Significant Reduction in HIV Virologic Failure During a 15-Year Period in a Setting With Free Healthcare Access

Delaugerre, Constance; Ghosn, Jade; Pialoux, Gilles; Cuzin, Lise; Ménard, Amélie; Abgrall, Sophie; Barin, Françis; Billaud, Éric; Boué, François; Boyer, L.; Cabie, André; Caby, Fabienne; Costagliola, Dominique; Cotte, Laurent; Truchis, Pierre de; Duval, Xavier; Duvivier, Claudine; Enel, P.; Grill, Jacques; Gaud, C.; Gilquin, Jacques; Grabar, Sophie; Khuong, M. A.; Launay, Odile; Bail, J. Le; Mahamat, Aba; Mary‐Krause, Murielle; Matheron, Sophie; Meynard, Jean Luc; Pavie, Juliette; Piroth, Lionel; Poizot‐Martin, Isabelle; Pradier, Christian; Reynes, Jacques; Rouveix, É.; Salat, E.; Simon, Anne; Tattevin, Pierre; Tissot‐Dupont, Hervé; Viard, Jean‐Paul; Viget, N.; Bronnec, C.; Martin, David; Guiguet, Marguerite; Lang, Sylvie; Lièvre, Laurence; Selinger-Leneman, Hana; Lacombe, Jean‐Marc; Potard, Valérie

doi:10.1093/cid/ciu834

Cited by 31 publications

(25 citation statements)

References 44 publications

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“…In agreement with other studies, we found that older age15, 16 and later calendar year13, 20 at start of ART were associated with a reduced risk of viral rebound. Older age is associated with better adherence,21, 22 which could explain the reduced rate of rebound in older people in our study.…”

Section: Discussionsupporting

confidence: 93%

Durability of viral suppression with first-line antiretroviral therapy in patients with HIV in the UK: an observational cohort study

O'Connor¹,

Chadwick²,

Dunn³

et al. 2017

The Lancet HIV

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SummaryBackgroundThe length of time that people with HIV on antiretroviral therapy (ART) with viral load suppression will be able to continue before developing viral rebound is unknown. We aimed to investigate the rate of first viral rebound in people that have achieved initial suppression with ART, to determine factors associated with viral rebound, and to use these estimates to predict long-term durability of viral suppression.MethodsThe UK Collaborative HIV Cohort (UK CHIC) Study is an ongoing multicentre cohort study that brings together in a standardised format data on people with HIV attending clinics around the UK. We included participants who started ART with three or more drugs and who had achieved viral suppression (≤50 copies per mL) by 9 months after the start of ART (baseline). Viral rebound was defined as the first single viral load of more than 200 copies per mL or treatment interruption (for ≥1 month). We investigated factors associated with viral rebound with Poisson regression. These results were used to calculate the rate of viral rebound according to several key factors, including age, calendar year at start of ART, and time since baseline.ResultsOf the 16 101 people included, 4519 had a first viral rebound over 58 038 person-years (7·8 per 100 person-years, 95% CI 7·6–8·0). Of the 4519 viral rebounds, 3105 (69%) were defined by measurement of a single viral load of more than 200 copies per mL, and 1414 (31%) by a documented treatment interruption. The rate of first viral rebound declined substantially over time until 7 years from baseline. The other factors associated with viral rebound were current age at follow-up and calendar year at ART initiation (p<0·0001) and HIV risk group (p<0·0001); higher pre-ART CD4 count (p=0·0008) and pre-ART viral load (p=0·0003) were associated with viral rebound in the multivariate analysis only. For 1322 (29%) of the 3105 people with observed viral rebound, the next viral load value after rebound was 50 copies per mL or less with no regimen change. For HIV-positive men who have sex with men, our estimates suggest that the probability of first viral rebound reaches a plateau of 1·4% per year after 45 years of age, and 1·0% when accounting for the fact that 29% of viral rebounds are temporary elevations.InterpretationA substantial proportion of people on ART will not have viral rebound over their lifetime, which has implications for people with HIV and the planning of future drug development.FundingUK Medical Research Council.

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Section: Discussionsupporting

confidence: 93%

Durability of viral suppression with first-line antiretroviral therapy in patients with HIV in the UK: an observational cohort study

O'Connor¹,

Chadwick²,

Dunn³

et al. 2017

The Lancet HIV

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“…27 To build on the near universal reach of community-based HIV testing, decentralized ART delivery services have the potential to overcome bottlenecks in care at overburdened clinics. 28 Current ART regimens are often once-daily, safe and well-tolerated, 29 thus, moving ART initiation and refill supply into the community, in addition to testing, would overcome barriers to care for HIV-positive persons who do not need clinic services. 19 To reach the UNAIDS goal of 73% of HIV-positive persons virally suppressed 11 and 80% of HIV-negative men accessing male circumcision, 9 requires highly effective combination HIV prevention.…”

Section: Discussionmentioning

confidence: 99%

Uptake of antiretroviral therapy and male circumcision after community-based HIV testing and strategies for linkage to care versus standard clinic referral: a multisite, open-label, randomised controlled trial in South Africa and Uganda

et al. 2016

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Background We hypothesized that community-based HIV testing with counselor support and point-of-care CD4 count testing would increase uptake of antiretroviral therapy (ART) and male circumcision. Methods We conducted a randomized study of linkage strategies following community-based HIV testing in rural South Africa and Uganda. HIV-positive persons were randomized to 1) lay counselor follow-up home visits, lay counselor clinic linkage facilitation, or standard clinic referral; and then to either 2) point-of-care CD4 testing, or referral for CD4. HIV-negative uncircumcised men who could receive secure text messages were randomized to text message reminders, lay counselor visits, or referral. The primary outcomes were viral suppression at 9 months in HIV-positive persons and uptake of male circumcision by HIV-negative, uncircumcised men at 3 months. The study was registered at ClinicalTrials.gov (NCT02038582). Findings Between June 2013 and February 2015, 15,332 participants were tested; 1,325 HIV-positive persons and 750 HIV-negative uncircumcised men were randomized to linkage strategies. Among HIV-positive persons, overall clinic linkage was 93% (1,218/1,303) but ART initiation was only 37% (488/1,303). The proportion of persons who were virally suppressed ranged from 47%-52% (214/422 in the clinic referral arm, 219/419 in the clinic facilitation arm, and 202/431 in the lay counselor follow-up arm; p=0.668 and p=0.273, for the clinic facilitation and lay counselor follow-up arms, respectively, compared with clinic referral). There was no difference in viral suppression at 9 months by study arm. In the male circumcision clinic referral (standard of care) arm, 62/224 men (28%) were circumcised, compared to 137/284 (48%) in the text message reminder arm (RR=1.72, 95% CI 1.36-2.17) and 106/226 (47%) in the lay counselor follow-up arm (RR=1.67, 95% CI 1.29-2.14). Interpretation All the community-based strategies achieved very high rates of linkage of HIV positive persons to HIV clinics, approximately one-third of whom initiated ART, and approximately half were virally suppressed by 9 months. Clinic barriers to ART initiation must be addressed in future strategies to increase knowledge of HIV serostatus and linkage to HIV care. Uptake of male circumcision was almost two-fold higher among men who received text message reminders or lay counselor visits.

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“…Virologic failure was also associated with initiating treatment in earlier calendar years, which is consistent with trends seen in other studies. 24,26,27 Improvements in efficacy and tolerability of antiretroviral agents, changes in clinical care such as increased clinician experience, and other unmeasured variables may be contributing to this trend. In contrast, incidence of major regimen change increased over time.…”

Section: Discussionmentioning

confidence: 99%

Incidence of virological failure and major regimen change of initial combination antiretroviral therapy in the Latin America and the Caribbean: an observational cohort study

César¹,

Jenkins²,

Shepherd³

et al. 2015

The Lancet HIV

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Background Access to combination antiretroviral therapy (cART) is expanding in Latin America and the Caribbean (LAC). There is little information in this region regarding incidence of and factors associated with regimen failure and regimen change. Methods Antiretroviral-naïve adults starting cART from 2000-2014 at sites in seven countries throughout LAC were included. Cumulative incidence of virologic failure and major regimen change were estimated with death considered a competing event. Findings 14,027 cART initiators (60% male, median age 37 years, median CD4 156 cells/mm3, median HIV-RNA 5·0 log10 copies/mL, and 28% with clinical AIDS) were followed for a median of 3·9 years. 1,719 patients presented virologic failure and 1,955 had a major regimen change. Excluding GHESKIO-Haiti (which did not regularly measure HIV-RNA), cumulative incidence of virologic failure was 7·8%, 19·2%, and 25·8% at one, three, and five years after cART initiation, respectively; cumulative incidence of major regimen change was 5·9%, 12·7%, and 18·2%. Incidence of major regimen change at GHESKIO-Haiti at five years was 10·7%. Virologic failure was associated with younger age (adjusted hazard ratio[aHR]=2·03 for 20 vs. 40 years; 95% confidence interval[CI] 1·68-2·44), infection through injection-drug use (IDU) (aHR=1·60; 95%CI 1·02-2·52), initiation in earlier calendar years (aHR=1·28 for 2002 vs. 2006; 95%CI 1·13-1·46), and starting with a boosted protease inhibitor (aHR=1·17 vs. non-nucleoside reverse transcriptase inhibitor; 95%CI 1·00-1·64). Interpretation Incidence of virologic failure was generally lower than in North America/Europe. Our results suggest the need to design strategies to reduce failure and major regimen change among younger patients and those with a history of IDU. Funding US National Institutes of Health: U01 AI069923.

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Significant Reduction in HIV Virologic Failure During a 15-Year Period in a Setting With Free Healthcare Access

Cited by 31 publications

References 44 publications

Durability of viral suppression with first-line antiretroviral therapy in patients with HIV in the UK: an observational cohort study

Durability of viral suppression with first-line antiretroviral therapy in patients with HIV in the UK: an observational cohort study

Uptake of antiretroviral therapy and male circumcision after community-based HIV testing and strategies for linkage to care versus standard clinic referral: a multisite, open-label, randomised controlled trial in South Africa and Uganda

Incidence of virological failure and major regimen change of initial combination antiretroviral therapy in the Latin America and the Caribbean: an observational cohort study

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