Dr. Andrew Hill, MD, is a senior visiting Research Fellow in the Pharmacology Department at Liverpool University. His main research is on antiretroviral treatment for developing countries.  He is an advisor to the Clinton Foundation and the Bill and Melinda Gates Foundation, designing clinical trial programs of dose optimization for antiretrovirals.

Dr. Hill is graduated from Oxford University, and later completed a PhD at Amsterdam University.  He has worked on the development of antiretrovirals for HIV since 1992, starting with 3TC at GlaxoWellcome, and later on saquinavir at Roche.  He does consultancy work for Tibotec on the clinical trial programsfor darunavir, etravirine, and rilpivirine. 

 Andrew Hill is the author of over 40 research papers on HIV. He has been on the editorial board of “AIDS” and is currently an editor for the “Journal of Antimicrobial Chemotherapy”. 

The title of his presentation at our Congress was “Assesing the weight of the evidence: 4 yearst after Advance”


What are the parameters you have considered in your clinical trials to determine the optimal doses of antiretrovirals: Safety, adverse reactions, toxicity, efficacy adherence, costs…? Should the same parameters be applied in developed and developing countries?

Decisions on the dose of antiretrovirals are a compromise between efficacy and safety.  In dose ranging Phase 2 trials, we look for doses which maximise HIV RNA suppression while minimising serious adverse events.  Phase 2 dose-ranginf trials are normally conducted in populations of mainly males in Europe and North America.  However women in developing countries experience more adverse events than those in Europe and North America.  We have seen this problem with d4T (lactic acidosis), weight gain (integrase inhibitors) and CNS adverse events (efavirenz).

What are the current differences in the choice, implementation and outcomes of antiretroviral treatment between developed and developing countries?

In developing countries, the most widely used combination is TDF/3TC/DTG, which costs $40 per person-year. In developing countries this fixed dose combination is not available.  People with HIV in Europe tend to take other similar combination treatments which have similar efficacy and safety profiles to TDF/3TC/DTG, but much higher prices.  For example the combination of TAF/FTC/BIC can cost over $10,000 per year.  From 2027 onwards, the patents on DTG will start to expire.  This will then allow people worldwide to take generic TDF/3TC/DTG.   It is not clear whether branded combination treatments will have a major role in the treatment of HIV after 2027.

What antiretroviral treatment would it be of choice to initiate in an adult newly diagnosed with HIV infection in a developed and developing country? What treatment would you use in the event of failure of the first antiretroviral treatment used in both cases?

The World Health Organisation guidelines recommend TDF/3TC/DTG as first-line treatment.  The use of TAF is only listed as an alternative treatment, because of higher risks of weight gain and clinical obesity.  It is not clear whether most people actually “fail” TDF/FTC/DTG when viraemia is first detected.  Most people experiencing viraemia can re-suppress their HIV RNA by re-starting TDF/3TC/DTG with enhanced adherence counselling.  There may only be a limited role for second-line therapy after TDF/3TC/DTG.

Do you think it will be possible to further simplify current antiretroviral treatment regimens? Are you currently conducting any clinical trials in this direction?

People taking protease inhibitors could be switched to fixed dose combinations of 2NRTI+INSTI.  This is already happening in sub-Saharan Africa and could be implemented elsewhere.

You have explained in some forums that the weight gain observed after starting the TAR is due to both individual drugs and certain combinations. According to the latest available data or studies, what drugs or combinations would we be talking about in relation to increased weight gain?

There are several risk factors for weight gain.  Women and people of black or Hispanic race tend to show greater rises in weight.  Also, low CD4 count and advanced HIV disease are associated with higher risks of clinical obesity.  The use of either TDF or EFV tends to suppress weight gain.  It is not clear whether all weight gain is a “return to health”.  People with the lowest CD4 counts tend to show the highest risks of clinical obesity when taking TAF-based treatment.

You have also expressed the need for the studies to include more black women, who are the majority of those infected, so that we can really move forward with an answer. …is it? What other aspects should be considered to improve these studies?

Worldwide, most people living with HIV infection are of black race: of these, most are women.  However, clinical trials conducted by pharmaceutical companies over-represent men and Caucasians.  We need to have new guidelines to ensure that at least 50% of people enrolled in clinical trials are women, and that races are represented fairly.

Can we quantify how this weight gain affects people with HIV in terms of health, e.g., increased risk of diabetes, kidney disease, cardiovascular disease, etc.? In other words, what data do we have on how administering drugs or combinations that have less impact on weight improves the health of our patients?

People with clinical obesity have a higher risk of many adverse outcomes: for example hypertension, metabolic syndrome, diabetes, cardiovascular disease and adverse birth outcomes. The first-line use of TDF/3TC/DTG leads to lower risks of clinical obesity than combinations like TAF/FTC/DTG or TAF/FTC/BIC, or dual therapies like DTG/3TC.