David Patient, Long Term AIDS Survivor, HIV/AIDS Educator & Motivational Speaker

Neil Orr & David PatientJune 2010 

Introduction There is a radical change of understanding – and thus methodology – that is occurring in the field of HIV transmission reduction, popularly termed HIV prevention.  Essentially, transmission-reduction methods based upon a new paradigm – the biology of transmission – are replacing methods based upon the current paradigm which is based upon modifying sexual behaviour. In developed countries, this shift has already occurred. However, in developing countries such as those in Southern Africa, we appear to be in limbo, largely due to the costs of the new methodologies, such as viral load testing.  In this article we examine some of the potential benefits of this new approach, and integrating the old with the new. We also highlight what we consider to be an astonishing oversight in transmission-reduction approaches, namely Primary HIV Infection (PHI). 

Biomedical Methods of reducing HIV transmission For at least a decade in Southern Africa, public messaging concerning reducing the risk of transmitting HIV from one person to the next has been static, namely the ever-present Abstain-Be Faithful-Condomise (ABC) behavioural risk-reduction approach, in addition to the screening of blood and reducing mother-to-child transmission. Most ‘HIV prevention’ programmes are based upon one or more of these methods.   However, there have been significant biomedical transmission-reduction developments in the area of reducing HIV transmission over the last few years, such as the recognition that male circumcision reduces forward transmission of HIV from women to men^1,2 by up to 60%, and strong evidence that ART is a highly effective means for serodiscordant couples to have babies with significantly reduced risk (between 92% and 100%) of transmitting HIV from one partner to the other^3,4.   In some developed countries the concept of PEP (Post Exposure Prophylaxis) has been extended to a ‘morning after pill’ application, where unprotected sex is dealt with in the same way as rape, using a course of ART medications commencing no less than 72 hours after possible exposure to HIV. There are even rumblings of PrEP – commencing ART before possible exposure to HIV - in order to remove the risk of infection from unprotected sex. Thusfar, these interventions are limited and controversial, and the implications are being hotly debated. However, it appears that the discourse on reducing transmission of HIV from one person to another has quietly shifted from behavioural risk-reduction methods towards biological risk-reduction methods, at least in developed nations.  

Viral load levels and HIV transmission This paradigm shift is based upon the undeniable biological fact that the amount of HIV in the sexual fluids (viral load) at the time of sex is the main determinant of the probability of transmission. If the person has an undetectable viral load at the time of sex, the chances are very small of HIV being transmitted to the other person^{5, 6}. ART reduces viral activity and viral replication. It is logical – and demonstrated in several large studies^3,4 – that HIV-positive people taking ART have a much lower forward transmission rate than those not taking ART.  An additional biological fact is that any untreated co-infection – including STIs, tuberculosis, malaria,  gastrointestinal infections, flu, etc – will cause spikes (sharp increases) in viral loads. This is because these co-infections cause the immune system  to strengthening the TH2 system to deal with these co-infections, at the expense of the mechanisms that keeps HIV under control (TH1 System)⁵.  Therefore, in viral reduction approaches, access to prompt and effective primary health care treatment is a fundamental requirement for effective viral load control, and consequently, HIV transmission reduction.  It goes without saying that an increase in the frequency of unprotected sex increases the probability of transmission.  However, the viral load at the time of sex far outweighs sexual frequency in determining the probability of transmission. Advocates for viral load reduction methodology say “It’s about the virus, stupid! No virus, no transmission.” This understanding of the importance of viral load levels in determining HIV transmission is widespread in developed countries with significant HIV-infected populations. However, in developing countries, this concept is rarely discussed in the public discourse of HIV transmission reduction, for the simple reason that most developing countries do not have the necessary finances to apply the viral load detection technology on a wide scale in national health systems.  We argue that, even if we cannot measure viral loads in a given population with significant HIV prevalence, we can certainly introduce measures that are likely to lower viral loads in those infected, and thus impact transmission rates. 

Resistance to the Viral Load approach A repeated argument in developing countries against introducing concepts such as the viral load in HIV/AIDS education materials - let alone mentioning fluctuating viral load levels at different periods of infection – is that many people do not have a basic understandings of biology and germ theory. The argument continues that discussions regarding viral activity will create undue confusion, and jeopardise behavioural risk-reduction messaging and practices. For this same reason many developing countries rely heavily upon simplistic public explanations of HIV transmission, mainly ABC prevention methods.   Despite a decade or more of evidence showing how sporadic the success of these simplistic messages are in terms of reducing the number of new infections – if at all – we valiantly reiterate and advocate this approach. Why? Perhaps it is because we don’t know what to replace it with, or because, logically, it should work, and we are somewhat perplexed about why it doesn’t.  For many agencies, this has resulted in a paralysis of analysis: We don’t quite know why the ABC approach doesn’t work, but we need to keep promoting it until we figure out what else to do.  It is our belief – and experience – that low literacy has no connection to intelligence. Instead, the desire to learn more about the body, biology, and germ theory is strong, regardless of literacy. People are perfectly capable of learning new concepts and terminology: Let us teach them what they need to know to understand exactly how HIV transmission occurs. Perhaps it is time to uncover the details?   

Integrating behavioural and biological approaches To be clear: We do not oppose the ABC approach. On the contrary, we are quite certain that the ABC methods can have a significant impact when promoted within a meaningful context of understanding exactly how HIV transmission occurs.  When people understand how HIV transmission actually occurs – including fluctuating viral levels due to co-infections - then targeted ABC methods suddenly make sense to many people who otherwise view such methods as a failure. Furthermore, the authors advocate a systematic top-down dissemination of the necessary information and appropriate messaging and applications, commencing with clinicians, then educators, and finally the general public.  For example, very rarely does one hear in a public forum that for the majority of HIV infection that the person has a very low viral load. This refers to the asymptomatic period after the Window Period and before the immune system weakens to the pre-AIDs and AIDS stages.  Consequently, the probability of transmitting HIV is very low (approximately 1 in 500 to 1 in 10,000 sexual acts⁵) during this asymptomatic stage of HIV infection. This phenomena results in the perplexing situation – serodiscordant couples - where one partner is HIV-positive, the other partner is HIV-negative, and the partner without HIV remains uninfected despite repeated exposure through unprotected sex.  However, with a single co-infection of, for example an untreated STI, the viral load can spike sufficiently to permit transmission during unprotected sex between serodiscordant couples.   Given this understanding, is it not probable that there is a much higher chance of persuading a person living with HIV to either abstain or wear a condom during any period of co-infection (illness), and thus reduce the risk of transmitting HIV to his or her partner? Simplistically, if seeking rapid medical treatment for illness plus abstinence or condoms were the recommended courses of action when a person living with HIV is ill in any way, the ABC methods would be more easily accepted, and - dare we say - more effective because they are being used in a targeted fashion when they are needed most: During periods of high viral loads.  

Viral load reduction in developing countries
When the notion of reducing viral load becomes the primary goal of HIV transmission-reduction programmes, the importance of effective primary health care becomes evident, as does the importance of ensuring, for example, clean water supplies to a community to prevent co-infections with gastrointestinal infections.  Government and other agencies involved in housing development, sanitation, agriculture, poverty alleviation, trade and industry, transportation, and water supply and quality – to name a few – become necessary partners in the drive to lower HIV transmission by contributing towards healthier communities with greater access to medical care. It is no coincidence that previous pandemics in Europe, such as the Black Death and the Bubonic Plague, were largely eradicated due to macro social infrastructural changes, not medical interventions.  Also, methods of supporting those living with HIV can become more focused upon viral-load reduction methods, such as recommending specific nutritional elements (e.g., selenium⁷) that appear to lower viral load, or those that support immune function and control of HIV (e.g  zinc⁸, and Vitamin A⁹), versus the current generic ‘eat well’ guidelines. Also, other methods of reducing HIV viral load levels – such as deworming ^10,11  – and the prevention of other common co-infections can be promoted.  It is for similar reasons that the recent change in the criteria for qualifying for ART by the South African Department of Health, from a CD4 count of 200 to 350, will have a significant impact upon reducing the number of HIV transmissions. The simple fact of the matter is that sick people – people with weak immune systems and opportunistic infections – have much higher viral loads, and are thus a high risk population in terms of transmitting HIV. Reported transmission probabilities are between 1 in 100 and 1 in 1,000 sexual acts². If we place people on ART before AIDS illnesses develops, they have lower viral loads, and transmission is less likely. 

Primary HIV Infection (HIV): The overlooked transmission period  Shifting the dialogue from sexual ‘rules’ to dealing with the virus itself also reveals an extraordinary oversight in risk-reduction programmes:  Primary HIV Infection (PHI).  PHI is sometimes called Acute HIV Infection, and is commonly referred to as the Window Period^{5, 6, 12}.   The following facts concerning PHI are pertinent: 

·         Fact 1: The highest viral load level ever achieved by HIV during the entire disease progression – reaching levels of up to 1,000,000 particles per millilitre – occurs during the so-called Window Period (PHI).

·         Fact 2: This extraordinarily high viral load directly translates into the highest probability of onward transmission during unprotected sex.  At no other point of infection is the probability of transmission this high, including during AIDS. According to some studies, the probability of transmitting HIV to another person during PHI is 12 times higher than during AIDS: 1 in 50 to 1 in 250⁵ sexual acts.  

·         Fact 3: When a person in the Primary HIV Infection stage is tested for HIV using HIV antibody tests, they test HIV-negative.  What are the implications? 

·         Up to 50% of all new sexually transmitted infections are caused by people who test HIV negative that are in the Primary HIV Infection period. The precise extent of onward transmission during PHI is unclear, with differences found between studies in the US (9%)¹³, Quebec (50%)¹⁴, and Uganda (50%)¹⁵.  In the Ugandan study, 43% of those in the PHI stage infected their partners during a ten weeks period before seroconversion, 8% of those in the asymptomatic period infected their partners over one year, and 37% of those with AIDS symptoms infected their partners between 6 months and 3 years before their deaths. 

·         On average, after infection the viral load peaks in the blood at about day 17, and then peaks in sexual fluids between 28 and 31 days (4 weeks) after infection. Once antibodies are formed, the viral load collapses dramatically. By the time of seroconversion (approximately 10 weeks after infection), the viral load has dropped to 125,000 parts per ml in blood, and 1,000 parts per l in semen.⁶ 

·         Between 50% and 90% of people infected with HIV, who are in the PHI stage, experience clinical symptoms that resemble flu or mononucleosis, but  -significantly - without nasal congestion: Fever, maculopapular rash, muscle or joint pains, and night sweats. These symptoms are the most significant predictors of PHI, and are called ARS (Acute Retroviral Syndrome). Other common symptoms (but not significant predictors of ARS) include swollen lymph nodes, a sore throat, diarrhoea, and headache. ARS symptoms are nonspecific, and a differential diagnosis for ARS would include mononucleosis, viral hepatitis, secondary syphilis, herpes, and meningitis. ARS symptoms tend to commence anywhere from 2 days to 6 weeks after infection, last on average 14 days, and disappear at the same time as seroconversion from HIV-negative to HIV-positive.¹⁶ 
·         Many of the people experiencing ARS symptoms seek medical services for their symptoms. Most clinicians are unaware of the significance of PHI and the existence of ARS. Consequently, when patients present with such ARS symptoms they are usually misdiagnosed^{12, 18}. Also, no HIV risk assessment is done (checking for recent high risk sexual activities), and – most importantly – the opportunity to advocate risk-reduction behaviours to protect sexual partners is missed entirely.   

·         Although research is still in its early stage, it appears that the severity of ARS – and the treatment thereof – is a highly significant predictor of the speed of subsequent progression of HIV to AIDS.  This relates to the ‘viral set point’ established by HIV during PHI. ¹² 

·         Current HIV testing and counselling procedures do not take ARS symptoms into consideration when assessing risk for HIV.  The opportunity for partner-notification and protection when a person tests HIV-negative is lost.  Although standard HIV testing protocols advise those who test HIV-negative to return 3 months later to confirm their status, rarely is much time spent on educating the person on the extreme risks associated with being in the PHI period, or what to look out for in terms of ARS. In developed countries such as the USA, PHI is detected using either PCR or a viral load test. For example, if a person is indeed infected with HIV but is in the PHI period, then a viral load test will detect 97% of such cases: Any viral load above 1,000 is considered evidence for being infected with HIV, even if the antibody test is negative. A cheaper option is the P24 antigen test, which can detect approximately 80% of such cases. It is more accurate when the person is experiencing ARS symptoms, and less accurate once those symptoms subside.^{12, 17} 

Applications and recommendations 

Developed countries have already implemented routine screening of viral load levels, and protocols exist for detecting and treating PHI.  However, in developing countries – where viral load testing is not routine in the public health sector – different strategies are required to apply these developments.  It is inevitable that debate will ensue regarding the increased availability of equipment and trained personnel to conduct routine viral load testing, not only for those living with HIV, but also for those who test negative and are suspected of being in the PHI stage of infection. Our primary initial objective should be to engage health care workers, and inform such personnel of the nature and details of both viral load fluctuations and PHI. Apart from the treatment and management of symptoms, health care workers need to be informed of the implications for transmission of HIV, and begin conscious screening for PHI, provide risk-reduction advice and referrals, as well as provide accurate information regarding various health and lifestyle practices that impact viral load levels. Guidelines in this regard need to be urgently developed. In preparation of the inevitable technological and medical applications of viral load monitoring, HIV/AIDS health educators need to broaden their curricula to include germ theory, primary health care, the dynamic relationship between TH1 and TH2 immune systems, and the nature of viral activity. It is no longer adequate to merely deliver simplistic – and inaccurate – information about HIV transmission to the public.  HIV/AIDS educators would also be advised to ‘mainstream’ HIV education to include primary health prevention methods, as these would reduce the number and severity of co-infections that cause viral load spikes, which in turn increase probabilities of HIV transmission. In the absence of widespread viral load technology, interim public messaging needs to be developed so that the public may benefit from this increase in knowledge. For example, it is a simple biological fact that viral loads will spike when a person living with HIV has some other illness. Therefore, messaging concerning taking precautions – such as abstaining from sex and wearing condoms – when you are ill would be appropriate. There is also an urgent need to various sectors involved in social development and service delivery to become aware of the impact that their services have upon aggregated viral load activity in communities, due to issues such as the state of a community’s primary health, and access to health services.   The private sector – especially those involved in food supplies – need to become aware of the impact that specific nutritional elements (e.g., selenium) have upon HIV transmission. Government subsidies of suppliers needs to be linked to both the quantity and quality of fortification of foods. It is also evident that research needs to be conducted to ascertain the precise extent of the impact of PHI in HIV transmission in Southern Africa.  It is apparent that there is already a range of practical steps that can be implemented to integrate the new paradigm into existing HIV transmission reduction methods, without throwing ABC out of the window. Neither the biological or behavioural paradigms are article of faith: They are methods to achieve an objective. We merely need to revise and integrate the old and the new strategies, keeping our collective eyes firmly on the ultimate goal: Zero HIV transmission.    

References 1.       How does male circumcision protect against HIV infection?: Szabo, R. & Short, R.V., British Medical Journal, 2000 (10 June), 320: 1592-1594. 2.       Why is HIV prevalence so severe in Southern Africa? Halperin D.T. & Epstein, H., The Southern African Journal of HIV Medicine, March 2007: 19-25. 3.       Swiss experts say individuals with undetectable viral load and no STI cannot transmit HIV during sex; http://www.aidsmap.com/en/news/4E9D555B-18FB-4D56-B912-2C28AFCCD36B.asp: Comment on: Les personnes séropositives ne souffrant d’aucune autre MST et suivant untraitment antirétroviral efficace ne transmettent pas le VIH par voie sexuelle; Vernazza P et al., Bulletin des médecins suisses 89 (5), 2008. 4.       Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: A prospective cohort analysis; Donnell, D. et al; June 2010;  Lancet 275(9731):2092-2098.  5.       Amplified HIV Transmission and New Approaches to HIV Prevention: Cohen, M.S. & Pilcher, C.D.; Journal of Infectious Diseases, May 2005:191 (1391-1393). 6.       Amplified transmission of HIV-1: comparison of HIV-1 concentrations in semen and blood during acute and chronic infection: Pilcher, C.D. et al., August 2007, AIDS 21(13): 1723-1730. 7.       Suppression of human immunodeficiency virus type 1 viral load with selenium. A randomised controlled trial: Hurwitz BE et al.; 2007,  Archives of  Internal Medicine, 167: 148-154 8.       Randomized, Controlled Clinical Trial of Zinc Supplementation to Prevent Immunological Failure in HIV‐Infected Adults: Baum, M. K., et al., June 2010, Journal of Clinical Infectious Diseases.  9.       Nutrients and HIV: Part 2- Vitamins A and E,  Zinc, B-vitamins and Magnesium, Painter, F.M., http://www.chiro.org/ nutrition/ABSTRACTS/Nutrients_and_HIV_2.shtml, extracted from Alternative Medicine Review, Patrick, L., 2000 (Feb), 5(1), 39-51.  10.    Treatment of intestinal worms is associated with decreased HIV plasma viral load; Wolday, D., et al., Journal of AIDS, September 2002, 31(1), p56-62.   11.    Treatment of helminth co-infection in HIV-1 infected individuals in resource-limited settings: Walson JL, John-Stewart, G., Cochrane Database Syst Rev. 2008 Jan 23;(1):CD006419. 12.    Recognising and Diagnosing Primary HIV Infection; http:/thebody.com 13.    How many sexually-acquired infections in the USA are due to acute-phase HIV transmission?:  Pinkerton, S.D., et al 2007, Journal of AIDS, 21:pp1625-1629. 14.    High rates of forward transmission events after acute/early HIV-1 infection: Brenner, B.G. et al., April 2007, Journal of Infectious Diseases, 195:pp.951-959. 15.    Rates of HIV-1 transmission per coital act by stage of HIV-1 infection, in Rakai, 16.    Primary HIV Infection; http:/thebody.com 17.    Primary HIV Infection: Clinical manual for management of the HIV-inf

18.    Prevention during Acute HIV Infection (AHI): New York/New Jersey AETC, 01/2006; www.aids-ed.org