Rates of emergence of HIV drug resistance in resource-limited settings: A systematic review
ABSTRACT BACKGROUND: The increasing availability of antiretroviral therapy (ART) has improved survival and quality of life for many infected with HIV, but can also engender drug resistance. This review summarizes the available information on drug-resistance in adults in resource-limited settings (RLSs). METHODS: The online databases PubMed and Google Scholar, pertinent conference abstracts, and references from relevant articles were searched for publications available before November 2011. Data collected after ART rollout were reviewed. RESULTS: Seven studies fulfilled the criteria for the analysis of acquired drug resistance while 22 fulfilled the criteria for the analysis of transmitted drug resistance (TDR). Acquired resistance was detected in 7·2% of patients on ART for 6-11 months, 11·1% at 12--23 months, 15·0% at 24-35 months, and 20·7% at (3)36 months. Multi-class drug resistance increased steadily with time on ART. The overall rate of TDR in all resource-limited countries studied was 6·6% (469/7063). Patients in countries in which ART had been available for (3)5 years were 1.7 times more likely to have transmitted drug-resistance than those living in a country where ART had been available for <5 years (p<0·001). The reported prevalence of transmitted HIVDR was 5·7% (233/4069) in Africa, 7·6% (160/2094) in Asia, and 8·4% (76/900) in Brazil. CONCLUSIONS: The emergence of drug resistance following access to antiretroviral therapy in RLSs resembles what was seen in resource-rich countries and highlights the need for virologic monitoring for drug failure, drug resistance testing, and alternative drug regimens that have proven beneficial in these resource-rich settings.
- The Journal of Infectious Diseases 04/2013; DOI:10.1093/infdis/jit154 · 5.78 Impact Factor
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ABSTRACT: Background The World Health Organization Antiretroviral Treatment Guidelines recommend phasing-out stavudine because of its risk of long-term toxicity. There are two mutational pathways of stavudine resistance with different implications for zidovudine and tenofovir cross-resistance, the primary candidates for replacing stavudine. However, because resistance testing is rarely available in resource-limited settings, it is critical to identify the cross-resistance patterns associated with first-line stavudine failure. Methods We analyzed HIV-1 resistance mutations following first-line stavudine failure from 35 publications comprising 1,825 individuals. We also assessed the influence of concomitant nevirapine vs. efavirenz, therapy duration, and HIV-1 subtype on the proportions of mutations associated with zidovudine vs. tenofovir cross-resistance. Results Mutations with preferential zidovudine activity, K65R or K70E, occurred in 5.3% of individuals. Mutations with preferential tenofovir activity, ≥two thymidine analog mutations (TAMs) or Q151M, occurred in 22% of individuals. Nevirapine increased the risk of TAMs, K65R, and Q151M. Longer therapy increased the risk of TAMs and Q151M but not K65R. Subtype C and CRF01_AE increased the risk of K65R, but only CRF01_AE increased the risk of K65R without Q151M. Conclusions Regardless of concomitant nevirapine vs. efavirenz, therapy duration, or subtype, tenofovir was more likely than zidovudine to retain antiviral activity following first-line d4T therapy.The Journal of Infectious Diseases 06/2013; 207 Suppl 2:S70-7. DOI:10.1093/infdis/jit114 · 5.78 Impact Factor
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ABSTRACT: Access to combination antiretroviral treatment (ART) has improved greatly over recent years. At the end of 2011, more than eight million HIV-infected people were receiving ART in low-income and middle-income countries. ART generally works well in keeping the virus suppressed and the patient healthy. However, treatment only works as long as the virus is not resistant against the drugs used. In the last decades, HIV treatments have become better and better at slowing down the evolution of drug resistance, so that some patients are treated for many years without having any resistance problems. However, for some patients, especially in low-income countries, drug resistance is still a serious threat to their health. This essay will review what is known about transmitted and acquired drug resistance, multi-class drug resistance, resistance to newer drugs, resistance due to treatment for the prevention of mother-to-child transmission, the role of minority variants (low-frequency drug-resistance mutations), and resistance due to pre-exposure prophylaxis.Infectious disease reports 06/2013; 5(Suppl 1):e5. DOI:10.4081/idr.2013.s1.e5