The validity of self-reported antiretroviral use in persons living with HIV

Grabowski, Mary Kathryn; Reynolds, Steven J.; Kagaayi, Joseph; Gray, Ronald H.; Clarke, William; Chang, Larry W.; Nakigozi, Gertrude; Laeyendecker, Oliver; Redd, Andrew D.; Billioux, Veena G.; Ssekubugu, Robert; Nalugoda, Fred; Wawer, Maria J.; Serwadda, David; Quinn, Thomas C.; Tobian, Aaron A.R.

doi:10.1097/qad.0000000000001706

Cited by 48 publications

(44 citation statements)

References 16 publications

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“…We also used self-reported data to assess ART use, which may be subject to reporting bias. However, in a validation study we found a high specificity (99%) and moderate sensitivity (76%) of self-reported ART use compared to detection of antiretroviral drugs in plasma, regardless of migrant status 56 . Lastly, while our results may not be generalizable to hotspots outside of the Lake Victoria basin, they should motivate investigation into the epidemic and population dynamics that give rise to hotspots elsewhere and caution assumptions about them in the absence of data.…”

Section: Discussionmentioning

confidence: 65%

Migration, hotspots, and dispersal of HIV infection in Rakai, Uganda

Grabowski¹,

Lessler²,

Bazaale³

et al. 2020

Nat Commun

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HIV prevalence varies markedly throughout Africa, and it is often presumed areas of higher HIV prevalence (i.e., hotspots) serve as sources of infection to neighboring areas of lower prevalence. However, the small-scale geography of migration networks and movement of HIV-positive individuals between communities is poorly understood. Here, we use population-based data from~22,000 persons of known HIV status to characterize migratory patterns and their relationship to HIV among 38 communities in Rakai, Uganda with HIV prevalence ranging from 9 to 43%. We find that migrants moving into hotspots had significantly higher HIV prevalence than migrants moving elsewhere, but out-migration from hotspots was geographically dispersed, contributing minimally to HIV burden in destination locations. Our results challenge the assumption that high prevalence hotspots are drivers of transmission in regional epidemics, instead suggesting that migrants with high HIV prevalence, particularly women, selectively migrate to these areas.

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Section: Discussionmentioning

confidence: 65%

Migration, hotspots, and dispersal of HIV infection in Rakai, Uganda

Grabowski¹,

Lessler²,

Bazaale³

et al. 2020

Nat Commun

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“…Of note, a number of studies have reported denial of ART use among individuals determined to be taking therapy based on drug level testing. [35][36][37] Whether the mechanism of effect is due to poor adherence or virologic mechanisms, our nding that NNRTI resistance, present in 10-20% of individuals initiating DTG in the region, is associated with a reduction in e cacy of DTG-based ART is has multiple public health implications. First, ensuring adequate virologic monitoring occurs with DTG-based regimens will remain a priority.…”

Section: Discussionmentioning

confidence: 99%

Reduced efficacy of HIV-1 integrase inhibitors in patients with drug resistance mutations in reverse transcriptase

Siedner¹,

Moorhouse²,

Simmons³

et al. 2020

Preprint

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Background: Little is known about the impact of pre-treatment drug resistance (PDR) to non-nucleoside reverse transcriptase inhibitors (NNRTIs) on the efficacy of second generation integrase inhibitors, now the standard of care drug class for HIV-1 treatment globally.Methods: We conducted next-generation sequencing on stored plasma specimens from the ADVANCE trial collected prior to treatment initiation. Our primary outcome was 96-week virologic success, defined as achievement of a viral load < 1000 copies/mL from 12 weeks, < 200 copies/mL from 24 weeks, and < 50 copies/mL from 48 through 96 weeks. We estimated the impact of PDR, defined by the presence of drug resistance on the World Health Organization (WHO) mutation list, on virologic outcomes in the entire cohort, and stratified by EFV-based versus DTG-based regimens. In sensitivity analyses, we allowed virologic failure with re-suppression, assessed FDA 48 and 96-week Snapshot outcomes, and considered minority resistance mutations (5–20% frequency).Results: Of 1,053 trial participants, 873 (83%) had plasma available and successful sequencing completed. Of these, 288 (33%) were randomized to an EFV-based regimen and 585 (67%) were randomized to a DTG-based regimen. Fourteen percent (122/873) had at least one WHO-defined mutation, of which over 98% (120/122) had NNRTI mutations. NRTI mutations were rare (20/873, 2%). Rates of virologic suppression were significantly lower in those with PDR 65% (73/112) compared to those without PDR (85% [605/713], P < 0.001). This phenomenon was consistent for both EFV-based (60% [12/20] versus 86% [214/248], P = 0.002) and DTG-based ART (61/92 [66%] versus 84% [391/465] P < 0.001, P for interaction by regimen 0.49). In multivariable models adjusted for clinical characteristics and treatment adherence, PDR strongly predicted failure [adjusted OR 0.38 (0.23–0.61), P < 0.001]. Although suppression rates were greater when allowing for non-consecutive visits with failure, PDR significantly predicted greater risk of failure for both regimens in all outcome definitions. We found no effect of mutations at frequencies 5–20% on any of our outcomes.Interpretation: NNRTI resistance prior to treatment initiation is associated with failure of integrase inhibitor-containing first-line regimens. These results portend high rates of first-line treatment failure in sub Saharan Africa, where circulating NNRTI resistance is common.

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“…Failure to disclose HIV status and ART use has been confirmed in at least two settings namely a multinational clinical trial reported by Fogel et al (5) and population studies in Kenya (6) and Uganda (7). This suggests that this phenomenon might be more widespread than previously thought and should be of concern in other blood donor populations or cohort studies of putative EC.…”

Section: Introductionmentioning

confidence: 87%

Discovery of False Elite Controllers: HIV Antibody-Positive RNA-Negative Blood Donors Found To Be on Antiretroviral Therapy

Sykes

Berg

Jacobs

et al. 2019

The Journal of Infectious Diseases

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Background An increase in potential HIV elite controllers (EC) and anecdotal reports of antiretroviral therapy (ART) use among South African blood donors led us to verify EC status. Methods Stored plasma samples from potential EC were tested for ART drugs. Demographic and temporal associations were examined using multivariable logistic regression. Results Of 226 potential EC, 150 (66.4%) had detectable ART with increasing prevalence by year (OR = 7.57 for 2016 vs 2010, 95% confidence interval, 1.96–32.17). Discussion False presumptive EC status due to undisclosed ART represents a growing proportion of potential EC donors in South Africa coincident with the country’s ART rollout.

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The validity of self-reported antiretroviral use in persons living with HIV

Cited by 48 publications

References 16 publications

Migration, hotspots, and dispersal of HIV infection in Rakai, Uganda

Migration, hotspots, and dispersal of HIV infection in Rakai, Uganda

Reduced efficacy of HIV-1 integrase inhibitors in patients with drug resistance mutations in reverse transcriptase

Discovery of False Elite Controllers: HIV Antibody-Positive RNA-Negative Blood Donors Found To Be on Antiretroviral Therapy

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