HTB

South African antiretroviral treatment guidelines (2010)

2 April 2010. Related: Treatment access, Guidelines.

Polly Clayden, HIV i-Base

The South African Antiretroviral Treatment guidelines have finally been updated. [1]

These have been long-awaited as the last full edition was in 2004.

Important revisions include the use of tenofovir (TDF) in first line treatment (replacing d4T), more complex prophylaxis regimens and earlier treatment for pregnant women and universal treatment for infants <12 months of age.

The treatment guidelines are also summarised in an abridged version with a series of tables incorporating key recommendations from all three documents.

Management of adults and adolescents

When to start?

Antiretrovirals should be started in all HIV-positive patients with CD4 <200 cells/mm3 irrespective of clinical stage.

People with TB/HIV and pregnant women should start antiretroviral treatment at CD4 <350 cells/mm3. People with WHO stage 4 or DR TB should start treatment irrespective of their CD4 count.

What to start?

The recommended first line regimens for all new patients are:

  • TDF+3TC or FTC+EFV
  • TDF+3TC or FTC+NVP

Already
receiving d4T-based regimen

If d4T is well tolerated patients should remain on this regimen. An early switch is recommended for any toxicity. People at high risk for toxicity (high BMI, low Hb, older female) should switch d4T for TDF.

Fast track

Pregnant women indicated for treatment, people with very low CD4 (<100 cells/mm3) and stage 4 with CD4 count not yet available and those with MDR/XDR TB, should be fast tracked ie start ART within two weeks of being eligible.

When to switch

Virlogical failure (>1000 copies/mL) over 3 months despite adherence interventions.

Second-line ART

Failing on d4T-based regimen:

  • TDF+3TC or FTC +LPV/r

Failing on a TDF-based regimen:

  • AZT+3TC+LPV/r

Third-line ART

Specialist referral where possible, but maintain on a failing regimen.

comment

That these guidelines did not adopt <350 cells/mm3 as the threshold for starting treatment for all, in line with the WHO, the Southern African Clinicians Society and many national guidelines, has raised much discussion. [2 ] Arguably this consideration may be largely academic in a country where the median CD4 count at initiation is still about 100 cells/mm3 despite a massive scaling up of testing. [3]

However, now that the SA Ministry of Health is about to launch a campaign to test 15 million people by June next year, this situation is likely to change. Earlier treatment for select groups and fast track for those most at risk however are very welcome.

An important change is the replacement of d4T with TDF for first-line regimens. As well as following guidance to avoid the more dramatic effects of lactic acidosis, hopefully “well tolerated” and “early switch” will be interpreted in the very best interests of patients who have endured peripheral neuropathy or lipoatrophy associated with this drug.  Equally dropping ddI from second-line regimens, though not affecting such large numbers of people, is a vast improvement.

Prevention of mother to child transmission

These guidelines make recommendations for pregnant women both eligible and ineligible for treatment and for infant feeding.

When to start?

As above, CD4 <350 cells/mm3.

What to start?

TDF+3TC or FTC +NVP

Women already receiving ART should substitute EFV with NVP if in first 12 weeks of pregnancy. Women contraindicated to TDF should receive AZT+3TC+NVP.

Prophylaxis for women CD4 >350 cells/mm3

AZT from 14 weeks + single dose NVP + AZT three hourly during labour; TDF+FTC single dose post delivery.

Infant regimens

Breast fed or formula fed infants of mothers on HAART: NVP at birth and daily for 6 weeks.

Breast fed or formula fed infants of mothers receiving prophylaxis: NVP at birth and daily for 6 weeks if formula fed or until cessation of breast feeding.

comment

Guidance for pregnant women is broadly similar to WHO recommendations. However, the approach to use of efavirenz is far more cautious. Whereas the WHO interpreted the low quality, conflicting evidence for the risks of in utero exposure to confine the contraindication to the first trimester, these guidelines do not recommend its inclusion at all in pregnancy.  From an operational point of view this will make treatment of pregnant women a bit more complicated and inconsistent with general adult recommendations. Efavirenz has a number advantages where simplification is important, it can be taken once daily in a fixed dose combination with TDF and FTC, unlike nevirapine there is no extra monitoring for rash and/or hepatoxicity risk and it can be used in conjunction with TB treatment.

The choice of a single dose of TDF/FTC “tail” coverage is an interesting one, whereas the WHO recommend 7 days of 3TC/AZT and this has been adopted
by several national programmes, some have suggested that this may be too complicated to implement.

Chi et al showed a reduction in resistance using a single dose of TDF/FTC from approx 30% to 14% among women with CD4 cell counts of about 475 cells/mm3 receiving single dose nevirapine (women with CD4 <200 cells/mm3 were excluded and received HAART), of which approximately 80% received
antepartum AZT for a median of about 37 days, and 30% had undetectable viral load at delivery. [4]

It is likely that a treatment threshold of <350 CD4 cells/mm3 will further exclude women most at risk for NNRTI resistance and this approach may offer a reasonable compromise between reduction of resistance risk and ease of implementation.

Management of HIV in children

When to start?

  • Universal treatment for infants <12 months old.
  • Clinical stage 3 or 4 or CD4 <25% or absolute CD4 <750 cells/mm3 for children age 1-5 years.
  • Clinical stage 3 or 4 or CD4 < 350 cells/mm3 for children >5 years
    to 15 years.

What to start?

  • Infants and children <3 years old: ABC+3TC+LPV/r.
  • Children >3 years old:
    ABC+3TC+EFV.

Second line

Children >3 years old failing ABC+3TC+EFV: AZT+ddI+LPV/r

Children >3 years old failing an AZT- or ddI-based regimen: ABC+3TC+LPV

Children failing a LPV/r-based regimen and/or  <3 years old who are failing first-line require specialist referral.

comment

Universal treatment for infants <12 months old and initiation at CD4 350 cells/mm3 for children >5 years old reflects current international consensus. Treatment for children between 1 and 5 years has little data to guide us, and WHO and national guidelines all give slightly different recommendations.

That the threshold for initiation for children and adolescents between 5 and 15 years old is 350 cells/mm3 for all differs from adult recommendations, where a considerable number of people will not be eligible for treatment until CD4 drops to 200 cells/mm3.

References

  1. 1. SA Dept of Health. The South African Antiretroviral Treatment Guidelines, 2010.
    http://www.sanac.org.za/resources/art-guidelines
  2. WHO. New HIV recommendations to improve health, reduce infections and save lives. (01 December 2009).
    http://www.who.int/mediacentre/news/releases/2009/world_aids_20091130/en/index.html
  3. Geffen N. Guidelines on when to start treatment in resource poor settings. HTB, October 2009.
    https://i-base.info/htb-south/190
  4. Chi BH et al. Single-dose tenofovir and emtricitabine for reduction of viral resistance to non-nucleoside reverse transcriptase inhibitor drugs in women given intrapartum nevirapine for perinatal HIV prevention: an open-label randomised trial. Lancet. 2007 Nov 17;370(9600):1698-705. Epub 2007 November.
    http://www.ncbi.nlm.nih.gov/pubmed/17997151

Links to other websites are current at date of posting but not maintained.