Doctor's Guide Global Edition - 2012-07-27Tweet
By Nancy A. Melville - WASHINGTON, DC - July 27, 2012 - As antiretroviral therapy (ART) for HIV becomes widely accessible in Southern Africa, the risk for drug resistances is on the rise, and as many as 1 in 6 adults show acquired drug resistance to standard second-line drug regimens, researchers said here on July 24 at the 19th International AIDS Conference.
Justen Manasa, PhD, University of KwaZulu-Natal, Africa Centre for Health and Population Studies, Somkhele, South Africa, and colleagues evaluated data from the 17 clinics in the Hlabisa HIV Treatment and Care Programme.
The data included clinical records as well as drug resistance genotyping performed using the in-house SATuRN/Life Technologies system. Sequences were analysed and genotypic susceptibility scores (GSS) were calculated using RegaDB and Stanford HIVDB 6.0.5 algorithms.
Using the criteria of HIV-infected patients aged older than 16 years with virological failure (2 x viral load >1,000 copies/mL) on first-line non-nucleoside reverse transcriptase inhibitors (NNRTI)-based ART, the researchers identified 240 genotyped patients for analysis.
Their median time on ART was 42 months, and the median time on a failing regimen was 27 months.
The genotyping showed that as many as 208 of the 240 (87%) had at least 1 drug resistance mutation. Of the patients showing resistance, 199 (83%) had NNRTI resistance and 195 (81%) had NRTI resistance.
Thymidine analogue mutations (TAMs) were detected in 88 (36.1%) patients, and 39 (16.3%) patients had > 3 TAMs. The K65R and Q151M mutations were found in 5% and 2% of patients, respectively.
In total, 40 individuals (70%) had a significantly compromised standardised second-line regimen, defined as GSS scores of <2, according to the authors.
A univariate analysis showed a history of NRTI substitution to be significantly associated with a GSS score <2 (odds ratio, 4.39; P <.001).
Other factors, including time on a failing regimen, gender, the regimen at initiation or the time of genotyping, and baseline viral load, were not significantly associated with a GSS of <2.
Limitations of the study include that only patients that started stavudine and zidovudine-based regimens were evaluated, while tenofovir is now the standard first-line regimen, however subtype C seems to develop resistance very fast, the authors noted.
Our results suggest a role for genotypic resistance testing in routine care and highlights the need for increased attention to quality of care and to virological monitoring guidelines.
[Presentation title: High Levels of Drug Resistance After Failure of First-Line Antiretroviral Therapy in Rural South Africa: Impact on Standardised Second-Line Regimens. Abstract TUAB0304]