Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, northern Tanzania

Mziray, Shabani Ramadhani; Kumburu, Happiness; Assey, Hellen B; Sonda, Tolbert; Mahande, Michael Johnson; Msuya, Sia E.; Kiwelu, Ireen

doi:10.1101/2020.04.21.052902

Cited by 2 publications

(1 citation statement)

References 28 publications

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“…Suboptimal adherence leads to virologic failure, development of resistance, and onward transmission, including transmission of resistant mutations. [20][21][22] Commonly used adherence measures such as pill counts may inadequately predict virologic outcomes. [23][24][25] Drug concentrations in hair provide an objective measure of cumulative adherence.…”

Section: Introductionmentioning

confidence: 99%

Antiretroviral Therapy Adherence During and Postbreastfeeding Cessation Measured by Tenofovir Levels in Hair

Nematadzira

Murnane

Odiase

et al. 2022

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background: We examined change in antiretroviral treatment (ART) adherence after breastfeeding (BF) cessation using hair tenofovir (TFV) concentrations as an objective metric of medication consumption.Methods: A subset of postpartum women in Zimbabwe randomized in IMPAACT PROMISE to take ART while BF and post-BF cessation had hair TFV measured longitudinally. Using linear mixedeffect models, we estimated differences in hair TFV levels after BF cessation, accounting for trends in levels over time regardless of BF status and change in slope after breastfeeding cessation. We also estimated the relative risk of viremia (.50 copies/mL) per doubling of hair TFV concentration.Results: Among 55 women (median age 26, interquartile range 24-29 years), hair TFV levels (n = 305) were available for a median of 9 visits per woman between 3 and 29 months postpartum. Hair TFV levels ranged from undetected to 0.25 ng/mg (median 0.04 ng/mg). Controlling for trends since delivery [decline of 2.2% per month, 95% confidence interval (CI): 25.3 to 1.0], TFV levels averaged 24.4% higher (95% CI: 25.1 to 63.1) post-BF cessation than during BF, with no change in slope (0.0% per month, 95% CI: 23.8 to 3.9). Postpartum, 42% of women were ever viremic. Higher TFV levels were strongly protective; relative risk of viremia per doubling of TFV was 0.52 (95% CI: 0.43 to 0.63; P , 0.0001). Conclusions:Leveraging an objective metric of ART use, we observed modestly declining adherence across the postpartum period, but no additional decline associated with breastfeeding cessation. High viremia frequency and varying postpartum TFV levels observed highlight the importance of enhanced adherence support with viral load monitoring among postpartum women.

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Section: Introductionmentioning

confidence: 99%

Antiretroviral Therapy Adherence During and Postbreastfeeding Cessation Measured by Tenofovir Levels in Hair

Nematadzira

Murnane

Odiase

et al. 2022

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Spectrum of Atazanavir-Selected Protease Inhibitor-Resistance Mutations

et al. 2022

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Ritonavir-boosted atazanavir is an option for second-line therapy in low- and middle-income countries (LMICs). We analyzed publicly available HIV-1 protease sequences from previously PI-naïve patients with virological failure (VF) following treatment with atazanavir. Overall, 1497 patient sequences were identified, including 740 reported in 27 published studies and 757 from datasets assembled for this analysis. A total of 63% of patients received boosted atazanavir. A total of 38% had non-subtype B viruses. A total of 264 (18%) sequences had a PI drug-resistance mutation (DRM) defined as having a Stanford HIV Drug Resistance Database mutation penalty score. Among sequences with a DRM, nine major DRMs had a prevalence >5%: I50L (34%), M46I (33%), V82A (22%), L90M (19%), I54V (16%), N88S (10%), M46L (8%), V32I (6%), and I84V (6%). Common accessory DRMs were L33F (21%), Q58E (16%), K20T (14%), G73S (12%), L10F (10%), F53L (10%), K43T (9%), and L24I (6%). A novel nonpolymorphic mutation, L89T occurred in 8.4% of non-subtype B, but in only 0.4% of subtype B sequences. The 264 sequences included 3 (1.1%) interpreted as causing high-level, 14 (5.3%) as causing intermediate, and 27 (10.2%) as causing low-level darunavir resistance. Atazanavir selects for nine major and eight accessory DRMs, and one novel nonpolymorphic mutation occurring primarily in non-B sequences. Atazanavir-selected mutations confer low-levels of darunavir cross resistance. Clinical studies, however, are required to determine the optimal boosted PI to use for second-line and potentially later line therapy in LMICs.

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Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, northern Tanzania

Cited by 2 publications

References 28 publications

Antiretroviral Therapy Adherence During and Postbreastfeeding Cessation Measured by Tenofovir Levels in Hair

Antiretroviral Therapy Adherence During and Postbreastfeeding Cessation Measured by Tenofovir Levels in Hair

Spectrum of Atazanavir-Selected Protease Inhibitor-Resistance Mutations

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