Pretreatment HIV Drug Resistance and HIV-1 Subtype C Are Independently Associated With Virologic Failure: Results From the Multinational PEARLS (ACTG A5175) Clinical Trial

Kantor, Rami; Smeaton, Laura; Vardhanabhuti, Saran; Hudelson, Sarah E.; Wallis, Carole L.; Tripathy, Srikanth; Morgado, Mariza G.; Saravanan, S.; Balakrishnan, Pachamuthu; Reitsma, Marissa B; Hart, Stephen A.; Mellors, John W.; Halvas, Elias K.; Grinsztejn, Beatriz; Hosseinipour, Mina C.; Kumwenda, Johnstone; Rosa, Alberto La; Lalloo, Umesh; Lama, Javier R.; Rassool, Mohammed; Santos, Breno; Supparatpinyo, Khuanchai; Hakim, James; Flanigan, Timothy P.; Kumarasamy, Nagalingeswaran; Campbell, Thomas; Eshleman, Susan H.

doi:10.1093/cid/civ102

Cited by 73 publications

(64 citation statements)

References 37 publications

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“…The few studies that evaluated resistance in TDF-based first-line regimens in RLS, mostly in subtypes C, G and CRF02_AG from Southern Africa and Nigeria, do not report overall resistance but estimate NRTI- (94 to 100%) and NNRTI-associated resistance (57 to 97%) to be high [9–11,13,16]. Though mutation frequencies in this study, other than K65R, were similar to prior reports [13], unique mutation patterns in 58% of the patients and specific mutation co-occurrence support the need for continued research on subtype-specific resistance, particularly with changing treatment guidelines [38]. …”

Section: Discussionsupporting

confidence: 67%

Treatment failure and drug resistance in HIV‐positive patients on tenofovir‐based first‐line antiretroviral therapy in western Kenya

Brooks

Diero

DeLong

et al. 2016

Journal of the International AIDS Society

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IntroductionTenofovir-based first-line antiretroviral therapy (ART) is recommended globally. To evaluate the impact of its incorporation into the World Health Organization (WHO) guidelines, we examined treatment failure and drug resistance among a cohort of patients on tenofovir-based first-line ART at the Academic Model Providing Access to Healthcare, a large HIV treatment programme in western Kenya.MethodsWe determined viral load (VL), drug resistance and their correlates in patients on ≥six months of tenofovir-based first-line ART. Based on enrolled patients’ characteristics, we described these measures in those with (prior ART group) and without (tenofovir-only group) prior non-tenofovir-based first-line ART using Wilcoxon rank sum and Fisher's exact tests.ResultsAmong 333 participants (55% female; median age 41 years; median CD4 336 cells/µL), detectable (>40 copies/mL) VL was found in 18%, and VL>1000 copies/mL (WHO threshold) in 10%. Virologic failure at both thresholds was significantly higher in 217 participants in the tenofovir-only group compared with 116 in the prior ART group using both cut-offs (24% vs. 7% with VL>40 copies/mL; 15% vs. 1% with VL>1000 copies/mL). Failure in the tenofovir-only group was associated with lower CD4 values and advanced WHO stage. In 35 available genotypes from 51 participants in the tenofovir-only group with VL>40 copies/mL (69% subtype A), any resistance was found in 89% and dual-class resistance in 83%. Tenofovir signature mutation K65R occurred in 71% (17/24) of the patients infected with subtype A. Patients with K65R had significantly lower CD4 values, higher WHO stage and more resistance mutations.ConclusionsIn this Kenyan cohort, tenofovir-based first-line ART resulted in good (90%) virologic suppression including high suppression (99%) after switch from non-tenofovir-based ART. Lower virologic suppression (85%) and high observed resistance levels (89%) in the tenofovir-only group impact future treatment options, support recommendations for widespread VL monitoring in such resource limited settings to identify early treatment failure and suggest consideration of individualized resistance testing to design effective subsequent regimens.

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Section: Discussionsupporting

confidence: 67%

Treatment failure and drug resistance in HIV‐positive patients on tenofovir‐based first‐line antiretroviral therapy in western Kenya

Brooks

Diero

DeLong

et al. 2016

Journal of the International AIDS Society

Self Cite

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“…In PEARLS, ART was initiated at lower CD4 cell counts (<300 cells/mm 3 ); the frequency of baseline resistance in PEARLS was 9.4% among those who failed ART, and 4.3% among those in a case control group of those who did not fail ART. 19 …”

Section: Discussionmentioning

confidence: 99%

Brief Report: HIV Drug Resistance in Adults Failing Early Antiretroviral Treatment: Results From the HIV Prevention Trials Network 052 Trial

Fogel

Hudelson

et al. 2016

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Early initiation of antiretroviral therapy (ART) reduces HIV transmission and has health benefits. HIV drug resistance can limit treatment options and compromise use of ART for HIV prevention. We evaluated drug resistance in 85 participants in the HPTN 052 trial who started ART at CD4 counts of 350–550 cells/mm3 and failed ART by May 2011; 8.2% had baseline resistance and 35.3% had resistance at ART failure. High baseline viral load and less education were associated with emergence of resistance at ART failure. Resistance at ART failure was observed in 7/8 (87.5%) participants who started ART at lower CD4 cell counts.

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“…Transmitted drug resistance is more commonly detected among persons with recent HIV infection (Yanik et al, 2012) and may be higher among certain demographic and transmission risk groups, such as whites and gay, bisexual, and other men who have sex with men (MSM) (Buchacz et al, 2015; Ross et al, 2007; Weinstock et al, 2004; Yanik et al, 2012). People who take ART medications to which their HIV infection is resistant may not achieve viral suppression (Gill et al, 2010; Kantor et al, 2015; Little et al, 2002). Thus, identifying drug resistance before initiation of treatment may help ensure selection of appropriate ART regimens, viral suppression, and improved overall survival.…”

Section: Introductionmentioning

confidence: 99%

Receipt and timing of HIV drug resistance testing in six U.S. jurisdictions

et al. 2017

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The Department of Health and Human Services recommends drug resistance testing at linkage to HIV care. Because receipt and timing of testing are not well characterized, we examined testing patterns among persons with diagnosed HIV who are linked to care. Using surveillance data in six jurisdictions for persons aged ≥13 years with HIV infection diagnosed in 2013, we assessed the proportion receiving testing, and among these, the proportion receiving testing at linkage. Multivariable log-binomial regression modeling estimated associations between selected characteristics and receipt of testing (1) overall, and (2) at linkage among those tested. Of 9,408 persons linked to care, 66% received resistance testing, among whom 68% received testing at linkage. Less testing was observed among male persons who inject drugs (PWID), compared with men who have sex with men (adjusted prevalence ratio [aPR]: 0.88; 95% confidence interval [CI]: 0.81–0.97) and persons living in areas with population <500,000 compared with those in areas with population ≥2,500,000 (aPR: 0.88; CI: 0.84–0.93). In certain jurisdictions, testing was lower for persons with initial CD4 counts ≥500 cells/mm3, compared with those with CD4 counts <200 cells/mm3 (aPR range: 0.80–0.85). Of those tested, testing at linkage was lower among male PWID (aPR: 0.85; CI: 0.75–0.95) and, in some jurisdictions, persons with CD4 counts ≥500 cells/mm3 (aPR range: 0.63–0.73). Two-thirds of persons with diagnosed HIV who were linked to care received resistance testing, and most received testing at linkage as recommended. Improving receipt and timing of testing among male PWID, persons in less populous settings, and in all jurisdictions, regardless of CD4 count, may improve care outcomes.

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Pretreatment HIV Drug Resistance and HIV-1 Subtype C Are Independently Associated With Virologic Failure: Results From the Multinational PEARLS (ACTG A5175) Clinical Trial

Abstract: NCT00084136.

Cited by 73 publications

References 37 publications

Treatment failure and drug resistance in HIV‐positive patients on tenofovir‐based first‐line antiretroviral therapy in western Kenya

Treatment failure and drug resistance in HIV‐positive patients on tenofovir‐based first‐line antiretroviral therapy in western Kenya

Brief Report: HIV Drug Resistance in Adults Failing Early Antiretroviral Treatment: Results From the HIV Prevention Trials Network 052 Trial

Receipt and timing of HIV drug resistance testing in six U.S. jurisdictions

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