Elizabeth Irungu

This session moderated by the IAS co-chairs highlighted results from a comparative analysis of HIV accessory proteins nef and vpu, 26-week data on long-acting subcutaneous lenacapavir, recent HIV infection from surveillance activities in Cambodia and impact of COVID-19 on HIV treatment programs in Africa

Gisele Umviligihozo reported that Vpu mediated CD4 and Tetherin downregulation functions were similar between long-term non-progressors and chronic progressors from Africa, but that Nef-mediated HLA downregulation was lower among long-term non-progressors compared chronic progressors. Week 26 data from the Phase 2/3 Capella study of long-acting subcutaneous lenacapavir among PLWH failing their current regimen with multidrug-resistance demonstrated sustained virologic suppression in 81% of participants, clinical improvements in CD4 counts and high tolerability, as presented by Jean-Michel Molina. Of four participants who developed emergent lenacapavir resistance, two resuppressed without change in their background regimens. HIV infection surveillance conducted between Mar-Dec 2020 in Cambodia revealed that of those newly diagnosed with HIV, 7% were recent infections. Penh Sun Ly reported that recent infections were more frequent among those aged 20-34 years, entertainment workers, and men who have sex with men (MSM). Neha Mehta reviewed treatment interruptions during the COVID period among individuals in seven PEPFAR-supported countries. Overall, 42,133 patients experienced interruptions in the quarter with most restrictive measures (April-June 2020), compared to 51,966 in the quarter prior and 37,780 in the quarter after. Interruptions did not increase likely because innovative strategies like multi-month dispensing and community ART access were rapidly adopted.

Advances in our understanding and management of HIV treatment were highlighted. Delayed clinical disease among long-term non-progressors is not fully characterized and knowledge of the functional diversity of HIV accessory proteins may help address this gap. The 26-week efficacy of results from the Capella study which demonstrate high potency are encouraging for people struggling with drug resistance resulting from poor adherence to daily regimens. However, further work is required to understand emergent lenacapavir resistance. Finally, the COVID pandemic has propelled implementation of adaptations in HIV programs that have simplified ART delivery and it is hoped that these will be sustained.

Rayner Tan

The IAS 2021 co-chairs’ choice session showcased late-breaker abstracts across each scientific track. These abstracts highlighted the role of HIV-1 accessory proteins in African LTNPs and chronic progressors, efficacy and safety of long-acting subcutaneous Lenacapavir, recent HIV infection surveillance in Cambodia, and the impact of COVID-19 on HIV treatment interruption.

Gisele UMVILIGIHOZO (Canada) presented a comparative functional analysis of HIV-1 accessory proteins Nef and Vpu in African long term non-progressors (LNTP) and chronically infected individuals (CI). Results indicated variable Nef and Vpu activity in LTNPs versus CI, and that reduced ability of Nef to downregulate HLA may contribute to slower disease progression in African LNTPs. Jean-Michel MOLINA (France) presented week 26 (W26) results of the Capella study, which showed that for highly treatment-experience people living with HIV, subcutaneous Lenacapavir, in combination with an optimized background regimen led to high rates of virologic suppression (81%), and meaningful increases in CD4 counts (22% CD4<50 at baseline; none by W26). Penh SUN LY (Cambodia) utilized national data in Cambodia from March through December 2020 when recent HIV infection surveillance was introduced, and found that recent infections were significantly higher among clients aged 20-34 years (p<0.001), entertainment workers (p=0.001), and men who have sex with men (p<0.001) compared to those with long-term infections. Neha MEHTA (United States) analyzed quarterly program data from CDC HIV treatment sites across seven PEPFAR-supported countries with high ART coverage, and found that treatment interruptions were 23% higher, and 10% lower in the quarters before and after the lockdowns, respectively.

Presenters pointed out future directions and study implications. First, further characterization of Nef and Vpu sequences linked to their functional diversity may identify specific motifs that influence natural variation in viral pathogenesis and differential disease outcomes. Second, LEN may potentially be a safe and effective agent for highly treatment-experienced people living with HIV. Third, continued surveillance of recent HIV infections will inform prevention programs and differentiated service delivery models for key populations in Cambodia. And last, given variations in treatment interruption across countries, that more work should be done to examine the implications of country-specific COVID-19 policies on such interruptions.