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HIV and AIDS
Further Developments in Therapeutic Strategies for HIV-infected Adults
a report by
Anja Potthoff, Norbert H Brockmeyer and Adriane Skaletz-Rorowski
German Competence Network for HIV/AIDS
There is hardly any other medical field that has experienced changes their limitations, explore potential new drugs, novel mechanisms and
and developments as dramatic as those seen in the field of treatment targets and consider ongoing developments for genetic therapies
of HIV infection in the last few years. There are now 25 antiretroviral against HIV.
substances approved worldwide, and some of the new substances are
effective against multidrug-resistant viruses. The classes of chemokine Current Therapy – New Options
receptor 5 (CCR-5) antagonists and integrase inhibitors are new Antiretroviral treatment has undergone extensive developments within
therapeutic options for heavily pre-treated patients. In spite of this the last 20 years. In 1987, zidovudine monotherapy was the only
success many problems remain unsolved. Most importantly, HIV therapeutic option. With the introduction of didanosine and zalcitabine
infection and lifelong chemotherapy regimens result in an increase in in 1991 and 1992, respectively, the first combination of nucleoside
side effects, such as lipodystrophy, osteoporosis, cardiovascular analogues was possible.
2
Stavudine and lamivudine were registered in
diseases and an increased number of tumours, as well as increased 1994 and 1995, respectively. A turning point was the introduction of the
viral resistance. protease inhibitors (PIs) saquinavir and indinavir in 1995, and nevirapine
and the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs)
In addition, the ideal point at which to initiate therapy has been in 1996. This was the beginning of the highly active antiretroviral therapy
discussed in the last few years. In this context, the recent shift towards (HAART) era. The combination of a ‘backbone’ of two NRTIs and an
initiating therapy when the CD4 count is in the range of NNRTI or a PI still forms the basis of antiretroviral therapy.
1
The addition
300x10
6
–350x10
6
/l and to offer treatment to patients with CD4 of low-dose ritonavir to PIs (‘booster’) results in a high plasma
counts of 350–500x10
6
/l if the viral load is >10
5
copies/ml may prevent concentration of co-administrated PI and decreases pill burden, number
new infections and improve the course of HIV infection.
1
However, of doses and food restrictions.
3
So far, enfurvirtide is the only substance
increasing resistance to existing drugs, the need for better-tolerated in the class of fusion inhibitors. By binding to gp41 it inhibits the fusion
treatment options and the fact that an effective vaccine is at best a of HIV with the cellular membrane of CD4 cells. Parenteral administration
distant prospect make the development of new treatment strategies and local side effects are the disadvantages of this promising substance.
4
necessary. In this article, we review the current therapy options and
Multiple new drugs have been approved lately, including combinations of
substances that are already on the market, e.g. emtricitabine plus
Anja Potthoff is a Consultant in Dermatology at the
Interdisciplinary Immunological Clinic at the University of
tenofovir plus efavirenz (Atripla
®
), US Food and Drug Administration
Bochum, Germany. She is a specialist in sexually transmitted
(FDA)-approved in July 2006. Also, new substances of old classes that can
diseases and HIV/AIDS. Dr Potthoff is a member of the
be used in heavily pre-treated patients are being developed, such as the
German AIDS Society (DAIG) and the German Dermatology
Society (DDG). She received her MD from the University of NNRTI etravirin (TMC 125), approved in January 2008. Hopes of fewer
Aachen in 2005.
side effects and better efficacy have arisen for the class of integrase
E:
a.potthoff@klinikum-bochum.de inhibitors. Raltegravir (MK0518) is the first substance of this class and
was approved in October 2007. The CCR-5 receptor antagonist
Norbert H Brockmeyer is Director of Medical Research and
Teaching in the Department of Dermatology and Sexually
maraviroc, approved in October 2007, can be used only after tropism
Transmitted Disease (STDs) at Ruhr University Bochum. A testing, as patients with chemokine (C-X-C motif) receptor 4 (CXCR4)-
specialist in HIV/AIDS and STDs, he is Chairman of the
tropic viruses do not profit from maraviroc treatment. In addition, the
German Competence Network for HIV/AIDS, Past President
of the German AIDS Society (DAIG) and a member of the
dose has to be adjusted to background therapy.
Board of Directors of the Telematic Platform for Medical
Research Networks (TMF).
Limitations of Current Therapeutic Approach
E:
n.brockmeyer@derma.de
Shortly after the first antiretroviral substances became available, the
problem of resistance could be seen.
5
Primary resistance has been seen
Adriane Skaletz-Rorowski is the Chief Operating Manager
and Scientific Co-ordinator of the German Competence
in up to 14% of therapy-naïve patients.
3,6
Although genotypic
Network for HIV/AIDS. She gradiated as an Assistant
resistance testing and the combination of at least two active
Professor of Medical Molecular Biology at the University of
substances have improved the outcome even of heavily pre-treated
Münster in Germany. She is a member of the German
AIDS Society (DAIG). patients, drugs for multiple-resistant viruses are still needed.
E:
a.skaletz@klinikum-bochum.de
The use of antiretroviral therapy is also limited by side effects. The
mitochondrial toxicity of the old NRTIs is associated with lipodystrophy,
32 © TOUCH BRIEFINGS 2008
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