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HIV and AIDS
Table 1: Summary of Patient Considerations for Optimising
kidney and central nervous disease, may influence the choice of initial
Therapeutic Outcome
antiretroviral therapy. Antiretroviral therapy may be deferred until treatment
for the co-morbidity has been initiated and/or completed, but this clearly
Major Significance Minor Significance
needs to be balanced against the risks associated with drug–drug
Genetic factors
interactions, overlapping toxicities, immune reconstitution disease and
HLA genotype B*5701: abacavir HSR HLA: nevirapine HSR
Cytochrome P450 CYP2B6: efavirenz toxicity
unopposed viral replication. Faced with the realisation that progressive liver
Lipid metabolism APOC3: hypertriglyceridaemia
disease makes a substantial contribution to long-term morbidity and
Other UGT1A1*28: atazanavir mortality in patients co-infected with HIV and hepatitis B and/or hepatitis C,
hyperbilirubinaemia
and that effective HIV treatment reduces the risk of hepatic
Demographic factors
complications,
51–53
international guidelines now recommend HIV treatment
Gender Female: increased toxicity
in co-infected patients, irrespective of the CD4 cell count.
15
This is
potential/pregnancy
particularly important for hepatitis B management, where tenofovir +
Behavioural Risk of non-adherence/
lifestyle considerations
lamivudine or emtricitabine NRTI combinations allow for effective long-term
Age Elderly: slower immune recovery
treatment of both HIV and hepatitis B infection.
Co-morbidities
HBV, HCV, TB Early treatment initiation; With regard to HIV-associated opportunistic infections, results from
drug interactions
the AIDS Clinical Trials Group (ACTG) 5164 study have demonstrated the
Opportunistic infection Consider ART choice;
benefit of the early introduction of antiretroviral therapy in patients with
ensure optimised therapy
AIDS-related opportunistic infection.
54
In this study, patients who received
Metabolic, cardiovascular Early treatment initiation
immediate antiretroviral therapy after a median of 12 days of starting
HLA = human leukocyte antigen; HSR = hypersensitivity reaction; HBV = hepatitis B virus;
HCV = hepatitis C virus; TB = tuberculosis; ART = antiretroviral therapy.
acute opportunistic infections treatment benefited from fewer
deaths/AIDS progressions, longer time to death/AIDS progression and
gender appears to be significant, with increased rates of adverse events and shorter time to achieving increase in CD4 cell count compared with those
discontinuations observed among women treated with nucleoside reverse who started after a median of 45 days. Obviously, any choice of initial
transcriptase inhibitors (NRTIs), non-NRTIs and PIs (reviewed in Umeh and antiretroviral drugs should take into account known interactions with
Currier 2006).
35
The disparity in the rates of observed drug toxicity is concomitant non-antiretroviral drugs. Table 1 summarises the
potentially due to differences in pharmacokinetics, with women often recommendations concerning patient considerations.
achieving higher drug exposures than men.
36
Women also appear to be
more susceptible to didanosine-induced pancreatic toxicity
37
and to HIV Disease Considerations
nevirapine-associated rash and hepatotoxicity.
38,39
There is a striking The findings from a number of prospective analyses have demonstrated that
association between female gender and risk of lactic acidosis with certain the initiation of antiretroviral therapy in patients with low CD4 cell counts
NRTIs (e.g. stavudine and didanosine).
40
For example, a US Food and Drug (<200 cells/mm
3
) is associated with a significantly increased risk of disease
Administration (FDA) report of 60 cases of NRTI-associated lactic acidosis progression and death.
55–57
However, in many cases a significant proportion
found that 83% occurred in women, including 85% of fatal cases.
41
(up to 50%) of HIV-infected patients initiating treatment have CD4 cell
counts <200 cells/mm
3
.
58
In general, guideline recommendations on
The increasing age of patients diagnosed with HIV infection poses a initiating treatment are based on CD4 cell counts. All guidelines recommend
potential challenge to initiating treatment. Virological responses to that antiretroviral treatment is started in all patients with CD4 cell levels
antiretroviral therapy appear similar in the elderly compared with younger <350 cells/mm
3
(IAS,
15
BHIVA,
16
EACS,
17
DHHS
18
). However, there are
patients; however, immune recovery may be somewhat slower.
42,43
Other subsets of patients who may benefit from earlier initiation of treatment,
considerations for treatment initiation in older patients are dose adjustment even when CD4 cell counts exceed 350 cells/mm
3
. These groups include
for impaired renal or hepatic function and increased risk of cardiovascular patients with a high viral load (>100,000 copies/ml), hepatitis B or C
disease and lipodystrophy, which may influence drug selection. co-infection, HIV-associated neuropathy, a high cardiovascular risk or rapidly
declining CD4 counts (>50–100 cells/mm
3
/year). The initiation of
Behavioural factors must be considered before the initiation of antiretroviral therapy should not constitute an emergency since time needs
antiretroviral therapy. An assessment of the risk of poor adherence is to be allowed for completion of pre-treatment assessments such as viral
important, since low adherence is linked with detectable viraemia, disease resistance and HLA-B*5701 testing.
progression and death.
44–47
A number of important steps can be taken to
improve adherence, such as providing education on medication, The choice of initial antiretroviral therapy in treatment-naïve patients
improving low mood, reducing levels of substance abuse, reviewing and should take into account baseline viral load levels, since virological efficacy
anticipating drug side effects and providing an accessible, trusting for most antiretroviral combinations is generally inversely related to
healthcare team.
16,18
Simplification of treatment regimens has also been baseline viral load. Potent regimens with proven efficacy should be
shown to significantly improve adherence.
48,49
Lifestyle factors, work and administered in patients with high viral load levels. An interim analysis of
family situations should be considered before treatment initiation, as these data from the ongoing study ACTG 5202 comparing the NRTI backbones
can also influence adherence.
50
abacavir/lamivudine and tenofovir/emtricitabine given in combination with
either efavirenz or atazanavir/ritonavir has shown that time to virological
Effects of Co-morbidity failure was significantly shorter among patients with baseline viral load
Infectious co-morbidities, such as hepatitis B and C and tuberculosis, and levels >100,000 copies/ml in the abacavir/lamivudine arm.
59
In addition,
non-infectious co-morbidities, such as metabolic, cardiovascular, liver, the completed Abacavir/Lamivudine Versus Emtricitabine/Tenofovir Both
18 EUROPEAN INFECTIOUS DISEASE
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