Acyclovir in combination with zidovudine does not prolong survival in advanced HIV disease

The aim of this study was to evaluate the association between acyclovir use and survival in HIV-infected patients. To achieve this, we used survival analysis in an observational cohort of HIV-infected patients enrolled in primary care at an urban HIV clinic. We measured survival in a cohort of HIV-infected patients who had CD4 cell counts < or = 500/mm3 and who enrolled for care at a single urban HIV clinic between December 1988 and April 1995. We compared survival in users of acyclovir alone, zidovudine alone, and acyclovir and zidovudine in combination with the survival of those using neither drug. Factors associated with improved survival were identified using Cox proportional hazards analysis. Among the 1408 patients enrolled, there were no significant differences in overall survival between acyclovir users and non-users. After adjustment for CD4 cell count, the use of other antiretroviral agents, race, transmission risk and a history of herpesvirus infection, acyclovir use alone was independently associated with a relative hazard (RH) of death of 1.008 (P = 0.969); zidovudine use alone with a RH of 0.559 (P < 0.001); and combination use of acyclovir and zidovudine associated with a RH of 1.062 (P = 0.788). Therefore we conclude that the use of acyclovir is not associated with prolonged survival in this cohort of HIV-infected patients.     

Ethical issues.

The HIV virus and the associated worldwide pandemic pose enormous biomedical, clinical, and social dilemmas for health care providers, biomedical researchers, policy analysts, and the public at large 10 years after its discovery. Many of these dilemmas and challenges are captured in the difficult ethical issues the HIV epidemic has highlighted for primary care physicians. Given the vanishingly small risk to primary care providers of acquiring HIV infection in office practice and the rapidly increasing prevalence of the virus, a clear ethical obligation to care for HIV-infected patients exists for primary care physicians. Primary care providers should be sensitive to the potentially sensitive nature of patient risk status and HIV testing results and balance confidentiality in the medical record with the "need to know" the patient's clinical status by other health care professionals. Every attempt should be made by the primary care provider to encourage HIV-infected patients to act responsibly toward their intimate sexual partners and inform them of their HIV status to take appropriate precautions against acquiring the virus. Primary care providers should also model responsible shared decision making and goal setting with HIV-infected patients early in the course of the disease, laying the foundation for subsequent decision making later in the course of the illness. Finally, considerable controversy exists about the responsibilities of HIV-infected providers to inform patients of their status; professional and public policy in this area is in rapid flux. Undoubtedly, the HIV epidemic will continue to challenge us and force careful examination of many of the critical dilemmas in modern biomedical ethics.     

Health care providers' influence on HIV-infected women's beliefs and intentions related to AZT therapy

This study examined how women's relationship with their primary health care provider (PHP) and their perceptions about how effective their PHPs believe zidovudine (AZT) to be in decreasing perinatal transmission related to women's AZT beliefs and intentions. It used a cross-sectional design to collect data from 59 HIV-infected African American women. Almost half the women (45%) had given birth since HIV diagnosis. Most of the babies born to HIV-infected mothers (87%) were seronegative. Data analysis with Pearson's r indicated that the quality of the women's relationship with their PHP was positively correlated to how important the PHP would be in decision making related to AZT therapy. Significant positive correlation was observed between women's perceptions about how effective their PHPs believed AZT to be in decreasing perinatal HIV transmission and the women's own beliefs about AZT, their intent to take AZT if pregnant, and intent to give AZT to a newborn.     

Prevention of perinatal HIV transmission during pregnancy

Transmission of the human immunodeficiency virus (HIV) from mother to child can occur in utero, during labour or after delivery from breastfeeding. The majority of infants are infected during delivery. Maternal HIV-1 plasma viral load at delivery is the most important predictor of vertical transmission. For this reason, efforts to interrupt transmission have focused on the use of antiretroviral therapy. Zidovudine has been shown to reduce significantly vertical HIV transmission when used antepartum and intrapartum by the mother and postpartum by the newborn for 6 weeks. However, zidovudine monotherapy increases the risk of developing zidovudine resistance and may jeopardize the goal of durable viral suppression and allow HIV disease progression in the mother and transmission to the infant. Potent antiretroviral therapy is now recommended for all HIV-infected pregnant women using the same criteria for non-pregnant individuals. If possible, combination antiretroviral regimens should include the use of zidovudine but not at the expense of long-term viral suppression. The use of elective Caesarean section should probably be reserved for women who fail to achieve viral suppression at the time of delivery or if indicated for obstetrical reasons. The practice of breastfeeding has been shown to diminish the long-term efficacy of perinatal antiretroviral therapy. All HIV-infected mothers should avoid breastfeeding the newborn if possible. This review summarizes major prospective and retrospective antiretroviral treatment studies in HIV-infected pregnant women. Pharmacokinetic information as it relates to pregnancy and adverse event profiles of antiretroviral agents are also discussed. The impact of recent advances in the management of HIV infection in pregnancy is discussed with regard to their feasibility in resource-poor countries.     

Primary care of HPV management in HIV-infected women

The natural history of human papillomavirus (HPV) differs in women infected with (human immunodeficiency virus) HIV when compared with the general population. This report provides insight into the complexities of treating HPV infection and the differences found in HIV-infected women. By understanding the challenges associated with this opportunistic infection in HIV-infected women, nurse practitioners will be better prepared to provide primary care to this specific population.     

HIV感染者/AIDS患者心理状态及护理干预研究进展

通过CHKD和Medline查找资料，对HIV感染者/AIDS患者心理状态及其影响因素、护理干预方法等方面的研究进行综述，旨在为国内开展相关的HIV感染者/AIDS患者心理护理研究提供依据。     

Are nurse practitioners prepared for the AIDS epidemic?

Treatment of HIV-infected individuals will become a regular part of mainstream medical practice because of the increasing numbers of infected persons, the geographical dispersion of the disease, and the routine nature of much of the care required by seropositive patients. Nurse practitioners, like other health care professionals, need to be willing and able to provide such primary care. One hundred sixty-five NPs constituted an opportunity sample that was surveyed using an instrument that had been adapted from one used successfully in studies of other health professionals. The instrument consisted of 80 forced-answer and six open-ended questions. The response rate was 63 percent. It was found that nurse practitioners believed there was moderate risk of occupational contraction of HIV. NPs were more likely to agree on activities they believed to be of low risk than about the danger of perceived higher-risk activities. The respondents judged themselves as fairly competent in their ability to provide counseling and information to patients about HIV and risk-reduction. Half believed that their lack of knowledge was the biggest barrier to providing care to HIV-infected persons. Eighty-five percent thought courses on the medical aspects of AIDS were necessary, and 78 percent wanted courses in the social, ethical and legal implications of the disease. This study shows that there is a widely perceived need for continuing education on both medical and social aspects of AIDS in order to enable nurse practitioners to play a greater role in primary care provision for persons with AIDS.     

Management of cancer in the elderly

More than 1 million Americans may now be infected with the human immunodeficiency virus (HIV), which may not progress to acquired immunodeficiency syndrome (AIDS) for 10 years. Therefore, primary care physicians should be prepared to care for HIV-infected patients in the early stages of their illness. In this article, Dr Sarti provides specific advice on counseling and managing these patients.     

Susceptibility of Treponema pallidum and other selected spirochaetes to zidovudine.

The antiviral nucleoside derivative zidovudine (3'-azido-3'-deoxythymidine) previously has been shown to be an effective antibacterial agent in animals infected with Escherichia coli or Salmonella typhimurium. Since HIV infection can alter the course of human syphilis with serious consequences, it was of interest to determine if the noncultivable spirochaetal agent of syphilis, Treponema pallidum, is susceptible to this compound. The progression of experimental rabbit syphilis over a three week period was unchanged in animals receiving either 50 or 150 mg/kg oral zidovudine daily. In addition, a number of cultivable pathogenic and nonpathogenic spirochaetes were tested for susceptibility to zidovudine in vitro. At a concentration of 100 mg/L, zidovudine had no detectable effect on spirochaete growth, morphology, or motility. Thus it appears that spirochaetes are generally not susceptible to this compound, and that long-term zidovudine therapy will not be of benefit in preventing or controlling syphilis or other spirochaetoses in HIV-infected humans receiving this drug.     

Recent advances in the treatment of HIV/AIDS

In industrialized countries, highly active antiretroviral therapy has resulted in significant reductions in morbidity and mortality in patients with HIV/AIDS. At the same time, the management of the HIV-infected individual has become exceedingly complex due to the increasing number of antiretroviral medications and resistance to them. New medications are needed that are effective against the drug-resistant virus. The key advances in the management of HIV/AIDS as seen through the eyes of a front-line HIV physician who has been actively involved in patient care, clinical drug trials and as an educator for the past 15 years will be discussed.     

Clinical review: Respiratory failure in HIV-infected patients - a changing picture

Respiratory failure in HIV-infected patients is a relatively common presentation to ICU. The debate on ICU treatment of HIV-infected patients goes on despite an overall decline in mortality amongst these patients since the AIDS epidemic. Many intensive care physicians feel that ICU treatment of critically ill HIV patients is likely to be futile. This is mainly due to the unfavourable outcome of HIV patients with Pneumocystis jirovecii pneumonia who need mechanical ventilation. However, the changing spectrum of respiratory illness in HIV-infected patients and improved outcome from critical illness remain under-recognised. Also, the awareness of certain factors that can affect their outcome remains low. As there are important ethical and practical implications for intensive care clinicians while making decisions to provide ICU support to HIV-infected patients, a review of literature was undertaken. It is notable that the respiratory illnesses that are not directly related to underlying HIV disease are now commonly encountered in the highly active antiretroviral therapy (HAART) era. The overall incidence of P. jirovecii as a cause of respiratory failure has declined since the AIDS epidemic and sepsis including bacterial pneumonia has emerged as a frequent cause of hospital and ICU admission amongst HIV patients. The improved overall outcome of HIV patients needing ICU admission is related to advancement in general ICU care, including adoption of improved ventilation strategies. An awareness of respiratory illnesses in HIV-infected patients along with an appropriate diagnostic and treatment strategy may obviate the need for invasive ventilation and improve outcome further. HIV-infected patients presenting with respiratory failure will benefit from early admission to critical care for treatment and support. There is evidence to suggest that continuing or starting HAART in critically ill HIV patients is beneficial and hence should be considered after multidisciplinary discussion. As a very high percentage (up to 40%) of HIV patients are not known to be HIV infected at the time of ICU admission, the clinicians should keep a low threshold for requesting HIV testing for patients with recurrent pneumonia.     

Recent advances in the treatment of HIV/AIDS

In industrialized countries, highly active antiretroviral therapy has resulted in significant reductions in morbidity and mortality in patients with HIV/AIDS. At the same time, the management of the HIV-infected individual has become exceedingly complex due to the increasing number of antiretroviral medications and resistance to them. New medications are needed that are effective against the drug-resistant virus. The key advances in the management of HIV/AIDS as seen through the eyes of a front-line HIV physician who has been actively involved in patient care, clinical drug trials and as an educator for the past 15 years will be discussed.     

Data and safety monitoring in the Concorde and Alpha trials.

Concorde was a randomized trial to compare immediate and deferred zidovudine (AZT) treatment for persons with asymptomatic HIV infection. Alpha was a randomized trial to compare the efficacy of two doses of didanosine (ddI), in persons with symptomatic HIV disease who were intolerant of zidovudine. The two trials overlapped in time, and a single Data and Safety Monitoring Committee (DSMC) monitored accumulating data from both trials. This paper describes the deliberations of the DSMC and its recommendations to the parent steering committee during the course of each trial. In the discussion on Concorde, I draw attention to the problems of interpreting early survival data and trends in surrogate markers. With Alpha, interest focusses on the conflicting considerations that arose in discussions about possible termination at an interim stage.     

Simplified treatments for HIV infection

The treatment of HIV infection is reputedly complicated. Indeed, in 1996 and 1997, the most widely used regimen implied five separate pill ingestions every day: A heavy burden even without side effects. Since then, however, treatment has been greatly simplified. The most widely used regimen in Switzerland is the combination of zidovudine, lamivudine and efavirenz, with 1 pill in the morning and 2 pills in the evening. The Swiss HIV Cohort has shown that simplifying therapy increases the success of HIV treatment. Once daily administration will soon be part of standard care, as clinical trials have shown promising results. In the future, many patients may well treat their HIV infection intermittently. Scheduled treatment interruptions are under intensive investigation in Switzerland and elsewhere. Large scale studies with long follow-up are necessary and the first results can not be expected before the end of 2005.     

Late presentation of HIV-infected individuals

Late presentation remains a major concern despite the dramatically improved prognosis realized by ART. We define a first presentation for HIV care during the course of HIV infection as 'late' if an AIDS-defining opportunistic disease is apparent, or if CD4+ T-cells are <200/microl. In the Western world, approximately 10 and 30% of HIV-infected individuals still present with CD4+ T-cells <50 and <200/microl, respectively; estimates are substantially higher for developing countries. Diagnosis and treatment of opportunistic diseases and intense supportive in-hospital care take precedence over ART. Benefits of starting ART without delay, that is, when opportunistic diseases are still active, include faster resolution of opportunistic diseases and a decreased risk of recurrence. The downside of starting ART without delay could include toxicity, drug interactions and immune reconstitution inflammatory syndrome (IRIS). Among asymptomatic or oligosymptomatic individuals presenting late, where ART and primary prophylaxis are initiated, approximately 10-20% will become symptomatic from drug toxicity or undiagnosed opportunistic complications, including IRIS, which require appropriate therapies. In this review we describe late presentation to HIV care, the scale of the problem, the evaluation of a late-presenting patient and challenges associated with initiation of potent antiretroviral therapy (ART) in the setting of acute opportunistic infections and other comorbidities.     

Report of the symposium on the use of intravenous gammaglobulin in adults infected with the human immunodeficiency virus.

On July 27, 1989, the International Conference on Molecular Aspects of Immune Response and Infectious Diseases devoted a symposium to the subject of the use of intravenous gamma globulin (IVIG) in acquired immunodeficiency syndrome (AIDS). The information presented confirmed that IVIG benefits human immunodeficiency virus (HIV)-infected children with recurrent infections and that much remains to be learned about the influence of IVIG in adult AIDS. The symposium participants recognized the urgent need to develop randomized clinical trials using a control group to assess the efficacy of a treatment with IVIG in PGL (persistent generalized lymphadenopathy), ARC (AIDS-related complex), and AIDS. To prepare this report, a committee was established, including individuals with expertise in immunology, immunopharmacology, microbiology, virology, infectious diseases, general medicine, and pediatrics and representing research experience in academia and hospitals. After an introduction to the report with a summary of immunotherapeutic agents under evaluation to treat HIV infection, section 1 lays out the present understanding of the disease pathogenesis. Section 2 then outlines the treatment of HIV-seropositive individuals, discussing the uncertainties that any treatment entails. Section 3 discusses the rationale for treating HIV-infected individuals with IVIG, and Section 4 examines the major differences between IVIG and hyperimmunoglobulins for the treatment of HIV infection. Section 5 looks at IVIG as a mean to delay the emergence of opportunistic infections and restore immunocompetence in AIDS and related illnesses, and Sections 6 and 7 suggest a pilot protocol on the use of IVIG in association with low-dose or standard-dose zidovudine (AZT).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hydroxyurea and didanosine is a more potent combination than hydroxyurea and zidovudine

The in vitro and in vivo antiviral activity of hydroxyurea in combination with either zidovudine or didanosine was evaluated in primary human peripheral mononuclear cells and in a cohort of 29 asymptomatic patients infected with HIV. In vitro, hydroxyurea alone did not significantly affect HIV replication, whereas the combination of hydroxyurea with didanosine was more effective than the combination of hydroxyurea with zidovudine. Our clinical results confirmed these studies. Patients were randomly assigned to five arms (zidovudine, hydroxyurea or didanosine monotherapy, or hydroxyurea in combination with either zidovudine or didanosine) to evaluate preliminary safety and efficacy. Bone-marrow toxicity occurred in two patients treated with zidovudine plus hydroxyurea, alopecia was reported in one patient treated with hydroxyurea monotherapy, and there were no toxic effects recorded in the remaining three groups. Plasma viraemia was not influenced by hydroxyurea monotherapy, and the hydroxyurea-zidovudine combination did not give any advantage over either zidovudine or didanosine monotherapy (0.3-0.5 log decrease in plasma viraemia). In contrast, a 1.1 log drop in plasma viraemia was observed in patients treated with hydroxyurea plus didanosine, this reduction was sustained throughout the 24-week course of the treatment. Combination therapy with hydroxyurea and didanosine exhibited statistically significant improvements compared with the other therapeutic approaches. Although further clinical trials are required, these results suggest that hydroxyurea in combination with didanosine might be an effective and well-tolerated, simple and affordable, treatment for HIV infection.