Keiser O, Orrell C, Egger M, Wood R, Brinkhof MW, Furrer H, van Cutsem G, Ledergerber B, Boulle A; for the Swiss HIV Cohort Study (SHCS) and the International Epidemiologic Databases to Evaluate AIDS in Southern Africa (IeDEA-SA). Public-Health and Individual Approaches to Antiretroviral Therapy: Township South Africa and Switzerland Compared. PLoS Med. 2008;5(7):e148.
The provision of highly active antiretroviral therapy in resource-limited settings follows a public health approach, which is characterised by a limited number of regimens and the standardisation of clinical and laboratory monitoring. In industrialized countries doctors prescribe from the full range of available antiretroviral drugs, supported by resistance testing and frequent laboratory monitoring. Keiser and colleagues compared virologic response, changes to first-line regimens, and mortality in HIV-infected patients starting highly active antiretroviral therapy in South Africa and Switzerland. The authors analysed data from the Swiss HIV Cohort Study and two highly active antiretroviral therapy programmes in townships of Cape Town, South Africa. They included treatment-naïve patients aged 16 y or older who had started treatment with at least three drugs since 2001, and excluded injecting drug users. Data from a total of 2,348 patients from South Africa and 1,016 patients from the Swiss HIV Cohort Study were analysed. Median baseline CD4(+) T cell counts were 80 cells/mul in South Africa and 204 cells/mul in Switzerland. In South Africa, patients started with one of four first-line regimens, which was subsequently changed in 514 patients (22%). In Switzerland, 36 first-line regimens were used initially, and these were changed in 539 patients (53%). In most patients HIV-1 RNA was suppressed to 500 copies/ml or less within one year: 96% (95% confidence interval [CI] 95%-97%) in South Africa and 96% (94%-97%) in Switzerland, and 26% (22%-29%) and 27% (24%-31%), respectively, developed viral rebound within two years. Mortality was higher in South Africa than in Switzerland during the first months of highly active antiretroviral therapy: adjusted hazard ratios were 5.90 (95% CI 1.81-19.2) during months 1-3 and 1.77 (0.90-3.50) during months 4-24. Compared to the highly individualised approach in Switzerland, programmatic highly active antiretroviral therapy in South Africa resulted in similar virologic outcomes, with relatively few changes to initial regimens. Further innovation and resources are required in South Africa to both achieve more timely access to highly active antiretroviral therapy and improve the prognosis of patients who start highly active antiretroviral therapy with advanced disease.
Editors´note: It is reassuring that the public health treatment approach in South Africa is as effective virologically as is the individualized approach of Switzerland: 96% of patients in both South Africa and Switzerland suppressed viral load to less than 500 copies/ml within a year. Although similar percentages developed viral rebound within two years, there were differences in mortality primarily due to the much lower CD4 count in South Africans (median 80) compared to Swiss (median of 204) at baseline. Know your status campaigns that provide social support for HIV testing and counselling would permit earlier initiation of treatment and reduce early mortality in South Africans on treatment. On the Swiss side, Switzerland could well consider simplifying its 36 first-line regimens.
Youngpairoj AS, Masciotra S, Garrido C, Zahonero N, de Mendoza C, García-Lerma JG. HIV-1 drug resistance genotyping from dried blood spots stored for 1 year at 4 degrees Celsius. J Antimicrob Chemother. 2008 Mar 15 [Epub ahead of print]
Dried blood spots are an attractive alternative to plasma for HIV-1 drug resistance testing in resource-limited settings. Youngpairoj and colleagues recently showed that HIV-1 can be efficiently genotyped from dried blood spots stored at -20 degrees C for prolonged periods (0.5-4 years). Here, the authors evaluated the efficiency of genotyping from dried blood spots stored at 4 degrees C for 1 year. A total of 40 dried blood spots were prepared from residual diagnostic specimens collected from HIV subtype B-infected persons and were stored with desiccant at 4 degrees C. Total nucleic acids were extracted after 1 year using a modification of the Nuclisens assay. Resistance testing was performed using the ViroSeq HIV-1 assay and an in-house nested Reverse Transciptase PCR method validated for HIV-1 subtype B that amplifies a smaller (1 kb) pol fragment. Using the ViroSeq assay, only 23 of the 40 (57.5%) dried blood spot specimens were successfully genotyped; 22 of these specimens had plasma viraemia >10 000 RNA copies/mL. When the specimens were tested using the in-house assay, 38 of the 40 dried blood spots (95%) were successfully genotyped. Overall, resistance genotypes generated from the dried blood spots and plasma were highly concordant. The authors show that drug resistance genotyping from dried blood spots stored at 4 degrees C with desiccant is highly efficient but requires the amplification of small pol fragments and the use of an in-house nested PCR protocol with quality-controlled reagents. These findings suggest that 4 degrees Celsius may represent a suitable temperature for long-term storage of dried blood spots.
Editors´note: Dried blood spots are easy to transport, can be stored for long periods, and can be used now for a variety of micro-level diagnostic tests. The HIV drug resistance genotyping test described here would require product development to move it from an “in-house” modified test to a standardized procedure that could be used in national resistance surveillance.
November 4th, 2009 at 10:57 am