High mortality persists among people presenting with advanced HIV disease

Mortality in the first 3 months on antiretroviral therapy among HIV-positive adults in low- and middle-income countries: a meta-analysis.

Brennan AT, Long L, Useem J, Garrison L, Fox MP. J Acquir Immune Defic Syndr. 2016 Sep 1;73(1):1-10. doi: 10.1097/QAI.0000000000001112.

Previous meta-analyses reported mortality estimates of 12-month post-antiretroviral therapy (ART) initiation; however, 40%-60% of deaths occur in the first 3 months on ART, a more sensitive measure of averted deaths through early ART initiation. To determine whether early mortality is dropping as treatment thresholds have increased, we reviewed studies of 3 months on ART initiation in low- to middle-income countries. Studies of 3-month mortality from January 2003 to April 2016 were searched in 5 databases. Articles were included that reported 3-month mortality from a low- to middle-income country; nontrial setting and participants were ≥15. We assessed overall mortality and stratified by year using random effects models. Among 58 included studies, although not significant, pooled estimates show a decline in mortality when comparing studies whose enrollment of patients ended before 2010 (7.0%; 95% CI: 6.0 to 8.0) with the studies during or after 2010 (4.0%; 95% CI: 3.0 to 5.0). To continue to reduce early HIV-related mortality at the population level, intensified efforts to increase demand for ART through active testing and facilitated referral should be a priority. Continued financial investments by multinational partners and the implementation of creative interventions to mitigate multidimensional complex barriers of accessing care and treatment for HIV are needed.

Abstract access [1] 

Editor’s notes: Early mortality among people initiating antiretroviral therapy (ART) remains high, presumed to be because many people living with HIV present when already very sick with advanced HIV disease. This systematic review included 43 studies from Africa and 13 from Asia. Its main aim was to see whether the evolution of guidelines recommending ART initiation at progressively higher CD4 counts over this period had reduced early mortality (defined as death within three months of ART start) and, by implication, the proportion of people starting ART who had advanced disease. To investigate this, the authors compared studies where enrolment ended before 2010 with studies that had started later.

Overall early mortality was six percent.  Because of the large numbers lost to follow up this will be an underestimate. The authors attempted to compensate for this, and calculated an adjusted overall figure of more than 10%. There was a fall in early mortality from seven percent to four percent (unadjusted) between the early and late periods but although the trend was consistent the difference was not significant.

In only four of the 58 studies was the median CD4 count at ART initiation above 200x106/l. It seems likely that even when policies to initiate ART at high CD4 counts are adopted, additional efforts will be necessary to promote initiation of ART and retention in care for people who feel well.  This is in order to reduce the number of people starting ART with advanced disease and consequently at very high risk of early death.   

Epidemiology [3], Health care delivery [4], HIV Treatment [5]
Africa [6], Asia [7], Latin America [8]
Argentina [9], Brazil [10], Cambodia [11], Cameroon [12], Chile [13], China [14], Côte d'Ivoire [15], Ethiopia [16], Gambia [17], Haiti [18], Honduras [19], India [20], Kenya [21], Laos [22], Lesotho [23], Malawi [24], Mexico [25], Mozambique [26], Nepal [27], Pakistan [28], Peru [29], Rwanda [30], South Africa [31], Uganda [32], United Republic of Tanzania [33], Zambia [34]
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