Associations With Virologic Treatment Failure in Adults on Antiretroviral Therapy in South Africa
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.
Case-control study, matched on facility and on starting date and duration of HAART.
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 <400 copies per milliliter at the time of case incidence.
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.
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.
Available from: David Van de Vijver
- "The use of NVP as opposed to EFV seemed a risk factor for virological failure, although this association was not significant in multivariate analysis (OR 2.02, P ¼ 0.06). This difference has also been reported by studies from India and Africa [Kamya et al., 2007; Datay et al., 2010], but caution is warranted as the prescribed regimens may have been subject to indication bias. "
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ABSTRACT: The virological response and development of drug resistance during first-line anti-retroviral treatment (ART) were studied in Indonesia where the majority of patients infected with HIV have a history of injecting drug use, which is often linked with lower treatment adherence and development of drug-resistance. As many as 575 patients starting ART between September 2007 and March 2010 in Hasan Sadikin Hospital Bandung were followed prospectively. Clinical and laboratory monitoring was performed every 6 months. Plasma samples with HIV-RNA ≥400 copies/ml were examined for drug resistance mutations. Most patients were male (72.3%), 59.7% had a history of injecting drug use, and the median CD4+ cells count before start of ART was 35 cells/mm(3) (IQR 10-104). From 438 HIV patients with HIV-RNA measurements, 40 (9.1%) subjects had HIV-RNA ≥400 copies/ml after 24 weeks (median follow-up 16 (IQR 8-25) months). Of these failing patients 16 (47%) subjects had drug resistance mutations, predominantly M184V (35.3%), Y181C (23.5%), K103N (11.7%), and TAMs (11.7%). A history of treatment discontinuation ≥1 month, reported by 5.3% (23) of patients, was strongly associated with virological failure (adjusted OR 12.64, 95% CI 4.51-35.41); and a history of injecting drug use was not (OR 0.75, 95% CI 0.38-1.46). This is the largest and most systematic evaluation of virological response to first line ART in Indonesia. Patients in this cohort responded well to first line ART, with low rates of virological failure and drug resistance. A history of injecting drug use should not be a reason to withhold ART in this setting. J. Med. Virol. 9999:XX-XX, 2013. © 2013 Wiley Periodicals, Inc.
Available from: Katharina Kranzer
- "The majority of studies reported that patients experienced virologic suppression once treatment was restarted (Chen et al. 2002; Yozviak et al. 2002; Gibb et al. 2004; Wolf et al. 2005; Touloumi et al. 2008; Mussini et al. 2009). However, treatment interruptions were associated with an increased risk of rebound and virologic failure in developed and developing countries (Murri et al. 2002; Parienti et al. 2004, 2008; Spacek et al. 2006; Laher et al. 2007; Oyugi et al. 2007; Bansi et al. 2008; Boileau et al. 2008; Kouanfack et al. 2008; Knobel et al. 2009; Datay et al. 2010; Ekstrand et al. 2010). A study from Spain differentiated treatment interruptions because of patients' choice and adherence difficulties or physician's advice for toxicity, severe side effects, or intercurrent illness. "
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ABSTRACT: Objective To characterize the frequency, reasons, risk factors, and consequences of unstructured anti-retroviral treatment interruptions. Method Systematic review. Results Seventy studies were included. The median proportion of patients interrupting treatment was 23% for a median duration of 150 days. The most frequently reported reasons for interruptions were drug toxicity, adverse events, and side-effects; studies from developing countries additionally cited treatment costs and pharmacy stock-outs as concerns. Younger age and injecting drug use was a frequently reported risk factor. Other risk factors included CD4 count, socioeconomic variables, and pharmacy stock outs. Treatment interruptions increased the risk of death, opportunistic infections, virologic failure, resistance development, and poor immunological recovery. Proposed interventions to minimize interruptions included counseling, mental health services, services for women, men, and ethnic minorities. One intervention study found that the use of short message service reminders decrease the prevalence of treatment interruption from 19% to 10%. Finally, several studies from Africa stressed the importance of reliable and free access to medication. Conclusion Treatment interruptions are common and contribute to worsening patient outcomes. HIV/AIDS programmes should consider assessing their causes and frequency as part of routine monitoring. Future research should focus on evaluating interventions to address the most frequently reported reasons for interruptions.
Available from: Ashraf Coovadia
- "Although exposure to sdNVP in the prior 18-36 months was not associated with a reduced likelihood of achieving and sustaining viral suppression, women with minority K103N mutations before treatment had a reduced durability of virologic suppression as observed in other studies[20,22,35,36]. Some studies, however, have reported poor virologic response to NNRTI-based therapy even if exposure is quite distant. These differences between studies may, in part be explained by different levels of adherence. "
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ABSTRACT: Adherence is a necessary part of successful antiretroviral treatment (ART). We assessed risk factors for incomplete adherence among a cohort of HIV-infected women initiating ART and examined associations between adherence and virologic response to ART.
A secondary data analysis was conducted on a cohort of 154 women initiating non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART at a single site in Johannesburg, South Africa. Ninety women had been enrolled in a prevention of mother-to-child transmission (pMTCT) program and were exposed to single-dose nevirapine (sdNVP) >18 months earlier. Women were interviewed pre-treatment and clinical, virologic and adherence data were collected during follow-up to 24 weeks. Incomplete adherence to ART was defined as returning >5% of medications, estimated by pill counts at scheduled visits. Multivariable logistic regression analysis and unadjusted odds ratio (95%CI) were performed, using STATA/SE (ver 10.1).
About half of the women (53%) were <30 years of age, 63% had <11 years of schooling, 69% were unemployed and 37% lived in a shack. Seven percent of women had a viral load >400 copies/ml at 24 weeks and 37% had incomplete adherence at one or more visits. Incomplete adherence was associated with less education (p = 0.01) and lack of financial support from a partner (p = 0.02) after adjustment for confounders. Only when adherence levels dropped below 80% was there a significant association with viremia in the group overall (p = 0.02) although adherence <95% was associated with viremia in the sdNVP-exposed group (p = 0.03). The main reasons for incomplete adherence were being away from home, busy with other things and forgetting to take their medication.
Virologic response to NNRTI-treatment in the cohort was excellent. However, women who received sdNVP were at greater risk of virologic failure when adherence was <95%. Women exposed to sdNVP, and those with less education and less social support may benefit from additional adherence counseling to ensure the long-term success of ART. More than 80% adherence may be sufficient to maintain virologic suppression on NNRTI-based regimens in the short-term, however complete adherence should be encouraged.
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