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Page 4 of 39 Guideline

possible to decrease the overall pill burden. Many NRTIs agents) should be avoided. Tenofovir disoproxil fumarate also
require dose adjustment in patients with renal failure (see causes a decrease in bone mineral density; however, this is
section 21). generally mild and non-progressive, and most studies have not
found an increase in fracture risk.
Lamivudine and emtricitabine
Lamivudine and FTC are well-tolerated drugs recommended Abacavir
as part of a first-line regimen. Although there are minor Abacavir can be used in patients with a CrCl < 50 mL/min at
differences between them, 3TC and FTC are considered baseline, rather than TDF. Abacavir does not require dose
functionally interchangeable. Their use may be continued in adjustment in patients with renal failure and is especially
the presence of ‘high-level resistance’ caused by the M184V useful in patients with chronic renal failure, where TDF is
mutation because this mutation impairs the replication ability nephrotoxic and AZT could aggravate anaemia in patients
of HIV, causing a ~0.5 log decrease in VL. Therefore, the with renal failure. A meta-analysis showed that virological
drugs are often used in second- and third-line therapies (see suppression is equivalent with ABC- and TDF-containing
the management of patients on second-line ART in section 13). first-line regimens regardless of baseline VL. 6
Lamivudine and FTC are active against hepatitis B, but when
° Common pitfall: Avoiding ABC at high HIV VLs.
used in the absence of a second drug active against hepatitis This is unnecessary as viral suppression rates are
B, such as TDF, then resistance rates of approximately 50% at equivalent in meta-analyses.
3
1 year, and 90% at 5 years, are seen . See section 20.
Abacavir has been associated with an increased risk of
Tenofovir disoproxil fumarate myocardial infarction in some but not all cohort studies;
Tenofovir disoproxil fumarate is the preferred drug in this however, the association was not confirmed in a meta-
class for use with 3TC or FTC in first-line therapy because it analysis of randomised controlled trials (RCTs). 6,7,8
aligns with public sector programmes, is widely available as Nevertheless, caution is recommended when considering
an FDC and is generally well tolerated. Tenofovir disoproxil ABC for patients who are at significant risk of or have
fumarate also offers durable therapy against hepatitis B virus established ischaemic heart disease. Abacavir hypersensitivity
(HBV). Hepatitis B virus resistance against TDF is extremely is a systemic reaction occurring within the first 8 weeks of
rare. In a minority of patients, TDF may cause a tubular wasting therapy in approximately 3% of cases. Fatalities may occur
4
syndrome (including wasting of phosphate and potassium). If on rechallenge. Abacavir must be discontinued and never re-
patients receiving TDF develop muscle weakness or other introduced if hypersensitivity is suspected. The manifestations of
muscle symptoms, then potassium and phosphate levels must hypersensitivity include fever, rash, fatigue and abdominal
be assessed. Tenofovir disoproxil fumarate can also cause acute or respiratory symptoms. If there is any doubt concerning the
and chronic renal failure, but this is uncommon. diagnosis (e.g. if the patient has a cough with fever), then the
5
patient should be admitted for observation of the next dose;
Tenofovir disoproxil fumarate should be switched to ABC or symptoms progress if hypersensitivity is present. The
an alternative NRTI immediately in patients with acute renal hypersensitivity reaction has been shown to occur on a
failure, as it may exacerbate injury even if it is not the primary genetic basis, with a very strong association with the
cause. Consider recommencing TDF with careful monitoring HLA-B*5701 allele. This allele is very uncommon in people of
when creatinine level is normal if an alternative cause of African descent; thus, ABC hypersensitivity is less frequent.
renal failure is established.
If testing is affordable and available, then the presence of
HLA-B*5701 should be excluded prior to prescribing ABC,
We recommend estimating the CrCl before commencing especially in patients who are not of African descent.
TDF; the drug should not be used if the estimated glomerular
filtration rate (eGFR) or CrCl is < 50 mL/min. For monitoring
whilst on TDF, see Table 2. Where TDF is avoided because Zidovudine
CrCl is < 50 mL/min at baseline, it may be possible to switch We now recommend reserving AZT for use only in special
to TDF at a later point if renal function improves. This is often circumstances in first-line therapy. If both TDF and ABC are
the case where patients had diarrhoea or other opportunistic unavailable or contraindicated, then AZT should be used,
infections (OIs) at the time of ART initiation. provided that the Hb is > 8 g/dL.

° Common pitfall: Permanently discontinuing TDF in Additional syndromes related to nucleoside
patients with transiently decreased CrCl. Most cases reverse transcriptase inhibitors
of acute kidney injury (AKI) are not because of TDF,
and if another cause of AKI is identified (e.g. severe Haematological toxicity
diarrhoea or pneumonia), then TDF can be re- Cytopenias occur commonly in patients with HIV infection
introduced with monitoring once renal function without exposure to ART. Patients receiving AZT or
improves. cotrimoxazole (CTX) may experience full blood count (FBC)
abnormalities. Zidovudine can cause anaemia and
The long-term use of TDF together with other nephrotoxic neutropenia; platelet counts generally rise with the use of the
agents (e.g. aminoglycosides or non-steroidal anti-inflammatory drug. Monitoring is necessary with AZT (see Table 2). It is

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