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Page 9 of 39 Guideline

Atazanavir presenting with CM or tuberculosis meningitis (TBM) –
Atazanavir is generally better tolerated than LPV and can be see below.
taken once daily: It has important drug interactions with drugs Benefits of antiretroviral therapy in reducing morbidity
that reduce stomach acidity, such as PPIs. Atazanavir may cause and mortality
an unconjugated hyperbilirubinaemia as a result of inhibition of the +
hepatic enzyme Uridine 5'-diphospho-glucuronosyltransferase. With ART-induced viral suppression, the CD4 lymphocyte
Although the hyperbilirubinaemia is harmless and does not count usually increases, which is accompanied by a
restoration of pathogen-specific immune function. For most
reflect a drug-induced liver injury (DILI), a minority of patients patients, this results in a dramatic reduction in the risk of
will become visibly jaundiced, and this may require changing HIV-associated morbidity and mortality. For patients who
ART regimens for cosmetic reasons.
+
start ART with preserved CD4 counts, ART is able to prevent
+
° Common pitfall: Mistaking the unconjugated the decline in CD4 count observed in untreated patients
hyperbilirubinaemia sometimes seen with ATV use and thereby prevent clinical complications of HIV infection.
with a DILI. Conversely, it is equally important to The benefits in morbidity and mortality extend to patients
note that ARVs can also cause a true DILI, and with relatively preserved CD4 counts. The START and
+
therefore a complete liver function test (LFT) panel TEMPRANO ANRS 12136 trials showed significant
should be performed to distinguish between the two individual clinical benefits when starting ART immediately
possibilities. in patients with CD4 counts > 500 cells/μL rather than
+
+
deferring until a certain lower CD4 threshold or clinical
Darunavir indication was met. 35,36
Darunavir has the highest barrier to resistance of any PI:
Mutations selected by ATV or LPV can compromise DRV Benefits of antiretroviral therapy in reducing transmission
efficiency. For patients with mutations that confer any degree The HPTN 052 trial showed that treating the HIV-positive
of resistance to DRV (e.g. I50V, L76V and I84V), the dose partner in a serodiscordant relationship with ART was
should be DRV/r 600 mg/100 mg twice daily. For patients associated with a 93% reduction in transmission risk to the
without any DRV mutations, the drug can be taken at a dose uninfected partner, with the only linked transmissions
of DRV/r 800 mg/100 mg once daily. There is evidence, occurring from partners without a suppressed VL. Further
37
however, that DRV/r 400 mg/100 mg once daily may be evidences in serodiscordant couples from the PARTNER,
sufficient in this scenario, especially for patients with PARTNER2 and Opposites Attract trials have confirmed
suppressed VLs at the time of the switch. 33,34 Compared with a that HIV is essentially not transmittable when the VL is
twice-daily dosing, a once-daily dosing offers the benefits of suppressed. 38,39,40 Community-level evidence has also
reduced pill burden and better side effect profile. As with ATV, demonstrated a reduction in HIV incidence as ART rollout is
DRV cannot be co-prescribed with RIF-based TB treatment.
scaled up. Therefore, early ART initiation has significant
° Common pitfall: Prescribing ATV or DRV in public health benefits.
patients receiving RIF-based TB treatment.
Lopinavir/ritonavir is the only PI combination that Antiretroviral therapy in primary human
can be co-prescribed safely with RIF, but the dose of immunodeficiency virus infection
LPV/r must be adjusted as above. In patients who are diagnosed with HIV during acute
seroconversion, we advise counselling and initiating ART as
6. Initiation and timing of soon as possible. Expedited ART initiation is preferable as
antiretroviral therapy there is evidence that this may limit the size of the HIV
reservoir. Once the patient is established on ART, additional
41
Key points counselling may be required for patients who start ART in
this acute stage because there is limited time for extensive
ÿ All individuals diagnosed with HIV should be initiated pre-ART counselling, and there is often considerable
on ART. psychological distress around this time.
ÿ Delays to start ART should be minimised. Several studies
have demonstrated that it is safe to initiate. Antiretroviral therapy initiation in ‘elite
ÿ ART on the same day as diagnosis or on receipt of CD4 controllers’
+
count result, with the main benefit being improved
retention in care. A minority of patients (< 1%) have very effective immune
ÿ Screening for TB, cryptococcal meningitis (CM) and control of HIV infection and can control HIV viraemia at
other OIs prior to ART initiation is important, as these undetectable levels even in the absence of ART; these patients
conditions may necessitate delaying ART initiation. are termed ‘elite controllers’.

Overview Although definitive data are lacking for this patient subgroup,
we advise initiating ART in elite controllers too, as indirect
All patients who are diagnosed with HIV should be initiated evidence suggests a potential benefit. Elite controllers still
on ART as soon as possible. Exceptions include patients have evidence of chronic immune activation and

http://www.sajhivmed.org.za 27 Open Access