Page 52 - AIDSBK23C

Page 52

of IL-6 and soluble IL-6 receptor, high levels of CD30 and CD26 activity, increased interferon
gamma-producing inflammatory cells such as macrophages with delayed type hypersensitivity
reactions, increased chemokine expression on inflammatory cells, and features of a TH17 or TH1
cell mediated immune response.[285] There may be “compartmentalization” of the
inflammatory response, with immune cells in greatest number at the tissue site of inflammation
and not in peripheral blood.[286]
Infectious diseases which may manifest with immune restoration most often include
Mycobacterium tuberculosis, Mycobacterium avium-complex, Cryptococcus neoformans,
Leishmania, viral hepatitis, CMV retinitis, herpes zoster dermatitis, herpes simplex virus, and JC
papovavirus (progressive multifocal leukoencephalopathy) infections. Cases of sarcoid-like non-
caseating granulomatous inflammation have been reported with IRD in the absence of a defined
infection, and they can occur up to 3 years following institution of antiretroviral therapy.[286]
Antiretroviral therapy is recommended for all persons who are in the advanced stage of
HIV infection. Problems associated with therapy at this stage include drug interactions with
agents used to treat opportunistic infections, as well as problems with toxicity less tolerated by
very ill persons. Such persons may not respond as well to initial therapy or may require more
frequent changes in therapy.[210]
Persons diagnosed with acute HIV infection may derive benefit from antiretroviral
therapy, but the clinical guidelines for treatment remain variable. Such therapy may suppress the
initial burst of viremia, potentially lower the “set point” of viremia that determines the rate of
disease progression, and may reduce the rate of viral mutation. Conversely, antiretroviral drug
resistance may occur earlier in the course of infection, limiting future options. In addition, there
are potential adverse effects of drug therapy.[194,287] In addition, early antiretroviral therapy
does not appear to alter abnormalities in gut-associated lymphoid tissue, one of the major
reservoirs for ongoing viral proliferation.[288]
Therapy for acute retroviral infection may include a combination of two NRTI’s and one
protease inhibitor. However, if the patient is infected with a drug resistant HIV strain, or if
viremia is not suppressed significantly, then there is the risk for increasing drug resistance that
limits the effectiveness of future therapy. After a year of therapy, assessment of HIV-1 RNA
levels and CD4 lymphocyte counts will determine whether continued therapy during
asymptomatic HIV infection is warranted.[210] A dramatic reduction in the numbers of infected
CD4 lymphocytes is demonstrated following potent antiretroviral therapy.[198]
Pediatric patients may also benefit from antiretroviral therapy. In infants and children
with HIV infection, combination therapy begun early, particularly in those infants whose HIV-1
viral load is high, has shown effectiveness. Adverse drug reactions are not significant in most
cases.[289] Adolescents with HIV infection who acquired their infection during adolescence
will typically have a clinical course of infection similar to adults. The use of antiretroviral
therapy (ART) has been shown to markedly reduce mortality in children and adolescents infected
with HIV.[290]
Treatment of HIV-infected pregnant women with antiretroviral therapy is a complex
issue. For women already on a treatment regimen when pregnancy is diagnosed, treatment may
be discontinued because of a potential risk for teratogenicity during the first trimester, but the
inevitable rise in HIV-1 RNA levels following discontinuation of therapy may place the fetus at
greater risk for transmission of HIV later in pregnancy. HIV-infected women not on therapy
who are diagnosed as pregnant may wish to delay instigation of antiretroviral therapy until after