Clinical and Virological Outcomes of TB/HIV Coinfected Patients Treated With Dolutegravir-Based HIV Antiretroviral Regimens: Programmatic Experience From Botswana

Modongo, Chawangwa; Wang, Qiao; Dima, Mbatshi; Matsiri, Ogopotse; Kgwaadira, Botshelo; Rankgoane-Pono, Goabaone; Shin, Sanghyuk S.; Zetola, Nicola M.

doi:10.1097/qai.0000000000002126

Cited by 32 publications

(28 citation statements)

References 6 publications

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“… 3 A recent observational study from Botswana reported similar virologic outcomes in patients on rifampicin taking DTG 50 mg 12-hourly versus 50 mg daily. 9 The RADIANT-TB trial is being conducted in Cape Town and is enrolling patients on TB treatment and starting first-line ART who are being randomised to TDF/FTC/DTG 50 mg 12-hourly versus TDF/FTC/DTG 50 mg daily ( https://clinicaltrials.gov/ct2/show/NCT03851588 ). Until data from this trial are available, we recommend DTG be dosed at 50 mg 12-hourly in all patients on rifampicin.…”

Section: Discussionmentioning

confidence: 99%

Case report: Emergence of dolutegravir resistance in a patient on second-line antiretroviral therapy

Mahomed¹,

Wallis

Dunn

et al. 2020

Southern African Journal of HIV Medicine

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Introduction: The integrase strand transfer inhibitor dolutegravir (DTG) has a high genetic barrier to resistance. Only rare cases of resistance to DTG have been reported when it is used as a component of antiretroviral therapy regimens in treatment-experienced patients unless there was prior use of a first-generation integrase inhibitor.Patient presentation: A 38-year-old woman diagnosed with tuberculosis was switched to a second-line antiretroviral regimen of zidovudine, lamivudine and dolutegravir 50 mg 12-hourly together with rifampicin-based TB treatment. Based on treatment history and a previous resistance test there was resistance to lamivudine but full susceptibility to zidovudine. The patient did not suppress her viral load on this regimen and later admitted to only taking dolutegravir 50 mg in the morning because of insomnia.Management and outcome: A second resistance test was performed which showed intermediate level of resistance to dolutegravir. Her regimen was changed to tenofovir, emtricitabine and ritonavir-boosted atazanavir with rifabutin replacing rifampicin for the remainder of her TB treatment. She achieved viral suppression on this regimen.Conclusion: To our knowledge this is the first case report from South Africa of emergent dolutegravir resistance in a treatment-experienced, integrase inhibitor-naïve patient. Factors that may have contributed to resistance emergence in this patient were that there was only one fully active nucleoside reverse transcriptase inhibitor in the regimen and lower exposure to dolutegravir because of the reduced dosing frequency while on rifampicin.

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Section: Discussionmentioning

confidence: 99%

Case report: Emergence of dolutegravir resistance in a patient on second-line antiretroviral therapy

Mahomed¹,

Wallis

Dunn

et al. 2020

Southern African Journal of HIV Medicine

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“…The advantages of TLE400 STR over TLD STR (current WHO-recommended preferred first-line ART) include noninferior virological and immunological efficacy [26], lower incidence of obesity [19,20,26], safety and efficacy in pregnancy [27], and no need for dose adjustment in cases of HIV/TB coinfection (doubling of DTG dose needed when used with rifampicin) [36]. In a study by Lamorde et al, switching PWH who were on various NNRTI-containing first-line ART regimens to DTG-containing first-line ART led to an increased incidence of new-onset hyperglycaemia.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of a single‐tablet regimen containing tenofovir disoproxil fumarate 300 mg, lamivudine 300 mg and efavirenz 400 mg as a switch strategy in virologically suppressed HIV‐1‐infected subjects on nonnucleoside reverse transcriptase inhibitor‐containing first‐line antiretroviral therapy in Pune, India

Dravid

Betha²,

Sharma³

et al. 2020

HIV Medicine

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Objectives As per National AIDS Control Organization (NACO) estimates, there are 2.1 million people living with HIV (PWH) in India, of whom 1.2 million are on first‐line antiretroviral therapy (ART). This study explored the use of a single‐tablet regimen containing tenofovir disoproxil fumarate 300 mg + lamivudine 300 mg + efavirenz 400 mg (TLE400 STR) as a first‐line switch strategy in PWH in Pune, India. Methods This retrospective cohort study was conducted in private sector ART clinics in three tertiary‐level hospitals in Pune, India. PWH > 12 years of age (n = 502) who initiated first‐line ART (predominantly TLE600 STR), completed ≥ 6 months of follow‐up and achieved virological suppression [plasma viral load (VL) < 1000 HIV‐1 RNA copies/mL] were identified and switched to TLE400 STR. The virological and immunological efficacy of TLE400 STR at 6 and 12 months of follow‐up were noted. Grade 3/4 adverse events (especially efavirenz‐related neuropsychiatric adverse events) leading to regimen discontinuation were also noted. Results Of 502 PWH who switched to TLE400 STR, complete virological suppression (VL < 20 copies/mL) was maintained in more than 97% of patients at follow‐up. TLE400 STR was successful in maintaining CD4 counts within the range observed at the start of the regimen. Grade 3/4 adverse events leading to TLE400 STR discontinuation were seen in 11 (2.2%) patients. Virological failure (VL > 1000 copies/mL) and treatment regimen failure were seen in six (1.2%) and 49 (9.8%) subjects, respectively. Conclusions TLE400 STR exhibits excellent efficacy and safety as a switch strategy and should be introduced in the Indian National ART Program, especially for PWH who are virologically suppressed on TLE600 STR.

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“…Regardless of these limitations, our study has strengths resulting in significant contributions to the body of scientific evidence available to HIV programs in DRC. Our findings coupled with the emerging evidence show that patients with TB/HIV coinfection require special attention and treatment, including TB-HIV integrated care and specific first-line therapies (e.g., dolutegravir) to improve treatment outcomes [ 35 , 36 ]. Our study utilizes a robust sample size to allow stable estimates of the influence of TB/HIV coinfection on outcome variables, after controlling for several sociodemographic and clinical variables included in the multivariable analysis.…”

Section: Discussionmentioning

confidence: 94%

Risk Factors for TB/HIV Coinfection and Consequences for Patient Outcomes: Evidence from 241 Clinics in the Democratic Republic of Congo

Shah

Ewetola²,

Etheredge

et al. 2021

IJERPH

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(1) Background: In resource-limited countries, patients with tuberculosis (TB)/HIV coinfection commonly face economic, sociocultural, and behavioral barriers to effective treatment. These barriers manifest from low treatment literacy, poverty, gender inequality, malnutrition, societal stigmas regarding HIV, and an absence of available care. It is critical for intervention programs to understand and assist in overcoming these barriers and any additional risks encountered by patients with TB/HIV coinfection. This study analyzes variation in TB/HIV coinfection and risks of negative outcomes among patients with TB/HIV coinfection compared to those without coinfection. (2) Methods: This quantitative study used data from 49,460 patients receiving ART from 241 HIV/AIDS clinics in Haut-Katanga and Kinshasa, two provinces in the Democratic Republic of Congo. Chi-square and logistic regression analysis were performed. (3) Results: Significantly higher proportions of patients with TB/HIV coinfection were men (4.5%; women, 3.3%), were new patients (3.7%; transferred-in, 1.6%), resided in the Kinshasa province (4.0%; Haut-Katanga, 2.7%), and were in an urban health zone (3.9%) or semi-rural health zone (3.1%; rural, 1.2%). Logistic regression analysis showed that after controlling for demographic and clinical variables, TB/HIV coinfection increased the risk of death (adjusted odds ratio (AOR), 2.26 (95% confidence interval (CI): 1.94–2.64)) and LTFU (AOR, 2.06 (95% CI: 1.82–2.34)). TB/HIV coinfection decreased the odds of viral load suppression (AOR, 0.58 (95% CI: 0.46–0.74)). (4) Conclusions: TB/HIV coinfection raises the risk of negative outcomes such as death, LTFU, and lack of viral load suppression. Our findings can help HIV clinics in Democratic Republic of Congo and other African countries to customize their interventions to improve HIV care and reduce care disparities among patients.

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Clinical and Virological Outcomes of TB/HIV Coinfected Patients Treated With Dolutegravir-Based HIV Antiretroviral Regimens: Programmatic Experience From Botswana

Cited by 32 publications

References 6 publications

Case report: Emergence of dolutegravir resistance in a patient on second-line antiretroviral therapy

Case report: Emergence of dolutegravir resistance in a patient on second-line antiretroviral therapy

Risk Factors for TB/HIV Coinfection and Consequences for Patient Outcomes: Evidence from 241 Clinics in the Democratic Republic of Congo

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