Systemic lupus erythematosus and related autoimmune manifestations in people living with HIV-1 in the antiretroviral therapy era: phenotypes, mechanisms and clinical implications

People living with human immunodeficiency virus type 1 (HIV-1) who take antiretroviral therapy (ART) now have near-normal life expectancy, and clinicians increasingly meet autoimmune features in this population. Low-titre autoantibodies are common, lupus-like organ disease such as HIV-associated immune complex kidney disease occurs, and classifiable systemic lupus erythematosus (SLE) is reported infrequently, which seems paradoxical in an infection defined by loss of CD4 T cells. This narrative review summarises recent clinical and immunological literature on lupus-like autoimmunity in people with HIV on ART. It separates three phenotypes (serological autoreactivity, lupus-like organ disease without SLE, and classifiable SLE) and summarises epidemiological studies, which conflict, and serological studies, which often lack comparators and standardised assays. Case-level reports, including a 2026 review of 165 published cases, indicate that SLE tends to remit as HIV advances and that manifestations cluster after ART-driven immune recovery. The review examines mechanisms discussed in the literature, including polyclonal B-cell activation, T follicular helper and extrafollicular B-cell pathways, type I interferon, neutrophil extracellular traps, envelope mimicry and immune reconstitution, and uses three evidence tiers to distinguish human tissue data from ex vivo, animal or indirect evidence. Persistence of virus in lymphoid tissue and macrophages during ART is established, but we found no study linking viral persistence to autoantibody production or lupus-like disease. The review also presents a differential diagnosis for lupus-like features in people with HIV, summarises management considerations, and identifies gaps in the evidence, with attention to high-burden settings such as sub-Saharan Africa.