CD4 count recovery and associated factors among individuals enrolled in the South African antiretroviral therapy programme: An analysis of national laboratory based data

Abstract

Background 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. Methods 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. Results 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. Conclusion 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.

Monitoring HIV infection in Minas Gerais state: 15-year assessment of adults living with HIV initiating Antiretroviral Therapy

“…Finally, the increasing demand for laboratory monitoring generated from earlier ART initiation can be a challenge for low- and middle-income countries in providing adequate coverage for both T-CD4+ counts and VL tests. In an African study to predict T-CD4+ count recovery, the number of participants was reduced by 83% (from 3,981,104 to 1,070,900) mainly due to the lack of T-CD4+ lymphocyte exams 42 . Similar results can be observed in Sub-Saharan Africa, where 11 million PLHIV are receiving ART.…”

Immune recovery after antiretroviral therapy initiation: a challenge for people living with HIV in Brazil

“…This could partially explain the borderline effect on the time to immune recovery according to regions. Concerning gender, there are several evidences indicating that time to achieve immune recovery is usually higher among men than women 8,35,36 . Although, our findings showed that the median time and HR to immune recovery was barely influenced by gender.…”

“…Lastly, the increased demand for laboratory monitoring, generated from the early ART initiation, can be a challenge for low-and middle-income countries in providing adequate coverage of both T-CD4+ count and viral load tests. In an African study aimed at predicting T-CD4+ count recovery, the number of participants was reduced by 83% (from 3,981,104 to 1,070,900) mainly due to the missing data on T-CD4+ lymphocytes exams 8 . National studies of Melchior et al 47 evaluated the quality of HIV public healthcare in seven Brazilian States between 2000 and 2001 (N = 92,400 patients: 72% of all Brazilian HIV-patients); they showed that T-CD4+ counts and viral load measurements were available in the majority of services, and yet approximately 50% did not perform those exams.…”

“…Multifactorial determinants may delay, or prevent, immune recovery even after effective response to ART; and the mechanisms that lead to discordant immune response are not well understood 4,7 . Older age, persistent immune activation, low level of continuous HIV replication, coinfections, and low pre-therapeutic and lower T-CD4+ counts after ART initiation may predispose individuals to have poor immune recovery 7,8,9 . Additionally, some studies have shown that antiretroviral agents -such as zidovudine -may be toxic for hematopoietic progenitor cells 2 , further delaying immune recovery.…”

Immune reconstitution inflammatory syndrome‐associated Graves disease in HIV‐infected patients: clinical characteristics and response to radioactive iodine therapy

“…[2–4] Despite the widespread availability of safe and effective ART and the current recommendation of treating all HIV‐infected patients regardless of their CD4 cell level, a significant proportion of patients are diagnosed with HIV and commenced on ART at a very advanced disease stage. [5] For this reason IRIS remains a condition of clinical significance even in the ART era. [4] In IRIS, immune reconstitution manifesting as a rise in CD4 cell level that occurs in response to effective ART leads to host recognition of foreign antigen (from microbial agents and tumours), causing antigen‐specific immune responses.…”