Second-line failure and first experience with third-line antiretroviral therapy in Mumbai, India

These guidelines are intended as an update to those published in the Southern African Journal of HIV Medicine in January 2008. Since the release of the previous guidelines, the scale-up of antiretroviral therapy (ART) in Southern Africa has continued to grow. Cohort studies from the region show excellent clinical outcomes; however, ART is still being started late (in advanced disease), resulting in relatively high early mortality rates. New data on antiretroviral (ARV) tolerability in the region and several new ARV drugs have become available. Although currently few in number, some patients in the region are failing protease inhibitor (PI)-based second-line regimens. To address this, guidelines on third-line (or ‘salvage’) therapy have been expanded.

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Diverse Human Immunodeficiency Virus–1 Drug Resistance Profiles at Screening for ACTG A5288: A Study of People Experiencing Virologic Failure on Second-line Antiretroviral Therapy in Resource-limited Settings

Clinical Infectious Diseases ◽

10.1093/cid/ciz1116 ◽

2019 ◽

Vol 71 (7) ◽

pp. e170-e177 ◽

Cited By ~ 2

Author(s):

Carole L Wallis ◽

Michael D Hughes ◽

Justin Ritz ◽

Raquel Viana ◽

Carlos Silva de Jesus ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Drug Resistance ◽

Antiretroviral Therapy ◽

Virologic Failure ◽

Cd4 T Cell ◽

Second Line ◽

Drug Classes ◽

Immunodeficiency Virus ◽

Third Line ◽

Second Line Antiretroviral Therapy

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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From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults

BMC Research Notes ◽

10.1186/s13104-016-2309-7 ◽

2016 ◽

Vol 9 (1) ◽

Cited By ~ 7

Author(s):

Ivan Namakoola ◽

◽

Ivan Kasamba ◽

Billy N. Mayanja ◽

Patrick Kazooba ◽

...

Keyword(s):

Drug Resistance ◽

Antiretroviral Therapy ◽

Second Line ◽

Resistance Mutations ◽

Hiv Drug Resistance ◽

Drug Resistance Mutations ◽

Third Line

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Predictors of failure on second-line antiretroviral therapy with protease inhibitor mutations in Uganda

AIDS Research and Therapy ◽

10.1186/s12981-021-00338-y ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Hellen Musana ◽

Jude Thaddeus Ssensamba ◽

Mary Nakafeero ◽

Henry Mugerwa ◽

Flavia Matovu Kiweewa ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Protease Inhibitor ◽

Tuberculosis Treatment ◽

Categorical Variables ◽

Control Analysis ◽

Second Line ◽

Paired Data ◽

Factors Associated ◽

Third Line ◽

Second Line Antiretroviral Therapy

Abstract Introduction Failure on second-line antiretroviral therapy (ART) with protease inhibitor (PI) mutations (VF-M) is on the rise. However, there is a paucity of information on the factors associated with this observation in low-income countries. Knowledge of underlying factors is critical if we are to minimize the number of PLHIV switched to costly third-line ART. Our study investigated the factors associated with VF-M. Methods We conducted a matched case–control analysis of patients' records kept at the Joint Clinical Research Center, starting from January 2008 to May 2018. We matched records of patients who failed the second-line ART with major PI mutations (cases) with records of patients who were virologically suppressed (controls) by a ratio of 1:3. Data analysis was conducted using STATA Version 14. Categorical variables were compared with the outcomes failure on second-line ART with PI mutations using the Chi-square and Fisher's exact tests where appropriate. Conditional logistic regression for paired data was used to assess the association between the outcome and exposure variables, employing the backward model building procedure. Results Of the 340 reviewed patients' records, 53% were women, and 6.2% had previous tuberculosis treatment. Males (aOR = 2.58, [CI 1.42–4.69]), and patients concurrently on tuberculosis treatment while on second-line ART (aOR = 5.65, [CI 1.76–18.09]) had higher odds of VF-M. ART initiation between 2001 and 2015 had lower odds of VF-M relative to initiation before the year 2001. Conclusion Males and patients concomitantly on tuberculosis treatment while on second-line ART are at a higher risk of VF-M. HIV/AIDS response programs should give special attention to this group of people if we are to minimize the need for expensive third-line ART. We recommend more extensive, explorative studies to ascertain underlying factors.

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High rate of virological re-suppression among patients failing second-line antiretroviral therapy following enhanced adherence support: A model of care in Khayelitsha, South Africa

Southern African Journal of HIV Medicine ◽

10.4102/sajhivmed.v14i4.52 ◽

2013 ◽

Vol 14 (4) ◽

pp. 170-176 ◽

Cited By ~ 6

Author(s):

D B Garone ◽

K Conradie ◽

G Patten ◽

M Cornell ◽

W Goemaere ◽

...

Keyword(s):

Drug Resistance ◽

Antiretroviral Therapy ◽

High Rate ◽

Second Line ◽

Viral Loads ◽

Support Programme ◽

Adherence Support ◽

Third Line ◽

Second Line Antiretroviral Therapy

Objective. To describe and evaluate the outcomes of a support programme for patients with virological failure while receiving second-line antiretroviral therapy (ART) in South Africa.Method. We described a comprehensive medical and counselling patient support programme for patients receiving secondline ART and with two consecutive viral loads (VLs) >1 000 copies/ml. Patients with >3 months follow-up and at least one VL measurement after inclusion in the programme were eligible for analysis.Results. Of 69 patients enrolled in the programme, 40 had at least one follow-up VL and no known drug resistance at enrolment; 27 (68%) of these re-suppressed while remaining on second-line ART following enhanced adherence support. The majority (18/27; 67%) achieved re-suppression within the first 3 months in the programme. Five patients with diagnosed second-line drug resistance achieved viral re-suppression (<400 copies/ml) after being switched to third-line ART. Seven patients (7/40; 18%) did not achieve viral re-suppression after 9 months in the programme: 6 with known adherence problems (4 without drug resistance on genotype) and 1 with a VL <1 000 copies/ml. Overall, 3 patients (4%) died, 3 (4%) were lost to follow-up and 2 (3%) were transferred out.Conclusion. Our experience from a routine programme demonstrates that with targeted adherence support, the majority of patients who were viraemic while receiving second-line ART returned to an undetectable VL within 3 months. By increasing the time receiving second-line ART and decreasing the need for genotypes and/or third-line ART, this intervention may reduce costs.

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A retrospective descriptive investigation of adult patients receiving third-line antiretroviral therapy in the North West province, South Africa

African Health Sciences ◽

10.4314/ahs.v20i2.2 ◽

2020 ◽

Vol 20 (2) ◽

pp. 549-559

Author(s):

Christian Rudman ◽

Michelle Viljoen ◽

Malie Rheeders

Keyword(s):

Antiretroviral Therapy ◽

Adult Patients ◽

Second Line ◽

First Line ◽

Hiv Diagnosis ◽

North West ◽

The North ◽

North West Province ◽

Resistance Patterns ◽

Third Line

Background: Greater access and prolonged exposure to ART may inevitably lead to more treatment failure and increase the need for third-line ART (TLART) in a resource-limited setting. Objective: To describe characteristics and resistance patterns of adult patients initiated on TLART in three districts of the North West province. Method: All-inclusive retrospective descriptive investigation. Demographics and clinical variables were recorded from adult patient health records (2002-2017) and analysed. Results: 21 Patients (17 females, 4 males) with median (IQR) age of 34 years (30.2-37.8) at HIV diagnosis and 45 years (39.5-47) at TLART initiation were included. Median duration (days) from HIV diagnosis to first-line ART initiation was 101 (37-367), treatment duration on first-line, second-line and between second-line failure and TLART initiation were: 1 269 (765-2 343); 1 512 (706-2096) and 71 (58-126) days respectively. High-level resistance most prevalent were: nelfinavir/r (85.7%), indinavir/r (80.9%), lopinavir/r (76.2%), emtricitabine and lamivudine (95.2%), nevirapine (76.2%) and efavirenz (71.4%). Resistance to 3 major PI mutations in 95% of patients and cross resistance were documented extensively. Conclusion: This study support the need for earlier resistance testing. It firstly reported on time duration post diagnosis on various ART regimens and secondly resistance patterns of adults before TLART was initiated in these districts. Keywords: HIV; Human immunodeficiency virus; third-line antiretroviral therapy; drug resistance patterns; salvage therapy.

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Predictors of Failure on Second-line Antiretroviral Therapy with Protease Inhibitor Mutations in Uganda

10.21203/rs.3.rs-30512/v1 ◽

2020 ◽

Author(s):

Hellen Musana ◽

Ssensamba Jude Thaddeus ◽

Mary Nakafeero ◽

Henry Mugerwa ◽

Flavia Matovu Kiweewa ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Protease Inhibitor ◽

Tuberculosis Treatment ◽

Categorical Variables ◽

Control Analysis ◽

Second Line ◽

Paired Data ◽

Factors Associated ◽

Third Line ◽

Second Line Antiretroviral Therapy

Abstract Introduction Failure on second-line antiretroviral therapy (ART) with protease inhibitor (PI) mutations is on the rise. However, there is a paucity of information on the factors associated with this observation in the context of low-income countries. Knowledge of underlying factors is key if we are to minimize the number of PLHIV switched to costly third-line ART. Our study investigated the factors associated with failure on second-line ART with PI mutations. Methods We conducted a matched case-control analysis of patients' records kept at the Joint Clinical Research Center, starting from January 2008 to May 2018. We matched records of patients who failed the second-line ART with major PI mutations (cases) with records of patients who were virologically suppressed (controls) by a ratio of 1:3. Data analysis was conducted using STATA Version 14, and descriptive statistics comparing cases and controls were generated. Categorical variables were compared with the outcome, failure on second line ART with PI mutations using the Chi-square and Fisher's exact tests where appropriate. Conditional logistic regression for paired data was used to assess the association between the outcome and exposure variables, employing the backward model building procedure was done. Results Of the 340 reviewed patients' records, 53% were women, and 6.2% had previous Tuberculosis treatment. Males (aOR 2.64 CI: 1.0-4.64), type of second-line ART (aOR 3.92 CI: 1.15-13.38), and Tuberculosis treatment while on second-line ART (aOR7.08 CI: 2.35-21.29) highly predicted failure on second-line ART with PI mutations. Conclusion Males and patients concomitantly on Tuberculosis treatment while on second-line ART are at a higher risk of failing on second-line ART with PI mutations. HIV/AIDS response programs should give special attention to this group of people if we are to minimize the need for expensive third-line ART. More extensive explorative studies to ascertain underlying factors are recommended.

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