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Earlier Antiretroviral Therapy Initiation and Decreasing Mortality Among HIV-infected Infants Initiating Antiretroviral Therapy Within 3 Months of Age in South Africa, 2006-2017.

ABSTRACT: BACKGROUND:Early infant diagnosis of HIV and antiretroviral therapy (ART) has been rapidly scaled-up. We aimed to examine the effect of expanded access to early ART on the characteristics and outcomes of infants initiating ART. METHODS:From 9 cohorts within the International epidemiologic Databases to Evaluate AIDS-Southern Africa collaboration, we included infants with HIV initiating ART ?3 months of age between 2006 and 2017. We described ART initiation characteristics and the probability of mortality, loss to follow-up (LTFU) and transfer out after 6 months on ART and assessed factors associated with mortality and LTFU. RESULTS:A total of 1847 infants started ART at a median age of 60 days [interquartile range: 29-77] and CD4 percentage (%) of 27% (18%-38%). Across ART initiation calendar periods 2006-2009 to 2013-2017, ART initiation age decreased from 68 (53-81) to 45 days (7-71) (P < 0.001), median CD4% improved from 22% (15%-34%) to 32% (22-43) (P < 0.001) and the proportion with World Health Organization clinical disease stage 3 or 4 declined from 81.6% to 32.7% (P < 0.001). Overall, the 6-month mortality probability was 5.0% and LTFU was 20.4%. Mortality was 10.6% (95% confidence interval: 7.8%-14.4%) in 2006-2009 and 4.6% (3.1%-6.7%) in 2013-2017 (P < 0.001), with similar LTFU across calendar periods (P = 0.274). Pretreatment weight-for-age Z score <-2 was associated with higher mortality. CONCLUSIONS:Infants with HIV are starting ART younger and healthier with associated declines in mortality. However, the risk of mortality remained undesirably high in recent years. Focused interventions are needed to optimize the benefits of earlier diagnosis and treatment.

SUBMITTER: Iyun V

PROVIDER: S-EPMC7073445 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe benefits of antiretroviral therapy (ART) underpin the recommendations for the early detection of HIV infection and ART initiation. Late initiation (LI) of antiretroviral therapy compromises the benefits of ART both individually and in the community. Indeed, it promotes the transmission of infection and higher HIV-related morbidity and mortality with complicated and costly clinical management. This study aims to analyze the evolutionary trends in the median CD4 count, the median time to initiation of ART, the proportion of patients with advanced HIV disease at the initiation of ART between 2006 and 2017 and their factors.Methods and findingsHIV-positive adults (≥ 16 years old) who initiated ART between January 1, 2006 and December 31, 2017 in 25 HIV care facilities in Kinshasa, the capital of DRC, were eligible. The data were processed anonymously. LI is defined as CD4≤350 cells/μl and/or WHO clinical stage III or IV and advanced HIV disease (AHD), as CD4≤200 cells/μl and/or stage WHO clinic IV. Factors associated with advanced HIV disease at ART initiation were analyzed, irrespective of year of enrollment in HIV care, using logistic regression models. A total of 7278 patients (55% admitted after 2013) with an average age of 40.9 years were included. The majority were composed of women (71%), highly educated women (68%) and married or widowed women (61%). The median CD4 was 213 cells/μl, 76.7% of patients had CD4≤350 cells/μl, 46.1% had CD4≤200 cells/μl, and 59% of patients were at WHO clinical stages 3 or 4. Men had a more advanced clinical stage (p <0.046) and immunosuppression (p<0.0007) than women. Overall, 70% of patients started ART late, and 25% had AHD. Between 2006 and 2017, the median CD4 count increased from 190 cells/μl to 331 cells/μl (p<0.0001), and the proportions of patients with LI and AHD decreased from 76% to 47% (p< 0.0001) and from 18.7% to 8.9% (p<0.0001), respectively. The median time to initiation of ART after screening for HIV infection decreased from 40 to zero months (p<0.0001), and the proportion of time to initiation of ART in the month increased from 39 to 93.3% (p<0.0001) in the same period. The probability of LI of ART was higher in married couples (OR: 1.7; 95% CI: 1.3-2.3) (p<0.0007) and lower in patients with higher education (OR: 0.74; 95% CI: 0.64-0.86) (p<0.0001).ConclusionDespite increasingly rapid treatment, the proportions of LI and AHD remain high. New approaches to early detection, the first condition for early ART and a key to ending the HIV epidemic, such as home and work HIV testing, HIV self-testing and screening at the point of service, must be implemented.

Project description:The relationship between the timing of the initiation of antiretroviral therapy (ART) after infection with human immunodeficiency virus type 1 (HIV-1) and the recovery of CD4+ T-cell counts is unknown.In a prospective, observational cohort of persons with acute or early HIV-1 infection, we determined the trajectory of CD4+ counts over a 48-month period in partially overlapping study sets: study set 1 included 384 participants during the time window in which they were not receiving ART and study set 2 included 213 participants who received ART soon after study entry or sometime thereafter and had a suppressed plasma HIV viral load. We investigated the likelihood and rate of CD4+ T-cell recovery to 900 or more cells per cubic millimeter within 48 months while the participants were receiving viral-load-suppressive ART.Among the participants who were not receiving ART, CD4+ counts increased spontaneously, soon after HIV-1 infection, from the level at study entry (median, 495 cells per cubic millimeter; interquartile range, 383 to 622), reached a peak value (median, 763 cells per cubic millimeter; interquartile range, 573 to 987) within approximately 4 months after the estimated date of infection, and declined progressively thereafter. Recovery of CD4+ counts to 900 or more cells per cubic millimeter was seen in approximately 64% of the participants who initiated ART earlier (?4 months after the estimated date of HIV infection) as compared with approximately 34% of participants who initiated ART later (>4 months) (P<0.001). After adjustment for whether ART was initiated when the CD4+ count was 500 or more cells per cubic millimeter or less than 500 cells per cubic millimeter, the likelihood that the count would increase to 900 or more cells per cubic millimeter was lower by 65% (odds ratio, 0.35), and the rate of recovery was slower by 56% (rate ratio, 0.44), if ART was initiated later rather than earlier. There was no association between the plasma HIV RNA level at the time of initiation of ART and CD4+ T-cell recovery.A transient, spontaneous restoration of CD4+ T-cell counts occurs in the 4-month time window after HIV-1 infection. Initiation of ART during this period is associated with an enhanced likelihood of recovery of CD4+ counts. (Funded by the National Institute of Allergy and Infectious Diseases and others.).

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Earlier Antiretroviral Therapy Initiation and Decreasing Mortality Among HIV-infected Infants Initiating Antiretroviral Therapy Within 3 Months of Age in South Africa, 2006-2017.

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