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Full Article In AIDS Reviews 2005;7:181-3 Hot News Hot News Welcome to “Hot News”, a section of AIDS Reviews written by the editors and invited experts which focuses on recently reported information believed to be of both impact and higher interest to the readership. British HIV Guidelines for the Management of population; e.g. the recommendation about the use and du- Hepatitis B and C in HIV-Coinfected Patients ration for nucleos(t)ide analogues (NRTI). The discontinuation of NRTI once anti-HBe seroconversion has been achieved Chronic infection with the hepatitis B virus (HBV), but es- may not necessarily apply in patients who are receiving pecially with the hepatitis C virus (HCV), has acquired great highly active antiretroviral therapy (HAART). Several reports importance over the last few years in the setting of HIV infec- have highlighted that clearance of HBsAg can be attained tion. Given the increased liver-related morbidity and mortal- over time by a growing proportion of patients receiving pro- ity in this population, efforts are currently being made to treat, longed, anti-HBV, active HAART. and more ambitiously, to cure these coinfections, in order to The guidelines are very cautious in advising not to use halt the progression to end-stage liver disease. However, the interferon in cirrhotic HBV/HIV-coinfected patients. However, management of HBV and HCV coinfections in HIV-infected while this is clear in cases of decompensated cirrhosis, patients is often challenging. Numerous questions such as, early cirrhosis is not a contraindication and these patients “What is the assessment needed?”, “Who needs to be treat- may be treated with interferon if the chances of clearing HBV ed?”, “When?” and “How?” are still in the air, and there are are high (i.e., elevated transaminase levels, positive HBeAg no definitive answers. With the purpose of guiding HIV care and/or low HBV-DNA). providers in the management of coinfected patients, experts have gathered on several occasions and then released their Marina Nuñez recommendations. Hospital Carlos III The latest guidelines published on this subject are those Madrid, Spain developed by the British HIV Association (HIV Medicine 2005;6 [suppl 2]:84-106). These recommendations are well written and organized, and therefore easy to follow. They are HIV Chemotherapy Revisited supported by abundant information published on every is- sue, although the reviews are sometimes incomplete. Nearly 60 million people have been infected with HIV since The HCV guidelines are thorough, but skip relevant mat- the beginning of the pandemic, and of these one third have ters. For instance, the question of treatment duration is not already died. For those infected more recently, however, the addressed at all. This is a very important issue given the high life expectancy has improved dramatically due to the favor- incidence of relapses after initial response in some of the able impact of highly active antiretroviral therapy (HAART). trials conducted in HIV/HCV-coinfected subjects. Studies Unfortunately, antiretrovirals are moving only slowly into the evaluating the potential benefit of prolonging anti-HCV ther- developing world, where most persons are infected and apy to prevent relapses are underway. In contrast, the points where their benefit will have the largest impact. of how important it is to give high enough doses of ribavirin, The drawbacks of HAART are mainly associated to its side or the need for an individualized approach to manage these effects, particularly because the medication should be taken patients are very well elaborated. indefinitely in most cases as HIV can not be eradicated. The comments pertaining to the need for a liver biopsy as Long-term toxicities of antiretrovirals, including metabolic part of the assessment prior to the treatment of HCV indicate abnormalities (hyperlipidemia, diabetes, etc) and the lipodys- that this is a highly controversial subject. However, vague trophy syndrome, have halted its widespread use. It is some- statements as well as phrases strongly recommending its what paradoxical that, despite more than 20 antiretrovirals performance can be found throughout the text. There is no being currently approved for the treatment of HIV infection, mention of the new noninvasive tools to assess liver fibrosis, the consideration of their strong efficacy along with their risk such as elastography (FibroScanNo® ) partand/or serum of thisbiochemi- publicationof adverse events may has resulted be in the restriction of their pre- cal tests (i.e., Fibrotest®). At the end, the expression “con- scription only to patients with evidence of immunodeficiency sider liver biopsy” in the algorithm leaves the door open to (i.e. < 350 CD4+ T-cells per microliter). For the rest, peri- the readers to follow their own judgmentreproduced in each case. or photocopyingodic controls are usually enough. Regarding HBV recommendations, the first comment that The second drawback of antiretroviral therapy regards the can be made is that the lag between the preparation and the selection of drug-resistant viruses. Moreover, given that publication of the guidelines has been sufficiently long so as cross-resistance between compounds within the same drug without the prior written permission to explain some limitations. For instance, entecavir, a drug class is common, new inhibitors are needed for a growing which is already approved as an anti-HBV agent, should be number of patients who already have bourn the current med- considered the first choice for patients requiring anti-HBV ications. of the publisher therapy but not antiretrovirals, given the potential risk of adefo- The book “HIV Chemotherapy”, recently released and ed- vir for selecting resistance mutations in HIV. On the other hand, ited by Salvatore Buttera, represents a comprehensive and the principles established for HBV-mono-infected patients may updated description of the state of the art of antiretroviral have been too rigorously applied to the HBV/HIV-coinfected therapy. Some of the best experts in the field have summa- © Permanyer Publications 2010 181 AIDS Reviews 2005;7 rized their views about how to use anti-HIV drugs, how to receiving placebo per arm). All doses were given with a prevent and manage drug resistance, and how to deal with moderate-fat meal. Antiretroviral-experienced patients ab- the need to implement HAART in the developing world. The stained from treatment for 12 weeks prior to entry. All patients reading of Buttera’s book provides a new sentiment in which had a viral load of ≥ 5,000 copies/ml and a CD4 count nadir the knowledge of HIV therapeutics by health care providers > 200 cells/mm3. All patients were infected with R5-tropic is mandatory if they are to be useful for the many HIV-in- HIV. A > 1 log, dose-dependent, viral load decrease was fected persons who will need them. observed in patients taking 400 mg once daily and 200 or The opening chapters deal with the management of HIV 600 mg twice daily. The greatest viral load reduction was infections and include a fascinating review of current mo- observed between 24 and 36 hours after Aplaviroc discon- lecular strategies to protect and strengthen the host immune tinuation, suggesting a long CCR5 coreceptor occupancy. system at the cellular level. The following chapter summa- Evidence of viral tropism conversion to dual-tropic virus was rizes the strategies required for the implementation of effec- seen in one patient on day 10, but virus reverted back to tive anti-HIV therapies in developing countries (90% of world- R5-tropic virus on day 24. wide AIDS cases). Thereafter, two excellent chapters Aplaviroc appears safe and well tolerated when taken comprehensively review the genetics of drug resistance and orally. The most common adverse effects noted in the 10-day, technologies. The remaining chapters provide cutting-edge monotherapy, dose-ranging study were loose stools, diar- reviews of the latest viral and cellular targets for anti-HIV rhea, abdominal pain, nausea, and flatulence. Headache, chemotherapy, including the development of iRNA and other dizziness, and fatigue also occurred. Most adverse effects molecular-based strategies that target latent virus reservoirs resolved within the first three days. No serious Grade 3 or 4 in infected individuals. adverse effects were reported. No changes in laboratory or This is essential reading for scientists and clinicians work- ECG abnormalities were observed. ing on AIDS, HIV, and other retroviruses as well as for all The drug displays additive or synergistic activity when health care professionals interested in expanding their cur- combined with other antiretroviral agents. In PBMC exposed rent understanding of the subject. to R5-tropic HIV, Aplaviroc had synergistic effects when com- Juan Gonzalez-Lahoz bined with zidovudine, nevirapine, indinavir, and enfuvirtide, Service of Infectious Diseases and additive effects when combined with another investiga- tional CCR5 antagonist, SCH-C. Potent synergism was ob- Hospital Carlos III served in PBMC exposed to dual-tropic HIV and treated with Madrid, Spain Aplaviroc when combined with investigational CXCR4 inhibi- tors AMD3100 or TE14011. No antagonistic effects or syner- gistic cellular toxicities were observed in vitro. Discontinuation of Aplaviroc Trials due Aplaviroc is a cytochrome P450-3A substrate in vitro, and to Hepatotoxicity therefore ritonavir boosts plasma levels of the drug. In a trial CCR5 is the major chemokine coreceptor that HIV uses to conducted in eight HIV-uninfected
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