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Individuals capable of naturally controlling HIV infection in the absence of ART represent both a diagnostic and a management challenge for the treating clinician. In this chapter, we review what is known about the epidemiology, biology, and clinical outcomes of individuals across the clinical spectrum of natural HIV control and provide suggestions for the management of such individuals in a clinical setting.

AIDS Clinical Trials Group study A5308 found reduced T-cell activation and exhaustion in human immunodeficiency virus (HIV) controllers start antiretroviral therapy (ART). We further assessed HIV-specific T-cell responses and post-ART viral loads. Before ART, the 31% of participants with persistently undetectable viremia had more robust HIV-specific T-cell responses. During ART, significant decreases were observed in a broad range of T-cell responses. Eight controllers in A5308 and the Study of the Consequences of the Protease Inhibitor Era (SCOPE) cohort showed no viremia above the level of quantification in the first 12 weeks after ART discontinuation. ART significantly reduced HIV-specific T-cell responses in HIV controllers but did not adversely affect controller status after ART discontinuation.

Background Limited data are available on whether there are differences in the immune response to SARS-CoV-2 vaccination by HIV status or by mRNA vaccine type. Methods We saved residual outpatient laboratory samples of all previously mRNA-vaccinated individuals in the adult medicine clinics of a public hospital with a large outpatient HIV clinic during May 2021, and then excluded individuals with prior SARS-CoV-2 infection. We next 1:1 matched 100 PLWH to 100 outpatient HIV-negative adult medicine patients receiving care for chronic medical conditions on days since completion of second vaccination (minimum 10), sex, age +/-5 years, and the type of mRNA vaccine received. We defined a non-response as reciprocal pseudovirus neutralizing titer< 10 and anti-RBD IgG< 10 relative fluorescent units, and compared non-response by HIV status using mixed models. Results In each matched group there were 13 women; 25 received the mRNA-1273 vaccine and 75 received the BNT162b2 vaccine; the median age was 59. The median time from second vaccination was 35 days (IQR: 20–63). Among PLWH, the median CD4+ T-cell count was 511 (IQR: 351–796) and 5 individuals had HIV RNA > 200. We found 2.4-fold greater odds of pseudovirus neutralizing antibody non-response among PLWH compared to people without HIV (95% CI=1.1–5.4). Although few individuals in each group did not mount an IgG response (12 among PLWH vs. 5; p=0.08), continuous anti-RBD IgG concentrations were 43% lower among PLWH (95% CI=0.36–0.88). Among PLWH, when adjusting for age, sex, and days post-vaccination, each 100-cell increase in CD4+T-cell count was associated with 22% higher neutralizing antibody titers (GMR 1.22; 95% CI=1.09–1.37). Unsuppressed HIV RNA >200 was associated with 89% lower neutralizing antibody titers (GMR 0.11; 95% CI=0.01–0.84). Receipt of the BNT162b2 vs. mRNA-1273 vaccine was associated with 77% lower neutralizing titers (GMR 0.23; 95% CI=0.08–0.65) among PLWH. Post-mRNA Vaccination SARS-CoV-2 IgG Concentrations and Pseudovirus Neutralizing Titers by HIV Status and Vaccine Conclusion PLWH had lower than expected response to mRNA SARS-CoV-2 vaccines, with the highest non-response among those with low CD4+ counts, unsuppressed HIV RNA, and those who received the BNT162b2 vaccine. Immunization strategies to improve immune responses among PLWH should be studied, and may include booster vaccination or preference of the mRNA-1273 vaccine in this group. Disclosures Matthew A. Spinelli, MD, MAS, Nothing to disclose Monica Gandhi, MD, MPH, Nothing to disclose

Background Identification of nonviral markers of human immunodeficiency virus (HIV) infection that increase before viral rebound during analytical treatment interruption (ATI) may affect HIV persistence research. We previously showed that HIV ribonucleic acid (RNA) is enriched in CD30+CD4+ T cells in many individuals. Here, we studied CD30+CD4+ T-cell dynamics before ATI, during ATI (before detectable plasma RNA), and after HIV rebound. Methods Peripheral blood mononuclear cells from 23 participants collected longitudinally from 5 Adult AIDS Clinical Trials Group studies incorporating ATI were included in this study. Flow cytometric characterization of expression of CD30 and markers of T-cell activation and exhaustion were performed along with HIV-1 RNA and deoxyribonucleic acid quantification and measurement of soluble plasma CD30 and CD30 ligand. Results The percentage of CD4+ T cells expressing CD30 significantly increased from pre-ATI to postinterruption time points before detectible viremia (1.65 mean relative increase, P = .005). Seventy-seven percent of participants experienced an increase in CD30+ cells before viral rebound. In contrast, there were no significant differences between pre-ATI and postinterruption pre-rebound time points in percentages of lymphocytes expressing CD69, CD38/HLA-DR, or PD-1 until after HIV recrudescence. Conclusions CD30 may be a surrogate marker of early replication or viral transcriptional activity before detection by routine peripheral blood sampling.

Disseminated sporotrichosis may present with inflammatory arthritis and cutaneous ulcerations that mimic noninfectious skin conditions such as pyoderma gangreonsum (PG). Sporotrichosis must therefore be ruled out before administering immunosuppressive agents for PG. Furthermore, dimorphic fungi such as sporotrichosis may grow as yeast in bacterial cultures, even before fungal cultures become positive. We present a case of disseminated cutaneous and osteoarticular sporotrichosis mimicking PG and describe the differential diagnosis and the diagnostic and treatment approach to this condition.

Background The use of immunomodulatory drugs (IMDs) is increasingly common. However, data on outcomes of IMD use in people living with HIV (PLWH) are limited and may be biased due to selective reporting of certain outcomes. Institution-level data reflecting patient-time at risk have not been described. Methods We systematically identified all PLWH prescribed non-steroidal IMDs from 2012 to 2019 at two centers. We defined a treatment episode (TE) as an uninterrupted period on a particular IMD regimen. Patients contributed multiple TEs if interrupting or switching therapy. We excluded those with lymphoproliferative disorders or transplants. We quantified infections and blips, defined as a detectable viral load following an undetectable result. Results 35 patients contributed 55 TEs comprising 24,020 patient-days at risk. 29/35 (83%) were male, median age was 53 (IQR 39–59), median CD4 nadir was 197 (IQR 100–314), and 12/35 (34%) had a prior opportunistic infection. TEs utilized TNF inhibitors (19/55, 35%), PD-1 inhibitors (11/55, 20%), antimetabolites (7/55, 13%), interleukin inhibitors (7/55, 13%), and other agents (7/55, 13%). 4/55 (7%) involved in dual therapy. 32/35 (94%) patients were on antiretroviral therapy (ART) at IMD initiation; one was off therapy, one already on IMDs-acquired HIV, and one was an elite controller. Median CD4 count was 472 (IQR 337–807); CD4 was < 500 in 28/55 TEs (51%). Preceding plasma HIV RNA was undetectable in 36/55 (65%) TEs. Of these, 18 (50%) were associated with a viral blip within 1 year; one blip was >200 copies and none resulted in sustained viremia. Compared with other agents, PD-1 inhibitors were associated with a higher blip rate (incidence rate ratio 4.3, 1.3–12.3). 17/55 (32%) TEs were initiated with detectable plasma HIV RNA, which declined on ART in 13/15 (87%) TEs with follow-up testing; one patient stopped ART and one later suppressed. 9/55 (16%) TEs involved an infectious complication (7 soft-tissue infections, 2 pneumonias), although none was clearly attributed to IMDs. 36/55 (65%) TEs had good therapeutic response. Conclusion IMDs can be used without major complications in PLWH on ART, including those not yet suppressed or with CD4 counts < 500. PD-1 inhibitors may be associated with a higher rate of viral blips, although the clinical significance is unclear. Disclosures All authors: No reported disclosures.