understood the food-dosing restrictions, whereas only 63% understood both. The percentage of patients with a correct understanding of dosing decreased with increasing regimen complexity (increased dosing frequency and food-dosing restrictions). Patients were more likely to have missed doses in the previous 3 days if they were taking ART medications three or more times per day or had to take one or more antiretrovirals on an empty stomach. A multivariate logistic regression model demonstrated that patients with less complex regimens (twice daily or less in frequency, no food-dosing restrictions) who correctly understood the dosing and food restrictions of their ART regimen were less likely to have skipped doses in the past three days (odds ratio [OR], 0.4; 95% confidence interval [CI], 0.2–0.7) than those with more complex regimens. Younger age and higher CD4 count were also associated with a reduced likelihood of skipping doses. No association was found between adherence and race/ethnicity, current or past injection drug use, or education.ConclusionsSelf-reported adherence is better among patients with less complex ART regimens. This is in part because patients' understanding of regimen dosing decreases as regimen complexity increases. Therefore, simplifying antiretroviral regimens may have an important role in improving patients' adherence.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Exclusive breast feeding has been associated with a lower rate of mother-to-child HIV transmission than breast feeding plus other foods. To obtain further information on biologic outcomes of different feeding modes, we examined 272 infants of HIV-infected South African women at ages 1, 6, and 14 weeks. At each visit information about infant diet and morbidity was collected and infants underwent a lactulose/mannitol dual sugar intestinal permeability test. In a subset of infants, urinary neopterin excretion was measured as an indicator of immune system activation. Infants who had themselves become HIV-infected by 14 weeks had higher (p< .01) intestinal permeability at 6 and 14 weeks and slightly (.05 <p< .1) higher neopterin excretion at all times than uninfected infants. At 1 week infants given no breast milk had higher (p< .05) intestinal permeability than infants given breast milk exclusively or with other foods. Intestinal permeability in infants fed breast milk plus other foods was never increased relative to that of exclusively breastfed infants. Feeding mode had no effect on neopterin excretion. Thus, infant HIV infection induces changes in gut permeability and possibly immune system activation before clinical symptoms become apparent. The effects of feeding mode on infant intestinal permeability or urinary neopterin excretion do not explain a possible protective effect of exclusive breast feeding on mother-to-child transmission of HIV.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

BackgroundInsurance coverage facilitates access to life-saving medications for many patients with HIV disease. Thus, the effects of insurance coverage changes, such as the gain or loss of coverage, may be important in explaining patient access and adherence to the medications used in the treatment of HIV disease.ObjectivesThe study's objective was to examine whether changes in health insurance coverage affect rates of prescription drug use by patients with HIV disease.MethodsData were ascertained from adults participating in a series of up to six interviews as part of the AIDS Costs and Services Utilization Survey (ACSUS). ACSUS was an 18-month panel survey of patients in care for HIV/AIDS at 26 sites located in 10 U.S. cities. Poisson regression analyses with generalized estimating equations were conducted to determine the effects of demographic and socioeconomic variables on the acquisition rate of antiretrovirals, antipneumocystics, and antidepressants. The analytic sample consisted of 1566 respondents who provided 6518 interviews.ResultsAlthough changes in insurance coverage were common, complete loss of insurance was reported in only 1.5% of the interviews whereas gaining insurance was reported in 3.3% of interviews. Having no coverage was associated with significantly lower rates of antiretroviral (rate ratio [RR], 0.73), antipneumocystic (RR, 0.58) and antidepressant use (RR, 0.31). Gaining insurance coverage was associated with lower antiretroviral (RR, 0.75) and antipneumocystic (RR, 0.70) use whereas losing insurance was associated with lower antiretroviral use (RR, 0.58). In multivariate analyses, these associations remained.ConclusionsChanges in health insurance coverage are associated with lower rates of drug use for some medications used by patients with HIV disease.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

BackgroundA new enteric-coated (EC) didanosine (ddI) formulation (Videx EC; Bristol-Myers Squibb, Princeton, NJ, U.S.A.) may be better tolerated than the tablet form because it lacks the buffer component thought to be responsible for diarrhea and other gastrointestinal (GI) side effects.ObjectiveTo evaluate the frequency and magnitude of GI side effects (nausea, bloating, GI upset, diarrhea, abdominal cramps, gas [flatus]) before and after switching the formulation of ddI, in study subjects who were experiencing one or more GI symptom(s) of at least moderate severity.MethodsA 6-week open label crossover study of current didanosine tablet users comparing daily symptom scores (7 point scale, 0 = absent to 6 = very severe) during weeks 1 to 2 (on tablets) to weeks 4 and 6 (on EC capsules). Formulation palatability and preference, lifestyle effects, and use of antidiarrheals or other medications for symptom relief were also assessed.ResultsGI symptom scores (7-day means) on tablets were diarrhea 2.11, gas 2.00, bloating 1.23, abdominal cramps 0.74, GI upset 0.69, nausea 0.66. After switching to EC (week 4 and week 6), mean scores decreased for diarrhea (mean scores 0.99 week 4, 0.79 week 6), gas (0.95, 0.79), bloating (0.49, 0.32), abdominal cramps (0.21, 0.05), GI upset (0.16, 0.14), and nausea (0.32, 0.22). Severity of all GI symptoms was significantly reduced after 4 weeks on EC capsules (p< .01 by pairedt-test). Negative impact of side effects on routine activities was significantly reduced (41% on tablet vs. 7% on EC;p< .01). All 42 study subjects preferred the EC form.ConclusionsAccording to patients' diary scores, switching to ddI in EC form significantly reduces nausea, bloating, GI upset, diarrhea, abdominal cramps, and gas for individuals who experienced GI side effects while taking the buffered tablet form. The striking tolerability advantages appear to support routine switching to EC for such patients and may suggest that widespread preferential selection of the EC form is appropriate to enhance didanosine tolerability and promote treatment adherence.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo assess the effects of five-drug combination therapy on HIV-1 load in lymph nodes and subsequent maintenance with four and three drugs.MethodsTen pharmacotherapeutically naive patients received a combination of zidovudine, lamivudine, didanosine, ritonavir, and saquinavir for 24 weeks, then zidovudine, lamivudine, didanosine, and saquinavir for the next 24 weeks, and finally zidovudine, lamivudine, and saquinavir for the last 24 weeks. HIV-1 RNA in lymph nodes was measured using quantitative polymerase chain reaction (PCR) at baseline, after 12, 24, 48, and 78 weeks. Plasma HIV-1 RNA, proviral DNA in peripheral blood mononuclear cells (PBMCs), circulating lymphocyte subsets, and protease inhibitor levels in blood were also regularly measured. Genotypic resistance was assessed in the different compartments in 2 patients who were failed by therapy.ResultsHIV-1 RNA decreased in lymph nodes in 9 patients and was stable in 1 despite initial control of plasma replication <20 copies/ml in each patient. Lymph node levels rebounded in 1 patient at week 72 as a result of lack of adherence and remained stable in the 8 others despite maintenance regimens. This represents a mean drop of −3.17 log in lymph nodes for the 8 patients maintaining undetectable viremia at 72 weeks. In the patient with stable lymph node viral RNA, selection of the M184V mutation was demonstrated at this level before detection in plasma and low blood saquinavir levels were found throughout the study. Continuous improvements in immune parameters were observed in all cases, although PBMC proviral DNA levels either showed a continuous decrease or stabilized to a plateau.ConclusionsMore complex regimens do not perform better in lymph nodes than classic triple therapy. The persistence of HIV-1 RNA in lymph nodes could be related with cellular resistance mechanisms rather than an insufficient potency of the regimens.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo evaluate the effect of time from seroconversion to a given CD4 cell count on progression to AIDS after that count after adjusting for updated CD4 cell counts.MethodsUsing pooled data from 19 seroconverter cohorts, we examined the association between the time from a CD4 <500 cells/mm3, (<350, <200) to the first AIDS-defining event and time from seroconversion to that CD4 threshold. We adjusted for age, gender, exposure category, and HIV test interval in Cox models stratified by cohort. We estimated the residual effect of time from seroconversion, adjusting for updated CD4 cell counts. A cause-specific competing-risks model was then used to evaluate this residual effect on progression to each AIDS-defining disease. Analyses were censored on December 31, 1995.ResultsOf 3825, 3006, and 1804 individuals reaching CD4 thresholds of 500, 350, and 200, respectively, 1274, 1192, and 985, respectively, developed AIDS. We found a significant effect of time from seroconversion on the risk of AIDS even after adjusting for updated CD4 counts. For individuals reaching a CD4 threshold of 350 cells/mm3, a 1-year increase from seroconversion was associated with an increase in risk of AIDS of 6% (3%–9%) (p= .01). This effect appeared to be nonlinear. In the first 4 years, a 1-year increase from seroconversion was associated with an 11% increase in the risk of AIDS, but there was no apparent increase in risk after 4 years. The residual effect of time from seroconversion was significantly heterogeneous (p= .002), with respect to the risk of individual AIDS-defining diseases. Findings were similar for CD4 thresholds of 500 and 200 cells/mm3, respectively.ConclusionsWe found a small, statistically significant, residual effect of time from seroconversion on the risk of AIDS. In practical terms, when considering an infected individual's risk of AIDS from a given CD4 cell count, there is little to be gained from knowing the time of seroconversion. However, this effect differs significantly among specific AIDS-defining diseases.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesTo determine predictors for sexual risk behavior among immigrant men in Amsterdam.MethodsFrom May 1997 to July 1998, 650 men from Surinam, the Antilles, and Ghana were recruited by convenience sampling. Multivariate logistic regression was used to find independent predictors for 1) multiple sex partners (>sexual 1 partner in the past year), 2) unprotected sex with casual partners in The Netherlands, 3) sexual activity in country of origin, and 4) unprotected sex in country of origin.Results1) Multiple sex partners were reported by 50% of respondents. Independent predictors were a recent infection with a sexually transmitted disease (STD), youth, low educational level, Afro-Surinamese origin, lack of a long-term relationship and history of commercial sex contact. 2) Unprotected sex occurred in 24% of casual partnerships. Independent predictors were a recent STD infection, low educational level, use of hard drugs, age between 20 and 29, few sexual partners, unprotected sex in country of origin, and a partner from the respondent's ethnic group. 3) During the past 5 years, 24% were sexually active in country of origin. Independent predictors were Ghanaian origin, age over 20, a relatively high income, and multiple partners. 4) Unprotected sex occurred in 39% of the partnerships in country of origin. Independent predictors were low educational level, history of STDs, lack of health insurance, Ghanaian origin, frequent visits to home country, few sexual partners, and unprotected sex with casual partners in The Netherlands.ConclusionAmong immigrant men in Holland, important target groups for AIDS prevention programs have been identified. Men who visit their country of origin should be made aware of the risk of sexual contact with local women. Furthermore, it should be taken into account that immigrant men use condoms less frequently with women of their own ethnic group than with Dutch women.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveCritical review of worldwide legislation on HIV/AIDS, with a focus on the issue of HIV testing, mainly in a military context.DesignAnalysis of health legislation on HIV/AIDS among 121 of the 191 member states of the World Health Organization (WHO), representing 85% of the world's population.MethodsThe WHO Directory of Legal Instruments Dealing with HIV Infection and AIDS has been the main source consulted. Relevant findings of two global surveys were used to examine HIV testing in the military.ResultsAIDS cases are reportable in 60% of the 121 countries, whereas HIV infections in no more than 26%.Notifications are kept confidential by law in 20% of countries. Only 17% have developed HIV-specific legislation against social discrimination, whereas 10% have passed legislation establishing financial reimbursement to those who have acquired HIV infection after injection of HIV-contaminated biologic material, support for occupational risk, and/or social protection for patients.Only 42% of the 121 countries report having legal instruments that require screening of donated blood. Legislative measures that address, generally in a prescriptive but sometimes also in a protective way, vulnerable groups, such as commercial sex workers, men who have sex with men, injecting drug users, and recipients of multiple transfusions of blood or blood-derivatives, are reported in 27% of countries. Other categories considered potentially vulnerable, for which specific legislation has been passed, include immigrants (17% of countries), prisoners (5%), and health personnel (14%). Further legislative measures for HIV prevention address testing pregnant women in the prenatal period (7% of countries), supporting condom promotion (11%), measures requiring quarantine, isolation, or coercive hospitalization of HIV-infected people or AIDS patients (9%), or imposing penal sanctions for HIV-infected people who deliberately expose others to the risk of transmission (10%). A National AIDS Committee responsible for addressing issues related to HIV/AIDS has been established by law in 39% of the 121 countries.Global surveys show that 27 countries carry out compulsory HIV screening on recruitment of military personnel.ConclusionsThese data represent a useful tool to make governments aware of the problem of underreporting of legal instruments to the WHO and of the need to promote legislation in line with the idea that public health and human rights are complementary, not conflicting, goals.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID