When to StartWhen Not to Start

Anna Maria Geretti

University of Liverpool

Starting ART in 2016

ART always recommended irrespective of the CD4 cell counta

Reduction of clinical events and risk of transmission

aWith the possible exception of elite controllers with high and stable CD4 cell counts

European AIDS Clinical Society (EACS) Guidelines 2015

ART always recommended irrespective of the CD4 cell count

Time should be taken to prepare the person, in order to optimise compliance and adherence

Starting ART in 2016

EACS Guidelines 2015

Genetic barrier and cross-resistance

Class Genetic Barrier

CrossResistance

NRTIs +/++ +++

NNRTIs +/++ +++

PIs +/++/+++/++++ ++/+++

T20 + NA

Maraviroc +/++ NA

Integrase inhibitors +/++/+++ +++

Women as Share of People Living with HIV by Region, 2014a

Based on UNAIDS – HOW AIDS Changed Everything 2015

a15 yrs and above

• HIV/AIDS is the leading cause of death in women aged 15-49 yrs

• In 2014, ~62% of all new HIV infections among adolescents occurred among adolescent girls

ART Access Among Men & Women- 12 Countries, 2002-2013

Records from 765,087 adults (≥15 yrs) from 12 countries in 5 regions

Women more likely to access ART in SSA & Haiti - gender-related disparities

Auld et al. MMWR Morb Mortal Wkly Rep. 2015

% difference between female-to-male new ART enrollee ratios and corresponding UNAIDS HIV-positive females-to-male ratios

Virological Responses to First-Line ART

Geretti et al. CROI 2016

UK HIV CHIC Study

Virological Responses to First-Line ART

Geretti et al. CROI 2016

Adjusted HR for female vs. male 0.96 (95% CI 0.78-1.18; p=0.69)

Treatment in HIV-Positive Women in Germany – 2015 vs. 2008

Comparative multicentre analysis

77

91

48

88

0

20

40

60

80

100

2008 2015

% w

ith

VL

<50

cp

s/m

l

Treated

Suppressed

Knecht et al. 6th International Workshop on HIV & Women, Abs 11; 2016

Reality Checks

Young women who experience partner violence 50% more likely to have HIV than women who do not report partner violence

In 2014, 73% of pregnant women living with HIV received effective ART to prevent HIV transmission to their children

Based on UNAIDS – HOW AIDS Changed Everything 2015

Gender relations prohibit women from seeking

health care outside their community without husbands’ approval

Gender norms divest women of the power to

allocate money for health care

Gender norms place the burden of spending on health care for minor illnesses on women

Reality Checks

Women suffer more stigma and

discrimination than men

Repeated, out-of-pocket expenditures at the village

level1 and caring for dependents2 make it

difficult for women to save money for major health

needs

Clinics open when women are usually engaged in

income-generating activities

1. Oshi et al. J Biosoc Sci 2016; 2. Dovel et al. Cult Health Sex 2015

Women in Ebonyl State, Nigeria1

Women in Uganda2

Reality Checks

In 2014 non-Hispanic black or African American black women accounted for 62% of all HIV diagnoses among women in the US despite constituting 13% of the female population1

• 13.5% decrease in diagnoses from 2012 to 2014

Among newly diagnosed black women, the percentage linked to care within 90 days was 34% in 2012 and 50% in 2014

• Short of the 85% target set in 2010 by the National HIV/AIDS Strategy

1. Stein et al. MMWR Morb Mortal Wkly Rep 2016

Reality Checks

In 2014 non-Hispanic black or African American black women accounted for 62% of all HIV diagnoses among women in the US despite constituting 13% of the female population1

• 13.5% decrease in diagnoses from 2012 to 2014

Among newly diagnosed black women, the percentage linked to care within 90 days was 34% in 2012 and 50% in 2014

• Short of the 85% target set in 2010 by the National HIV/AIDS Strategy

Insured US population accessing ART (Optum Research & Impact National

Benchmark Database, 2010-2014): ≥1 in 4 women reported adherence levels <80%2

1. Stein et al. MMWR Morb Mortal Wkly Rep 2016; 2. Forlenza et al. 6th International Workshop on HIV & Women, Abs 12; 2016

Readiness to Start ART

Successful ART requires a person's readiness to start and commit to maintaining adherence

Langewitz et al. BMJ 2002

Experience or fear of violence

Isolation

Alcohol abuse

Drug dependency

Depression

Beliefs

Socio-economic

circumstances

Multiple Factors Influence Access, Engagement and Treatment Adherence in Women

Mental health vulnerabilities

Fear of disclosure

Fear of blame

Fear of prosecution

Food security

The Experience of ART for HIV-Positive Black African Women in London

Intrinsic and social motivators could act as spurs to adherence

In-depth interviews with 10 HIV positive, West African women of black heritage living in London

ART can be considered difficult and unrelenting and may be disconnected from the women's sense of health or illness

Participants' social context often exacerbated the difficulties• Some reported an improvement in their feelings about ART over time

Spiers et al. AIDS Behav. 2016

How Does Living with HIV Impact on Women’s Mental Health?

Orza et al. J Int AIDS Soc 2015

0 20 40 60 80

Depression

Self-blame

Feeling of rejection

A strong sense of isolation

Anxiety

Anorexia

Spiritual isolation

Suicidal feelings

Harmful use of drugs/alcohol

PercentageBefore diagnosis

After diagnosis

Online survey of respondents from 94 countries 3.5-fold higher number of mental health issues after HIV diagnosis 46% had multiple socially disadvantaged identities (SDIs) Number of SDIs positively correlated with experiencing mental health issues

N= 489

Despite PubMed citing ~800 peer-reviewed articles on mental health in relation to women with HIV, the issue is either lacking or

has been insufficiently addressed in global policy guidelines

Stigma & ART Adherence in Women

Studies, mainly with white men, have suggested an association between internalized stigma and sub-optimal adherence to ART Scarcity of research with women

Women's Interagency HIV Study (WIHS): Cohort of women living with HIV who complete interviewer-administered questionnaires semi-annually

Cross-sectional analyses of 1168 women on ART (2013-2014)

– Medication adherence and internalized stigma

Turan et al. J Acquir Immune Defic Syndr. 2016

Stigma & ART Adherence in Women

Association between internalized stigma and self-reported sub-optimal ART adherence

• significant for ethnic minority groups

AdjOR 0.69 (95%CI 0.52, 0.91; p=0.009)

• not for non-Hispanic whites

AdjOR 2.15 (95%CI 0.69, 6.73; p=0.19)

Turan et al. J Acquir Immune Defic Syndr. 2016

Stigma & ART Adherence in Women

Association between internalized stigma and self-reported sub-optimal ART adherence

• significant for ethnic minority groups

AdjOR 0.69 (95%CI 0.52, 0.91; p=0.009)

• not for non-Hispanic whites

AdjOR 2.15 (95%CI 0.69, 6.73; p=0.19)

Depressive symptoms, loneliness, and low perceived social support mediated the association between internalized stigma and sub-optimal adherence

Internalized stigma predicted less perceived social support (or higher loneliness), which predicted more depressive symptoms, which predicted sub-optimal medication adherence

Turan et al. J Acquir Immune Defic Syndr. 2016

Loneliness and Substance Use

Cross-sectional study of 96 HIV-positive Black/African American adults (Florida, 2013-2014)

Interviewer-administered assessment of mental and behavioural health

Among women, loneliness associated with

• Illicit drug use AdjOR = 3.37 (95%CI: 1.23-9.21; p= 0.018)

• Heavy drinking AdjOR = 2.47 (95%CI: 1.07-5.71; p =0.033)

No significant associations between loneliness and illicit drug use and heavy drinking in men

Mannes et al. AIDS Care. 2015

Readiness to Start ART

Successful ART requires a person's readiness to start and commit to maintaining adherence

Open questions

“I would like to talk about HIV medicines”

“What do you think about them?”

WEMS Technique: Waiting (>3 sec), Echoing, Mirroring, Summarising

Identify the stage of readiness and intervene accordingly

Langewitz et al. BMJ 2002

I don’t need it, I feel wellI don’t want to think about it

Respect - Understand - Establish trust -Provide concise individualised information

I don’t need it, I feel wellI don’t want to think about it

I am weighing things upI feel torn about what to do

Respect - Understand - Establish trust -Provide concise individualised information

Allow ambivalence - Support weighing Pros & Cons - Assess and support information needs and information seeking

I don’t need it, I feel wellI don’t want to think about it

I am weighing things upI feel torn about what to do

I believe the drugs will help meI want to start

Respect - Understand - Establish trust -Provide concise individualised information

Allow ambivalence - Support weighing Pros & Cons - Assess and support information needs and information seeking

Reinforce decision - Discuss convenient regimen and integration in daily life -Educate on adherence, resistance, side effects - Assess self-efficacy and training & support needs

I don’t need it, I feel wellI don’t want to think about it

I am weighing things upI feel torn about what to do

I believe the drugs will help meI want to start

Respect - Understand - Establish trust -Provide concise individualised information

Allow ambivalence - Support weighing Pros & Cons – Assess and support information needs and information seeking

I will start now Final check

Reinforce decision - Discuss convenient regimen and integration in daily life -Educate on adherence, resistance, side effects - Assess self-efficacy and training & support needs

I don’t need it, I feel wellI don’t want to think about it

I am weighing things upI feel torn about what to do

I believe the drugs will help meI want to start

Respect - Understand - Establish trust -Provide concise individualised information

Allow ambivalence - Support weighing Pros & Cons – Assess and support information needs and information seeking

I will start now Final check

I will continue

I have difficulties continuing

Assess adherence - Respect success -Identify problems and beliefs - Assess barriers and facilitators

Reinforce decision - Discuss convenient regimen and integration in daily life -Educate on adherence, resistance, side effects - Assess self-efficacy and training & support needs

Limited published evidence that comprehensively addresses factors that impact on access, engagement, treatment, care and well-being of HIV-positive women

Conclusions: Starting ART

Walcott et al. Cult Health Sex 2015; Kumar et al. J Int AIDS Soc 2015; Amin et al. J Int AIDS Soc. 2015;

Loutfy et al. J Int AIDS Soc. 2015 ; Turan et al. J Acquir Immune Defic Syndr. 2016

Limited published evidence that comprehensively addresses factors that impact on access, engagement, treatment, care and well-being of HIV-positive women

Interconnected psycho-social mechanisms affect women's health seeking behaviour and decision-making, and their ability to engage in HIV care and adhere to treatment

Conclusions: Starting ART

Walcott et al. Cult Health Sex 2015; Kumar et al. J Int AIDS Soc 2015; Amin et al. J Int AIDS Soc. 2015;

Loutfy et al. J Int AIDS Soc. 2015 ; Turan et al. J Acquir Immune Defic Syndr. 2016

Limited published evidence that comprehensively addresses factors that impact on access, engagement, treatment, care and well-being of HIV-positive women

Interconnected psycho-social mechanisms affect women's health seeking behaviour and decision-making, and their ability to engage in HIV care and adhere to treatment

Providing adequate support requires multi-faceted interventions addressing both mental health and interpersonal factors

• Going beyond a narrow biomedical/clinical approach and addressing the social and structural context of women's lives

• Engaging women in the development of policies and programmes

• Strengthening monitoring, evaluation, and accountability procedures to provide good quality data

Conclusions: Starting ART

Walcott et al. Cult Health Sex 2015; Kumar et al. J Int AIDS Soc 2015; Amin et al. J Int AIDS Soc. 2015;

Loutfy et al. J Int AIDS Soc. 2015 ; Turan et al. J Acquir Immune Defic Syndr. 2016

Mission: promote the welfare of HIV-positive women in Europe through equality of access and good standards of care

Thank you