An update on HIV prevention and treatment Prof Francois Venter Wits Reproductive Health and HIV Institute (WRHI) University of the Witwatersrand Oct 2012

AIDS in Africa

Tensions… Prevention versus HIV treatment HIV versus other illnesses Public health versus human rights versus the law Government versus donor responsibility

Who is at fault? Politicians and voters Public Health experts Clinicians Researchers Donors

Eastern & Southern Africa 1.5 million (57% Rest of the world 1.2 million (43%) Global new infections, 2.7 million ESA new infections, Prov. estimate 1.5m Estimates of New Infections in Eastern and Southern Africa, 2007

South Africa Brazil Namibia Chile Measurement of Generally Accepted Indicators Reveals that the South African Healthcare System is Functioning Poorly by International Standards 1,900 1,800 Afghanistan India South Africa Iraq China Namibia Brazil Chile United Kingdom Netherlands Note: MMR = Number of Maternal deaths per 100,000 *Public Sector deliveries estimated. Live births is used as a proxy for the number of pregnancies annually.MMR is an indicator of the quality of a health care system Source: WHO Maternal Mortality Report, 2007, StatsSA Maternal Mortality Rates by Geography (2000 vs 2005) MDG 2015 Target Trend Projection for Maternal Mortality Rate until

Since the SA ARV rollout started… 2 million people on treatment (& million worldwide) 5 million deaths 5 million new infections

Implications HCT campaign 1 st April 2010…. 15 million tests, linked to TB, other chronic illness screening

New guidelines

CD 4 Gets HIV! Needs ARV’s 8 to 10 years What happens if you get HIV? Wellness – nutrition, exercise, stop smoking, safe sex, mental health, ↓ alcohol

How good are the antiretrovirals?

Before and after initiation of ARV therapy!

Thapelo Before and after initiation of ARV therapy!

ART outcomes - good news National programmes reporting good outcomes 1 year survival estimated as 93-95% 2 year survival 91% SA life expectancy up

How long will people live for? ? 20 years or more on the treatment package !! – CROI 2005 Danish study – 39 years! American – lose 12 years French – NORMAL after 6 years Uganda – normal! Geriatrics, fertility

In summary, what has changed: CD4 350, for all Initiation of infants immediately New maternal health/ PMTCT New 1 st line drugs for adults, kids Altered second line Expedited referral with timelines Decreased monitoring TB Nurse initiation focus

Therapy for Early HIV Infection < CD4 Count (cell/mm 3 ) Symptomatic (Stages 3 & 4) Symptomatic (Stages 3 & 4) Asymptomatic (Stages 1 & 2) Asymptomatic (Stages 1 & 2) Clinical Symptoms

 Review of data from from 176 sites in 42 countries (N = 33,008) When Is Antiretroviral Therapy Started? Egger M, et al. CROI Abstract 62.

Children All children less than 1 year of age Children 1 – 5 years with clinical stage 3 or 4 or CD4 ≤ 25 % or absolute CD4 count < 750 cells/µl Children ≥ 6 years to 15yrs with clinical stage 3 or 4 or CD4 < 350 cells/µl. Huge implications for PCR screening!

MDR and XDR?

Treatment as prevention Prevention programmes results very disappointing Can reducing the viral load earlier have a public health impact? Convenient convergence!

Essentially, treatment IS prevention

1 st line adults All new patients needing treatment, including pregnant women - TDF + 3TC/FTC +EFV/NVP Contraindication to TDF: renal disease AZT+ 3TC +EFV/NVP For those on existing d4T, remain, but vigilance urged

ddI d4T AZT 3TC 2 Nukes Non-nuke Efavirenz/ nevirapine Protease Kaletra Failure – VL>5000 Toxic!

Who is still taking d4T? Marlink R et al, IAC 2008 (WEAXO106) Westreich DJ, et al, Tuberculosis treatment and risk of stavudine substitution in first-line antiretroviral therapy, Clin Infect Dis Jun 1;48(11): Side effects potentiated by TB Rx

Major issue: PMTCT Complex regimens – being updated

What can stop us? Human resources Budget and treasury Beaurocracy and legislation

Context of care

Challenges

The difference? What we want INH CTX Regular monitoring Pap smears, fertility planning ‘Wellness’ – ‘prevention for positives’ (no weekend work, patient in clinic when suits us, keep their appointments) What patients want Being valued No queues Same health care worker Tablets that work Confidentiality Files and blood tests that don’t go missing Information that is appropriate Grants! Appointments, hours that don’t impact on work

The biggest challenge to our programmes is NOT safe or effective drugs or HIV testing – it is retention in care after HIV diagnosis

1 st prize is a bulletproof 1 st line ARV regimen Tolerability > forgiveness (NNRTI vs PI) BUT – presupposes good support and adherence 2-3% migration to 2 nd line – accumulating body of patients Long haul – probably 50% of patients need minimal support

FDCs More for pharmacists than patients! Packaging and colours would be great

Issues around paediatrics The least “system proofed” group Try to harmonise with adults Weight of liquid formulations – score tablets, pay attention to ‘crushability’

OI drug needs Amphotericin B Macrolides - MAC Gancyclovir – CMV, possibly for other illnesses MDR treatment (Rifabutin)

PoC technologies? Proliferation of technologies with parallel lab system - ?justified in an HIV silo ?toxicity monitoring required Gene Xpert Viral load ?CD, ?Resistance ?POC rapid HIV test re-evaluation Sober reflection on the tech requirements

Summary of big ‘short term’ treatment and systems gaps? Earlier diagnosis and retention Bigger emphasis on more sophisticated adherence, esp toxicity management – preserve 1 st line Better packaging of drugs, FDCs New drugs for toxicity OI drugs Better and faster diagnosis of TB, VL; Reassess rapid HIV Simpler guidelines, align paeds and adult guidelines Expansion of who gives ART

HIV has showed what we can do Opportunity to fix the whole health care system now Heed our marching orders for 2012!

The End