The impact of HIV on chronic kidney disease outcomes.

Chronic kidney disease (CKD) is a known complication of the human immunodeficiency virus (HIV) but outcomes among HIV-infected patients with kidney disease are unknown. We studied a national sample of 202,927 patients with CKD (stage 3 or higher) for death, end-stage renal disease (ESRD) and the mean annual rate of decline in estimated glomerular filtration rate (eGFR) over a median period of 3.8 years. Within this sample, 0.3% of the patients were diagnosed with HIV, 43.5% were diabetic, whereas the remainder had neither disease. In this national CKD cohort, HIV-infected black patients were at higher risk of death, a similar risk for ESRD and loss of eGFR than black patients with diabetes. HIV-infected white patients experienced higher rates of death but a lower risk of ESRD than their counterparts with diabetes. Our results highlight a need to study mortality and mechanisms of ESRD in the HIV infected population.

Toward a definition of HIV expertise: a survey of experienced HIV physicians.

Medical care for human immunodeficiency virus (HIV)-infected persons has grown increasingly complex, yet few studies have examined experienced HIV physicians' views about current HIV medical care. The objective of this study was to examine the relationship between physicians' HIV experience, self-perceived expertise, and confidence with providing 18 aspects of HIV medical care and between confidence in aspects of care and medical specialty. At geographically diverse, HIV continuing medical education programs conducted in the fall of 1999, 359 currently practicing HIV physicians completed a written survey measuring participants' demographic characteristics, experience, HIV expertise, and level of confidence providing essential aspects of HIV care. Participants currently managed a median of 50 HIV-infected patients with a career total of 300. Significant correlations were found between experience and expertise items and experience and 15 of 18 confidence items. Confidence levels varied from 11% to 85% highly confident across 18 aspects of HIV care. Physicians' confidence with providing aspects of HIV care varied by the three predominant specialty groups (infectious diseases, internal medicine, and family practice/general medicine). Physicians who have informally specialized in HIV care reported a range of self-perceived expertise and confidence, indicating the complexity of HIV medical care today. Our results suggest that even the most experienced HIV physicians in the United States continue to benefit from more experience and that each medical specialty examined in this study brings its own set of skills needed to provide optimal HIV care. This study constitutes a first step toward defining and formalizing HIV medical care.

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.

Advances in the medical management of patients with HIV-1 infection: an overview.

New guidelines for the management of patients with HIV-1 infection emphasize early aggressive treatment using multi-drug combination regimens. Accurate assessment of the effectiveness of these treatments and their potential (small as it now seems) to eradicate HIV-1 infection requires testing for viral levels in the blood, and in other compartments that may serve as long-term viral reservoirs, using the most sensitive assays. At present, most of our information regarding triple-drug combination therapies (usually two nucleosides and a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor) has come from the assessment of viral levels in blood. Available results strongly support the virologic superiority of such treatments over monotherapy and two-drug combinations. There are important questions that remain to be answered regarding these highly effective therapies. Questions regarding the durability of these treatments in preventing the evolution of drug resistance can be addressed by using sensitive reverse transcription/polymerase chain reaction assays to assess treatment response. Others, such as how best to treat patients who have failed potent drug therapy, await results from new, large-scale, clinical trials. An important concern with respect to newer antiretroviral therapies is their complexity and thus the increased risk for non-compliance and resultant viral resistance. In addition, longer-term side-effects are increasingly recognized. Programs that enhance compliance with these treatments will increase the probability that they will provide durable suppression of viral replication and arrest the clinical progression of HIV disease.

Novel four-drug salvage treatment regimens after failure of a human immunodeficiency virus type 1 protease inhibitor-containing regimen: antiviral activity and correlation of baseline phenotypic drug susceptibility with virologic outcome.

Twenty human immunodeficiency virus-infected patients experiencing virologic failure of an indinavir- or ritonavir-containing treatment regimen were evaluated in a prospective, open-label study. Subjects received nelfinavir, saquinavir, abacavir, and either another nucleoside analog (n=10) or nevirapine (n=10). Patients treated with the nevirapine-containing regimen experienced significantly greater virologic suppression at week 24 than those not treated with nevirapine (P=.04). Baseline phenotypic drug susceptibility was strongly correlated with outcome in both treatment arms. Subjects with baseline virus phenotypically sensitive to 2 or 3 drugs in the salvage regimen experienced significantly greater virus load suppression than those with baseline virus sensitive to 0 or 1 drug (median week-24 change=-2.24 log and -0.35 log, respectively; P=.01). In conclusion, non-nucleoside reverse transcriptase inhibitors may represent a potent drug in salvage therapy regimens after failure of an indinavir or ritonavir regimen. Phenotypic resistance testing may provide a useful tool for selecting more effective salvage regimens.

Antiretroviral therapy for HIV infection in 1998: updated recommendations of the International AIDS Society-USA Panel.

OBJECTIVE: To provide recommendations for antiretroviral therapy based on information available in mid-1998. PARTICIPANTS: An international panel of physicians with expertise in antiretroviral research and care of patients with human immunodeficiency virus (HIV) infection, first convened by the International AIDS Society-USA in December 1995. EVIDENCE: The panel reviewed available clinical and basic science study results (including phase 3 controlled trials; clinical, virologic, and immunologic end point data; data presented at research conferences; and studies of HIV pathophysiology); opinions of panel members were also considered. Recommendations were limited to drugs available in mid-1998. CONSENSUS PROCESS: Panel members monitor new clinical research reports and interim results. The full panel meets regularly to discuss how the new information may change treatment recommendations. Updated recommendations are developed through consensus of the entire panel at each stage of development. CONCLUSIONS: Accumulating data from clinical and pathogenesis studies continue to support early institution of potent antiretroviral therapy in patients with HIV infection. A variety of combination regimens show potency, expanding choices for initial regimens for individual patients. Plasma HIV RNA assays with increased sensitivity are important in monitoring therapeutic response; however, more data are needed to determine precisely the HIV RNA levels that define treatment failure. Long-term adverse drug effects are beginning to emerge, requiring ongoing attention. Some issues regarding optimal long-term approaches to antiretroviral management are unresolved. The increased complexity in HIV management requires ongoing monitoring of new data for optimal treatment of HIV infection.

An aggressive approach to HIV antiretroviral therapy.

The introduction of highly active antiretroviral therapy offers the first real hope of durable control of HIV infection and prevention of clinical sequelae. But success hinges on early and complete suppression of viral replication. That demands near-perfect adherence to a complex regimen involving three or more drugs, each with its own dosage and dietary requirements.

Predictors and impact of patients lost to follow-up in a long-term randomized trial of immediate versus deferred antiretroviral treatment.

We studied predictors for losses to follow-up and the impact of such losses in the AIDS Clinical Trials Group 019 protocol, a long-term randomized trial of immediate versus deferred antiretroviral therapy in asymptomatic HIV-1-infected patients with >500 CD4 cells/mm3. The trial was selected because of its key importance in determining guidelines for antiretroviral therapy, and because it had the longest follow-up among all antiretroviral trials and the largest percentage of patients whose vital status was unknown at study end. Younger age, a history of parenteral drug use, and nonwhite race were associated with higher rates of loss to follow-up, but race was not an important predictor after adjusting for clinical site. There was large and statistically significant variability in the rates of losses among different clinical sites (p < 0.001). Patient retention was significantly better in clinical sites that enrolled many participants, with 25% of enrollees lost to follow-up in sites enrolling >100 patients and 44% in sites enrolling <33 patients each. As a group, patients lost to follow-up after the 2nd year had steeper declines of CD4 cell counts, and a significantly larger proportion had reached a CD4 cell count <300/mm3 in the year before being lost, compared with patients remaining in the study. Losses to follow-up probably decreased substantially the observed number of primary endpoints, curtailed the power of the trial to demonstrate any difference between immediate and deferred initiation of antiretroviral therapy, and may have introduced large bias in the estimated hazard ratio for the primary endpoint and its statistical significance.

Antiretroviral therapy for HIV infection in 1997. Updated recommendations of the International AIDS Society-USA panel.

OBJECTIVE: To provide current recommendations for antiretroviral therapy for human immunodeficiency virus (HIV) disease. PARTICIPANTS: The original International AIDS Society-USA 13-member panel representing international expertise in antiretroviral research and care of patients with HIV infection. EVIDENCE: The following were considered: Newly available clinical and basic science study results, including phase 3 controlled trials; clinical, virological, and immunologic end-point data; interim analyses of studies presented at national and international research conferences; studies of HIV pathophysiology; and expert opinions of panel members. Recommendations were limited to the drugs available in mid 1997. PROCESS: The full panel met on a regular basis (July 1996, September 1996, November 1996, January 1997, and April 1997) since the publication of its initial recommendations in mid 1996 to review new research reports and interim results. The panel discussed whether and how new information changed its initial recommendations. The recommendations contained herein were determined by group consensus. CONCLUSIONS: New data have provided a stronger rationale for earlier initiation of more aggressive therapy than previously recommended and reinforce the importance of careful selection of initial drug regimen for each patient for optimal long-term clinical benefit and adherence. The plasma viral load is a crucial element of clinical management for assessing prognosis and the effectiveness of therapy, and such testing must be done properly. Treatment failure is most readily indicated by a rising plasma HIV RNA level and should be confirmed prior to a change of treatment. Therapeutic approaches must be updated as new data, particularly on the long-term clinical effect of aggressive antiretroviral treatment, continue to emerge.

Antiretroviral therapy for HIV infection in 1996. Recommendations of an international panel. International AIDS Society-USA.

OBJECTIVE: To provide clinical recommendations for antiretroviral therapy for human immunodeficiency virus (HIV) disease with currently (mid 1996) available drugs. When to start therapy, what to start with, when to change, and what to change to were addressed. PARTICIPANTS: A 13-member panel representing international expertise in antiretroviral research and HIV patient care was selected by the international AIDS Society-USA. EVIDENCE: Available clinical and basic science data, including phase 3 controlled trials, clinical endpoint data, virologic and immunologic endpoint data, interim analyses, studies of HIV pathophysiology, and expert opinions of panel members were considered. Recommendations were limited to drugs available in mid 1996. PROCESS: For each question posed, 1 or more member(s) reviewed and presented available data. Recommendations were determined by group consensus (January 1996); revisions as warranted by new data were incorporated by group consensus (February-May 1996). CONCLUSIONS: Recent data on HIV pathogenesis, methods to determine plasma HIV RNA, clinical trial data, and availability of new drugs point to the need for new approaches to treatment. Therapy is recommended based on CD4+ cell count, plasma HIV RNA level, or clinical status. Preferred initial drug regimens include nucleoside combinations; at present protease inhibitors are probably best reserved for patients at higher progression risk. For treatment failure or drug intolerance, subsequent regimen considerations include reasons for changing therapy, available drug options, disease stage, underlying conditions, and concomitant medication(s). Therapy for primary (acute) infection, high-risk exposures to HIV, and maternal-to-fetal transmission are also addressed. Therapeutic approaches need to be updated as new data continue to emerge.

HIV viral load markers in clinical practice.

Plasma HIV RNA determinations are an important prognostic marker of disease progression and, when used appropriately, provide a valuable tool for the management of individual patients. But what constitutes appropriate use?