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.
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ABSTRACT: Our aim was to review the global disparities of transmitted HIV drug resistance (TDR) in antiretroviral-naive MSM, people who inject drugs (PWID) and heterosexual populations in both high-income and low/middle-income countries. We undertook a systematic review of the peer-reviewed English literature on TDR (1999-2013). Random-effects meta-analyses were performed to pool TDR prevalence and compare the odds of TDR across at-risk groups. A total of 212 studies were included in this review. Areas with greatest TDR prevalence were North America (MSM: 13.7%, PWID: 9.1%, heterosexuals: 10.5%); followed by western Europe (MSM: 11.0%, PWID: 5.7%, heterosexuals: 6.9%) and South America (MSM: 8.3%, PWID: 13.5%, heterosexuals: 7.5%). Our data indicated disproportionately high TDR burdens in MSM in Oceania (Australia 15.5%), eastern Europe/central Asia (10.2%) and east Asia (7.8%). TDR epidemics have stabilized in high-income countries, with a higher prevalence (range 10.9-12.6%) in MSM than in PWID (5.2-8.3%) and heterosexuals (6.4-9.0%) over 1999-2013. In low/middle-income countries, TDR prevalence in all at-risk groups in 2009-2013 almost doubled than that in 2004-2008 (MSM: 7.8 vs. 4.2%, P = 0.011; heterosexuals: 4.1 vs. 2.6%, P < 0.001; PWID: 4.8 vs. 2.4%, P = 0.265, respectively). The risk of TDR infection was significantly greater in MSM than that in heterosexuals and PWID. We observed increasing trends of resistance to non-nucleoside reverse transcriptase and protease inhibitors among MSM. TDR prevalence is stabilizing in high-income countries, but increasing in low/middle-income countries. This is likely due to the low, but increasing, coverage of antiretroviral therapy in these settings. Transmission of TDR is most prevalent among MSM worldwide.AIDS (London, England) 11/2014; 28(18):2751-2762. DOI:10.1097/QAD.0000000000000494 · 6.56 Impact Factor
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ABSTRACT: To assess HIV-1 diversity, transmission dynamics and prevalence of transmitted drug resistance (TDR) in Angola, five years after ART scale-up. Population sequencing of the pol gene was performed on 139 plasma samples collected in 2009 from drug-naive HIV-1 infected individuals living in Luanda. HIV-1 subtypes were determined using phylogenetic analysis. Drug resistance mutations were identified using the Calibrated Population Resistance Tool (CPR). Transmission networks were determined using phylogenetic analysis of all Angolan sequences present in the databases. Evolutionary trends were determined by comparison with a similar survey performed in 2001. 47.1% of the viruses were pure subtypes (all except B), 47.1% were recombinants and 5.8% were untypable. The prevalence of subtype A decreased significantly from 2001 to 2009 (40.0% to 10.8%, P = 0.0019) while the prevalence of unique recombinant forms (URFs) increased>2-fold (40.0% to 83.1%, P<0.0001). The most frequent URFs comprised untypable sequences with subtypes H (U/H, n = 7, 10.8%), A (U/A, n = 6, 9.2%) and G (G/U, n = 4, 6.2%). Newly identified U/H recombinants formed a highly supported monophyletic cluster suggesting a local and common origin. TDR mutation K103N was found in one (0.7%) patient (1.6% in 2001). Out of the 364 sequences sampled for transmission network analysis, 130 (35.7%) were part of a transmission network. Forty eight transmission clusters were identified; the majority (56.3%) comprised sequences sampled in 2008-2010 in Luanda which is consistent with a locally fuelled epidemic. Very low genetic distance was found in 27 transmission pairs sampled in the same year, suggesting recent transmission events. Transmission of drug resistant strains was still negligible in Luanda in 2009, five years after the scale-up of ART. The dominance of small and recent transmission clusters and the emergence of new URFs are consistent with a rising HIV-1 epidemics mainly driven by heterosexual transmission.PLoS ONE 12/2014; 9(12):e113626. DOI:10.1371/journal.pone.0113626 · 3.53 Impact Factor
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ABSTRACT: Treatment with antiretroviral therapy dramatically increases the survival of HIV-infected individuals. However, treatment has to be continued for life because it does not lead to the full eradication of infection. HIV persists in resting CD4(+) T cells, and possibly other cell types, and can reemerge from these cells when therapy is interrupted. Here, we review molecular mechanisms that have been proposed to contribute to HIV latency, as well as the relative roles of cis- and trans-acting mechanisms. We also discuss existing and future therapeutic opportunities regarding HIV latency that might lead to a future cure for HIV infection.Annual Review of Medicine 01/2015; 66(1):407-21. DOI:10.1146/annurev-med-092112-152941 · 15.48 Impact Factor