South African treatment guidelines need to consider viral load, not CD4 count, to achieve greater impact of treatment as prevention: study

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Recommendations about the initiation of antiretroviral therapy (ART) need to change for the use of HIV treatment as prevention to have maximum benefit, according to an international team of investigators writing in the March edition of PLOS ONE.

They found that over a third of patients newly diagnosed with HIV in Soweto who did not qualify for immediate ART on the basis of their CD4 count nevertheless had a potentially highly infectious viral load.

“Consideration should be given to replacing CD4 count threshold with viral load threshold for ART initiation when planning treatment as prevention (TasP) interventions,” write the authors.


treatment as prevention (TasP)

A public health strategy involving the prompt provision of antiretroviral treatment in people with HIV in order to reduce their risk of transmitting the virus to others through sex.


A serodiscordant couple is one in which one partner has HIV and the other has not. Many people dislike this word as it implies disagreement or conflict. Alternative terms include mixed status, magnetic or serodifferent.

Fully suppressive HIV treatment greatly reduces the risk of HIV transmission at the individual level. Starting ART has been shown to reduce the risk of HIV transmission in discordant heterosexual couples by 96% and interim results from the ongoing PARTNER study showed that no HIV-positive individual, gay or straight, with a suppressed viral load transmitted the virus to a partner.

The benefits of treatment at a population level depend on very high rates of HIV diagnosis, uptake of antiretroviral therapy and suppression of viral load.

However, not all HIV-positive patients are taking ART. In most settings, decisions about the best time to start ART are primarily guided by CD4 count and symptoms. South African guidelines set a CD4 count of 350 cells/mm3 as the threshold to initiate ART. Investigators were therefore concerned that some people with CD4 counts above this level might nevertheless have potentially infectious levels of viral load (above 10,000 copies/ml). They therefore monitored CD4 count and viral load in people testing HIV positive at the ZAZI clinic, a voluntary counselling and testing facility in Soweto, South Africa.

The study population comprised 348 people who were identified as HIV positive in their first test.

The study participants had a median age of 34 years and overall median CD4 cell count was 364 cells/mm3 (range: 238-542). Median CD4 count was higher in females than males (419 cells/mm3 vs 303 cells/mm3, p = 0.0001).

Just over half (53%) of participants had a CD4 count above 350 cells/mm3 and were thus, on the basis of current guidelines, ineligible for ART. Women were more likely than men to have a count above this level (60 vs 40%, respectively).

The participants had a median viral load of 13,000 copies/ml (range: 2050-98,171). Females had significantly lower median viral loads than males (9100 vs 34,000 copies/ml, p = 0.0005).

Overall, 54% of participants had a viral load above 10,000 copies/ml. This was the case for 64% of men and 48% of women.

Of the 183 participants who did not qualify for ART on the basis of their CD4 count, 34% had a viral load above 10,000 copies/ml. Similar proportions of men and women (39 vs 32%, respectively) had CD4 counts above 350 cells/mm3 and a high viral load.

“A large proportion of HIV infected adults did not qualify for immediate ART and at the CD4 cell threshold of 350 cells/mm3 had high viral loads,” comment the authors.

They believe the use of treatment as prevention means that guidelines for the initiation of ART should be reconsidered.

“Viral load estimation at the time of HIV diagnosis might be a better measure than CD4 count when making decisions about the initiation of ART in the context of TasP,” conclude the authors. “Our data suggest that for TasP to succeed, ART treatment initiation criteria require revision, with a view to commencing therapy irrespective of CD4 counts.”

Govender S et al. CD4 counts and viral loads for newly diagnosed HIV-infected individuals: implications for treatment as prevention. PLOS ONE 9(3): e90754. doi:10/1371/journal.pone.0090754, 2014.