Public Health Priorities: Stock Outs, Treatment Interruption and HIV Drug Resistance.

Author: Lenias Hwenda

UN City, Copenhagen: There is widespread hope that the HIV/AIDS epidemic ceases to be a major global public health threat, but the gains made are in grave danger of being reversed as a result of growing resistance to HIV medicines. The world is increasingly facing an urgent public health crisis of growing resistance to HIV treatment. This crisis is greatest in the Africa region, where increased access HIV treatment has significantly reduced AIDS-related deaths. 

In nine African countries surveyed in a recent survey carried out between 2011 and 2016 that included Cameroon, Eswatini, Malawi, Mozambique, Nigeria, South Africa, Togo, Uganda and Zimbabwe shows, one in two children newly diagnosed with HIV showed resistance to the most commonly used ARV medicines before treatment initiation. The data showed changes to the structure of the virus in newly diagnosed infants, mutations that reduced the ability of particular treatment combinations to prevent the replication of the virus rendering it resistant to specific treatment.
 
The most troubling trend is that people with no history of HIV treatment and therefore exposure to medications or those re-initiating first line treatment are showing pre-treatment drug resistance. The levels of resistance can be quite high with countries like Cameroon, Eswatini, Namibia and Uganda reporting pre-treatment resistance levels to the commonly used first-line HIV treatment exceeding 10%. This means there are no treatment options entire cohort of patients within populations who will require more costly second line treatments to achieve viral suppression and minimize transmission. 
 
Children and adolescents on treatment are at higher risk of resistance emergence. This presents a huge challenge in a global context in which we have very limited availability of pediatric formulations and limited treatment options for children in the first place. Losing the few available treatments available for children due to due viral resistance, diminishes our ability to treat children even further. 
 
Optimizing treatment regimes in order to prevent drug resistance is a critical public health intervention, especially in the Africa region, which is home to 66% of all new infections and 70% of the world’s people living with HIV. The WHO has updated its treatment guidelines in 2019 recommending that countries transition to integrase-based inhibitor with a high genetic barrier to resistance such as Dolutegravir (DTG). Integrase inhibitors are expected to have lower HIV drug resistance, in fact lower than current first line treatments, even if there is still a risk that drug resistance may develop. DTG is taken in a single dose daily, is well tolerated, causes rapid viral load suppression. It demonstrates a high genetic barrier to resistance, has few drug interactions, is available in fixed dose generic formulation and its price is comparable to efavirenz (EFV) containing regimens in low- and middle-income countries (LMICs). DTG has demonstrated superior outcomes in the majority of critical outcomes supported by high quality evidence than efavirenz (EFV). 
 
DTG is now the preferred option in first line treatment due to its improved efficacy and durability. EFV400 is an alternative 1st line option as it shows improved tolerability and less treatment discontinuation when compared with EFV600. It is comparable in terms of critical efficacy outcomes, but it better tolerated and is less frequently discontinued due adverse effects compared with EFV600 containing regimens. The is moderate to high quality of evidence supporting this. It can be safely used in TB and fixed-dose generic formulations are available. 
 
With all current antiretroviral drugs, including newer classes facing the risk of becoming partially or fully inactive, countries need to closely monitor, prevent and respond to drug resistance. Countries need to develop national HIV drug resistance strategic plans that are fully integrated into routine monitoring and evaluation activities. National strategic plans will need to ensure effective demand forecasting and timely procurement in order to prevent frequent stock outs of ARVs which contributes to viral drug resistance. Similarly, poor retention lead to treatment interruption which fuels resistance and undermine treatment.
 
The new treatment guidelines recommends the use of TAF only in special situations in adults with renal impairment/osteoporosis. It is also an alternative option in children. There are no demonstrated significant clinical advantage with the use of TAF over TDF in adults without renal or bone problems. Critical efficacy and toxicity outcomes are comparable and differences occur only in lab markers. Safety data in young children is limited. The biggest challenges going forward is ensuring that there is global supply security for the recommended treatment regimens, and global supply pipeline shows great promise in new products coming to market.