How have ART treatment programmes changed the patterns of excess mortality in people living with HIV? Estimates from four countries in East and Southern Africa

Figures & data

Table 1 Dates for the introduction of ART, the full rollout of ART, and the start of demographic surveillance and HIV serosurveys

			Start dates for ART phases
Site	Start of demographic data collection	Start of HIV serosurveys	Pre-ART phase	ART introductory phase	Post-ART phase
Karonga	August 2002	October 2005	July 2000	July 2005	October 2006
Kisesa	May 1994	August 1994	January 2000	March 2005	October 2008
Masaka	November 1989	November 1989	January 1999	January 2004	January 2005
Rakai	April 1999	April 1999	June 1999	June 2004	June 2006
uMkhanyakude	January 2000	October 2002	January 1999	January 2005	January 2007

Table 2 Classification of deaths and exposure time by HIV status

HIV-negative	HIV-positive	HIV status unknown
Between successive negative tests	Following any positive test	Never tested
Up to X years following a negative test with no other subsequent test		Not yet tested (i.e. Before first test, whether or not that first test was positive or negative)
In a seroconversion interval less than X years duration (negative test followed by positive test)		More than X years following the last negative test

X was based on observed incidence rates in the sites, and the values used were 2 years in uMkhanyakude, 3 years in Rakai, and 5 years elsewhere.

Table 3 Number of subjects and person years contributed to the analysis, mortality rate and period prevalence of HIV amongst persons with known HIV status, and the proportion of all deaths that were of individuals known to be HIV positive

ART phase	Number of subjects	Person years	Deaths	Mortality rate	Period prevalence	HIV-positive deaths (% of total)
Karonga
0–5 years before ART	*	*	*	*	*	*
ART introduction	*	*	*	*	*	*
ART available	18,159	46,134	316	6.8	7.4	25.9
Kisesa
0–5 years before ART	13,153	34,491	412	11.9	5.2	31.8
ART introduction	12,014	27,234	317	11.6	5.0	25.6
ART available	11,303	21,639	185	8.5	5.6	25.4
Masaka
0–5 years before ART	10,873	31,336	500	16.0	5.6	42.8
ART introduction	8,275	7,268	107	14.7	5.8	34.6
ART available	12,610	39,867	436	10.9	6.6	25.9
Rakai
0–5 years before ART	22,845	66,327	616	9.3	12.8	79.7
ART introduction	20,814	31,426	243	7.7	12.7	77.8
ART available	28,289	72,732	588	8.1	12.6	67.0
uMkhanyakude
0–5 years before ART	12,470	10,177	177	17.4	20.6	82.5
ART introduction	18,458	25,625	405	15.8	22.3	75.8
ART available	29,346	72,987	1,349	18.5	27.1	55.6
All sites pooled
0–5 years before ART	59,341	142,330	1,705	12.0	9.9	57.6
ART introduction	59,561	91,553	1,072	11.7	12.5	57.3
ART available	99,707	253,359	2,874	11.3	14.3	48.2

*Estimate not available.

Table 4 Age-standardized mortality rates (per 1,000 person years) by site, sex, HIV status, and ART phase: rates for HIV-negative people and PLWH, the excess mortality rate among PLWH (rate difference), and the standardized mortality ratio (SMR)

	Men				Women
Site and ART phase	HIV-negative mortality rate	HIV-positive mortality rate	Attributable	SMR	HIV-negative mortality rate	HIV-positive mortality rate	Attributable	SMR
Karonga
0–5 years before ART	–	–	–		–	–	–
ART introduction	–	–	–		–	–	–
ART available	2.5	24.4	22.0	10	1.7	15.0	13.7	8.8
Kisesa
0–5 years before ART	3.6	55.2	51.6	15.3	4.2	52.4	48.7	12.5
ART introduction	5.2	47.1	42.2	9.1	3.2	39.8	36.9	12.4
ART available	3.2	33.8	30.8	10.6	1.8	19.6	18.3	10.9
Masaka
0–5 years before ART	3.9	88.0	84.8	22.6	3.2	91.5	88.3	28.6
ART introduction	2.8	77.4	75.4	27.6	3.5	60.5	58.0	17.3
ART available	3.8	43.6	39.9	11.5	2.3	30.3	28.3	13.2
Rakai
0–5 years before ART	2.3	42.5	40.6	17.7	1.7	45.7	43.9	25.8
ART introduction	2.2	31.1	28.9	13.1	1.0	32.8	31.8	31.8
ART available	3.2	49.4	46.2	14.4	2.5	28.3	25.8	10.3
uMkhanyakude
0–5 years before ART	7.6	63.4	56.2	8.3	1.8	56.7	54.9	31.5
ART introduction	8.3	47.4	39.5	5.7	2.1	38.3	36.1	18.2
ART available	5.7	43.2	37.5	7.6	1.6	22.6	21.1	14.1

Fig. 1 Estimated excess mortality rate among PLWH by age, sex, and ART phase.

Fig. 2 Hazard ratios from an age-stratified exponential regression model comparing the mortality of PLWH to that of HIV-negative individuals, by ART availability. Estimates are controlled for sex and study site; these results are given in Table 5.

Table 5 Hazard ratios and 95% confidence intervals from an age-stratified exponential model comparing the mortality of PLWH and HIV-negative individuals by ART phase

ART phase and HIV status	15–19	20–24	25–29	30–34	35–39	40–44	45–49	50–54
Pre-ART HIV−	1.53 (1.14–2.05)	0.75 (0.44–1.25)	0.83 (0.69–1.00)	1.31 (0.48–3.54)	1 (0.57–1.74)	1.2 (0.51–2.82)	1.4 (0.70–2.84)	0.94 (0.54–1.62)
Pre-ART HIV+	8.29 (6.21–11.0)	17.38 (13.66–22.1)	22.96 (18.32–28.7)	30.3 (18.17–50.5)	18.27 (10.04–33.2)	19.2 (15.96–23.1)	17.83 (11.87–26.7)	11.49 (5.73–23.0)
Pre-ART HIV?	2.07 (1.55–2.76)	4.22 (2.85–6.25)	7.11 (4.63–10.9)	9.45 (6.51–13.7)	5.85 (4.37–7.83)	4.97 (3.80–6.50)	3.66 (3.09–4.33)	1.9 (1.74–2.07)
ART intro HIV−	0.97 (0.59–1.59)	1.39 (0.78–2.46)	1.3 (0.80–2.10)	1.26 (0.45–3.52)	1.18 (0.33–4.22)	1 (0.57–1.74)	1.18 (0.83–1.67)	1.17 (0.72–1.92)
ART intro HIV+	3.76 (1.79–7.90)	12.22 (9.27–16.1)	12.57 (9.31–16.9)	17.38 (12.22–24.7)	17.76 (15.81–19.9)	15.1 (14.49–15.7)	11.33 (8.76–14.6)	9.45 (5.20–17.1)
ART intro HIV?	2.01 (1.69–2.38)	3.11 (1.62–6.00)	6.56 (4.45–9.67)	8.79 (4.92–15.6)	4.72 (3.15–7.10)	4.19 (2.82–6.23)	2.75 (2.04–3.70)	2.18 (1.77–2.67)
Post-ART HIV−	1	1	1	1	1	1	1	1
Post-ART HIV+	11.85 (8.81–15.9)	8.7 (7.02–10.7)	11.33 (7.95–16.1)	13.09 (10.99–15.5)	9.4 (7.89–11.2)	8.35 (5.33–13.0)	6.84 (5.14–9.11)	5 (4.23–5.91)
Post-ART HIV?	2.26 (1.34–3.79)	3.72 (2.27–6.08)	6.34 (3.48–11.5)	7.93 (5.33–11.8)	5.03 (4.13–6.13)	4.07 (2.58–6.42)	2.87 (2.13–3.87)	2.07 (1.33–3.23)
Sex
Men	1	1	1	1	1	1	1	1
Women	1.02 (0.93–1.11)	1.32 (1.12–1.56)	1.06 (0.98–1.16)	0.9 (0.76–1.06)	0.75 (0.49–1.15)	0.59 (0.44–0.79)	0.57 (0.45–0.72)	0.53 (0.42–0.68)
Study site
Kisesa	1	1	1	1	1	1	1	1
Masaka	0.98 (0.88–1.09)	1.92 (1.66–2.21)	1.91 (1.75–2.10)	2.07 (1.85–2.30)	1.56 (1.42–1.71)	1.19 (1.06–1.34)	1.29 (1.18–1.40)	0.94 (0.92–0.96)
Rakai	0.94 (0.88–1.01)	1.35 (1.26–1.44)	1.74 (1.61–1.88)	1.87 (1.74–2.00)	1.62 (1.52–1.73)	1.12 (1.03–1.23)	0.99 (0.91–1.07)	1.18 (1.10–1.26)
uMkhanyakude	0.88 (0.79–0.99)	1.5 (1.39–1.62)	1.97 (1.84–2.11)	2.36 (2.10–2.64)	1.79 (1.54–2.08)	1.64 (1.40–1.92)	1.76 (1.56–1.99)	1.66 (1.47–1.87)

These results are from the same model as the estimates presented in Fig. 2.