Up to 40% of all patients receiving anti-HIV drugs in sub-Saharan Africa are thought to have either died or discontinued treatment within two years, according to a systematic review of African ART (antiretroviral treatment) treatment programmes published on October 16th in the journal PLoS Medicine.
Although a previous meta-analysis of 27 studies in sub-Saharan African countries found a higher short-term level of adherence to ART in the Africans studied (77%) than that among North American participants (55%), remaining in ART treatment programmes over a sustained period is a necessary requirement to avoid illness and death from AIDS in the longer term.
In order to ascertain what they termed “attrition” from ART treatment programmes, investigators from Boston University conducted a systematic search of the literature, and eventually found 32 scientific reports covering over 74,000 patients in 33 ART treatment programmes in 13 countries in sub-Saharan Africa that were either published in peer-reviewed journals or presented at scientific meetings between 2000 and 2007.
All adults commencing ART treatment were included in their analysis, as long as the studies were not clinical trials, information was provided regarding the proportion of patients who remained alive on ART, and median follow-up lasted for at least six months.
The average follow-up time was weighted (i.e. adjusted for the number of patients) and found to be 9.9 months, when an average of 77.5% of patients remained on ART. Of the patients no longer in the ART treatment programme, 40% were known to have died and 56% had been “lost to follow-up”. The investigators note that this phrase covered many different interpretations depending on each ART treatment programme, but that it most often meant that patients had missed clinic visits or had failed to pick up their anti-HIV drugs within a specific period of time.
The investigators used a variety of methods to estimate retention rates up to 24 months, even though only ten programmes reported actual 24-month retention rates: these ranged between 46% (in one Ugandan treatment programme) and 85% (in one South African treatment programme).
Estimated weighted mean retention rates were found to be 79%, 75% and 61.6% at 6, 12, and 24 months, respectively. Using Kaplan-Meier survival curves, overall retention rates were estimated to be 89%, 70% and 60% at 6, 12, and 24 months, respectively.
A final analysis, which, the investigators note, might help overcome reporting bias that overestimated retention rates, utilised sensitivity analyses which estimated three different scenarios: best (no further attrition following last reported follow-up), worst (attrition continues at the same rate as last reported follow-up) and midpoint.
In this analysis, they estimated that two-year retention in ART programmes at the estimated midpoint would be 50%, although the worse-case scenario saw 76% of patients lost to follow-up and the best-case scenario saw 76% of patients retained in an ART treatment programme after two years.
The investigators first focus on the “extraordinary accomplishment” of rapid ART rollout in sub-Saharan Africa. They note that since most patients in the African ART programmes initiated therapy once they had an AIDS diagnosis most ART recipients “would have died within a year if antiretroviral therapy had not been available. Each patient who is retained in care an on ART can thus be regarded as a life saved and a source of tremendous benefit to patients’ families and communities.”
However, they go on to state that “losing up to half of those who initiate ART within two years is cause for concern.”
They compare their findings to those of the ART-LINC Collaboration, which last year reported loss to follow-up rates in 13 sub-Saharan African cohorts (not included in the current analysis) that averaged 15% after one year, although this ranged between 0% and 44%. (Bratstein)
Since they were able to ascertain that at least 40% of patients no longer in ART treatment programmes died following initiation of ART, and that most patients began therapy with very low CD4 counts, they argue that earlier treatment should be carefully considered throughout sub-Saharan Africa.
They also discuss at great length the very practical difficulties faced by people running ART treatment programmes to ascertain more precise reasons why their patients are lost to follow-up, and argue that “better information on those who are lost to follow-up is urgently needed”.
Losses to follow-up accounted for the majority of attrition from ART treatment programmes in sub-Saharan Africa, conclude the investigators, and “the problem of attrition cannot be addressed effectively without better means to track patients. Only then can we address the pressing question of why patients drop out and what conditions, assistance, or incentives will be needed to retain them.”
A comprehensive review of reasons for loss to follow-up and approaches to treatment that promote better retention in care was published in the August 31st 2007 edition of HIV & AIDS Treatment in Practice, NAM's electronic newsletter on HIV treatment in resource-limited settings.
Rosen S et al. Patient retention in antiretroviral therapy programs in sub-Saharan Africa: A systematic review. PLoS Med 4(10): e298, 2007.
Bratstein P et al. Mortality of HIV-1 infection patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries. Lancet 367: 817-824, 2006.