Association between medication possession ratio, virologic failure and drug resistance in HIV-1-infected adults on antiretroviral therapy in Côte d'Ivoire

Abstract

Background: Adherence is a strong determinant of viral suppression with antiretroviral therapy (ART) but measuring it is challenging. Medication delivery can be measured accurately in settings with computerized prescription databases. We studied the association between medication possession ratio (MPR), virologic suppression, and resistance to ART in Côte d'Ivoire.

Methods: We conducted a prospective cohort study of HIV-1-infected adults initiating ART in 3 clinics using computerized monitoring systems. Patients had viral load (VL) tests at month 6 (M6) and month 12 (M12) after ART initiation and genotype tests if VL was detectable (≥300 copies/mL). MPR was defined as the number of daily doses of antiretroviral drug actually provided divided by the total number of follow-up days since ART initiation.

Results: Overall, 1573 patients started ART with stavudine/zidovudine plus lamivudine plus nevirapine/efavirenz. At M6 and M12, 996 and 942 patients were in active follow-up; 20% (M6) and 25% (M12) of patients had detectable VL, including 7% (M6) and 11% (M12) with ≥1 resistance mutation. Among patients with MPR of ≥95%, 80%-94%, 65%-79%, 50%-64%, and <50% at M12, the proportion with detectable VL [resistance] was 9% [4%], 17% [7%], 45% [24%], 67% [31%], and 85% [37%]. Among patients with ≥1 mutation at M12, 86% were resistant to lamivudine/emtricitabine and/or nevirapine/efavirenz but not to other drugs.

Conclusions: MPR was strongly associated with virologic outcomes. Half of those with detectable VL at M12 had no resistance mutations. MPR should be used at M6 to identify patients who might benefit from early interventions to reinforce adherence.

Figure 1

Flow chart of the study - lost to follow up before month 6: (i) last contact with study team

Figure 2

Virological status at month 6 and month 12, according to Medication Possession Ratio Figure 2A. Virological status at month 6, according to Medication Possession Ratio between ART initiation and month 6 Figure 2B. Virological status at month 12, according to Medication Possession Ratio between ART initiation and month 12 ART: Antiretroviral treatment; VL: viral load (plasma HIV-1 RNA)

Figure 2

Virological status at month 6 and month 12, according to Medication Possession Ratio Figure 2A. Virological status at month 6, according to Medication Possession Ratio between ART initiation and month 6 Figure 2B. Virological status at month 12, according to Medication Possession Ratio between ART initiation and month 12 ART: Antiretroviral treatment; VL: viral load (plasma HIV-1 RNA)

Figure 3

Distribution of the Medication Possession Ratio, according to virologic status at month 6 and month 12 Figure 3A. Distribution of the Medication Possession Ratio between ART initiation and month 6, according to virologic status at month 6 Figure 3B. Distribution of the Medication Possession Ratio between ART initiation and month 12, according to virologic status at month 12 ART: Antiretroviral treatment; VL: viral load (plasma HIV-1 RNA) MPR: Medication Possession Ratio M0: ART initiation; M6: month 6; M12: month 12 VL detectable, no resistance versus VL undetectable : p <0.0001 at month 6 and month 12 VL detectable with resistance versus VL undetectable : p <0.0001 at month 6 and month 12 VL detectable with resistance versus VL detectable, no resistance: p= 0.64 at month 6 and 0.76 at month 12

Figure 3

Distribution of the Medication Possession Ratio, according to virologic status at month 6 and month 12 Figure 3A. Distribution of the Medication Possession Ratio between ART initiation and month 6, according to virologic status at month 6 Figure 3B. Distribution of the Medication Possession Ratio between ART initiation and month 12, according to virologic status at month 12 ART: Antiretroviral treatment; VL: viral load (plasma HIV-1 RNA) MPR: Medication Possession Ratio M0: ART initiation; M6: month 6; M12: month 12 VL detectable, no resistance versus VL undetectable : p <0.0001 at month 6 and month 12 VL detectable with resistance versus VL undetectable : p <0.0001 at month 6 and month 12 VL detectable with resistance versus VL detectable, no resistance: p= 0.64 at month 6 and 0.76 at month 12