Preventing HIV Using ARV’s; The Feasibility.

In theory, behavior change that leads to total non-exposure to HIV would halt the further spread of the virus. This would entail complete abstinence from all sex or remaining totally faithful to a mutually faithful partner and at the very least, always correctly using condoms in all other sexual encounters. The reality however, is much different; behavior change responses need to be sustained and widespread to have any impact. In any case, behavior change strategies (the oldest tool in the prevention of HIV transmission) cannot stand alone in the control of HIV; they work best in complement to other strategies. Similarly, it is my opinion that Treatment as Prevention (TasP) is not the silver bullet in the control of transmission of HIV and will only have relevance in some limited contexts and not others.

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It needs no emphasis that HIV as a global epidemic has exacted an unwarranted toll on humanity since it was described slightly over thirty years ago; the statistics speak for themselves. Every viable effort against the epidemic will remain welcome and worth consideration. To date in addition to Anti-Retroviral Therapy (ART); male circumcision, condoms, microbicides, donor-blood screening, voluntary testing and behavior change strategies are all interventions in use against the spread of HIV/AIDS across the world. Variable successes have been noted with each or combinations of these strategies in different contexts. To this arsenal, the World Health Organisation (WHO) has since late 2010 recommended universal treatment as a preventive measure. By WHO’s definition, TasP is the prescription of antiretroviral (ARV) drugs to all persons infected with HIV as early as possible and irrespective of their CD4 cell counts for the rest of their lives. This definition excludes ARV microbicides and pre-exposure ARV prophylaxis. It is noteworthy that only the United States of America (USA) offers TasP as defined above in its national program so far.

Worldwide, majority of the HIV infections are acquired by heterosexual contact. These infections occur predominantly in low-income countries of sub-Saharan Africa and parts of Asia. Other modes include use of contaminated blood products and needles, mother-to-child and homosexual sex between men. The epidemic has a different face in different regions: generalized in Africa, concentrated among homosexual men in the USA, female sex workers in Thailand and injection drug users (IDU’s) in Russia. With these epidemiological differences, successful control strategies thus need to be context-specific and locally-adapted for most impact. The principle of TasP is based on knowledge from the experience with anti-retroviral drugs (ARV’s) in the management of HIV; particular for prevention of mother-to-child transmissions (PMTCT) and between sero-discordant couples. Properly administered, ARV’s progressively lower viral load in blood to near non-detectable levels; concomitantly lowering the risk of virus transmission. It is this benefit that on a population-level scale is postulated to slow if not halt the further spread of HIV.

The Proximate-determinants Conceptual Framework of infectious disease transmission requires the interaction of 3 key biological determinants; i) exposure, ii) duration of infectiousness and iii) efficiency of transmission of the infectious agent to propagate, halt or reverse the disease transmission process. An intervention on any one of these biological factors is important in any preventive strategy.

Multiple studies have demonstrated that viral load is a principle factor in the efficiency of transmission of HIV; the higher the load, the higher the likelihood of transmission between sexual partners. It is also known that viral loads are highest in the acute phase of infection; TasP therefore aims to start treatment as soon as possible after infection unlike regular ART. However, the efficiency of transmission is also influenced adversely by other factors like the presence of other sexually transmitted infections, sores, nature of sexual acts, circumcision and condom use. In addition to lowering the transmission efficiency, TasP also has an effect on the other two biological determinants of transmission; duration of infectivity and exposure to infectious material. By lowering viral load, ART greatly improves patients’ quality of life and as a result, they generally live much longer than they otherwise would. When the use of ART begins early in the course of the infection as in TasP, the additional length of healthy life provides a longer period upon which infection of others could potentially occur. On to the third determinant, certain studies have noted increased risk behavior in persons infected with HIV once treatment was widely available and quality of life greatly improved; the phenomenon of risk compensation. This has an influence on exposure; with more risky sexual encounters, there is a greater risk of (re)infection of oneself and partners.

It is noteworthy that the evidence basis for TasP has mostly been collected from observations of cohorts of sero-discordant couples on ART and small populations of generally high HIV prevalence (concentrated epidemics) of male homosexuals and injection drug users. A population-based cohort in British Columbia, Canada was the first major large scale study of the effect of increased ART coverage on a population. The results of this study, later mathematically extrapolated on computer models, have been a strong evidence basis that widespread ART coverage could potentially lower both individual and communal viral loads and thus halt or even reverse the spread of HIV by making transmission less efficient.

Despite the impressive mathematical models demonstrating the turnaround effect TasP can have on HIV incidence, these projections are yet to be demonstrated in large population-level treatment programs in generalized epidemics. In the United States (US), high treatment coverage for heterosexual HIV infected individuals has not resulted into significant decline towards elimination as predicted on some of these mathematical projections. Even worse, certain models have shown a potential rise in incidence if TasP is not accompanied by appropriate behavioral change. Further, key assumptions made by these models (100% of the population is tested and there are no financial or other barriers to initiation and sustenance of treatment) cannot be wished away in real life. To be successful, a TasP program would need to maintain three conditions: ART coverage of the population needs to be significantly high (>75%) and sustained, patients’ ART adherence rate needs to be high (>80%) and sustained, and lastly, treatment must be initiated at the earliest time since infection (healthy individuals).

Besides biomedical interventions like TasP; improved quality of life, female education and empowerment as well as support for the vulnerable of society (orphans, the poor) have been shown to have greater impact on the long-term sustainable control of the spread of HIV. Such interventions, when complemented by programs that strengthen existing local health systems and infrastructure, create effective and long-term systems for HIV control. It thus appears that keeping HIV in control would involve the engagement of other sectors and other strategies that address the underlying determinants in an integrated system.

The efficacy of ART and its role in lowering the efficiency of transmission of HIV is not in doubt. This has been demonstrated in the PMTCT programs and among sero-discordant couples in studies referred to above.  If adopted universally, TasP carries the promise of eradicating HIV or at the least significantly slowing its rate of transmission. This promise is however bound by lack of experience with TasP on a large-scale in generalized epidemics and the fact that the benefits are largely the product of mathematical projections of current observations. These may not be guaranteed to replicate as projected. On another note, achieving ART coverage of above 75% (a requirement for TasP) would be a huge leap forward in meeting unmet treatment needs for those who currently need ART and lack it. Only 47% of those who need ART have access to it in the low and mid-income countries. However, achieving this high level of coverage may be a mirage considering the fact that in the over one decade of availability of ARV’s, only half of those who need them can access them in some regions. Scaling up coverage to include those who are healthy and not in immediate need of these drugs would thus be a formidable challenge.

As mentioned before, initiation of ART needs to begin at the earliest opportunity upon infection. This portends a double challenge; finding newly infected persons and keeping them adherent to treatment for life despite their being asymptomatic and relatively healthy at the beginning. HIV infected persons are most infectious in the acute phase of the infection (up to first 6 months) during which most are generally healthy and unaware of their status. On average, these persons are up to 10 times more infectious than they will ever be at any other time in the course of the infection and will often continue with risky sexual behavior. Current universal testing practices have failed and large groups remain out of reach of the health system. Ethical considerations have also meant that testing remains only voluntary. This presents a major challenge to TasP programs of diagnosing asymptomatic infected individuals who remain the most infectious. Further, providing ART to persons who are healthy for the communal good comes with the risk of poor adherence as well as raises ethical and equity concerns. Poor treatment adherence coupled with long periods of ART would lead to the widespread development of resistant strains; a catastrophic situation in the absence of new drugs. Equity demands that those most at need of treatment get it first hence raising programmatic concerns for resource limited countries. To further complicate the matter, some patients develop a false sense of security in ART and may actually practice riskier sexual behavior once on treatment.

Finally, focus on TasP would take away much needed attention, focus and already-scarce resources from other interventions that would make a bigger impact on the incidence of HIV. Combination approaches to HIV prevention promise better and sustainable prospects at containing HIV. These programs are wholesome and encompass prevention, treatment and empowerment of the vulnerable members of the society. Termed as ‘Highly Active Prevention’ by Prof Holmes of the University of Washington School of Medicine, these strategies go beyond the medical realm into the underlying determinants of the HIV epidemic. This approach to HIV control takes advantage of strategies known to work directly in preventing the transmission of HIV (behavior change, treatment, circumcision) while addressing conditions that expose individuals to infection with HIV (poverty, poor education, gender disparity). It involves community participation in collaboration with their leadership to develop locally appropriate and sustainable solutions. This approach attempts to address health inequities, gender disparities and social injustices that make certain individuals vulnerable to exposure to HIV infection. I share the opinion that this approach is the surest way forward in the management of HIV particularly in the low-resource generalized-epidemic context. In concentrated epidemics, TasP may have a role particularly if those populations can be reached in totality and financial and other barriers to access to treatment be eliminated.

In summary, TasP is a novel concept with a noble cause whose prospects are yet to be agreed upon by various researchers as generally feasible. It presents challenging logistics in implementation as well as raises serious ethical and financial concerns. Curbing the spread of HIV will invariably involve concerted efforts that approach the problem from both the prevention and care perspectives. Even more importantly, improvement of the general quality of life for populations; including access to better quality education and employment will lay the foundation upon which health-sector interventions will make an impact. Health interventions (like TasP) on their own stand on shaky ground and may not hold long in the absence of programs that address the underlying determinants.

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