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Population-based monitoring of HIV drug resistance in Namibia with early warning indicators
Global Health Sciences Literature Digest
Published May 12, 2011
Journal Article

Hong SY, Jonas A, Dumeni E, Badi A, Pereko D, Blom A, Muthiani VS, Shiningavamwe AN, Mukamba J, Andemichael G, Barbara R, Bennett DE, Jordan MR. Population-based monitoring of HIV drug resistance in Namibia with early warning indicators. J Acquir Immune Defic Syndr. 2010 Dec 1;55(4):27-31.

Objectives

To pilot the monitoring of selected World Health Organization (WHO) Early Warning Indicators, in order to gauge the likelihood of development of HIV drug resistance (DR) in Namibia.

Setting

Nine public sector clinical sites providing antiretroviral therapy (ART) in Namibia.

Design

Data abstraction

Population

Adult patients newly initiating first-line ART; HIV treatment facilities with Electronic Dispensing Tools in use by the pharmacy.

Main Outcome Measures

Five WHO Early Warning Indicators (EWIs): ART prescribing practices (percentage of patients initiating ART who pick up an appropriate first-line regimen); patients initiating ART who are lost to follow-up (LTFU) at 12 months; patient retention on first line ART (percentage of patients initiating ART who were changed to a regimen with different drug class during the first 12 months); on-time antiretroviral (ARV) pick up (percentage of patients picking up all ARV drugs on time); ARV drug supply continuity (percentage of months per year in which there were no ARV drug stock-outs).

Methods

Nine sites were randomly chosen from among 15 that had data in a standardized pharmacy-based Electronic Dispensing Tool (EDT) available for abstraction. Data was abstracted into a WHO electronic tool, with data validation performed on 10% of variables. Data were obtained either for patients consecutively initiating first-line ART or consecutively picking up ARV drugs during 2007. Sample size estimates were calculated assuming a prevalence of 50% for the EWI, resulting in a sample size of 180 for all EWIs at all sites. Data on pharmacy stock-outs were abstracted for the period January 2008 to December 2008.

Results

Data from 3,240 patients were abstracted and analyzed. However, information on ‘on-time drug pick-up’ and ‘ARV drug-supply continuity’ was not available either because data were not entered or were incomplete. All patients from all nine sites achieved the target of 100% appropriate first line ART initiation or pick-up. Eight of nine sites (89%) met the target of ≤20% of patients LTFU at 12 months. The median percentage of patients LTFU at 12 months was 15%; 20.8% of patients had a period without ART coverage during the first year of treatment for a median of 2.3 months. Six of nine sites (67%) met the target of no-one switching to a second-line regimen in the first 12 months; one patient at each of two sites had been switched to appropriate second-line therapy after virological failure. At one site, one patient had been switched to inappropriate triple nucleoside reverse transcriptase inhibitor (NRTI) regimen. Data for ‘on time ARV drug pick up’ was unavailable, except for one site where 72% of patients picked up drugs on time.

Conclusions

No inappropriate prescribing practices were identified. The proportion of patients LTFU at 12 months was low, and met the WHO target. However, a substantial proportion had a two to three month absence from clinic. It is not known whether these patients were obtaining ART elsewhere. Data on stock-outs and on-time pick up were not available; thus, two out of five of the EWI could not be collected. Nevertheless, the results of this pilot were used constructively by the Namibian Ministry of Health to improve pharmacy and clinical patient records and to develop systems to trace patients.

Quality Rating

This was a good quality study, and provided important information on how results changed national practices. Data were only obtained from public sector sites, although 23% of patients receive ART in the private sector in Namibia. Pediatric patients were not included, although EWI are more difficult because of the specificity of pediatric ART formulations.

In Context

Various site and patient-related factors, called Early Warning Indicators, are associated with the emergence of HIV drug resistance.(1)These can be monitored to improve program performance and avoid the emergence of resistance,(2,3,4) without having to rely on expensive viral load and actual HIV DR testing. In Namibia, the 2008 estimate of national HIV prevalence among 15-49 year-olds was 17.8%, with up to 31% of the population infected in some areas.

Programmatic Implications

The monitoring of EWIs can have important programmatic implications, and should be initiated widely. Most of these indicators could easily be collected routinely, though it is important for countries to adopt these indicators as part of standardized data collection and record keeping. Even if not adopted at a national level, local programs could include EWIs. Appropriate monitoring of EWIs can reduce the emergence of early drug resistance, which can undermine ARV rollout. In response to this pilot survey’s finding of significant LFTU among patients in Namibia, that country’s MOH is implementing new measures to prevent loss. These measures include an intensification of an ART defaulter tracing mechanism, the establishment of a national patient data base with unique patient identifiers, and improvements in the pharmacy record system, allowing abstraction of all five EWI in the future. Namibia also plans to scale up monitoring of EWIs to all of its ART sites.

Some of the WHO recommended indicators, such as pharmacy refill adherence or ‘on-time ARV drug pick-up’ are difficult to monitor because the records needed to calculate this are rarely available. In cases where pills are left over from the previous prescription but not counted, the date of pharmacy pick-up may not reflect treatment interruptions. It is important, however, to try to identify patients with significant drug interruptions either because of repeated late pick-up or absence from clinic, because they may be more likely to develop drug resistance.(5,6)

References

  1. Diane E Bennett, Silvia Bertagnolio, Donald Sutherland and Charles F Gilks. The World Health Organization’s global strategy for prevention and assessment of HIV drug resistance. Antiviral Therapy Volume 13, 2008; Supplement 2: 1–13
  2. Vergne L, Malonga-Mouellet G, Mistoul I, Mavoungou R, Mansaray H, Peeters M, Delaporte E. Resistance to antiretroviral treatment in Gabon: need for implementation of guidelines on antiretroviral therapy use and HIV-1 drug resistance monitoring in developing countries. J Acquir Immune Defic Syndr. 2002;29:165–168.
  3. Marcellin F, Boyer S, Protopopescu C, Dia A, Ongolo-Zogo P, Koulla-Shiro S, Abega SC, Abé C, Moatti JP, Spire B, Carrieri MP; EVAL Study Group. Determinants of unplanned antiretroviral treatment interruptions among people living with HIV in Yaoundé, Cameroon (EVAL survey, ANRS 12-116). Trop Med Int Health. 2009;13:1470–1478
  4. Eholié SP, Tanon A, Polneau S, Ouiminga M, Djadji A, Kangah-Koffi C, Diakité N, Anglaret X, Kakou A, Bissagnené E. Field adherence to highly active antiretroviral therapy in HIV-infected adults in Abidjan, Co^te d´Ivoire. J Acquir Immune Defic Syndr. 2007;45:355–358
  5. Parienti JJ, Massari V, Descamps D, Vabret A, Bouvet E, Larouzé B, Verdon R. Predictors of virologic failure and resistance in HIV-infected patients treated with nevirapine- or efavirenz-based antiretroviral therapy. Clin Infect Dis. 2004;38:1311–1316.
  6. Oyugi JH, Byakika-Tusiime J, Ragland K, Laeyendecker O, Mugerwa R, Kityo C, Mugyenyi P, Quinn TC, Bangsberg DR. Treatment interruptions predict resistance in HIV-positive individuals purchasing fixed-dose combination antiretroviral therapy in Kampala, Uganda. AIDS. 2007;21: 965–971.