Date Published: May 31, 2019
Publisher: Public Library of Science
Author(s): Tendesayi Kufa, Zara Shubber, William MacLeod, Simbarashe Takuva, Sergio Carmona, Jacob Bor, Marelize Gorgens, Yogan Pillay, Adrian Puren, Jeffrey W. Eaton, Nicole Fraser-Hurt, Richard John Lessells.
We describe CD4 count recovery among HIV positive individuals who initiated antiretroviral therapy (ART) with and without severe immune suppression using complete laboratory data from South Africa’s national HIV treatment programme between 2010 and 2014 and discuss implications for CD4 count monitoring.
Retrospective analysis of routinely collected laboratory data from South Africa’s National Health Laboratory Service (NHLS). A probabilistic record linkage algorithm was used to create a cohort of HIV positive individuals who initiated ART between 2010 and 2014 based on timing of CD4 count and viral load measurements. A CD4 count < 50 copies/μl at ART initiation was considered severe immunosuppression. A multivariable piecewise mixed-effects linear regression model adjusting for age, gender, year of starting ART, viral suppression in follow up and province was used to predict CD4 counts during follow up. 1,070,900 individuals had evidence of starting ART during 2010–2014 and met the criteria for inclusion in the cohort -46.6% starting ART with CD4 < 200 cells/μl and 10.1% with CD4 < 50 cells/ μl. For individuals with CD4 counts < 200 cells/μl, predicted CD4 counts > 200 cells/μl, >350 cells/μl and >500 cells/μl corresponded with mean follow up durations of 1.5 years (standard deviation [s.d] 1.1), 1.9years (s.d 1.2) and 2.1 years (s.d 1.3 years). For those with CD4 counts < 50 cells/μl, predicted CD4 count above these threshold corresponded with mean follow up durations of 2.5 years (s.d 0.9 years), 4.4 years (s.d 0.4 years) and 5.0 years (s.d 0.1years) for recovery to the same thresholds. CD4 count recovery varied mostly with duration on ART, CD4 count at the start of ART and gender. For individuals starting with ART with severe immunosuppression, CD4 recovery to 200cells/μl did not occur or took longer than 12 month for significant proportions. CD4 monitoring and interventions recommended for advanced HIV disease should continue until full recovery.
Antiretroviral therapy (ART) reduces mortality and morbidity among HIV positive individuals as well as the onward transmission of HIV. [1–3] Untreated HIV infection is associated with decreases in CD4 count levels and increases in HIV plasma viral loads. The initiation of ART is typically followed by declines in viral loads and increases in CD4 count. CD4 count recovery following ART initiation is rapid in the first few months, as a result of redistribution of the existing CD4 cells from lymphoid organs, and then slows down as new CD4 cells are made as a result of thymic activation.[5,6] A number of factors are known to affect the extent of CD4 count recovery post ART initiation. These include CD4 count at ART initiation, gender -with males found to have lower CD4 recovery compared to females in some settings,  older age, [8,9] duration on ART and ART regimen,  as well as genetic and environmental factors that contribute to immune activation.
Some of the methods of this paper have been described elsewhere . Briefly the South African government has been providing ART at public health facilities through the comprehensive care, management and treatment (CCMT) programme since 2004. At inception of the programme, HIV positive individuals with CD4 counts <200 cells/μl OR those with WHO stage III/IV were eligible for ART while CD4 count and viral load monitoring was conducted at baseline and every six months. By the end of 2016, the guidelines recommended that all HIV positive individuals be started on ART irrespective of CD4 count, that the CD4 count be measured at ART initiation and at 12 months only and that VL be measured at 6 months, 12 months and annually thereafter.[25,26] The growth of the CCMT programme over this time has been exponential, from a few NGO supported ART sites in 2004 to 3775 public sector facilities in the country and supported by the National Health Laboratory Service’s (NHLS) 60 CD4 count and 17 viral load laboratories. We used a multivariable piecewise mixed-effects linear regression model adjusting for age, gender, eligible baseline CD4 count, virological suppression during follow up and province to predict the extent and magnitude of CD4 count recovery among individuals aged >15 years old initiating ART. Our analyses found that across all ages, provinces and baseline CD4 counts, CD4 recovery was lower and slower among males compared to females even after adjusting for CD4 count at ART start as well as duration on ART. The analysis also found that among individuals with CD4 counts <50 cells/μl at the start of ART, the predicted mean CD4 count after 12 months post ART initiation remained below 200 cells/μl and that it took a mean of 2.5 years for recovery to 200 cells/μl in this group. Our analyses also consistently found greater CD4 count recovery in KwaZulu Natal, Gauteng and Free State provinces. Source: http://doi.org/10.1371/journal.pone.0217742