Starting Tx immediately after diagnosis not harmful for adolescents

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A lack of lengthy preparation before starting HIV treatment does not result in an increased risk of death or loss to follow-up in adolescents, a study from Zimbabwe shows.

The researchers say their findings call into question the assumption that all adolescents need intensive preparation before starting antiretroviral treatment.

Preparation for beginning antiretroviral treatment varies widely. In some settings, people are offered the opportunity to begin treatment on the day they are diagnosed with HIV. A trial conducted in Haiti found that people who began treatment on the day of diagnosis were more likely to stay in care and more likely to have a viral load below 50 copies/ml after one year.

Guidelines for improving retention in care and treatment adherence recommend preparation for treatment by counselling and education, in order to ensure that young people have a good understanding of why it is necessary to take antiretroviral treatment, and how to manage issues such as confidentiality, disclosure, sexuality and adherence.
Preparation for treatment may take several weeks or even months, posing a risk that young people will either be lost to care or will experience disease progression. Adolescents with HIV may be at particular risk in these circumstances.

An analysis presented at the 2014 International AIDS Conference showed that whereas Aids deaths had fallen by a third in non-adolescents between 2005 and 2012, they increased by 50% in adolescents. Boys aged 15-19 were twice as likely to die as girls of the same age and were three times more likely to die of an Aids-defining illness in South Africa.

HIV infection may not lead to symptomatic illness for 10-15 years, meaning that infection around the time of birth can go undetected until the onset of illness in adolescence. Past weaknesses in infant HIV diagnosis and a lack of HIV testing activity targeted at adolescents place this age group at especially high risk of late presentation, by which time the need for treatment is urgent.

US research also shows that even after diagnosis, adolescents are at higher risk of dropping out of care before starting treatment than adults, and a large US cohort study has found that only one-third of young people aged 12-24 were retained in care and started treatment after diagnosis.

To address the question of whether fast initiation of treatment results in poorer outcomes for adolescents, researchers associated with Médecins sans Frontières conducted a retrospective cohort study of all adolescents diagnosed with HIV who became eligible to start antiretroviral treatment between 2004 and 2012 in Bulawayo, Zimbabwe.

Throughout the study period adolescents (aged 10-18 years) were eligible to start treatment if they had a CD4 cell count of 200 or below, and/or symptomatic HIV disease (World Health Organisation [WHO] stages 3 or4). Eligible individuals were required to attend two or three treatment preparedness visits before starting treatment.

Although WHO treatment guidelines now recommend treatment for everyone with HIV infection, these findings in people who started treatment very late by today’s standard are likely to remain relevant to adolescent care due to the high frequency of late presentation.

Out of 2,184 adolescents diagnosed with HIV and enrolled in HIV care during the study period, 1,506 (69%) became eligible for antiretroviral treatment and 1,499 had data available for analysis. 52% were female and 87% of those eligible for treatment had symptomatic disease. Half of those who started treatment had a CD4 cell count recorded; the median CD4 cell count at the point treatment was recommended was 145 cells/mm3. 10% of those eligible for antiretroviral therapy did not start treatment.

In this group of predominantly sick individuals, the median time to treatment initiation after confirmation of antiretroviral therapy eligibility was 17 days. Compared to those who initiated treatment within 7-14 days of being confirmed as eligible, those who started treatment less than 7 days or more than 14 days, 1 month or 2 months after being confirmed as eligible had no difference in their risk of loss to follow-up. The cumulative risk of death during 24 months of follow-up was higher in those who started less than 7 days after being confirmed as eligible, but the researchers argue that this finding is explained by the fact that health care workers prioritised the sickest people for rapid treatment initiation, and after adjusting for CD4 cell count, disease stage, sex and age, this difference was not significant.

“The fact that we did not find elevated [loss to follow up] in patients who initiated rapidly suggests that, contrary to current understanding, a long preparatory process is not needed to keep post-initiation LTFU low,” the authors write. “There is still no evidence that patients actually benefit from the currently prevailing initiation model with multiple obligatory preparation visits. Patients’ individual readiness should remain the guiding principle,” they conclude.

Abstract
Background: Age-specific retention challenges make ART initiation in adolescents difficult, often requiring a lengthy preparation process. This needs to be balanced against the benefits of starting treatment quickly. The optimal time to initiation duration in adolescents is currently unknown.
Objective: To assess the effect of time to ART initiation on mortality and loss to follow-up (LTFU) among treatment eligible adolescents.
Methods: We conducted a retrospective cohort analysis among 1,499 ART eligible adolescents aged >=10 to Results: Median follow-up duration was 1.6 years. Mortality HRs of patients who initiated at 0-<=7 days, >14 days to <=1 month, >1-<=2 months, >2 months, and prior to initiation were 1.59, 1.19, 1.56, 1.08, and 0.94, respectively, compared to the reference group of 7-14 days. LTFU HRs were 1.02, 1.07, 0.85, 0.97, and 3.96, respectively. Among patients not on ART, 88% of deaths and 85% of LTFU occurred during the first three months after becoming ART eligible, but only 37% and 29% among adolescents on ART, respectively.
Conclusions: Neither mortality or LTFU was associated with varying time to ART. The initiation process can be tailored to the adolescents[spacing acute] needs and individual life situations without risking to increase poor treatment outcomes. Early mortality was high despite rapid ART initiation, calling for earlier rather than faster initiation through HIV testing scale-up.

Authors
Vogt, Florian; Rehman, Andrea; Kranzer, Katharina; Nyathi, Mary; Van Griensven, Johan; Dixon, Mark; Ndebele, Wedu; Gunguwo, Hilary; Colebunders, Robert; Ndlovu, Mbongeni; Apollo, Tsitsi; Ferrand, Rashida A

Aidsmap material
Journal of Acquired Immune Deficiency Syndrome abstract


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