Low-level viraemia among people living with HIV in Nigeria: a retrospective longitudinal cohort study

Chun, Helen M.; Abutu, Andrew; Milligan, Kyle; Ehoche, Akipu; Shiraishi, Ray W.; Odafe, Solomon; Dalhatu, Ibrahim; Onotu, Dennis; Okoye, McPaul; Oladipo, Ademola; Gwamna, Jerry; Ikpeazu, Akudo; Akpan, Nseobong M.; Jahun, Ibrahim; Aliyu, Gambo; Boyd, Mary Adetinuke; Swaminathan, Mahesh; Ellerbrock, Tedd V.; Stafford, Kristen A.; Dirlikov, Emilio; Ene, Uzoma; Onyenuobi, Chidozie; Efuntoye, Timothy; Meribe, Chibuzor; Ogbanufe, Obinna; Bassey, Orji; Fagbamigbe, Omodele Johnson; Fagbemi, Ayodele; Bamidele, Moyosola; Audu, Israel; Adegoke, Dickson; Tapdiyel, Jelpe; Emeh, Anuri; Obanubi, Chris; Oke, Odafrenkhoa; Pals, Sherri; Boyd, Andrew T.; Zeh, Clement; Ellenberger, Dennis; Williams-Sherlock, Michelle; Adebajo, Sylvia; Sabo, Uba; Bassey, Grace; Etubi, Eruona; Omole, Temi; Okonkwo, Prosper; Kolade, Temitope; Dakum, Patrick; Olayiwola, Olanrewaju; Oko, John Okpanachi; Ayo, Inyang; Oyeledun, Bolanle; Odoh, Deborah; Adedokun, Oluwasanmi

doi:10.1016/s2214-109x(22)00413-2

Cited by 18 publications

(18 citation statements)

References 27 publications

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“…Although low-level viremia is defined in some contexts as any detectable viral load >50 copies/mL, 15,19 a VLS cutpoint of <200 HIV RNA copies/mL was selected for the present study to minimize statistical "noise" around the assay's lower limit of detection and distinguish unsuppressed persons with transmissible viremia from those exhibiting transient, low-risk viremic "blips". 17,20,21 Four longitudinal virologic outcomes were identified within visit-pairs: (1) durable VLS (<200 copies/mL across visits), (2) new/renewed VLS (<200 copies/mL at followup only), (3) viral rebound (<200 copies/mL at index visit only), and (4) persistent viremia (<200 copies/mL at neither visit). Viremia was stratified by two categories based on viral copy counts, per World Health Organization guidelines: low-level viremia (200-999 copies/mL) and highlevel viremia (>1,000 copies/mL).…”

Section: Viral Load Suppression Measuresmentioning

confidence: 99%

“…13,14 This study observed moderate levels of persistent viremia amidst large increases in durable VLS but did not distinguish between high-(>1,000 HIV RNA copies/mL) and low-level (200-999 copies/mL) viremia, 12 which has been linked to subsequent virologic failure and HIV-1 drug resistance. [15][16][17] All rights reserved. No reuse allowed without permission.…”

Section: Introductionmentioning

confidence: 99%

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Temporal dynamics and drivers of durable HIV viral load suppression and persistent high- and low-level viremia during Universal Test and Treat scale-up in Uganda: a population-based study

Rosen

Ssekubugu

Chang

et al. 2023

Preprint

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Introduction: Population-level data on durable HIV viral load suppression (VLS) following implementation of Universal Test and Treat (UTT) in Africa are limited. We assessed trends in durable VLS and viremia among persons living with HIV in 40 Ugandan communities during UTT scale-up. Methods: In 2015-2020, we measured VLS (defined as <200 RNA copies/mL) among participants in the Rakai Community Cohort Study, a longitudinal population-based HIV surveillance cohort in southern Uganda. Persons with unsuppressed viral loads were characterized as having low-level (200-999 copies/mL) or high-level (>1,000 copies/mL) viremia. Individual virologic outcomes were assessed over two consecutive RCCS survey visits (i.e., visit-pairs; ~18 month visit intervals) and classified as durable VLS (<200 copies/mL at both visits), new/renewed VLS (<200 copies/mL at follow-up only), viral rebound (<200 copies/mL at initial visit only), or persistent viremia (<200 copies/mL at neither visit). Population prevalence of each outcome was assessed over calendar time. Community-level prevalence and individual-level predictors of persistent high-level viremia were also assessed using multivariable Poisson regression with generalized estimating equations. Results: Overall, 3,080 participants contributed 4,604 visit-pairs over three survey rounds. Most visit-pairs (72.4%) exhibited durable VLS, with few (2.5%) experiencing viral rebound. Among those with viremia at the initial visit (n=1,083), 46.9% maintained viremia through follow-up, 91.3% of which was high-level viremia. One-fifth (20.8%) of visit-pairs exhibiting persistent high-level viremia self-reported antiretroviral therapy (ART) use for >12 months. Prevalence of persistent high-level viremia varied substantially across communities and was significantly elevated among young persons aged 15-29 years (versus 40-49-year-olds; adjusted risk ratio [adjRR]=2.96; 95% confidence interval [95%CI]:2.21-3.96), men (versus women; adjRR=2.40, 95%CI:1.87-3.07), persons reporting inconsistent condom use with non-marital/casual partners (versus persons with marital/permanent partners only; adjRR=1.38, 95%CI:1.10-1.74), and persons exhibiting hazardous alcohol use (adjRR=1.09, 95%CI:1.03-1.16). The prevalence of persistent high-level viremia was highest among men <30 years (32.0%). Conclusions: Following universal ART provision, most persons living with HIV in south-central Uganda are durably suppressed. Among persons exhibiting viremia, nearly half maintain high-level viremia for >12 months and report higher-risk behaviors associated with onward HIV transmission. Enhanced linkage to HIV care and optimized treatment retention could accelerate momentum towards HIV epidemic control.

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Section: Viral Load Suppression Measuresmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Temporal dynamics and drivers of durable HIV viral load suppression and persistent high- and low-level viremia during Universal Test and Treat scale-up in Uganda: a population-based study

Rosen

Ssekubugu

Chang

et al. 2023

Preprint

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show abstract

“…Likewise, another study was implemented in four hyperendemic Lake Victoria fishing communities [14], with demographic and sexual behaviour profiles atypical of most African communities [15, 16]—observing moderate levels of persistent viraemia amidst large increases in durable VLS during UTT scale‐up. Importantly, neither study distinguished high‐level viraemia (≥1000 HIV RNA copies/ml) from low‐level viraemia (200–999 copies/ml) [14], which has been linked to subsequent virologic failure and HIV‐1 drug resistance [17–19].…”

Section: Introductionmentioning

confidence: 99%

Temporal dynamics and drivers of durable HIV viral load suppression and persistent high‐ and low‐level viraemia during Universal Test and Treat scale‐up in Uganda: a population‐based study

Rosen,

Ssekubugu,

Chang

et al. 2024

J Int AIDS Soc.

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IntroductionPopulation‐level data on durable HIV viral load suppression (VLS) following the implementation of Universal Test and Treat (UTT) in Africa are limited. We assessed trends in durable VLS and viraemia among persons living with HIV in 40 Ugandan communities during the UTT scale‐up.MethodsIn 2015–2020, we measured VLS (<200 RNA copies/ml) among participants in the Rakai Community Cohort Study, a longitudinal population‐based HIV surveillance cohort in southern Uganda. Persons with unsuppressed viral loads were characterized as having low‐level (200–999 copies/ml) or high‐level (≥1000 copies/ml) viraemia. Individual virologic outcomes were assessed over two consecutive RCCS survey visits (i.e. visit‐pairs; ∼18‐month visit intervals) and classified as durable VLS (<200 copies/ml at both visits), new/renewed VLS (<200 copies/ml at follow‐up only), viral rebound (<200 copies/ml at initial visit only) or persistent viraemia (≥200 copies/ml at both visits). Population prevalence of each outcome was assessed over calendar time. Community‐level prevalence and individual‐level predictors of persistent high‐level viraemia were also assessed using multivariable Poisson regression with generalized estimating equations.ResultsOverall, 3080 participants contributed 4604 visit‐pairs over three survey rounds. Most visit‐pairs (72.4%) exhibited durable VLS, with few (2.5%) experiencing viral rebound. Among those with any viraemia at the initial visit (23.5%, n = 1083), 46.9% remained viraemic through follow‐up, 91.3% of which was high‐level viraemia. One‐fifth (20.8%) of visit‐pairs exhibiting persistent high‐level viraemia self‐reported antiretroviral therapy (ART) use for ≥12 months. Prevalence of persistent high‐level viraemia varied substantially across communities and was significantly elevated among young persons aged 15–29 years (vs. 40‐ to 49‐year‐olds; adjusted risk ratio [adjRR] = 2.96; 95% confidence interval [95% CI]: 2.21–3.96), males (vs. females; adjRR = 2.40, 95% CI: 1.87–3.07), persons reporting inconsistent condom use with non‐marital/casual partners (vs. persons with marital/permanent partners only; adjRR = 1.38, 95% CI: 1.10–1.74) and persons reporting hazardous alcohol use (adjRR = 1.09, 95% CI: 1.03–1.16). The prevalence of persistent high‐level viraemia was highest among males <30 years (32.0%).ConclusionsFollowing universal ART provision, most persons living with HIV in south‐central Uganda are durably suppressed. Among persons exhibiting any viraemia, nearly half exhibited high‐level viraemia for ≥12 months and reported higher‐risk behaviours associated with onward HIV transmission. Intensified efforts linking individuals to HIV treatment services could accelerate momentum towards HIV epidemic control.

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“…Sexual HIV transmission risk correlates directly to the HIV VL in the HIV infected partner [ 8 – 10 ], with those with undetectable VL being non-infectious [ 11 ]. While observational data quantifying HIV infectiousness at low viraemia levels are limited, some have raised concern that PLHIV with LLV could become an increasingly important population with HIV transmission risk as this population grows and the undiagnosed and untreated population shrinks [ 5 , 12 ]. This could particularly be the case if PLHIV with LLV engage in HIV risk behaviour due to a perception of being non-infectious.…”

Section: Introductionmentioning

confidence: 99%

HIV risk behaviour, viraemia, and transmission across HIV cascade stages including low-level viremia: Analysis of 14 cross-sectional population-based HIV Impact Assessment surveys in sub-Saharan Africa

Edun,

Okell,

Chun

et al. 2024

PLOS Glob Public Health

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As antiretroviral treatment (ART) coverage for people living with HIV (PLHIV) increases, HIV programmes require up-to-date information about evolving HIV risk behaviour and transmission risk, including those with low-level viremia (LLV; >50 to ≤1000 copies/mL), to guide prevention priorities. We aimed to assess differences in sexual risk behaviours, distribution of viral load (VL) and proportion of transmission across PLHIV subgroups. We analysed data from Population-based HIV Impact Assessment surveys in 14 sub-Saharan African countries during 2015–2019. We estimated adjusted prevalence ratios (aPR) of self-reported HIV high-risk behaviour (multiple partners and condomless sex) across cascade stages via generalised estimation equations. We modelled the proportions of transmission from each subgroup using relative self-reported sexual risk, a Hill function for transmission rate by VL, and proportions within cascade stages from surveys and UNAIDS country estimates for 2010–2020. Compared to PLHIV with undetectable VL (≤50 copies/mL), undiagnosed PLHIV (aPR women: 1.28 [95% CI: 1.08–1.52]; men: 1.61 [1.33–1.95]) and men diagnosed but untreated (2.06 [1.52–2.78]) were more likely to self-report high-risk sex. High-risk behaviour was not significantly associated with LLV. Mean VL was similar among undiagnosed, diagnosed but untreated, and on ART but non-suppressed sub-groups. Across surveys, undiagnosed and diagnosed but untreated contributed most to transmission (40–91% and 1–41%, respectively), with less than 1% from those with LLV. Between 2010 and 2020, the proportion of transmission from individuals on ART but non-suppressed increased. In settings with high ART coverage, effective HIV testing, ART linkage, and retention remain priorities to reduce HIV transmission. Persons with LLV are an increasing share of PLHIV but their contribution to HIV transmission was small. Improving suppression among PLHIV on ART with VL ≥1000 copies/mL will become increasingly important.

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Low-level viraemia among people living with HIV in Nigeria: a retrospective longitudinal cohort study

Cited by 18 publications

References 27 publications

Temporal dynamics and drivers of durable HIV viral load suppression and persistent high- and low-level viremia during Universal Test and Treat scale-up in Uganda: a population-based study

Temporal dynamics and drivers of durable HIV viral load suppression and persistent high- and low-level viremia during Universal Test and Treat scale-up in Uganda: a population-based study

Temporal dynamics and drivers of durable HIV viral load suppression and persistent high‐ and low‐level viraemia during Universal Test and Treat scale‐up in Uganda: a population‐based study

HIV risk behaviour, viraemia, and transmission across HIV cascade stages including low-level viremia: Analysis of 14 cross-sectional population-based HIV Impact Assessment surveys in sub-Saharan Africa

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