HIV Viral Load Response to Antiretroviral Therapy According to the Baseline CD4 Cell Count and Viral Load

For patients with asymptomatic HIV who have not received antiretroviral therapy (ART), it is unclear whether such therapy should be initiated immediately or deferred until CD4 cell count is lower, and/or the plasma viral load is higher. Early therapy brings immediate intervention against a virus known to be causing immune damage, provides the potential for preservation of HIV-specific CD4 cells and the micro-architecture of lymphoid organs, and lowers the viral load to reduce infectivity and prevent opportunistic diseases with high fatality rates. Delaying therapy, alternatively, means avoiding the risk of drug toxic effects, selection for drug resistance, and the inconveniences of adhering to a complex regimen for an extended time period.

Successful treatment of HIV requires a profound and prolonged virological response. A key consideration when deciding when to initiate ART is whether the virological response is likely to be compromised by any delay. However, the relationship between baseline CD4 cell count, baseline viral load, and viral load response has not been characterized in detail.

In order to characterize the relationship of viral load response to ART with baseline CD4 cell count and baseline viral load, the authors studied an inception cohort of 3,430 therapy-naive patients, of whom 3,226 patients had at least 1 viral load count after the initiation of ART. The cohort consisted of patients in the Swiss HIV Cohort Study (SHCS), Frankfurt HIV Clinic Cohort (FHCC), and EuroSIDA studies who initiated ART 1) consisting of at least 3 drugs in combination, 2) after January 1, 1996, 3) with a viral load and CD4 cell count measurement available 6 months before, and 4) when the most recent viral load was greater than 500 copies/ml. For viral load outcomes, the investigation required at least one measurement available after the start of therapy.

All 3 cohorts are clinic-based, capturing in a prospective fashion the ongoing clinical and laboratory marker status of complete populations of clinic patients, and for the EuroSIDA, a consecutive group of clinic attendees over a stipulated time period. For the EuroSIDA and SHCS, viral load and CD4 cell counts were measured approximately every 3 months. In the Frankfurt HIV Clinic Cohort, viral load and CD4 cell counts were measured every 1 to 2 months. For these analyses, the assays were sensitive to a viral load above 500 copies/mL.

Viral response used three measures. One measure was the time to viral load of less than 500 copies/mL. Thirty-two weeks was chosen as a period over which, from previous experience, the viral load would be expected to have declined to below 500 copies/mL. The second measure pertained to only those patients for whom there was at least 1 viral load measure available between weeks 22 and 40 and classified them according to whether the viral load measured closest to week 32 was below 500 copies/mL. The third measure -- restricted to those patients who achieved a viral load of less than 500 copies/mL by 32 weeks -- was the time from viral load first declining below 500 copies/mL to the time of the first of 2 consecutive values above this level.

The authors report that lower CD4 cell counts and higher viral loads at baseline were not associated with poorer virological outcome of ART. However, those with baseline viral loads of greater than 100,000 copies/mL had a lower rate of achieving viral suppression. "The decision of when to initiate therapy is complicated, and many factors must be taken into account. We have provided information concerning only 1 issue, albeit an important one. Until firm evidence from randomized trials is available, it is pieces of evidence such as this study that clinicians and patients must refer to when deciding on when to initiate therapy," the author concluded.

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