In the early 2010s, significant challenges emerged in the fight against HIV, particularly in Portuguese-speaking African countries where healthcare infrastructure struggled to provide adequate access to antiretroviral therapy (ART). The lack of ART availability in these countries at that time led to poorer health outcomes for those living with HIV. Now, with ART widely available, but with deficient clinical and laboratory follow-up of patients, the emergence and spread of drug resistance mutations pose a serious threat. Concurrently, the tuberculosis (TB) pandemic evolved into a crisis, characterized by increasing cases of drug-resistant TB, with Portugal experiencing one of the highest incidences of TB in Western Europe, raising alarms about multidrug-resistant TB (MDR-TB).
Recent Work on HIV
To address the pressing issue of HIV-1 drug resistance, GHTM collaborators Anne-Mieke Vandamme and Ricardo Camacho have focused on developing diagnostic tools and clinical decision-making algorithms tailored to patients with drug resistance mutations. One notable achievement is RegaDB, an open-source bioinformatics platform designed to store, manage, and analyze HIV patient data by integrating clinical and virological information. The collaboration between Camacho, Vandamme, the World Health Organization (WHO), and other leading international groups, such as those in Utrecht and Stanford, has also been pivotal for developing and standardizing testing and interpretation algorithms for HIV drug resistance, thereby influencing treatment protocols now employed internationally.
The BEST HOPE study, conducted in partnership with hospitals across Portugal, established a cohort of newly diagnosed HIV patients to examine the prevalence of transmitted drug resistance (TDR) and analyze factors associated with the transmission of HIV infection and the spread of HIV-1 drug-resistant strains. The research team, including GHTM members Ana Abecasis, Maria do Rosário Oliveira Martins, Marta Pingarilho, and Victor Pimentel, found that a significant portion of patients exhibited resistance to at least one class of antiretroviral drugs. These findings underscore the critical need for ongoing monitoring to inform effective first-line treatments. Insights gained from this initiative have enhanced the understanding of HIV transmission dynamics and drug resistance in Portugal, paving the way for more targeted treatment and prevention strategies nationwide.
Recent Work on TB
In collaboration with the London School of Hygiene and Tropical Medicine – Faculty of Infectious and Tropical Diseases, led by Prof. Taane Clarke, GHTM researchers have identified thousands of mutations linked to resistance against both first and second-line anti-TBdrugs thata are now gathered in the WHO Catalogue of mutations in Mycobacterium tuberculosis complex and their association with drug resistance.
This work culminated in the development of TB-Profiler, a global reference database that analyzes whole genome sequencing data of Mycobacterium tuberculosis to predict drug resistance and identify bacterial lineages. TB-Profiler is widely utilized to enhance tuberculosis management by detecting resistance mutations, thus facilitating personalized treatment decisions and targeted public health interventions. The database is accessible online and through command-line tools, featuring a continuously updated library of mutations contributed by the research community, making it an invaluable resource for TB diagnostics and epidemiological studies.
Notably, since 2017, Portugal has not reported any cases of extensively drug-resistant TB (XDR-TB), and instances of multidrug-resistant TB (MDR-TB) are minimal, with therapeutic success rates for TB exceeding 85%. This success highlights the impact of ongoing research and effective public health strategies in combatting TB.
Partnerships with Portuguese-Speaking Countries
GHTM is also committed to fostering a network of HIV-1 specialists in Portuguese-speaking African countries (PALOPs). Projects like MARVEL and Hitola leverage next-generation genomic surveillance to characterize the molecular epidemiology, transmission dynamics, and drug resistance patterns of the virus in these regions.
Additionally, GHTM has actively promoted the dissemination of cutting-edge knowledge through TB networks such as REDE-TB-Brasil, RIDES TB and CPLP-TB, in close collaboration with European entities like the European Society of Mycobacteriology and the European Society of Clinical Mycobacteriology and Infectious Diseases. These partnerships are crucial for enhancing regional capabilities in managing both HIV and TB, ultimately improving health outcomes across Portuguese-speaking nations.