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INCREASED RISK OF CART FAILURE AFTER LOW-LEVEL VIREMIA UNDER WHO GUIDELINES
Lucas E. Hermans1, Michelle A. Moorhouse2, Sergio Carmona2, Diederick Grobbee3, Laura Marije Hofstra3, Douglas D. Richman4, Hugo Tempelman5, Willem D. Venter2, Annemarie Wensing3
1Univ Med Cntr Utrecht, Utrecht, Netherlands,2Univ of Witwatersrand, Johannesburg, South Africa,3Univ Med Cntr Utrecht, Utrecht, Netherlands,4Univ of California San Diego, San Diego, California, USA,5Ndlovu Care Group, Groblersdal, South Africa
Current WHO guidelines for cART in HIV-1 infected patients define failure of cART as viremia above 1000 copies/mL during therapy. Detectable viral load (VL) below 1000 copies/mL during cART (low-level viremia; LLV) has been linked to subsequent failure of cART in studies performed in high-income settings, where more stringent VL cut-off values are used. We report the prevalence of LLV and its impact on subsequent failure of cART in a large South African cohort managed according to WHO guidelines.
HIV-positive patients from 19 urban and 38 rural South African HIV treatment sites were studied. Adult patients on cART for ≥20 weeks and with ≥1 VL performed ≥20 weeks after start of cART were included. LLV was defined as viremia between 50-1000 copies/mL and stratified according to level (51-199, 200-399, and 400-999 copies/mL) and duration. Studied outcomes were failure of cART (VL ≥1000 copies/mL) and switch to second line cART. In the subset of patients with ≥100 weeks of first line cART without failure and ≥3 VLs risk of failure after LLV was estimated with survival analysis using Cox proportional hazard models corrected for sex, age and nadir CD4.
69,615 patients met inclusion criteria. Virological suppression <1000 copies/mL during cART was maintained in 80.9% of patients. LLV occurred in 23.3% of patients. A single measurement of LLV (sLLV) was more common than persistent LLV (pLLV) (78.6% vs 21.4%). LLV between 51 and 199 copies/mL (LLV51-199) was most commonly encountered (59.1%). In survival analysis (26,305 patients) LLV was associated with increased hazard of failure of cART (HR 2.8; CI-95% 2.7-2.9) and of ever switching to second line (HR 3.2; CI-95% 3.0-3.3) when compared to patients with <50 copies/mL. Risk of failure increased proportionally to level of LLV: HR 1.7 (CI-95% 1.5-1.9) for sLLV51-199, 2.7 (CI-95% 2.5-3.0) for sLLV200-399 and 3.6 (CI-95% 3.4-3.8) for sLLV400-999. Risk of failure further increased in cases of pLLV, with a HR of 3.0 (CI-95% 2.9-3.2) for pLLV50-199, 4.2 (CI-95% 4.0-4. 4) for pLLV200-399 and 7.7 (CI-95% 7.4-7.9) for pLLV400-999. Lower nadir CD4 was independently associated with LLV.
In this large cohort prevalence of LLV was high and patients with LLV were at increased risk of subsequent failure and switching to second line cART. These risks increased further with higher levels and longer duration of LLV. This poses concerns for the long term success of first line cART in treatment programmes in resource limited settings.