The European AIDS Clinical Society (EACS) was established in 1991 to "bring together scientists from all over Europe to help exchange the latest medical and scientific knowledge regarding clinical aspects of HIV/AIDS and its complications." Through its website (www.europeanaidsclinicalsociety.org) one can access: (1) conference information (the 12th European AIDS conference/EACS was held in Cologne, Germany on November 11-14, 2009 and the 13th conference will be in Belgrade, Serbia on October 12-15, 2011 [www.eacs-conference2011.com]); (2) the latest European HIV treatment guidelines (discussed later in this document); (3) the EACS journal, HIV Medicine, now in its 10th year; (4) a direct connection to www.hiv-druginteractions.org (a useful tool for antiretroviral therapy); and (5) links to numerous other helpful material.
Each year on the first day of the European AIDS conference, a pre-educational course is offered primarily to young human immunodeficiency virus (HIV) clinicians; however, the course is open to others free of charge by registering before the conference. The course (9:45 to 17:15 in this conference) is very comprehensive and is structured around clinical case presentations and subsequent didactic lectures (eg, HIV testing and late diagnosis; when to start and what with; short-term and long-term management issues of antiretroviral use; and hepatitis coinfection [mainly chronic hepatitis B and hepatitis C]). This is an excellent review course and sets the stage for the full conference to follow.
Version 5 of the EACS treatment guidelines was presented in a 2-hour session in November 13, which focused on: (1) What is New?, (2) Why New Guidelines?, and (3) Aims, Differences from the Past Version. The guidelines can be downloaded from the aforementioned website (in English and 13 additional languages) or ordered in a printed pocket-size booklet from EACS. The European HIV Drug Resistance Guidelines 2009 Update was also circulated at the conference; this foldable front-and-back spreadsheet covers clinical indications for resistance testing, technical issues, and clinically available genotypic drug resistance interpretation systems (12 websites including http://hivdb.stanford.edu [USA], www.retic-ris.net [Spanish], www.hiv-grade.de [German], and www.euresist.org [European]).
With the publication of the newly updated Department of Health and Human Services (DHHS) guidelines on December 1, 2009 (www.aidsinfo.nih.gov), providers can now compare and contrast 2 major documents on the therapy of HIV infection. The following are highlights of the most recent EACS guidelines (with an emphasis on differences from the DHHS guidelines):
- Initial assessment of HIV-infected patients should include cytomegalovirus serology, body mass index (BMI; www.nhlbisupport.com/bmi), waist circumference, phosphate level, calculated creatinine clearance (www.kidney.org), assessment of cardiovascular risk (http://cvrisk.mvm.ed.ac.ak/calculator and other websites), genotypic resistance testing with determination of HIV subtype, and interferon gamma release assay (T.SPOT.TB or QuantiFERON®-TB Gold) in selected high-risk populations as an alternative to the tuberculin skin test if available.
Comment: BMI, waist circumference, cytomegalovirus serology (with a CD4 >50), and HIV subtyping are not part of the DHHS guidelines. European countries have a growing recognition of multiple subtypes with their immigrant populations. Monitoring phosphorus while on tenofovir is mentioned in the footnotes of the DHHS guidelines. The evaluation of cardiovascular and renal functions is increasingly important in all HIV patients and is mentioned in both guidelines.
- 2. Treatment of primary HIV infection (PHI) is "indicated" if the patient has an AIDS-defining event or a confirmed CD4 lymphocyte count <350 cells/mm3 at 3 months or longer. Treatment should be "considered" if the patient is experiencing severe illness or prolonged symptoms (especially central nervous system symptoms).
Comment: The EACS and DHHS guidelines are fairly similar in the treatment recommendations for primary (or acute) HIV infection. The DHHS guidelines state that "treatment should be considered optional at this time", but treatment would be indicated in any patient with an AIDS-defining event or a low CD4 (? <350 or <500 cells/mm3). Both guidelines support beginning with a ritonavir-boosted protease inhibitor regimen if genotypic resistance testing is not yet available.
- 3. It is recommended that clinicians begin treatment of HIV-positive patients earlier when the CD4 lymphocyte cell counts are 350 to 500 cells/mL. The EACS guidelines state that this is justified because of the availability of new data that suggest treating patients in this group positively affects their future including long-term outcomes and comorbidities such as cardiovascular disease, neuropsychological disturbances, and aging.
Comment: The DHHS guidelines panel was divided on the strength of the recommendation to treat with CD4 counts between 350 and 500 (55% voted for strong recommendation and 45% voted for moderate recommendation).
- 4. The EACS guidelines state that naive patients with a CD4 count of >500 cells/mL should be followed closely and treated if they meet certain criteria including:
- HIV-associated nephropathy (HIVAN)
- Hepatitis C (HCV) coinfection
- Hepatitis B (HBV) requiring therapy
- HIV RNA consistently high (>105 c/mL)
- Rapid CD4 decline (>50 - 100 mm3/yr)
- Age >50 years (this was >55 years in Version 4 but decreased secondary to most studies using the 50-year cutoff)
- High cardiovascular risk
Comment: Both guidelines support therapy despite CD4 lymphocyte count to prevent transmission (eg, a discordant couple who want to minimize chances of transmission). We will have more information when the Strategic Timing of AntiRetroviral Treatment (START) study results are available. The DHHS guidelines do not include hepatitis C, age, or cardiovascular risk; they also include rapidly declining CD4 but at >100 cells/mm3 decrease per year.
- 5. The recommended initial combination regimens for antiretroviral-naive patients in the EACS document include pairing a non-nucleoside reverse transcriptase inhibitor (efavirenz or nevirapine) or a ritonavir-boosted protease inhibitor (atazanavir, darunavir, lopinavir, or saquinavir) with either the fixed combinations of tenofovir/emtricitabine or abacavir/lamivudine.
Comment: The 2 guidelines differ significantly on the initial regimen for antiretroviral-naive patients. The preferred regimen in the DHHS guidelines is the fixed combination of tenofovir/emtricitabine (abacavir/lamivudine is in the "Alternative" category) plus the non-nucleoside reverse transcriptase inhibitor efavirenz (unless the patient is pregnant or plans on pregnancy) or 1 of 2 ritonavir-boosted protease inhibitors (atazanavir or darunavir) or the integrase inhibitor raltegravir. Note that the EACS guidelines have abacavir/lamivudine, lopinavir, and saquinavir as preferred and raltegravir as an alternative. Ritonavir-boosted lopinavir twice daily is a preferred regimen for pregnant women in the DHHS guidelines.
- 6. The EACS and the DHHS guidelines support treating hepatitis HIV in HBV-coinfected patients at any CD4 count if the patient otherwise meets the criteria for HBV therapy.
Comment: The EACS guidelines criteria for HBV treatment include patients with: (1) >2000 IU/mL DNA and alanine aminotransferase elevation and (2) <2000 IU/mL and a liver biopsy with Metavir >A2 and/or >F2. The DHHS guidelines stress using both tenofovir and emtricitabine (each with activity against HIV and HBV) as the nucleoside reverse transcriptase backbone of an antiretroviral regimen.
- 7. Because HCV treatment offers the possibility of eradicating HCV within a defined treatment period, the EACS guidelines state that every coinfected patient should be considered for treatment when the benefits of therapy outweigh the risks. The guidelines offer a proposed optimal duration of HCV therapy as follows:
- 24 weeks in patients who are HCV RNA-negative at week 4 with genotype 2/3.
- 48 weeks in patients who are HCV RNA-negative at week 4 with genotype 1/4 or patients who are HCV RNA-positive at week 4 but with >2 log drop in HCV RNA at week 12 with HCV RNA-negative at week 24 and genotype 2/3.
- 72 weeks in patients who are HCV RNA-positive at week 4 but with >2 log drop in HCV RNA at week 12 with HCV RNA-negative at week 24 and genotype 1/4
Comment: The DHHS guidelines also state that all patients with HCV/HIV coinfection should be evaluated for HCV therapy. Both guidelines support avoiding didanosine, zidovudine, stavudine, and possibly abacavir with ribavirin use.
Reading thoroughly both the EACS and the DHHS guidelines will be rewarding for all HIV providers.
For conference participants, a confidential username and password are provided to access the webcasted and video presentations from the 12th European AIDS Conference/EACS; for selected talks, the PowerPoint slides are available as well.
The World Health Organization (WHO) published online preliminary updated guidelines for HIV treatment almost simultaneously with the DHHS release. The WHO guidelines are very important because they apply worldwide to developing countries with limited resources. The full set of new guidelines is expected in February 2010. Changes include:
- All adolescents and adults with HIV infection and CD4 counts ≤350 cells/mm3 should be started on antiretroviral therapy (ART) immediately.
Comment: The previous set of guidelines, published in 2006, recommended starting ART at CD4 counts ≤200 cells/mm3.
- 2. First-line therapy should consist of a non-nucleoside reverse transcriptase inhibitor plus 2 nucleoside reverse transcriptase inhibitors, one of which should be zidovudine or tenofovir.
- 3. Countries using stavudine (d4T) in first-line regimens should start phasing it out because of its toxicity.
- 4. Continuation of ART throughout breast-feeding is encouraged.
- 5. Regardless of their CD4 cell counts, patients coinfected with tuberculosis (TB) should be started on ART as soon as possible after starting TB treatment.
Comment: There are conflicting studies on when to start ART in patients with active TB, and there are potential problems with the use of ritonavir-boosted protease inhibitors.
- 6. Second-line ART should consist of a ritonavir-boosted protease inhibitor plus 2 nucleoside reverse transcriptase inhibitors. Ritonavir-boosted atazanavir and lopinavir/ritonavir are the preferred protease inhibitors.