A Textbook of Clinical Pharmacology and Therapeutics

salvage therapy include azithromycin or clarithromycin
(Chapter 43) and atovaquone.

MYCOBACTERIUM TUBERCULOSISTHERAPY

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 isoniazidplusrifampicinandpyrazinamide,
plus either ethambutolor streptomycinis recommended.
This quadruple regimen should be given for two months and
thenrifampicinandisoniazidcontinued for nine months or
for six months after the sputum converts to negative for bacte-
rial 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 rela-
tively 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-

INTRACELLULARECOMPLEX THERAPY

This infection is a systemic multi-organ system infection in HIV-
infected patients. It has not been convincingly shown to be com-
municable to other individuals as has M. tuberculosis. The
regimens used for treatment are three- or four-drug combina-
tion therapies because of the resistance patterns of the organism.
One such successful regimen consists of rifabutin,ethambutol
andclarithromycin. 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
eitherclarithromycinorazithromycin.

ANTIFUNGAL THERAPY

For further information on antifungal therapy, see Chapter 45.

CANDIDA

If the disease is confined locally then initial therapy is with top-
icalnystatinoramphotericin. If infection is more extensive,
treatment should be with fluconazole. Alternatives are itra-
conazoleorvoriconazole. 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, some-

times in combination with intravenous flucytosine. However,

flucytosineoften causes bone marrow suppression in HIV-1-

infected patients. Such combination therapy is preferred in

severely ill patients. Fluconazoleand liposomal amphotericin

Bis a less toxic alternative.

HISTOPLASMOSIS

Treatment is with amphotericin Boritraconazole, daily intra-

venously for six weeks. Prophylactic maintenance itracona-

zoleis recommended.

COCCIDIOMYCOSIS

Treatment is with amphotericin Bdaily intravenously for six

weeks, followed by itraconazoleas maintenance prophylaxis.

ANTI-HERPES VIRUS THERAPY

For more information on anti-herpes therapy, see Chapter 45.

HERPES SIMPLEX VIRUS 1

Acicloviris used for treatment, and sometimes as mainte-

nance prophylaxis. Unfortunately, this has led to the develop-

ment of aciclovirresistance of herpes virus isolates in many

HIV patients. The aciclovirprodrugs (e.g. famciclovir) achieve

higher intracellular concentrations of aciclovirand are useful

here, as are foscarnetorcidofovir.

CYTOMEGALOVIRUS INFECTION

Cytomegalovirus (CMV) infection may be multi-system or

confined to the eyes, lungs, genito-urinary system or gastro-

intestinal tract. Therapeutic regimens are induction with either

ganciclovirorfoscarnet, followed by a maintenance regimen

(see also Chapter 45). In the treatment of CMV retinitis, studies

suggested that foscarnetwas superior and allowed the contin-

ued use of ZDV with an improved survival time. This was per-

haps due to its lack of bone marrow suppression, unlike

ganciclovir, which together with ZDV causes profound mar-

row suppression. The tolerance of ganciclovirin AIDS patients

is improved when it is combined with G-CSF to minimize gran-

ulocytopenia. Slow-release implants of ganciclovir from a

reservoir inserted into the vitreous humour are effective in

patients with retinal CMV infection.

ANTI-HERPESVIRUSTHERAPY 359