Change of treatment guidelines and evolution of ART initiation in rural South Africa: data of a large HIV care and treatment programme

Abstract

BackgroundWhile WHO recommendations are to treat people earlier and earlier, it will considerably increase the number of HIV infected people eligible for antiretroviral therapy (ART). In South Africa, a country which carries one of the highest HIV burden worldwide, very few studies are available on the impact of the ART guidelines on time to ART initiation in both individuals with low CD4 count and those newly eligible for ART. We thus aimed to describe ART initiation percentages in a large HIV programme in rural KwaZulu-Natal, South Africa, according to the temporal changes of national ART eligibility guidelines from 2007 to 2012.MethodsAdults who accessed the decentralized Hlabisa HIV treatment programme in 2007–2012 were included. Three periods following the temporal change of ART eligibility guidelines were defined (Period 1: until April 2010; Period 2: April 2010 - July 2011; Period 3: from August 2011). Percentages of ART initiation within three months of programme entry were estimated in men, in women of childbearing age (<40 years old) and in older women, and stratifying by CD4 count. Trend tests and logistic regression models were used to study the effects of change of guidelines on ART initiation percentages.ResultsIn individuals with CD4 count ≤200 cells/μL (N = 5709 men, N = 6743 women <40 years old and N = 2017 older women), percentages of ART initiation did not differ over time (p trend = 0.25; 0.28; and 0.14, respectively). In individuals with CD4 count = 201–350 cells/μL (N = 2680 men, N = 6086 women <40 years old and N = 1415 older women), percentages of ART initiation significantly increased over time (p trend <0.01 for the three groups): from 6 % in Period 1 to 20 % in Period 2 to 40 % in Period 3 in women of childbearing age, and from 7 % to 8-10 % to 42 % in men and in older women.ConclusionsAs temporal changes of guidelines, percentages of ART initiation significantly increased in newly ART eligible people and did not decrease in individuals with very low CD4 counts. It will be crucial to continue verifying the evolution of these percentages of ART initiation with future recommendations reaching near-to-universal access to ART, to ensure that individuals most in need of ART receive it.

Do HIV treatment eligibility expansions crowd out the sickest? Evidence from rural South Africa

“…One study in Rwanda found an increase in the median CD4 count at enrolment in care following extension of ART eligibility to patients with CD4 ≤ 350 cells/μl, but did not examine the specific impact on the sickest patients 27. Another study in rural KwaZulu‐Natal, South Africa, found that treatment initiation within 3 months of first clinic visit did not change for the sickest patients after this guideline change 28; however, this analysis did not control for long‐term secular trends. While crowd‐out effects seem plausible under a test‐and‐treat approach, there is no evidence to support this notion, even from previous guideline changes.…”

Test and Start for People Living With HIV and Who Use Drugs in Low and Middle Income Countries

“…There was also a reduction of the risk of death and co-morbidities, such as tuberculosis, when starting anti-retroviral treatment at times earlier in infection at higher CD4 counts. Studies also showed that starting anti-retroviral treatment at the initiation of care at higher CD4 counts, rather than deferring to start at a CD4 count of 250 cells/mm 3 , reduced the risk of disease progression. Based on these findings, the CD4 threshold to start anti-retroviral treatment in most national guidelines was raised to 350 cells/mm 3 by 2012 and later 500/ mm 3 around 2009-2013.…”

“…Studies also showed that starting anti-retroviral treatment at the initiation of care at higher CD4 counts, rather than deferring to start at a CD4 count of 250 cells/mm 3 , reduced the risk of disease progression. Based on these findings, the CD4 threshold to start anti-retroviral treatment in most national guidelines was raised to 350 cells/mm 3 by 2012 and later 500/ mm 3 around 2009-2013. 4,6,7 International guidelines have gone further and recommended treating all HIV-infected adults regardless of their CD4 count.…”

“…1 This "treat all" recommendation removes any and all limitations for receiving anti-retroviral treatment for all people living with HIV, including people who use drugs. Past treatment guidelines on when to start anti-retroviral treatment, relied on findings from early clinical trials of treatment naive people living with HIV, by comparing the initiation of anti-retroviral treatment during chronic infection at CD4 levels at or between 200-350 cells/ mm 3 . 4,5 The findings of these studies showed a statistically significant reduction in death when starting anti-retroviral treatment at higher CD4 counts.…”

“…[1][2][3][4] The most recent international treatment guidelines by the WHO recommend, for the first time, that all people living with HIV be provided antiretroviral treatment. 1 This "treat all" recommendation removes any and all limitations for receiving anti-retroviral treatment for all people living with HIV, including people who use drugs.…”