Treatment Interruption and Variation in Tablet Taking Behaviour Result in Viral Failure: A Case-Control Study from Cape Town, South Africa

BACKGROUND: Understanding of the impact of non-structured treatment interruption (TI) and variation in tablet-taking on failure of first-line antiretroviral therapy (ART) is limited in a resource-poor setting. METHODS: A retrospective matched case-control analysis. Individuals failing ART were matched by time on ART with 4 controls. Viral load (VL) and CD4 count were completed 4-monthly. Adherence percentages, from tablet returns, were calculated 4-monthly (interval) and from ART start (cumulative). Variation between intervals and TI (>27 days off ART) were recorded. Conditional multivariate logistic regression analysis was performed to estimate the effect of cumulative adherence 10% and TI on virological failure. Age, gender, baseline log VL and CD4 were included as possible confounders in the multivariate model. RESULTS: 244 patients (44 cases, 200 controls) were included. Median age was 32 years (IQR28-37), baseline CD4 108 cells/mm3 (IQR56-151), VL 4.82 log (IQR4.48-5.23). 94% (96% controls, 86% failures) had cumulative adherence >90%. The odds of failure increased 3 times (aOR 3.01, 95%CI 0.81-11.21) in individuals with cumulative adherence 10% and 4.01 times (aOR 4.01, 95%CI 1.45-11.10) in individuals with TIs. For individuals with TI and cumulative adherence >95%, the odds of failing were 5.65 (CI 1.40-22.85). CONCLUSION: It is well known that poor cumulative adherence increases risk of virological failure, but less well understood that TI and variations in tablet-taking also play a key role, despite otherwise excellent adherence

Adherence to Drug-Refill Is a Useful Early Warning Indicator of Virologic and Immunologic Failure among HIV Patients on First-Line ART in South Africa

Affordable strategies to prevent treatment failure on first-line regimens among HIV patients are essential for the long-term success of antiretroviral therapy (ART) in sub-Saharan Africa. WHO recommends using routinely collected data such as adherence to drug-refill visits as early warning indicators. We examined the association between adherence to drug-refill visits and long-term virologic and immunologic failure among non-nucleoside reverse transcriptase inhibitor (NNRTI) recipients in South Africa.In 2008, 456 patients on NNRTI-based ART for a median of 44 months (range 12-99 months; 1,510 person-years) were enrolled in a retrospective cohort study in Soweto. Charts were reviewed for clinical characteristics before and during ART. Multivariable logistic regression and Kaplan-Meier survival analysis assessed associations with virologic (two repeated VL>50 copies/ml) and immunologic failure (as defined by WHO).After a median of 15 months on ART, 19% (n = 88) and 19% (n = 87) had failed virologically and immunologically respectively. A cumulative adherence of <95% to drug-refill visits was significantly associated with both virologic and immunologic failure (p<0.01). In the final multivariable model, risk factors for virologic failure were incomplete adherence (OR 2.8, 95%CI 1.2-6.7), and previous exposure to single-dose nevirapine or any other antiretrovirals (adj. OR 2.1, 95%CI 1.2-3.9), adjusted for age and sex. In Kaplan-Meier analysis, the virologic failure rate by month 48 was 19% vs. 37% among adherent and non-adherent patients respectively (logrank p value = 0.02).One in five failed virologically after a median of 15 months on ART. Adherence to drug-refill visits works as an early warning indicator for both virologic and immunologic failure

Associations with virologic treatment failure in adults on antiretroviral therapy in South Africa.

OBJECTIVES: Highly active antiretroviral therapy (HAART) has been available in government facilities in the Western Cape Province of South Africa since 2001. We aimed to investigate factors associated with virologic treatment failure in this setting. DESIGN: Case-control study, matched on facility and on starting date and duration of HAART. METHODS: Cases and controls were identified from clinic registers from May 2001 to June 2006. Cases were patients who switched to second-line therapy after confirmed virologic failure (2 consecutive viral loads above 1000 copies/mL). Controls were on first-line treatment with viral load &lt;400 copies per milliliter at the time of case incidence. RESULTS: One hundred thirty cases and 238 controls were selected from 8 clinics (median 16.6 months on HAART, interquartile range: 12.2-24.6). Treatment interruptions [adjusted odds ratio (AOR) 8.6, 95% confidence interval: 3.6 to 20.8], prior nevirapine-based prevention of mother-to-child transmission (PMTCT) treatment (AOR: 9.6, 95% confidence interval: 2.9 to 32.2), a baseline CD4 count less than 50 cells per microliter or from 50-150 cells per microliter (AOR: 6.6, 95% confidence interval: 2.3 to 18.8 and AOR: 5.8, 95% confidence interval: 2.1 to 16.3 compared with a baseline CD4 count of more than 150 cells/microL), and the use of nevirapine in the initial regimen (AOR: 2.5, 95% confidence interval: 1.4 to 4.7) were all independently associated with virologic treatment failure. CONCLUSIONS: In this setting, nevirapine in the initial HAART regimen or for PMTCT treatment is associated with virologic treatment failure, together with low CD4 count at ART initiation. Earlier initiation of HAART and access to improved triple therapy and PMTCT regimens are priorities for HIV programs in Southern Africa