Evaluation of treatment outcomes for patients on first‐line regimens in <scp>US</scp> President's Emergency Plan for <scp>AIDS</scp> Relief (<scp>PEPFAR</scp>) clinics in <scp>U</scp>ganda: predictors of virological and immunological response from <scp>RV</scp>288 analyses

Crawford, Keith W.; Wakabi, Salim; Magala, Fred; Kibuuka, Hannah; Liu, M.; Hamm, Te

doi:10.1111/hiv.12177

Cited by 19 publications

(20 citation statements)

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“…The reasons for this increased risk are uncertain, although they might relate to socioeconomic conditions or inconsistent prioritisation of ART adherence over other challenges of daily life. We are uncertain about extrapolation of our findings to Africans living in sub-Saharan Africa, because the lower socioeconomic conditions and greater hardships resulting from taking time from work and getting to a clinic in these settings might mean that rebound rates would be higher than in our study 24, 25, 26. However, the proportion of people reported to be on ART and to have viral loads of less than 1000 copies per mL from studies and routine data from sub-Saharan Africa, 12 most recently from the population-based HIV impact assessments surveys in Malawi (91%), Zimbabwe (87%), and Zambia (89%), suggest that durability of virological suppression could be at least as great in Africa as in the UK 27 …”

Section: Discussionmentioning

confidence: 62%

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: Discussionmentioning

confidence: 62%

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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“…A recent analysis of cohorts from the United States and Europe also found an increased risk in treatment failure in patients started on nevirapine as compared to efavirenz-based regimens [31]. In addition, a recent large analysis of a South African cohort showed that patients started on nevirapine were 80% more likely to experience failure as compared to those started on efavirenz, regardless of the nucleoside backbone drug used [32], while in a recent cross-sectional study from Uganda, use of efavirenz was associated with a 50% decrease in risk of treatment failure [33]. We hypothesize that although nevirapine performance in attaining initial virologic suppression and short-term sustainment of virologic suppression seems to be inferior as compared to efavirenz, this effect fades away over time once suppression is achieved and maintained.…”

Section: Discussionmentioning

confidence: 99%

First‐line antiretroviral therapy durability in a 10‐year cohort of naïve adults started on treatment in Uganda

Castelnuovo

Kiragga

Mubiru

et al. 2016

Journal of the International AIDS Society

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IntroductionThe majority of studies from resource-limited settings only report short-term virological outcomes of patients on antiretroviral treatment (ART). We aim to describe the long-term durability of first-line ART and identify factors associated with long-term virological outcomes.MethodsAt the Infectious Diseases Institute in Kampala, Uganda, 559 adult patients starting ART in 2004 were enrolled into a research cohort and monitored with viral load (VL) testing every six months for 10 years. We report the proportion and cumulative probability of 1) achieving virologic suppression (at least one VL <400 copies/ml); 2) experiencing virologic failure in patients who achieved suppression (two consecutive VLs >1000 copies/ml or one VL >5000, for those without a subsequent one); 3) treatment failure (not attaining virologic suppression or experiencing virologic failure). We used Cox regression methods to determine the characteristics associated with treatment failure. We included gender, baseline age, WHO stage, body mass index, CD4 count, propensity score for initial ART regimen, VL, time-dependent CD4 count and adherence.ResultsOf the 559 patients enrolled, 472 (84.8%) had at least one VL (67 died, 13 were lost to follow-up, 4 transferred, 2 had no VL available); 73.6% started on d4T/3TC/nevirapine and 26.4% on AZT/3TC/efavirenz. Patients in the two groups had similar characteristics, except for the higher proportion of patients in WHO Stage 3/4 and higher VL in the efavirenz-based group. Four hundred thirty-nine (93%) patients achieved virologic suppression with a cumulative probability of 0.94 (confidence interval (CI): 0.92–0.96); 74/439 (16.9%) experienced virologic failure with a cumulative probability of 0.18 (CI: 0.15–0.22). In the multivariate analysis, initial d4T/3TC/nevirapine regimen (hazard ratio (HR): 3.02; CI: 3.02 (1.66–5.44, p<0.001)) and baseline VL ≥5 log10 copies/ml (HR: 2.29; CI: 1.29–4.04) were associated with treatment failures; patients of older age (HR: 0.87 per five-year increase; CI: 0.77–0.99), with adherence >95% (HR: 0.04; CI: 0.02–0.11) and with higher time-dependent CD4 count (HR: 0.94 per 50 cells/µl increase; CI: 0.92–0.99, p<0.001) were less likely to experience treatment failure.ConclusionsThe long-term virological outcomes from this cohort are promising and comparable to those from research-rich settings. Our results provide further evidence that efavirenz is associated with better virological outcomes.

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“…Spijkervet's mucositis index was used for quantifying the oral ulcerations and mucosal lesions. [1][2][3][4][5][6][7][8][9][10][11] Patient morbidity could be reduced by early diagnosis of HSV infections and treatment of immunocompromised HIV patients with acyclovir. Thus in all HIV + patients, diagnostic culture should be recommended for herpes simplex virus for all oral ulcers regardless of their location.…”

Section: Discussionmentioning

confidence: 99%

“…There was a positive association of virological suppression with efavirenz use and improvements in CD4 cell percentage and total lymphocyte count. 9 Oral health measures are to be effectively formulated for the HIV-infected individuals with the help of the reports from both developing and developed countries, as HIV infection is a major global health problem. Reports from developed countries on oral lesions in HIV infection are well-documented contrary to the inadequate reports of developing countries.…”

Section: Introductionmentioning

confidence: 99%

Low current Cd4+T cell count: prediction, for persistent herpetic gingivostomatitis in HIV-positive patients under antiretroviral therapy

Narendra¹,

Sahani²,

Das³

et al. 2017

Int J Basic Clin Pharmacol

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Background: Oral viral lesions associated with HIV infection are important since they affect the quality of life of the patient and are useful markers of disease progression and immunosuppression. The purpose of this study was to correlate the persistence of herpetic gingivostomatitis lesions with the current CD4+ T cell count for adherence of HIV-infected individuals to anti retroviral therapy (ART) and antiviral therapy.Methods: 302 HIV +ve patients developing oral ulcers were included in this study. The herpes simplex viral infections associated with the oral manifestations were detected through Immuno histochemical staining. The quantitative analysis of oral ulceration was done by using mucositis index.CD4T cell count was correlated with clinical manifestations of extensiveness of oral ulcers, acute febrile condition and other constitutional symptoms during follow up of cases for the treatment with anti viral therapies.Results: Association of herpes simplex viral infections was found in 72 out of 302 HIV+ ve cases. All the HSV +ve patients developed extensive oral mucsal lesions during the 1st week. Extensive lesions developed within 7 days in patients with CD4 count <200 due to HSV infection, remained more or less unchanged in the oral cavity up to 90 days although they were receiving antiretroviral and antiviral therapies. In HIV + patients with CD4 count >500, manifestation of mucosal ulcers due to acute herpetic gingivostomatitis was limited to a period of 1 to 2 weeks. Patients with CD4 count >200 <500 did not follow a definite pattern.Conclusions: Persistent oropharyngeal mucosal ulcers along with acute febrile condition due to herpes simplex virus infection are associated with low CD4 T cell count in HIV + patients under antiretroviral therapy.

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Evaluation of treatment outcomes for patients on first‐line regimens in US President's Emergency Plan for AIDS Relief (PEPFAR) clinics in Uganda: predictors of virological and immunological response from RV288 analyses

Cited by 19 publications

References 56 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

First‐line antiretroviral therapy durability in a 10‐year cohort of naïve adults started on treatment in Uganda

Low current Cd4+T cell count: prediction, for persistent herpetic gingivostomatitis in HIV-positive patients under antiretroviral therapy

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