Antiretroviral therapy in adults: updated recommendations of the International AIDS Society-USA Panel

OBJECTIVE: To update recommendations for antiretroviral therapy for adult human immunodeficiency virus type 1 (HIV-1) infection, based on new information and drugs that are available. PARTICIPANTS: A 17-member international physician panel with antiretroviral research and HIV patient care experience initially convened by the International AIDS Society-USA in December 1995. EVIDENCE: Available clinical and basic science data including phase 3 controlled trials; data on clinical, virologic, and immunologic end points; research conference reports; HIV pathogenesis data; and panel expert opinion. Recommendations were limited to therapies available (US Food and Drug Administration approved) in 1999. CONSENSUS PROCESS: The panel assesses new research reports and interim results and regularly meets to consider how the new data affect therapy recommendations. Recommendations are updated via full-panel consensus. Guidelines are presented as recommendations if the supporting evidence warrants routine use in the particular situation and as considerations if data are preliminary or incomplete but suggestive. CONCLUSIONS: The availability of new antiretroviral drugs has expanded treatment choices. The importance of adherence, emerging long-term complications of therapy, recognition and management of antiretroviral failure, and new monitoring tools are addressed. Optimal care requires individualized management and ongoing attention to relevant scientific and clinical information in the field.     

Evidence-based guidelines for universal counselling and offering of HIV testing in pregnancy in Canada

OBJECTIVE: To provide Canadian health care workers with evidence-based guidelines for universal counselling about HIV testing and the offering of such testing to all pregnant women. OPTIONS: Universal counselling and offering of HIV testing to all pregnant women versus targeted testing of only pregnant women at high risk for HIV infection. Antiretroviral treatment protocols for HIV-positive mothers and their infants are discussed as the intervention to reduce mother-to-child transmission rates. OUTCOMES: Main outcomes are mother-to-child HIV transmission rates and consequences of HIV testing on the mother and infant. EVIDENCE: Articles published from January 1985 to March 1997 identified through a MEDLINE search; articles published in pertinent medical journals in 1996 and 1997 identified through a manual search; and abstracts presented at international HIV/AIDS conferences. BENEFITS, HARMS AND COSTS: Early diagnosis of HIV infection in a pregnant woman optimizes her medical and psychosocial care, decreases the incidence of mother-to-child transmission and decreases the risk of horizontal transmission to sexual partners. New, third-generation HIV tests have reduced false-positive rates and thus diminished the harm of screening. RECOMMENDATIONS: A screening strategy consisting of universal counselling and offering of HIV testing is recommended for all pregnant women in Canada (grade B recommendation). Targeted testing of only pregnant women at high risk for HIV infection fails to identify a substantial proportion of HIV-positive pregnant women and is therefore not recommended (grade D recommendation). Women who identify themselves as being at high risk and whose initial HIV test result is negative should be counselled about the reduction of high-risk behaviours and retested in 6 months (grade B recommendation). Treatment of seropositive women and infants with zidovudine to prevent mother-to-child transmission is recommended (grade A or B recommendation depending on gestational age and CD4 count). VALIDATION: These guidelines are endorsed by the Canadian Pediatric AIDS Research Group and are in agreement with the recommendations of the Canadian Paediatric Society and the US Public Health Service Task Force.     

Reduction in mortality with availability of antiretroviral therapy for children with perinatal HIV-1 infection. Italian Register for HIV Infection in Children and the Italian National AIDS Registry

CONTEXT: Since the introduction of combined antiretroviral therapy, mortality rates in adults with human immunodeficiency virus type 1 (HIV-1) infection have decreased. However, little information is available outside the setting of controlled trials on survival of perinatally HIV-infected children treated with antiretroviral therapy. OBJECTIVE: To assess effect of availability of antiretroviral therapy on decreasing mortality in perinatally HIV-infected children. DESIGN: Population-based, multicenter longitudinal study involving data collected by the Italian Register for HIV Infection in Children. SETTING: A network of 106 pediatric clinical centers. SUBJECTS: A total of 1142 children born between November 1980 and December 1997 with perinatally acquired HIV infection with a median follow-up of 5.9 years. MAIN OUTCOME MEASURE: Time to HIV-related death calculated for birth cohort and calendar period and grouped by distribution of predominant type of antiretroviral therapy administered over time. RESULTS: Survival was longer in the 1996-1997 birth cohort (crude relative hazard [RH] of death, 0.39; 95% confidence interval [CI], 0.15-0.96) and 1996-1998 calendar period (crude RH of death, 0.65; 95% CI, 0.45-0.95) than in birth cohort and calendar period 1980-1995, but not when adjusted for maternal antiretroviral treatment during pregnancy and clinical condition at time of delivery, gestational age, and birth weight (adjusted RH of death, 0.55; 95% CI, 0.20-1.50, for birth cohort; and adjusted RH of death, 0.71, 95% CI, 0.43-1.16, for calendar period). In a multivariate model with 1980-1995 as comparison, the 1996-1997 birth cohort had an RH of 0.57 (95% CI, 0.22-1.47; P=.27) but RH for calendar period 1996-1998 was 0.63 (95% CI, 0.47-0.85; P<. 01). When the effects of birth cohort, calendar period, and type of antiretroviral therapy were evaluated simultaneously in the same model, the RH of death was not significantly different from 1.0 for the 1996-1997 birth cohort (P=.19) and calendar period 1996-1998 (P=. 83) suggesting a causal relationship between decreased risk of death and use of combination therapy. The RH of death in children receiving monotherapy or double or triple combination therapy was 0. 77 (95% CI, 0.55-1.08), 0.70 (95% CI, 0.42-1.17), and 0.29 (95% CI, 0.13-0.67), respectively, vs no antiretroviral therapy. CONCLUSION: Survival of perinatally HIV-infected children improved in 1996-1998 as a result of the introduction of combined antiretroviral therapies. JAMA. 2000;284:190-197     

Hope and caution: report from the XI International Conference on AIDS.

The XI International Conference on AIDS brought hope to people infected with HIV and to their physicians. The amount of HIV RNA in an infected person's plasma--the viral load--can be quantified to predict the course of the disease and provide a basis for therapeutic decisions. Various combinations of antiretroviral agents can reduce viral load and decrease the risk of progression to AIDS and death. The high cost of these drugs together with the potential for low patient compliance and for the emergence of drug-resistant mutations of HIV represent obstacles to successful treatment. Speakers at the conference explained the dynamics of viral replication and the immune response to HIV infection, and provided preliminary results of studies designed to test the feasibility of eradicating HIV from the body. New guidelines for antiretroviral therapy were presented at a satellite symposium, but the prospects for the long-term success of antiretroviral therapy are unknown.     

Use of interventions for reducing mother-to-child transmission of HIV in Australia

OBJECTIVE: To describe the extent and outcome of use of interventions for reducing the risk of HIV transmission from mother to child in Australia. DESIGN: National surveillance for perinatal exposure to HIV. PARTICIPANTS AND SETTING: Notified cases of HIV infection in women in Australia and their perinatally exposed children, 1982-1999. OUTCOME MEASURES: Trends over time in use of interventions (antiretroviral therapy in pregnancy, elective caesarean delivery and avoidance of breastfeeding) and perinatally acquired HIV infection. RESULTS: By 31 March 2000, 204 children were reported as having been born in 1982-1999 to 162 women whose HIV infection had been diagnosed by 31 December 1999. The child's HIV infection status was established for 182 (89.2%); the mother's HIV infection was diagnosed antenatally in 91 of these cases (50%). Among women diagnosed antenatally, use of elective caesarean delivery and antiretroviral therapy in pregnancy increased significantly, from 3% and 14% by women whose children were born in 1982-1993, to 21% (P=0.01) and 88% (P<0.001), respectively, by women whose children were born in 1994-1999. Most women (95%) diagnosed antenatally avoided breastfeeding their children. The percentage of infected children born to women diagnosed antenatally declined from 26% among children born in 1982-1993 to 19% among those born in 1994-1999. The percentage of infected children was significantly lower among those whose mothers used antiretroviral therapy in pregnancy (11% versus 36%; P=0.03). CONCLUSION: Antiretroviral use in pregnancy, elective caesarean delivery and avoidance of breastfeeding have been effective interventions for reducing the risk of mother-to-child HIV transmission in Australia. While the rate of perinatal HIV transmission has declined, it remains high in comparison with rates reported from other industrialised countries.     

Guidelines for the identification, investigation and treatment of individuals with concomitant tuberculosis and HIV infection. Bureau of Communicable Disease Epidemiology, Canada Department of National Health and Welfare.

The following recommended guidelines, jointly prepared by the Canadian Thoracic Society, the Tuberculosis Directors of Canada, and the Department of National Health and Welfare in consultation with the provincial and territorial epidemiologists, AIDS coordinators and HIV caregivers, and approved by the Canadian Lung Association and the Canadian Thoracic Society are provided to assist health care workers who are caring for patients in the overlapping group.     

Qualitative evaluation of the Canadian Medical Association's counselling guidelines for HIV serologic testing.

OBJECTIVE: To evaluate the face and content validity of the CMA's counselling guidelines for HIV serologic testing in order to prepare a revised edition. DESIGN: Qualitative evaluation by structured focus groups in September and October 1994 to assess the relevance, clarity and practicality of the guidelines, followed by content analysis of the discussions. SETTING: Vancouver, Winnipeg, Toronto, Montreal, Quebec City and St. John's. PARTICIPANTS: Primary care physicians randomly selected from the CMA database and nonrandomly selected from the Canadian Medical Directory who had limited experience with HIV testing and counselling and who provided an appropriate mix of characteristics in terms of practice type (solo and group), setting (urban and rural), age and sex. A total of 1247 physicians were approached for the study; a convenience sample of 68 were recruited, of whom 56 participated. The average size of each focus group was eight physicians. OUTCOME MEASURES: Clinical experience and information sources with respect to HIV testing, reactions to the counselling guidelines, and suggestions for revisions and improvements to the guidelines. RESULTS: Most (96% [54/56] of the participants had ordered HIV serologic testing for patients in the 6 months preceding the focus groups, and about half of them (52% [28/54]) had at least one patient with a positive test result. Many (59% [33/56]) of the participants had a copy of the guidelines at the time of recruitment; 19 (58%) of them had used the guidelines in the months before the focus groups. The parts of the guidelines most often read were the checklists and inset boxes. Recommendations for revisions in content were for more information on legal and ethical issues, information on new issues (e.g., rapid testing) and guidelines on how best to tell a patient about a positive test result; recommendations for revisions in format included more tables, algorithms, bulleted points and white space, less text, larger type and plainer language. CONCLUSIONS: The focus groups provided detailed, credible and consistent information about the face and content validity of the HIV counselling guidelines. They are a useful qualitative method for evaluating the relevance, clarity and practicality of clinical practice guidelines at the inception or revision stage.     

Epidemiology of HIV infection in Lebanon. Data from 1985-2005

Lebanon is considered among the countries where the HIV epidemic is still in its early phase of spread. Little information is available on the magnitude of the problem due to the lack of an efficient surveillance system. In this review, we report on the epidemiology of HIV infection in Lebanon, based on limited data generated by the Lebanese National AIDS Control Program (NAP). By May 2005, a cumulative number of 813 cases had been diagnosed. The most prevalent mode of HIV transmission in Lebanon is heterosexual exposure accounting for around 50% of the cases. Two hundred ninety-six patients (36.4%) fulfilled the AIDS case definition. Despite the availability of highly active antiretroviral therapy (HAART) provided by the Ministry of Health, the disease burden of HIV infection remains unknown in this country.     

Highly active antiretroviral therapy per se decreased mortality and morbidity of advanced human immunodeficiency virus disease in Hong Kong

Background Morbidity and mortality of advanced human immunodeficiency virus infection (HIV) have declined in Western industrialized countries since the availability of highly active antiretroviral therapy (HAART). It is unclear if this has also happened in Hong Kong.Methods We studied a retrospective cohort of patients with advanced HIV disease in Hong Kong, China. First, the mortality of advanced HIV disease per year was calculated for the decade 1993 to 2002, both annually and according to patient observation before and after 1997. Second, the event rates were estimated for the clinical end points of acquired immune deficiency syndrome (AIDS) and death. Univariate and multivariate analyses were then performed to identify associated factors. Results The crude mortality of advanced HIV disease declined from 10.8-30.4 per 100 patients during 1993-1996, to 0.8-6.9 per 100 patients during 1997-2002. A rate ratio of 4.04 (95% CI, 2.52-6.47) was evident for those observed in 1993-1996, compared to those in 1997-2002. In a multivariate analysis where calendar period was adjusted, use of highly active antiretroviral therapy was associated with rate ratios of 0.13 (95% CI, 0.05-0.33) for death after AIDS, 0.08 (95% CI, 0.04-0.19) for AIDS after a CD4 cell count &lt;200/μl, and 0.21 (95% CI, 0.07-0.67) for death after CD4 cell count &lt;200/μl. In the same analysis, calendar period ceased to be a significant factor after adjustment for use of HAART.Conclusions The mortality and morbidity of advanced human immunodeficiency virus disease have declined in Hong Kong. This improved prognosis was attributable to the use of highly active antiretroviral therapy.     

Developing ethics guidance for HIV prevention research: the HIV Prevention Trials Network approach

More than 25 years into the HIV epidemic, in excess of 2 million new infections continue to occur each year. HIV prevention research is crucial for groups at heightened risk for HIV, but the design and conduct of HIV prevention research with vulnerable populations worldwide raises considerable ethical challenges. The HIV Prevention Trials Network (HPTN) is a global collaborative network that conducts clinical and behavioural studies on non-vaccine interventions to reduce the transmission of HIV. In 2003, the HPTN developed ethical guidance to enhance the responsible conduct of its research activities and as a distinctive contribution to global research ethics. In what follows, the developments that motivated the drafting of a revised ethics document in 2009 are described, including the process by which that revision took place and some of the key differences between the HPTN ethics guidance and other relevant guidelines in the field.     

Routine prenatal screening for HIV in a low-prevalence setting

BACKGROUND: The objectives of this study were to assess the effect of British Columbia's June 1994 guidelines for prenatal HIV screening on the rate of maternal-fetal HIV transmission and to estimate the cost-effectiveness of such screening. METHODS: The authors conducted a retrospective review of pregnancy and delivery statistics, HIV screening practices, laboratory testing volume, prenatal and labour management decisions of HIV-positive women, maternal-fetal transmission rates and associated costs. RESULTS: Over 1995 and 1996, 135,681 women were pregnant and 92,645 carried to term. The rate of HIV testing increased from 55% to 76% of pregnancies on chart review at one hospital between November 1995 and November 1996. On the basis of seroprevalence studies, an estimated 50.2 pregnancies and 34.3 (95% confidence interval 17.6 to 51.0) live births to HIV-positive women were expected. Of 42 identified mother-infant pairs with an estimated date of delivery during 1995 or 1996, 25 were known only through screening. Of these 25 cases, there were 10 terminations, 1 spontaneous abortion and 14 cases in which the woman elected to carry the pregnancy to term with antiretroviral therapy. There was one stillbirth. One instance of maternal-fetal HIV transmission occurred among the 13 live births. The net savings attributable to prevented infections among babies carried to term were $165,586, with a saving per prevented case of $75,266. INTERPRETATION: A routine offer of pregnancy screening for HIV in a low-prevalence setting reduces the rate of maternal-fetal HIV transmission and may rival other widely accepted health care expenditures in terms of cost-effectiveness.     

HIV感染者合并肛门尖锐湿疣的临床特征及治疗

目的研究尖锐湿疣合并HIV感染的临床特征和治疗方法。方法对20例尖锐湿疣合并HIV感染者的临床资料做回顾性分析。患者男性19例,女性1例;年龄19～61岁,平均(40.7±11.3)岁,术前检测CD4T淋巴细胞水平和血常规。电刀切除尖锐湿疣,应用高效抗逆转录病毒治疗和应用抗生素控制感染,及时处理并发症。结果患者的CD4T淋巴细胞为22～363(156.84±84.93)cell/μl,CD4/CD8比值为0.305±0.456,明显低于正常。4例形成巨型尖锐湿疣,2例发生癌变。手术切除后3个月内有4例复发,12个月内有6例复发。结论尖锐湿疣合并HIV感染患者免疫力低下,容易形成巨型尖锐湿疣,容易发生癌变。电刀彻底切除病变结合应用抗逆转录病毒药物,可以取得较好的疗效,降低复发率。     

HIV and conflict in Nepal: Relation and strategy for response

Conflict and displacement make affected population more vulnerable to HIV infection. Refugees and internally displaced persons, in particular women and children, are at increased risk of exposure to HIV. In Nepal, there is considerable increase in the number of HIV infection since 1996 when conflict started. Along with poverty, stigma and lack of awareness, conflict related displacement, economic migration, and closure of HIV programmes have exacerbated the HIV situation in Nepal. Government has established "National AIDS Council" and launched HIV/AIDS Strategy. The strategy has not included the specific needs of displaced persons. While launching an HIV prevention programme in the conflict situation, the guidelines developed by Inter Agency Standing Committee (IASS) are important tools. This led to suggestion of an approach with implementations steps in the case of Nepal in this report. Key words: HIV, Conflict, Nepal, Response.     

Clinical trials in sub-Saharan Africa and established standards of care: a systematic review of HIV, tuberculosis, and malaria trials

Context  The minimum standard of care required for participants in clinical trials conducted in resource-poor settings is a matter of controversy; international documents offer contradictory guidance. Objective  To determine whether recently published trials conducted in sub-Saharan Africa met standards of care consistent with best current clinical standards for human immunodeficiency virus (HIV) treatment, tuberculosis treatment, and malaria prevention. Data Sources  Trials published during or after January 1998 that were indexed at the time of the MEDLINE and Cochrane Controlled Trials Register Search (November 20, 2003). Study Selection  All randomized clinical trials that were conducted in sub-Saharan Africa in 3 clinical domains: HIV disease, tuberculosis treatment, and malaria prophylaxis. Data Extraction  To establish criteria for best current standards of care, evidence from the literature and published guidelines accepted for well-resourced settings were analyzed; the actual care offered in the trial was then compared with these standards. Data Synthesis  A total of 128 eligible articles described data from 73 different randomized clinical trials. Only 12 trials (16%) provided care that met guidelines to both intervention and control patients. Only 1 of the 34 trials that enrolled patients with HIV disease provided antiretroviral treatment that conformed to guidelines. Conversely, all tuberculosis treatment trials (n = 13, including 3 for HIV-infected patients) provided tuberculosis therapy that conformed to guidelines. Twenty-one (72%) of 29 malaria prophylaxis trials tested interventions that met guidelines, but only 3 (10%) used any active prophylactic intervention in the control group. Of the 59 trials (81%) that reported on the process of ethical review, all were reviewed by a host African institution and 64% were additionally reviewed by an institution in a developed country. Conclusions  Rates of adherence to established clinical guidelines of care in randomized clinical trials of HIV treatment, tuberculosis treatment, and malaria prophylaxis varied considerably between disease categories. In determining clinical standards for trials in sub-Saharan Africa, researchers and ethics committees appear to take the local level of care into account.      

Periodic health examination, 1995 update: 1. Screening for human papillomavirus infection in asymptomatic women. Canadian Task Force on the Periodic Health Examination.

OBJECTIVE: To develop recommendations for practising physicians on the advisability of screening for human papillomavirus (HPV) infection in asymptomatic women. OPTIONS: Visual inspection, Papanicolaou testing, colposcopy or cervicography, use of HPV group-specific antigen, DNA hybridization, dot blot technique, Southern blot technique or polymerase chain reaction followed by physical or chemical therapeutic intervention. OUTCOMES: Evidence for a link between HPV infection and cervical cancer, sensitivity and specificity of HPV screening techniques, effectiveness of treatments for HPV infection, and the social and economic costs incurred by screening. EVIDENCE: MEDLINE was searched for articles published between January 1966 to June 1993 with the use of the key words "papillomavirus," "cervix neoplasms," "mass screening," "prospective studies," "prevalence," "sensitivity," "specificity," "human" and "female." VALUES: Proven cost-effective screening techniques that could lead to decreased morbidity or mortality were given a high value. The evidence-based methods and values of the Canadian Task Force on the Periodic Health Examination were used. BENEFITS, HARMS AND COSTS: Potential benefits are to prevent cervical cancer and eliminate HPV infection. Potential harmful effects include the creation of an unnecessary burden on the health care system and the labelling of otherwise healthy people as patients with a sexually transmitted disease for which therapy is generally ineffective. Potential costs would include expense of testing, increased use of colposcopy and treatment. RECOMMENDATIONS: There is fair evidence to exclude HPV screening (beyond Papanicolaou testing for cervical cancer) in asymptomatic women (grade D recommendation). VALIDATION: The report was reviewed by members of the task force and three external reviewers who were selected to represent different areas of expertise. SPONSORS: These guidelines were developed and endorsed by the task force, which is funded by Health Canada and the National Health Research and Development Program. The principal author (K.J.) was supported in part by the National Health Research and Development Program through a National Health Fellowship (AIDS).     

艾滋病相关神经系统并发症研究进展

HIV感染已成为严重威胁人类健康的全球性问题,即使给予有效的抗病毒治疗,艾滋病患者也常合并神经系统并发症,并增加患者死亡率。本文将重点讨论艾滋病相关神经系统并发症的临床表现及治疗进展,以加强对其的识别及防治。     

Epidemiological composition,clinical and treatment characteristics of the patient cohort of the german competence network for HIV/AIDS

Objective

As its central basis for research, the Competence Network for HIV/AIDS (KompNet) established a nationwide cohort study on HIV-positive patients being in medical care in Germany. In this paper, we describe the epidemiological composition, and clinical as well as treatment characteristics of the KompNet cohort over time.

Methods

The KompNet cohort is an open, retrospective and prospective, multi-center, disease-specific and nationwide cohort study that started gathering data in June 2004. Semiannually, follow up visits of the patients are documented, covering a wide range of clinical and sociodemographic data. At enrolment and three years afterwards, an EDTA-sample is taken; a serum-sample is taken at every follow up.

Results

As of 20.10.2008, a total of 15,541 patients were enrolled by 44 documenting sites. In September 2007, the cohort size was reduced to ten outpatient clinics and fifteen private practitioners, covering a total of 9,410 patients. The documentation of these patients comprised 24,117 years of follow up-time since enrolment (mean: 2.6 years), 62,862 person years inclusive data documented retrospectively on course of HIV-infection and antiretroviral therapy (ART, mean: 6.7 years). Due to the short period of recruitment till now, rates of death (0.3%-0.8%) and losses to follow up (1.1%-5.5%) were low.84.9% of patients were men. Main risk of transmission was sex between men (MSM: 62.9%). Mean age was 45 years. About two third of patients were classified as CDC-stage B or C. Therapy regimens of currently treated patients complied with recent guidelines. Trends of mean CD4 cell count/μl regarding the initial therapy and concerning the population under treatment reflected the developments and the changing standards of antiretroviral therapy over time.

Conclusion

The KompNet cohort covers about a quarter of all patients estimated as being under treatment in Germany. Its composition can be accounted approximately representative for the situation of clinical care and treatment in the scope of HIV/AIDS in Germany. Therefore, it is an important instrument for measuring the course of HIV/AIDS, the reality of use of antiretroviral therapy and its clinical and psychosocial outcomes in Germany.     

Metabolic and morphologic complications of HIV infection

In the era of highly active antiretroviral therapy, long-term complications of HIV infection and antiretroviral therapy deserve heightened attention. Morphologic and metabolic complications seen during the course of HIV infection encompass a variety of entities that may share a common pathophysiologic pathway. This review article will discuss clinical syndromes such as wasting, lipoatrophy/lipohypertrophy, polymetabolic syndrome as well as hyperlipidemia, cardiovascular disease, lactic acidosis, and metabolic bone disease in HIV-infected patients.     

The management of hypertension in Canada: a review of current guidelines, their shortcomings and implications for the future

CLINICIANS ARE EXPOSED to numerous hypertension guidelines. However, their enthusiasm for these guidelines, and the impact of the guidelines, appears modest at best. Barriers to the successful implementation of a guideline can be identified at the level of the clinician, the patient or the practice setting; however, the shortcomings of the guidelines themselves have received little attention. In this paper, we review the hypertension guidelines that are most commonly encountered by Canadian clinicians: the “1999 Canadian Recommendations for the Management of Hypertension,” “The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure” in the United States and the “1999 World Health Organization–International Society of Hypertension Guidelines for the Management of Hypertension.” The key points of these guidelines are compared and the shortcomings that may impede their ability to influence practice are discussed. The main implications for future guideline developers are outlined.