Monitoring HIV Drug Resistance Early Warning Indicators in Cameroon: A Study Following the Revised World Health Organization Recommendations

<div><p>Background</p><p>The majority (>95%) of new HIV infection occurs in resource-limited settings, and Cameroon is still experiencing a generalized epidemic with ~122,638 patients receiving antiretroviral therapy (ART). A detrimental outcome in scaling-up ART is the emergence HIV drug resistance (HIVDR), suggesting the need for pragmatic approaches in sustaining a successful ART performance.</p><p>Methods</p><p>A survey was conducted in 15 ART sites of the Centre and Littoral regions of Cameroon in 2013 (10 urban versus 05 rural settings; 8 at tertiary/secondary versus 7 at primary healthcare levels), evaluating HIVDR-early warning indicators (EWIs) as-per the 2012 revised World Health Organization’s guidelines: EWI₁ (<i>on-time pill pick-up</i>), EWI₂ (<i>retention in care</i>), EWI₃ (<i>no pharmacy stock-outs</i>), EWI₄ (<i>dispensing practices</i>), EWI₅ (<i>virological suppression</i>). Poor performance was interpreted as potential HIVDR.</p><p>Results</p><p>Only 33.3% (4/12) of sites reached the desirable performance for <i>“on-time pill pick-up”</i> (57.1% urban versus 0% rural; p<0.0001) besides 25% (3/12) with fair performance. 69.2% (9/13) reached the desirable performance for <i>“retention in care”</i> (77.8% urban versus 50% rural; p=0.01) beside 7.7% (1/13) with fair performance. Only 14.4% (2/13) reached the desirable performance of <i>“no pharmacy stock-outs”</i> (11.1% urban versus 25% rural; p=0.02). All 15 sites reached the desirable performance of 0% <i>“dispensing mono- or dual-therapy”</i>. Data were unavailable to evaluate <i>“virological suppression”</i> due to limited access to viral load testing (min-max: <1%-15%). Potential HIVDR was higher in rural (57.9%) compared to urban (27.8%) settings, p=0.02; and at primary (57.9%) compared to secondary/tertiary (33.3%) healthcare levels, p=0.09.</p><p>Conclusions</p><p>Delayed pill pick-up and pharmacy stock-outs are major factors favoring HIVDR emergence, with higher risks in rural settings and at primary healthcare. Retention in care appears acceptable in general while ART dispensing practices are standard. There is need to support patient-adherence to pharmacy appointments while reinforcing the national drug supply system.</p></div

Staff/Patient ratio in the overall study population.

<p>Staff/Patient ratio in the overall study population.</p

Socio-demographic and medical data of the study population.

<p><b>Legend </b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072680#pone-0072680-t001" target="_blank"><b>table 1:</b></a> ART: Antiretroviral therapy; HAART: Highly Active Antiretroviral therapy;</p><p>PMTCT: prevention of mother-to-child transmission; IQR: Interquartile range.</p

HIV drug resistance at enrollment on ART.

<p><b>Legend </b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072680#pone-0072680-t002" target="_blank"><b>table 2</b>:</a> PI: protease inhibitor; NRTI: nucleoside reverse transcriptase inhibitor; NNRTI: non-nucleoside reverse transcriptase inhibitor; HAART: highly active antiretroviral therapy; VL: viral load; LTFU: lost to follow-up; NVP: nevirapine; 3TC: lamivudine; AZT: zidovudine; d4T: stavudine; EFV: efavirenz.</p

Definition of EWIs and their respective performance targets.

<p>EWI, early warning indicator</p><p>EWI₄ is cross sectional in nature and is intended to assess pharmacy dispensing practices for populations on ART after any period of time on ART.</p><p>Definition of EWIs and their respective performance targets.</p

Drug resistance-associated mutations at 12 months of ART.

<p><b>Legend </b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072680#pone-0072680-t004" target="_blank"><b>table 4</b>:</a> PI: protease inhibitor; NRTI: nucleoside reverse transcriptase inhibitor; NNRTI: non-nucleoside reverse transcriptase inhibitor; HIVDR: HIV Drug Resistance.</p

Virologic outcome at the study endpoint (M12).

<p><u>Legend</u>: NA: not applicable.</p

Site Performance for “No Pharmacy ARV Stock-outs” in 2013.

<p>NV, Not Validated; green, desirable performance; red, poor performance. The horizontal line in “green” color indicates the lower limit threshold for a “desirable” performance.</p

Overall national ART performance for each EWI.

<p>Overall national ART performance for each EWI.</p

Evaluation of EWIs in each of the 40 surveyed sites during the year 2010.

<p>In <i>“</i><b><i>Bold</i></b><i>”</i>: EWI reaching the required target. NV: Not Validated. NA: Not Available.</p><p><u>EWI</u>: Early Warning Indicator.</p><p><u>EWI₁</u>: Percentage of patients initiated on an appropriate first line ARV drug regimen, following national guidelines (Required target performance: 100%);</p><p><u>EWI₂</u>: Percentage of patient lost to follow-up after 12 months of enrolment to ART (Required target performance: ≤20%);</p><p><u>EWI₃</u>: Percentage of patient retained on appropriate first line ART after 12 month of treatment (Required target performance: ≥70%);</p><p><u>EWI₄</u>: Percentage of patients picking-up their ARV drugs on-time at the pharmacy of the ART site (Required target performance: ≥90%);</p><p><u>EWI₅</u>: Percentage of months without ARV drug shutdown at the pharmacy of the ART site (Required target performance: 100%).</p