Outcomes after virologic failure of first-line ART in South Africa

Murphy, Richard A.; Sunpath, Henry; Lu, Zhigang; Chelin, N.; Losina, Elena; Gordon, Michelle; Ross, Douglas S.; Ewusi, Aba D.; Matthews, Lynn T.; Kuritzkes, Daniel R.; Marconi, Vincent C.

doi:10.1097/qad.0b013e3283333639

Cited by 60 publications

(60 citation statements)

References 10 publications

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“…In the group of patients treated with boosted PI, neither the presence of NRTI-associated mutations nor the history of previous suboptimal therapy were associated with virologic response, while in the group that received unboosted PI, the GSS score and the occurrence of single TAMs were associated with virological response. A similar result has been reported in a cohort of patient failing the salvage regimen after NNRTI failure [21]. A retrospective study on patients who failed an initial NNRTI-based regimen with M184V showed that a regimen comprising a boosted PI plus emtricitabine or lamivudine and a NRTI were as effective as the same regimen plus an additional agent [22].…”

Section: Discussionsupporting

confidence: 69%

Response to Antiretroviral Treatment After Failure of NNRTI Plus NRTIs-Based Therapy. Data from the ARCA Collaborative Group

Seminari

Silvestri²,

Meini³

et al. 2012

CHR

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Section: Discussionsupporting

confidence: 69%

Response to Antiretroviral Treatment After Failure of NNRTI Plus NRTIs-Based Therapy. Data from the ARCA Collaborative Group

Seminari

Silvestri²,

Meini³

et al. 2012

CHR

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“…[1][2][3] HIV drug resistance data emerging from South Africa have generally revealed patterns similar to those seen in HIV-1 subtype B virus. [4][5][6] In contrast to other countries in sub-Saharan Africa, studies from South Africa have reported fewer thymidine analogue mutations (TAMs) at failure of first-line ART, likely to be related to the use of viral load (VL) monitoring in the public sector program.…”

Section: Introductionmentioning

confidence: 82%

Accumulation of HIV Drug Resistance Mutations in Patients Failing First-Line Antiretroviral Treatment in South Africa

Sigaloff

Ramatsebe

Viana

et al. 2012

AIDS Research and Human Retroviruses

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Patients failing antiretroviral treatment for extended periods of time are at risk of accumulating HIV drug resistance mutations (DRMs), which negatively influences second-line treatment. This retrospective study assessed the rate of DRM accumulation among South African patients with continued virological failure. Serial genotypic resistance testing was performed and DRMs were scored according to the 2009 IAS-USA list. Among 43 patients, 38 (88.4%) harbored ‡ 1 DRM. The median time between two sequential resistance tests was 5 months (IQR: 3-10). Thymidine analogue mutations accumulated at a rate of 0.07 mutation per month of drug exposure, which is faster than previously reported. Routine virological monitoring should be implemented in resource-limited settings to preserve susceptibility to second-line regimens.

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“…High rates of acquired drug resistance suggest poor adherence (which can be improved with better counseling and minimizing supply stock-outs), suboptimal regimens, and a lack of monitoring for failure to reduce the continuing use of a failing regimen[58–60]. Drug-resistance monitoring programs in RLSs are limited by cost and laboratory availability [61]. Currently, the WHO recommends universal clinical monitoring for patients receiving ART in RLSs and symptom-directed laboratory monitoring for safety and toxicity.…”

Section: Discussionmentioning

confidence: 99%

“…Many individual country guidelines, however, recommend only clinical monitoring due to insufficient access to routine laboratory testing [11]. Immunologic and virologic testing have widely accepted clinical benefits, and examination of the cost-effectiveness of these strategies will prove an important part of developing and implementing new monitoring strategies [61]. In the absence of laboratory monitoring, strategies to monitor and improve treatment delivery and patient adherence may help minimize sustained virological failure more than clinical monitoring alone [52, 63].…”

Section: Discussionmentioning

confidence: 99%

Rates of Emergence of HIV Drug Resistance in Resource-Limited Settings: A Systematic Review

2013

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Background The increasing availability of anti-retroviral 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 roll-out 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, compared to 11·1% at 12—23 months, 15·0% at 24–35 months, and 20·7% at ≥36 months. Multi-class drug resistance also 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 ≥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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Outcomes after virologic failure of first-line ART in South Africa

Cited by 60 publications

References 10 publications

Response to Antiretroviral Treatment After Failure of NNRTI Plus NRTIs-Based Therapy. Data from the ARCA Collaborative Group

Response to Antiretroviral Treatment After Failure of NNRTI Plus NRTIs-Based Therapy. Data from the ARCA Collaborative Group

Accumulation of HIV Drug Resistance Mutations in Patients Failing First-Line Antiretroviral Treatment in South Africa

Rates of Emergence of HIV Drug Resistance in Resource-Limited Settings: A Systematic Review

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