Clinical Pharmacology and Therapeutics

ANTI-HERPES VIRUS THERAPY 359
salvage therapy include azithromycin or clarithromycin
(Chapter 43) and atovaquone.
MYCOBACTERIUM TUBERCULOSIS THERAPY
IN HIV PATIENTS
For more information, see also Chapter 44. Bacille Calmette–
Guérin (BCG) vaccine should not be given to HIV-1-infected
individuals as it is a live, albeit attenuated, strain. Quadruple
therapy with isoniazid plus rifampicin and pyrazinamide,
plus either ethambutol or streptomycin is recommended.
This quadruple regimen should be given for two months and
then rifampicin and isoniazid continued for nine months or
for six months after the sputum converts to negative for bacterial
growth, whichever is longer. If there is drug resistance, the
regimen is based on the sensitivities of the isolated organism.
This may require therapy with second-line anti-TB drugs.
Response rates in HIV patients are generally high (around
90%), provided that there is good compliance, with a relatively
low recurrence rate (10%). The incidence of adverse
effects from anti-tuberculous therapy is high in HIV patients,
and may necessitate a change in medication. M. tuberculosis
strains are becoming multi-drug resistant and are present in
this population, so in vitro sensitivity determinations are
essential.
MYCOBACTERIUM AVIUM-
INTRACELLULARE COMPLEX THERAPY
This infection is a systemic multi-organ system infection in HIVinfected
patients. It has not been convincingly shown to be communicable
to other individuals as has M. tuberculosis. The
regimens used for treatment are three- or four-drug combination
therapies because of the resistance patterns of the organism.
One such successful regimen consists of rifabutin, ethambutol
and clarithromycin. If a clinical response is produced (usually
within two to eight weeks), secondary prophylaxis (suppressive
therapy) should be given for life. Prophylactic treatment is with
either clarithromycin or azithromycin.
ANTIFUNGAL THERAPY
For further information on antifungal therapy, see Chapter 45.
CANDIDA
If the disease is confined locally then initial therapy is with topical
nystatin or amphotericin. If infection is more extensive,
treatment should be with fluconazole. Alternatives are itraconazole
or voriconazole. Prophylaxis is with fluconazole,
once weekly. Echinocandins (e.g. caspofungin/mycofungin)
are used for azole-resistant candida.
CRYPTOCOCCUS NEOFORMANS
First-line therapy is with intravenous amphotericin B, sometimes
in combination with intravenous flucytosine. However,
flucytosine often causes bone marrow suppression in HIV-1-
infected patients. Such combination therapy is preferred in
severely ill patients. Fluconazole and liposomal amphotericin
B is a less toxic alternative.
HISTOPLASMOSIS
Treatment is with amphotericin B or itraconazole, daily intravenously
for six weeks. Prophylactic maintenance itraconazole
is recommended.
COCCIDIOMYCOSIS
Treatment is with amphotericin B daily intravenously for six
weeks, followed by itraconazole as maintenance prophylaxis.
ANTI-HERPES VIRUS THERAPY
For more information on anti-herpes therapy, see Chapter 45.
HERPES SIMPLEX VIRUS 1
Aciclovir is used for treatment, and sometimes as maintenance
prophylaxis. Unfortunately, this has led to the development
of aciclovir resistance of herpes virus isolates in many
HIV patients. The aciclovir prodrugs (e.g. famciclovir) achieve
higher intracellular concentrations of aciclovir and are useful
here, as are foscarnet or cidofovir.
CYTOMEGALOVIRUS INFECTION
Cytomegalovirus (CMV) infection may be multi-system or
confined to the eyes, lungs, genito-urinary system or gastrointestinal
tract. Therapeutic regimens are induction with either
ganciclovir or foscarnet, followed by a maintenance regimen
(see also Chapter 45). In the treatment of CMV retinitis, studies
suggested that foscarnet was superior and allowed the continued
use of ZDV with an improved survival time. This was perhaps
due to its lack of bone marrow suppression, unlike
ganciclovir, which together with ZDV causes profound marrow
suppression. The tolerance of ganciclovir in AIDS patients
is improved when it is combined with G-CSF to minimize granulocytopenia.
Slow-release implants of ganciclovir from a
reservoir inserted into the vitreous humour are effective in
patients with retinal CMV infection.