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Durability of antiretroviral therapy and predictors of virologic failure among perinatally HIV-infected children in Tanzania: a four-year follow-up.

Dow DE, Shayo AM, Cunningham CK, Reddy EA - BMC Infect. Dis. (2014)

Bottom Line: Among those originally suppressed on a first-line (non-nucleoside reverse transcriptase based regimen) 76% remained suppressed.After viral load testing in 2008-09 many participants switched to second-line therapy.Though virologic testing would likely hasten the switch to second-line among those failing, methods to improve adherence is critical to maximize durability of ART and improve virologic outcomes among youth in resource-limited settings.

View Article: PubMed Central - PubMed

Affiliation: Division of Pediatric Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA. dorothy.dow@duke.edu.

ABSTRACT

Background: In Tanzania, HIV-1 RNA testing is rarely available and not standard of care. Determining virologic failure is challenging and resistance mutations accumulate, thereby compromising second-line therapy. We evaluated durability of antiretroviral therapy (ART) and predictors of virologic failure among a pediatric cohort at four-year follow-up.

Methods: This was a prospective cross-sectional study with retrospective chart review evaluating a perinatally HIV-infected Tanzanian cohort enrolled in 2008-09 with repeat HIV-1 RNA in 2012-13. Demographic, clinical, and laboratory data were extracted from charts, resistance mutations from 2008-9 were analyzed, and prospective HIV RNA was obtained.

Results: 161 (78%) participants of the original cohort consented to repeat HIV RNA. The average age was 12.2 years (55% adolescents ≥12 years). Average time on ART was 6.4 years with 41% receiving second-line (protease inhibitor based) therapy. Among those originally suppressed on a first-line (non-nucleoside reverse transcriptase based regimen) 76% remained suppressed. Of those originally failing first-line, 88% were switched to second-line and 72% have suppressed virus. Increased level of viremia and duration of ART trended with an increased number of thymidine analogue mutations (TAMs). Increased TAMs increased the odds of virologic failure (p = 0.18), as did adolescent age (p < 0.01).

Conclusions: After viral load testing in 2008-09 many participants switched to second-line therapy. The majority achieved virologic suppression despite multiple resistance mutations. Though virologic testing would likely hasten the switch to second-line among those failing, methods to improve adherence is critical to maximize durability of ART and improve virologic outcomes among youth in resource-limited settings.

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Comparison of HIV RNA results from 2008-09 and 2012-13 for 161 participants.
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Fig2: Comparison of HIV RNA results from 2008-09 and 2012-13 for 161 participants.

Mentions: For the 161 participants with viral loads available both from 2008-9 and 2012-13, results were compared in Figure 2. The majority of participants, 149/161 (92.5%) were receiving first-line therapy in 2008-9. Of those originally suppressed on first-line, 74/97 (76%) remained suppressed and on first-line treatment at the time of repeat HIV-1 RNA in 2012-13. Of the 52 participants unsuppressed on first-line therapy in 2008-9, 46 (88%) switched to second-line therapy and 33/46 (72%) had suppressed virus in 2012-13. Of the six who were not switched, all but one continued to fail on a first-line regimen. Of the eight who switched in the interim of the two studies, 3 did so due to immunologic failure, 3 due to virologic failure, 1 due to clinical failure, 1 for reasons that are unclear from chart review. Considering death, loss to follow up, and those who were unable to re-consent for testing (excluding transfers) to represent current virologic failure, a majority who enrolled in 2008-09, 118/193 (61.1%) remain suppressed on ART.Figure 2


Durability of antiretroviral therapy and predictors of virologic failure among perinatally HIV-infected children in Tanzania: a four-year follow-up.

Dow DE, Shayo AM, Cunningham CK, Reddy EA - BMC Infect. Dis. (2014)

Comparison of HIV RNA results from 2008-09 and 2012-13 for 161 participants.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4225040&req=5

Fig2: Comparison of HIV RNA results from 2008-09 and 2012-13 for 161 participants.
Mentions: For the 161 participants with viral loads available both from 2008-9 and 2012-13, results were compared in Figure 2. The majority of participants, 149/161 (92.5%) were receiving first-line therapy in 2008-9. Of those originally suppressed on first-line, 74/97 (76%) remained suppressed and on first-line treatment at the time of repeat HIV-1 RNA in 2012-13. Of the 52 participants unsuppressed on first-line therapy in 2008-9, 46 (88%) switched to second-line therapy and 33/46 (72%) had suppressed virus in 2012-13. Of the six who were not switched, all but one continued to fail on a first-line regimen. Of the eight who switched in the interim of the two studies, 3 did so due to immunologic failure, 3 due to virologic failure, 1 due to clinical failure, 1 for reasons that are unclear from chart review. Considering death, loss to follow up, and those who were unable to re-consent for testing (excluding transfers) to represent current virologic failure, a majority who enrolled in 2008-09, 118/193 (61.1%) remain suppressed on ART.Figure 2

Bottom Line: Among those originally suppressed on a first-line (non-nucleoside reverse transcriptase based regimen) 76% remained suppressed.After viral load testing in 2008-09 many participants switched to second-line therapy.Though virologic testing would likely hasten the switch to second-line among those failing, methods to improve adherence is critical to maximize durability of ART and improve virologic outcomes among youth in resource-limited settings.

View Article: PubMed Central - PubMed

Affiliation: Division of Pediatric Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA. dorothy.dow@duke.edu.

ABSTRACT

Background: In Tanzania, HIV-1 RNA testing is rarely available and not standard of care. Determining virologic failure is challenging and resistance mutations accumulate, thereby compromising second-line therapy. We evaluated durability of antiretroviral therapy (ART) and predictors of virologic failure among a pediatric cohort at four-year follow-up.

Methods: This was a prospective cross-sectional study with retrospective chart review evaluating a perinatally HIV-infected Tanzanian cohort enrolled in 2008-09 with repeat HIV-1 RNA in 2012-13. Demographic, clinical, and laboratory data were extracted from charts, resistance mutations from 2008-9 were analyzed, and prospective HIV RNA was obtained.

Results: 161 (78%) participants of the original cohort consented to repeat HIV RNA. The average age was 12.2 years (55% adolescents ≥12 years). Average time on ART was 6.4 years with 41% receiving second-line (protease inhibitor based) therapy. Among those originally suppressed on a first-line (non-nucleoside reverse transcriptase based regimen) 76% remained suppressed. Of those originally failing first-line, 88% were switched to second-line and 72% have suppressed virus. Increased level of viremia and duration of ART trended with an increased number of thymidine analogue mutations (TAMs). Increased TAMs increased the odds of virologic failure (p = 0.18), as did adolescent age (p < 0.01).

Conclusions: After viral load testing in 2008-09 many participants switched to second-line therapy. The majority achieved virologic suppression despite multiple resistance mutations. Though virologic testing would likely hasten the switch to second-line among those failing, methods to improve adherence is critical to maximize durability of ART and improve virologic outcomes among youth in resource-limited settings.

Show MeSH
Related in: MedlinePlus