Growing thrust for combination HIV prevention

Shobha Shukla *

Some slogans at World AIDS Day 2013 at MFDC Auditorium :: Pix - Ashok Ningthoujam

One size does not fit all. Likewise we need an expanded basket of evidence-based interventions and approaches to meet the unique needs and contexts of different key affected populations to prevent HIV. Deliberations on the first day of the 6th National Conference of AIDS Society of India (ASICON 2013), discussed amongst other things, effective strategies for HIV prevention and control.

Dr IS Gilada, President of AIDS Society of India and ASICON 2013; Dr Usha Sharma from the USA; Dr Vinay Kulkarni, Managing Director of Prayas in Pune; Dr GD Ravindran from Bangalore; and Dr Dilip Mathai, formerly with Christian Medical College (CMC), Vellore; gave their valuable inputs on this need of the hour. They agreed to Citizen News Service (CNS) that 30 years into the global HIV pandemic, there is critical need for effective prevention strategies that can be implemented with high level of population coverage. We not only have to treat HIV infected people but also protect and prevent HIV uninfected persons from getting infected.

Although HIV incidence in India has declined (except in some key populations like transgenders, long-distance truck drivers and injecting drug users - IDUs), in terms of sheer numbers it ranks number three in the world by way of HIV incidence.

No single stand-alone HIV intervention offers a magic bullet.

Voluntary HIV Counselling and Testing

Most people in low- and middle-income countries (LMICs) are not aware of their sero-status and even fewer know the status of their partner. This lack of knowledge has been found to be associated with 50-60% decreased likelihood of condom use. Evidence also indicates that most individuals testing positive reduce their sexual and other secondary HIV transmission behaviours. Hence expanding access to voluntary HIV counselling and testing in the general population (by 90% or more coverage) is an urgent global priority both to link HIV infected persons unaware of their status to clinical care and to prevent new infections.

Voluntary HIV counselling and testing may be implemented facility-based, workplace-based, or home-based. Facility-based voluntary HIV counselling and testing where other services are available on an ongoing basis is crucial in most LMICs to promote combination HIV prevention. Some home based voluntary HIV counselling and testing programmes have achieved 90% uptake among those present at home.

Treatment as prevention (TaSP)

Early antiretroviral therapy (ART) has considerable benefit, both as treatment and in preventing HIV and TB. The WHO has called for 15 million people to be on ART by 2015. It is certain that TasP needs to be considered as a key element of combination HIV prevention and as a major part of the solution to ending the HIV epidemic and countries need to maximize the use of ART for prevention purposes.

The focus should be on specific populations in whom the prevention impact is expected to be greatest like sero discordant couples, pregnant women and key populations.

Early ART for Prevention of Parent to Child Transmission of HIV (PPTCT) has been shown to be important in reducing HIV transmissions. Vertical transmission was reduced by 92-98% in some PPTCT intervention studies.

Pre-exposure Prophylaxis (PrEP)

PrEP is the ongoing use of one or two antiretroviral (ARV) medicines by HIV-negative individuals starting before an exposure occurs and continuing afterwards and has the potential to prevent infection from ongoing exposures to HIV during periods of risk.

Who all are Eligible for PrEP?

Those who are HIV uninfected or antibody negative immediately before starting PrEP. The

WHO guidelines say that it can be used in sero-discordant couples and men and transgender women who have sex with men and are at high risk of HIV. They must also have adequate renal function, should be screened for Hepatitis B infection, Hepatitis C infection, and screened and treated for sexually transmitted diseases (STDs).

How does PrEP work?

Infection does not occur instantly after an exposure to HIV as the virus needs to spread throughout the body and this may take up to 3 days (72 hours) after the exposure. So the window of opportunity for PrEP is this brief period of time after an exposure where HIV has not yet spread throughout the body, and during this time PrEP may be able to stop HIV from causing an infection.

Tenofovir Disoproxil Fumarate (TDF) and Emtricitabine (FTC) are together used as PrEP among sexually active adults at risk for HIV infection. TDF has been found to be potent (rapid antiretroviral activity); safe and easy to use (once daily dosing, few drug-drug interactions and well tolerated).

The dosage is one daily tablet of FTC 200mg/TDF 300mg. But it is important to test for HIV every 2-3 months, assess STD symptoms at each visit, test creatinine after 3 months on PrEP and annually thereafter. It must be discontinued if person has chronic Hepatitis B infection and/or if he/she tests HIV positive in which case the person should be linked to HIV care. If the person is HIV negative, risk-reduction support services should continue. Counselling should be done for continued behavioural risk reduction, and importance of adherence.

Long term toxicity of using PrEP in HIV negative persons is unknown. There is little we know on how much will behaviour change if PrEP is partially protective or how much will it impact efficacy.

Post Exposure Prophylaxis (PEP)

As the word implies, PEP is a combination of ART given to individuals who are previously HIV negative, but exposed to HIV through sex, blood or blood products. If started preferably within 8 hours of the exposure incident (and not later than 72 hours), and then continued for 28 days, it is likely to prevent HIV infection.

Who all are eligible for PEP?

People exposed to HIV through sexual exposure, sexual assault, injection drug use, human bites involving blood among other conditions, can be considered for PEP. Most countries of the west and few of the developing countries, including almost all countries of Sub-Saharan Africa, have adopted PEP for survivors of rape.

"PEP is a short-term and inexpensive ART which can prove effective if started within 8 hours of the rape incident. If started within 8 hours and given for 2-4 weeks, it will protect the person from HIV," said Dr IS Gilada.

How does PEP work?

After the HIV contaminated blood or semen or vaginal secretion enters the blood stream of the person exposed to infection, it takes some time to infect the tissues/blood of the exposed person. HIV is RNA type of virus and it cannot reproduce without becoming DNA, as our body DNA only allows integration of DNA, but denies integration to RNA. For this process the HIV virus uses an enzyme called Reverse Transcriptase. ART has at least two drugs that are from a class called Reverse Transcriptase Inhibitors (RTI). They stop the process of reversing RNA to DNA (or DNA to RNA). Thus by giving ART, the process of transcription is blocked.

Clinicians should perform baseline HIV testing within 3 days of exposure, but PEP should be started without waiting for the results of this test. Exposed persons who decline baseline testing should not receive PEP. If initial test result is positive, PEP should be continued until the positive test is repeated with a confirmatory assay. A new recommendation of US guidelines was that PEP medication regimens should have 3 or more ARV drugs for all occupational exposures to HIV and close follow-up for exposed personnel. Medication has to be taken for 1 month. After 2 weeks of the medication, one can do Polymerase Chain Reaction (PCR) test. If the test is negative PEP can be safely stopped.

Risk-reduction counselling must be provided to exposed persons to prevent secondary transmission during the 12 weeks follow up period. Users should also be advised to use condoms, avoid pregnancy and breastfeeding, avoid needle sharing and not donate blood, plasma, organ or semen during the treatment period.

Risks associated with PEP: It may foster increased high risk behaviour and changes in sexual behaviour associated with this intervention may counteract protective efficacy, resulting in increased incidence of HIV at population level, although the current available data does not support this.

Road ahead, though there, is long

Combination HIV Prevention thus represents the next generation of HIV prevention science. Interventions like expanded access to HIV testing and early initiation of ART as primary and secondary prevention, PrEP, PEP, microbicides (rectal, vaginal), male and female condom use, voluntary medical male circumcision, treatment of curable STDs, early initiation of ART, and linkages to care approach are some of the proven strategies of potentially high-impact in reducing HIV infections. But the problems could be operationalizing them, the costs involved and lack of training. The road ahead, though there, is long. (CNS)