Adherence to Highly Active Antiretroviral Therapy Assessed by Pharmacy Claims Predicts Survival in HIV-Infected South African Adults

Department of International Health, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD 21205, USA.
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.56). 09/2006; 43(1):78-84. DOI: 10.1097/01.qai.0000225015.43266.46
Source: PubMed


It is unclear how adherence to highly active antiretroviral therapy (HAART) may best be monitored in large HIV programs in sub-Saharan Africa where it is being scaled up. We aimed to evaluate the association between HAART adherence, as estimated by pharmacy claims, and survival in HIV-1-infected South African adults enrolled in a private-sector AIDS management program. Of the 6288 patients who began HAART between January 1999 and August 2004, 3805 (61%) were female and 6094 (97%) were black African. HAART adherence was >or=80% for 3298 patients (52%) and 100% for 1916 patients (30%). Women were significantly more likely to have adherence>or=80% than men (54% vs 49%, P<0.001). The median (interquartile range) follow-up time was 1.8 (1.37-2.5) years. As of 1 September 2004, 222 patients had died-a crude mortality rate of 3.5%. In a multivariate Cox regression model, adherence<80% was associated with lower survival (relative hazard 3.23; 95% confidence interval: 2.37-4.39). When medication adherence was divided into 5 strata with a width of 20% each, each stratum had lower survival rates than the adjacent, higher-adherence stratum. Among other variables tested, only baseline CD4+ T-cell count was significantly associated with decreased survival in multivariate analysis (relative hazard 5.13; 95% confidence interval: 3.42-7.72, for CD4+ T-cell count<or=50 cells/microL vs >200 cells/microL). Pharmacy-based records may be a simple and effective population-level tool for monitoring adherence as HAART programs in Africa are scaled up.

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    • "patient self-report) are subjective and can be prone to social desirability bias. To date, there are no recommended laboratory tests to directly evaluate adherence to ART in developing countries [13, 14]. Confirmation of treatment failure is limited by the high cost of definitive diagnostics (e.g. "
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    ABSTRACT: Background In resource limited settings access to laboratory monitoring of HIV treatment is limited and therapeutic drug monitoring is generally unavailable. This study aimed to evaluate nevirapine concentrations in saliva using low-cost thin-layer chromatography (TLC) and nevirapine concentrations in plasma and saliva using high performance liquid chromatography (HPLC) methods; and to correlate nevirapine plasma concentrations to HIV treatment outcomes in Ugandan patients. Methods Paired plasma and stimulated saliva samples were obtained from Ugandan, HIV-infected adults on nevirapine-based ART. Nevirapine concentrations were measured using a validated HPLC method and a novel TLC method. Plasma nevirapine concentrations <3.0 mg/L using HPLC were considered subtherapeutic. Negative/positive predictive values of different thresholds for subtherapeutic nevirapine concentrations in saliva were determined. Virologic testing and, if applicable, HIV drug resistance testing was performed. Results Median (interquartile range, IQR) age of 297 patients was 39.1 (32.8-45.2) years. Three hundred saliva and 287 plasma samples were available for analysis. Attempts failed to determine nevirapine saliva concentrations by TLC. Using HPLC, median (IQR) nevirapine concentrations in saliva and plasma were 3.40 (2.59-4.47) mg/L and 6.17 (4.79-7.96) mg/L, respectively. The mean (coefficient of variation,%) nevirapine saliva/plasma ratio was 0.58 (62%). A cut-off value of 1.60 mg/L nevirapine in saliva was associated with a negative/positive predictive value of 0.99/0.72 and a sensitivity/specificity of 87%/98% for predicting subtherapeutic nevirapine plasma concentrations, respectively. Only 5% (15/287) of patients had subtherapeutic nevirapine plasma concentrations, of which 3 patients had viral load results > 400 copies/mL. Patients with nevirapine concentrations in plasma <3.0 mg/L had an Odds Ratio of 3.29 (95% CI: 1.00 – 10.74) for virological failure (viral load >400 copies/mL). Conclusions The low-cost TLC technique for monitoring nevirapine in saliva was unsuccessful but monitoring nevirapine saliva and plasma concentrations using HPLC was shown to be feasible in the research/specialist context in Uganda. Further optimization and validation is required for the low-cost TLC technique.
    BMC Infectious Diseases 09/2014; 14(1):473. DOI:10.1186/1471-2334-14-473 · 2.61 Impact Factor
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    • "As Mills et al. (2011: 209 and 214) state, 'After adjustment for loss to follow-up, crude mortality rates (deaths per 1000 person-years) ranged from 26.9… in women to 43.9… in men… This finding builds on an emerging body of literature displaying consistent shortcomings in treatment programs involving men'. These gender discrepancies in ART uptake may reflect men's beliefs, informed by patriarchal ideas of what it means to 'be a man', that seeking health services is a sign of weakness or vulnerability, and that such services are not male-friendly (Nachega et al. 2006). Given that around 42 per cent of people living with HIV in sub-Saharan Africa are men (UNAIDS 2012), two conclusions become hard to dismiss: (1) we must take seriously the need to increase men's uptake of HIV services; and (2) we must do so through gender-transformative programmes and interventions that challenge the broader patriarchal power structures that perpetuate gender inequality. "
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    ABSTRACT: Evidence shows that men are significantly underrepresented in HIV and AIDS testing and treatment services – both in sub-Saharan Africa and globally. HIV policies within sub-Saharan Africa also have insufficient focus on ensuring national HIV responses encourage men to test, access anti-retroviral treatment and support the disproportionate burden of HIV care on women. Addressing these challenges is important for everyone's sake and must be approached within a context of addressing power differentials between men and women at all levels. This includes challenging the broader patriarchal power structures in which gender plays out, such as the assumption that care work is ‘women's work’ and therefore less valued, and the rigidity of gender norms that encourage men to participate in risk-taking behaviours that put their life and the life of those around them in jeopardy.
    IDS Bulletin 01/2014; 45(1). DOI:10.1111/1759-5436.12068 · 0.54 Impact Factor
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    • "For example, Chi et al reported a 1.7 fold increased risk of post 12 month mortality in a large scale public sector HIV care programme in Zambia in those with <80% drug possession ratio (DPR) based on pharmacy refill [16]. Lima et al[17] demonstrated a 3 fold increased risk of mortality for a DPR adherence threshold of <95%; Nachega et al[25] reported a 3 fold increased risk of mortality in a South African private sector HIV care programme for pharmacy claims adherence <80%. Like our study, most studies used indirect methods of adherence assessment based on self-reports, rather than electronic medication monitoring which is expensive and intrusive, although provides qualitatively and quantitatively different information about adherence behaviours [10]. "
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    ABSTRACT: Adherence is one of the most important determinants of viral suppression and drug resistance in HIV- infected people receiving antiretroviral therapy (ART). We examined the association between long-term mortality and poor adherence to ART in DART trial participants in Uganda and Zimbabwe randomly assigned to receive laboratory and clinical monitor- ing (LCM), or clinically driven monitoring (CDM). Since over 50% of all deaths in the DART trial occurred during the first year on ART, we focussed on participants continuing ART for 12 months to investigate the implications of longer-term adherence to treatment on mortality. Participants' ART adherence was assessed by pill counts and structured questionnaires at 4-weekly clinic visits. We studied the effect of recent adherence history on the risk of death at the individual level (odds ra- tios from dynamic logistic regression model), and on mortality at the population level (population attributable fraction based on this model). Analyses were conducted separately for both randomiza- tion groups, adjusted for relevant confounding factors. Adherence behaviour was also confounded by a partial factorial randomization comparing structured treatment interruptions (STI) with continuous ART (CT). In the CDM arm a significant association was found between poor adherence to ART in the previous 3-9 months with increased mortality risk. In the LCM arm the association was not significant. The odds ratios for mortality in participants with poor adherence against those with optimal adherence was 1.30 (95% CI 0.78,2.10) in the LCM arm and 2.18 (1.47,3.22) in the CDM arm. The estimated proportions of deaths that could have been avoided with optimal adherence (population attributable fraction) in the LCM and CDM groups during the 5 years follow-up period were 16.0% (95% CI 0.7%,31.6%) and 33.1% (20.5%,44.8%), correspondingly. Recurrent poor adherence determined even through simple measures is associated with high mortality both at individual level as well as at the ART programme level. The number of lives saved through effective interventions to improve adherence could be considerable particularly for individuals mon- itored without using CD4 cell counts. The findings have important implications for clinical practice and for developing interventions to enhance adherence.
    BMC Infectious Diseases 08/2013; 13(1):395. DOI:10.1186/1471-2334-13-395 · 2.61 Impact Factor
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