Rates of switching to second-line antiretroviral therapy and impact of delayed switching on immunologic, virologic, and mortality outcomes among HIV-infected adults with virologic failure in Rakai, Uganda

Abstract Background Human immunodeficiency virus (HIV) drug resistance profiles are needed to optimize individual patient management and to develop treatment guidelines. Resistance profiles are not well defined among individuals on failing second-line antiretroviral therapy (ART) in low- and middle-income countries (LMIC). Methods Resistance genotypes were performed during screening for enrollment into a trial of third-line ART (AIDS Clinical Trials Group protocol 5288). Prior exposure to both nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs and confirmed virologic failure on a protease inhibitor–containing regimen were required. Associations of drug resistance with sex, age, treatment history, plasma HIV RNA, nadir CD4+T-cell count, HIV subtype, and country were investigated. Results Plasma HIV genotypes were analyzed for 653 screened candidates; most had resistance (508 of 653; 78%) to 1 or more drugs. Genotypes from 133 (20%) showed resistance to at least 1 drug in a drug class, from 206 (32%) showed resistance to at least 1 drug in 2 drug classes, and from 169 (26%) showed resistance to at least 1 drug in all 3 commonly available drug classes. Susceptibility to at least 1 second-line regimen was preserved in 59%, as were susceptibility to etravirine (78%) and darunavir/ritonavir (97%). Susceptibility to a second-line regimen was significantly higher among women, younger individuals, those with higher nadir CD4+ T-cell counts, and those who had received lopinavir/ritonavir, but was lower among prior nevirapine recipients. Conclusions Highly divergent HIV drug resistance profiles were observed among candidates screened for third-line ART in LMIC, ranging from no resistance to resistance to 3 drug classes. These findings underscore the need for access to resistance testing and newer antiretrovirals for the optimal management of third-line ART in LMIC.

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Determinants of Virologic Failure Among Adults on Second Line Antiretroviral Therapy in Wollo, Amhara Regional State, Northeast Ethiopia

HIV/AIDS - Research and Palliative Care ◽

10.2147/hiv.s278603 ◽

2020 ◽

Vol Volume 12 ◽

pp. 697-706

Author(s):

Ali Seid ◽

Niguss Cherie ◽

Kemal Ahmed

Keyword(s):

Antiretroviral Therapy ◽

Virologic Failure ◽

Second Line ◽

Northeast Ethiopia ◽

Regional State ◽

Second Line Antiretroviral Therapy

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Virologic failure and switch to second-line antiretroviral therapy in children with HIV in Lilongwe, Malawi: an observational cohort study

Transactions of the Royal Society of Tropical Medicine and Hygiene ◽

10.1093/trstmh/trz087 ◽

2019 ◽

Author(s):

Hannock Tweya ◽

Caryl Feldacker ◽

Christine Kiruthu-Kamamia ◽

Lucion Billion ◽

Joe Gumulira ◽

...

Keyword(s):

Cohort Study ◽

Antiretroviral Therapy ◽

Virologic Failure ◽

Second Line ◽

Load Testing ◽

Kaplan Meier ◽

Observational Cohort ◽

Public Clinics ◽

Optimal Adherence ◽

Second Line Antiretroviral Therapy

Abstract Background As routine viral load testing among HIV-infected individuals on antiretroviral therapy (ART) expands, virologic failure (VF) among children in developing countries remains poorly understood. We assessed the rate of VF, the proportion failing who were subsequently switched to second-line ART and factors associated with VF among children ≤18 y. Methods An observation cohort study among 1312 children at two public clinics in Lilongwe, Malawi who initiated a first-line ART regimen between January 2014 and December 2017 and remained on treatment for ≥6 mo was conducted. Kaplan-Meier methods estimated the probabilities of VF. Univariable and multivariable Poisson regression models were used to explore predictors of VF. Result Overall, 16% (208/1312) of children experienced VF with an incidence rate of 10.1 events per 100 person-years. Of the 208, 184 (88%) were switched to second-line ART: 68 (43%) switched the same day VF was confirmed and 106 (66%) switched within 90 d of confirmed VF. Use of a Nevirapine (NVP)-based regimen and initiating ART in 2016–2017 compared with 2014–2015 were independent predictors of VF. Conclusion VF is common among children receiving ART. The findings suggest that VF can be reduced by phasing out NVP-based regimen and by ensuring optimal adherence to ART.

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