Mortality and causes of death among women living with HIV in the UK in the era of highly-active antiretroviral therapy

Sara Croxford, A Kitching, M Kall, M Edelstein and V Delpech

Centre for Infectious Disease Surveillance and Control (CIDSC)Public Health EnglandLondon, United Kingdom

2 Mortality and causes of death among women living with HIV in the UK in the era of HAART

Key findings

• AIDS is still the most common cause of death among HIV positive women in the era of effective treatment.

• This is mostly due to late diagnosis and the majority of deaths occurring within the first few months of diagnosis.

• Classification of causes of death can be challenging.

• Our cohort of women diagnosed since 1997 also had high rates of non-AIDS death causes which warrants further investigation.

3 Mortality and causes of death among women living with HIV in the UK in the era of HAART

Annual new HIV and AIDS diagnoses and deaths: UK, 1981-2012

First test for HIV

ART available

4 Mortality and causes of death among women living with HIV in the UK in the era of HAART

AIDS remains the silent

killer: Ten-year mortality

trends among persons

diagnosed with HIV:

England & Wales, 1999-

2008

Simmons RD, Ciancio BC, Kall MM, Rice BD and Delpech VC. Ten-year mortality trends among persons diagnosed with HIV infection in England and Wales in the era of antiretroviral therapy: AIDS remains a silent killer. HIV Med 2013 Nov; 14(10):596-694

Objectives

• Explore survival among the cohort of women diagnosed with HIV in the UK after the introduction of effective treatment.

• Describe AIDS and non-AIDS causes of death among this cohort and compare with general population

5 Mortality and causes of death among women living with HIV in the UK in the era of HAART

6 Mortality and causes of death among women living with HIV in the UK in the era of HAART

2003 2004 2005 2006 2007 2008 2009 2010 2011 20120%

20%

40%

60%

80%

100%

63% 62% 61%64%

60% 60% 60% 58% 57% 57%

Late diagnosis among women diagnosed with HIV post-ART: England & Wales, 2003-

2012

Year of diagnosis

Pro

po

rtio

n d

iag

no

se

d la

te

Women living with HIV in the UK

• In 2012, there were 31,700 women living with HIV in the UK, a quarter of which were undiagnosed.

• Late diagnosis among women is high.

• Majority of diagnoses made in antenatal care and STI clinics.

• Women are a population that is under studied

Methods• Population: Cohort of women (aged ≥15 years) diagnosed

with HIV in England and Wales between 1997-2012 and seen for HIV care.

• Data sources: National surveillance data reported to PHE were linked to death record data from the Office of National Statistics.

• Death categorisation: Deaths to the end of 2012 were categorised using a modified CoDe protocol* into AIDS and non-AIDS-related causes.

• Statistical analysis: Cumulative mortality was examined using Kaplan-Meier, with censoring at death or date last seen.

7 Mortality and causes of death among women living with HIV in the UK in the era of HAART

* Kowalska JD, Friis-Moller N, Kirk O, Bannister W, Mocroft A, Sabin C, et al. The Coding Causes of Death in HIV (CoDe) Project: initial results and evaluation of methodology. Epidemiology. 2011;22(4):516-23

National HIV cohort of women: England & Wales, 1997-2012

8 Mortality and causes of death among women living with HIV in the UK in the era of HAART

32,400 women diagnosed with

HIV

30,010 in HIV care

1,575 died (5.2%)• All-cause mortality rate 9.8 per

1,000 person years

• 95% infected through heterosexual sex

• 73% black African

• 59% diagnosed under the age of 35

• 160,710 person years

Cohort survival

9 Mortality and causes of death among women living with HIV in the UK in the era of HAART

Cohort time Number at risk DeathsSurvivor function

95% Confidence interval

0 0 0 1.00 . .1 42,651 2,039 0.96 0.9578 0.96122 37,492 354 0.95 0.9492 0.95305 25,011 625 0.93 0.9298 0.934610 8,911 535 0.90 0.8991 0.906015 938 170 0.87 0.8618 0.8753

Cohort time Number at risk DeathsSurvivor function

95% Confidence interval

0 0 0 1.00 . .1 24,067 975 0.97 0.9634 0.96772 21,540 130 0.96 0.9578 0.96245 14,916 231 0.95 0.9452 0.950710 4,477 194 0.93 0.9241 0.932115 269 45 0.90 0.8953 0.9135

0.8

50

.90

0.9

51

.00

0.8

0

0 2 4 6 8 10 12 14 16Years from diagnosis

CD4 <100 CD4 100-199CD4 200-349 CD4 350-499CD4 500+

Kaplan-Meier survival estimates by CD4 count at diagnosis (women)

0.8

00

.85

0.9

00

.95

1.0

0

0 2 4 6 8 10 12 14 16Years from diagnosis

CD4 <100 CD4 100-199CD4 200-349 CD4 350-499CD4 500+

Kaplan-Meier survival estimates by CD4 count at diagnosis (men)

Women Men

Characteristics of patients that died: England & Wales, 1997-2012

10 Mortality and causes of death among women living with HIV in the UK in the era of HAART

Variables Women All cause mortality*

Total 1,575 (5.2%) Median age at diagnosis [IQR] 37 [31-46]Ethnicity White 313 (22%)

Black Caribbean 76 (5.3%)Black African 955 (66%) Other 93 (6.7%)

Infection route Sex between men N/AHeterosexual contact 1,278 (92%) Injecting drug use 71 (5.1%) Other 44 (3.2%)

Median age at death [IQR] 40 [33-47]

Median survival post-diagnosis (months)[IQR] 4.6 [0.50-34]

Previous AIDS diagnosis** 919 (58%)Ever on treatment 744 (47%)Diagnosed late (CD4 <350 cells/mm3 within 91 days) 566 (80%)

Men All cause mortality*

3,727 (7.0%)42 [34-51]2,279 (66%)122 (3.5%)808 (23%) 243 (7.0%)1,710 (51%)1,370 (41%) 257 (7.6%) 27 (1.0%)44 [37-54]

7.9 [0.83-46]

2,058 (63%)1930 (52%)

1,358 (74%)

* Proportions where data are known.**Diagnosis with an AIDS-defining illness

Mortality among women by cause of death: England & Wales, 1997-2012

11 Mortality and causes of death among women living with HIV in the UK in the era of HAART

Mortality by cause of death and sex: E&W, 1997-2012

12 Mortality and causes of death among women living with HIV in the UK in the era of HAART

Mortality among women by cause of death: E&W, 1997-2012

13 Mortality and causes of death among women living with HIV in the UK in the era of HAART

1. Pneumocystis (PCP)2. Lymphoma 3. Tuberculosis

90%

• Median age of death 39 IQR [33-46]• 90% diagnosed late• Median survival of 55 days [9-374]

• Median age of death 41 [34-49]• 72% diagnosed late• Median survival of 424 days

[23-1,652]

72%

14 Mortality and causes of death among women living with HIV in the UK in the era of HAART

Non-AIDS related mortality among women by cause of death: E&W,

1997-2012

• Unspecified or non-recurrent pneumonia• Sepsis• 79% diagnosed late – AIDS?

15 Mortality and causes of death among women living with HIV in the UK in the era of HAART

• Breast cancer (21%) • Lung cancer (15%)• Median age of death was 44 [39-53]

Non-AIDS related mortality among women by cause of death: E&W,

1997-2012

16 Mortality and causes of death among women living with HIV in the UK in the era of HAART

Non-AIDS related mortality among women by cause of death: E&W,

1997-2012

11%

8%

29%

52%

Chart TitleMI or other ischemic heart disease

Pulmonary hypertension

Other cardiovascular causes

Stroke

17 Mortality and causes of death among women living with HIV in the UK in the era of HAART

Non-AIDS related mortality among women by cause of death: E&W, 1997-2012

Poster MOPE179 – Monday Deaths due to viral hepatitis and other causes of liver disease among a large national HIV cohort, England and Wales (1997-2010) A. Kitching, S. Croxford, M. Edelstein, M. Kall, V. Delpech

• Progression to complications of viral hepatitis (30%; 15)

• Alcoholic liver disease (35%; 17)

• 1/5 infected through injecting drug use.

18 Mortality and causes of death among women living with HIV in the UK in the era of HAART

Non-AIDS related mortality among women by cause of death: E&W,

1997-2012

• 58% of all deaths due to substance abuse were among people infected with HIV through injecting drug use.

• Low median age of death • Accident/suicide 28 [25-42]• Substance abuse 33 [24-39]

19 Mortality and causes of death among women living with HIV in the UK in the era of HAART

Non-AIDS related mortality among women by cause of death: E&W,

1997-2012

• COPD • Renal failure• Pancreatitis • Gastro-intestinal

haemorrhage

Limitations & future work • Challenges classifying deaths - AIDS vs. non-AIDS

• This analysis focuses on women diagnosed since 1997.

• Under-reporting of deaths

• Current and future work:

Age-standardised mortality rates

London Death Audit

• Improve quality of HIV care by reviewing the patient pathway of those who die with HIV in London, i.e. remediable factors

• Identify particular scenarios that are worthy of further case investigation, including periodic public case presentation and audit

20 Mortality and causes of death among women living with HIV in the UK in the era of HAART

Conclusions

• Despite high uptake of antenatal screening, there are high rates of late diagnosis and deaths among HIV positive women.

• The large majority of deaths are preventable.

• Our findings highlight the need for increased and expanded HIV testing in general practice and community settings.

• Good surveillance data on deaths and cause of deaths is crucial in monitoring the response to HIV epidemic

21 Mortality and causes of death among women living with HIV in the UK in the era of HAART

NO ONE SHOULD DIE OF AIDS IN

2014

Acknowledgements

23 Mortality and causes of death among women living with HIV in the UK in the era of HAART

The continuing collaboration of those who contribute to HIV surveillance in the UK is gratefully acknowledged. Without their generosity, time and effort the

current level of understanding of the epidemic could not have been obtained.

HIV/AIDS Reporting Team particularly Rajani Raghu and Graeme Rooney

All contributors to STI, HIV and AIDS research and surveillance, and to all those involved in providing treatment and care to persons diagnosed with

HIV in the UK.

The Office of National Statistics for providing death data.