Search

Background Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination reduces the risk and severity of coronavirus disease 2019 (COVID-19), several variables may impact the humoral response among patients undergoing hematopoietic stem cell transplantation (HSCT). Methods A retrospective chart review was conducted among SARS-CoV-2-vaccinated HSCT recipients between 2020 and 2022 at a single center in Boston, Massachusetts. Patients age ≥18 years who received doses of Pfizer, Moderna, or J&J vaccines were included. Anti-spike (S) immunoglobulin G (IgG) titer levels were measured using the Roche assay. Responders (≥0.8 U/mL) and nonresponders (<0.8 U/mL) were categorized and analyzed. Multivariable linear and logistic regression were used to estimate the correlation coefficient and odds ratio of response magnitude and status. Results Of 152 HSCT recipients, 141 (92.8%) were responders, with a median (interquartile range [IQR]) anti-S IgG titer of 2500 (107.9–2500) U/mL at a median (IQR) of 80.5 (36–153.5) days from last dose, regardless of the number of doses received. Higher quantitative titers were associated with receipt of more vaccine doses (coeff, 205.79; 95% CI, 30.10 to 381.47; P =.022), being female (coeff, 343.5; 95% CI, −682.6 to −4.4; P =.047), being younger (<65 years; coeff, 365.2; 95% CI, −711.3 to 19.1; P =.039), and not being on anti-CD20 therapy (coeff, −1163.7; 95% CI, −1717.7 to −609.7; P =.001). Being male (odds ratio [OR], 0.11; 95% CI, 0.01 to 0.93; P =.04) and being on anti-CD20 therapy (OR, 0.16; 95% CI, 0.03 to 0.70; P =.016) were associated with nonresponse. Conclusions Overall, most HSCT recipients had high SARS-CoV-2 antibody responses. More vaccine doses improved the magnitude of immune responses. Anti-S IgG monitoring may be useful for identifying attenuated vaccine-induced responses. [ABSTRACT FROM AUTHOR]

Background In 2019, the World Health Organization (WHO) recommended combined tenofovir disoproxil fumarate, lamivudine, and dolutegravir (TLD) as the preferred first-line regimen for adults and adolescents with human immunodeficiency virus (HIV), regardless of childbearing status. Nevertheless, final eligibility is determined by local policies, which may vary from WHO recommendations. We examined TLD transition by sex across 5 HIV care programs in sub-Saharan Africa supported by the United States President's Emergency Plan for AIDS Relief (PEPFAR) Methods The African Cohort Study (AFRICOS) enrolls people with HIV engaged in care in Uganda, Kenya (South Rift Valley and Kisumu West), Tanzania, and Nigeria. People with HIV with ≥1 study visit after the country introduced TLD were included. We generated Kaplan-Meier curves to compare TLD transition by sex from (1) the time countries introduced TLD and (2) the time of TLD eligibility according to local policies. Results Among 2476 participants enrolled through September 2021 at 4 sites in sub-Saharan Africa and eligible to transition to TLD, fewer women (68%) than men (80%; P <.001) were taking TLD. Kaplan-Meier analysis showed that time to transition varied by site, with women in Tanzania transitioning at the same rate as men. In Nigeria, women initially had a slower transition but caught up to men. After adjustment for local policies, women in Kisumu West transitioned at the same rate as men. In South Rift Valley and Uganda, women were less likely to be transitioned. Conclusions Although TLD has been the WHO's preferred regimen since 2019, transition of women to potentially lifesaving TLD has been slower than for men at certain clinical sites, even after accounting for local eligibility criteria. [ABSTRACT FROM AUTHOR]

Background Introduction of antiretroviral therapy (ART) has been associated with a decline in human immunodeficiency virus (HIV)-related mortality, although HIV remains a leading cause of death in sub-Saharan Africa. We describe all-cause mortality and its predictors in people living with HIV (PLWH) in the African Cohort Study (AFRICOS). Methods AFRICOS enrolls participants with or without HIV at 12 sites in Kenya, Uganda, Tanzania, and Nigeria. Evaluations every 6 months include sociobehavioral questionnaires, medical history, physical examination, and laboratory tests. Mortality data are collected from medical records and survivor interviews. Multivariable Cox proportional hazards models were used to calculate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for factors associated with mortality. Results From 2013 through 2020, 2724 PLWH completed at least 1 follow-up visit or experienced death. Of these 58.4% were females, 25.8% were aged ≥ 50 years, and 98.3% were ART-experienced. We observed 11.42 deaths per 1000 person-years (95% CI: 9.53–13.68) with causes ascertained in 54% of participants. Deaths were caused by malignancy (28.1%), infections (29.7%), and other non-HIV related conditions. Predictors of mortality included CD4 ≤ 350 cells/µL (aHR 2.01 [95% CI: 1.31–3.08]), a log10copies/mL increase of viral load (aHR 1.36 [95% CI: 1.22–1.51]), recent fever (aHR 1.85[95% CI: 1.22–2.81]), body mass index < 18.5 kg/m2 (aHR 2.20 [95% CI: 1.44–3.38]), clinical depression (aHR 2.42 [95% CI: 1.40–4.18]), World Health Organization (WHO) stage III (aHR 2.18 [95% CI: 1.31–3.61]), a g/dL increase in hemoglobin (aHR 0.79 [95% CI:.72–.85]), and every year on ART (aHR 0.67 [95% CI:.56–.81]). Conclusions The mortality rate was low in this cohort of mostly virally suppressed PLWH. Patterns of deaths and identified predictors suggest multiple targets for interventions to reduce mortality. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic and associated public health responses have disrupted daily living activities with economic and health consequences globally. We observed transient decreases in human immunodeficiency virus (HIV) clinic visit adherence and food security among persons living with HIV early in the pandemic, and an increase in viral suppression later in the pandemic. [ABSTRACT FROM AUTHOR]

Background Emerging HIV drug resistance (HIVDR) could jeopardize the success of standardized HIV management protocols in resource-limited settings. We characterized HIVDR among antiretroviral therapy (ART)-naive and experienced participants in the African Cohort Study (AFRICOS). Methods From January 2013 to April 2019, adults with HIV-1 RNA >1000 copies/mL underwent ART history review and HIVDR testing upon enrollment at 12 clinics in Uganda, Kenya, Tanzania, and Nigeria. We calculated resistance scores for specific drugs and tallied major mutations to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) using Stanford HIVDB 8.8 and SmartGene IDNS software. For ART-naive participants, World Health Organization surveillance drug resistance mutations (SDRMs) were noted. Results HIVDR testing was performed on 972 participants with median age 35.7 (interquartile range [IQR] 29.7–42.7) years and median CD4 295 (IQR 148–478) cells/mm3. Among 801 ART-naive participants, the prevalence of SDRMs was 11.0%, NNRTI mutations 8.2%, NRTI mutations 4.7%, and PI mutations 0.4%. Among 171 viremic ART-experienced participants, NNRTI mutation prevalence was 83.6%, NRTI 67.8%, and PI 1.8%. There were 90 ART-experienced participants with resistance to both efavirenz and lamivudine, 33 (36.7%) of whom were still prescribed these drugs. There were 10 with resistance to both tenofovir and lamivudine, 8 (80.0%) of whom were prescribed these drugs. Conclusions Participants on failing ART regimens had a high burden of HIVDR that potentially limited the efficacy of standardized first- and second-line regimens. Management strategies that emphasize adherence counseling while delaying ART switch may promote drug resistance and should be reconsidered. [ABSTRACT FROM AUTHOR]

Background. The central nervous system (CNS) is a likely reservoir of human immunodeficiency virus (HIV), vulnerable to viral rebound, inflammation, and clinical changes upon stopping antiretroviral therapy (ART). It is critical to evaluate the CNS safety of studies using analytic treatment interruption (ATI) to assess HIV remission. Methods. Thirty participants who started ART during acute HIV infection underwent CNS assessments across 4 ATI remission trials. ART resumption occurred with plasma viral load >1000 copies/mL. CNS measures included paired pre- vs post-ATI measures of mood, cognitive performance, and neurologic examination, with elective cerebrospinal fluid (CSF) sampling, brain diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS). Results. Median participant age was 30 years old and 29/30 were male. Participants’ median time on ART before ATI was 3 years, and ATI lasted a median of 35 days. Post-ATI, there were no differences in median mood scores or neurologic findings and cognitive performance improved modestly. During ATI, a low level of CSF HIV-1 RNA was detectable in 6 of 20 participants with plasma viremia, with no group changes in CSF immune activation markers or brain DTI measures. Mild worsening was identified in post-ATI basal ganglia total choline MRS, suggesting an alteration in neuronal membranes. Conclusion. No adverse CNS effects were observed with brief, closely monitored ATI in participants with acutely treated HIV, except an MRS alteration in basal ganglia choline. Further studies are needed to assess CNS ATI safety in HIV remission trials, particularly for studies using higher thresholds to restart ART and longer ATI durations. [ABSTRACT FROM AUTHOR]

Background Antiretroviral therapy (ART) initiation during acute and early human immunodeficiency virus infection (AEHI) limits HIV reservoir formation and may facilitate post-ART control but is logistically challenging. We evaluated the performance of AEHI diagnostic criteria from a prospective study of early ART initiation. Methods AIDS Clinical Trials Group A 5354 enrolled adults at 30 sites in the Americas, Africa, and Asia who met any 1 of 6 criteria based on combinations of results of HIV RNA, HIV antibody, Western blot or Geenius assay, and/or the signal-to-cutoff (S/CO) ratio of the ARCHITECT HIV Ag/Ab Combo or GS HIV Combo Ag/Ab EIA. HIV status and Fiebig stage were confirmed by centralized testing. Results From 2017 through 2019, 195 participants were enrolled with median age of 27 years (interquartile range, 23–39). Thirty (15.4%) were female. ART was started by 171 (87.7%) on the day of enrollment and 24 (12.3%) the next day. AEHI was confirmed in 188 (96.4%) participants after centralized testing, 4 (2.0%) participants were found to have chronic infection, and 3 (1.5%) found not to have HIV discontinued ART and were withdrawn. Retrospectively, a nonreactive or indeterminate HIV antibody on the Geenius assay combined with ARCHITECT S/CO ≥10 correctly identified 99 of 122 (81.2%) Fiebig II–IV AEHI cases with no false-positive results. Conclusions Novel AEHI criteria that incorporate ARCHITECT S/CO facilitated rapid and efficient ART initiation without waiting for an HIV RNA result. These criteria may facilitate AEHI diagnosis, staging, and immediate ART initiation in future research studies and clinical practice. Clinical Trials Registration NCT02859558. [ABSTRACT FROM AUTHOR]

Overcoming stigma affecting gay, bisexual, and other men who have sex with men (MSM) is a foundational element of an effective response to the human immunodeficiency virus (HIV) pandemic. Quantifying the impact of stigma mitigation interventions necessitates improved measurement of stigma for MSM around the world. In this study, we explored the underlying factor structure and psychometric properties of 13 sexual behavior stigma items among 10,396 MSM across 8 sub-Saharan African countries and the United States using cross-sectional data collected between 2012 and 2016. Exploratory factor analyses were used to examine the number and composition of underlying stigma factors. A 3-factor model was found to be an adequate fit in all countries (root mean square error of approximation = 0.02–0.05; comparative fit index/Tucker-Lewis index = 0.97–1.00/0.94–1.00; standardized root mean square residual = 0.04–0.08), consisting of "stigma from family and friends," "anticipated health-care stigma," and "general social stigma," with internal consistency estimates across countries of α = 0.36–0.80, α = 0.72–0.93, and α = 0.51–0.79, respectively. The 3-factor model of sexual behavior stigma cut across social contexts among MSM in the 9 countries. These findings indicate commonalities in sexual behavior stigma affecting MSM across sub-Saharan Africa and the United States, which can facilitate efforts to track progress on global stigma mitigation interventions. [ABSTRACT FROM AUTHOR]

Transient viral blips ≥20 copies/mL were observed in 16.9% of acutely treated adults with HIV. Blip incidence increased from 0.0 (95% CI, 0.0–2.9)/100 person-years after ART in Fiebig I to 15.9 (7.6–29.2) in Fiebig V. Increasing viral load and Fiebig stage at ART initiation were independently predictive of blips. [ABSTRACT FROM AUTHOR]

Background World Health Organization (WHO) guidelines identify human immunodeficiency virus (HIV) viral load <1000 copies/mL as the goal of antiretroviral therapy (ART). However, the clinical implications of viremia below this threshold are unclear in the African context. We examined factors associated with persistent low-level viremia (pLLV) and quantified the risk of subsequent virologic. Methods The African Cohort Study enrolled HIV-infected adults at clinics in Uganda, Kenya, Tanzania, and Nigeria, with assessments every 6 months. We evaluated participants prescribed ART for at least 6 months without virologic failure for pLLV. We used multinomial logistic regression to evaluate associations between prespecified factors of interest and 3 levels of pLLV (<200, 200–499, and 500–999 copies/mL). We used Anderson-Gill extended Cox proportional hazards to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for viremia category associations with time to failure. Results We included 1511 participants with 4382 person-years of follow-up. PLLV <200 copies/mL was observed at 20% of visits while 2% of visits had pLLV 200–499 and 500–999 copies/mL each, with substantial variation by site. Protease inhibitor–containing ART was associated with increased risk of pLLV. Compared to undetectable viral load, pLLV ≥200 copies/mL doubled the risk of developing virologic failure (pLLV 200–499: HR, 1.81 [95% CI, 1.08–3.02]); pLLV 500–999: HR, 2.36 [95% CI, 1.52–3.67]). Conclusions Participants with pLLV ≥200 copies/mL were at increased risk of subsequent virologic failure. Optimized HIV care in this setting should target viral suppression <200 copies/mL. [ABSTRACT FROM AUTHOR]

Background Noninfectious comorbid diseases (NCDs) contribute to morbidity and mortality in human immunodeficiency virus (HIV)–infected populations in resource-rich countries. With antiretroviral therapy (ART) scale-up in Africa, understanding burden NCD informs public health strategy. Methods At enrollment, participants at 11 HIV clinics in Kenya, Uganda, Tanzania, and Nigeria underwent medical history, physical, laboratory, and neuropsychological assessments to identify elevated blood pressure, hypercholesterolemia, dysglycemia, renal insufficiency, and cognitive impairment. Poisson regression models estimated adjusted relative risks (ARRs) and 95% confidence intervals (CIs) for the number of NCDs associated with factors of interest. Logistic regression was used to evaluate each NCD separately among HIV-infected participants. Results Among 2720 participants with complete NCD data, 2159 (79.4%) were HIV-infected. Of those, 1426 (66.0%) were taking ART and 813 (37.7%) had at least 1 NCD. HIV infection was associated with more NCDs, especially with ART (ARR, 1.42; 95% CI, 1.22–1.66). In addition to age, body mass index, and program site, ART usage was associated with more NCDs (ARR, 1.50; 95% CI, 1.27–1.78 for virologically suppressed and ARR, 1.38; 95% CI, 1.13–1.68 for viremic) among HIV-infected participants. In participants taking ART, CD4 nadir below 200 cells/mm3 was associated with more NCDs (ARR, 1.43; 95% CI, 1.06–1.93). ART use was independently associated with hypercholesterolemia and dysglycemia. Program site was significantly associated with all comorbidities except renal insufficiency. Conclusions HIV infection was a risk for NCDs, which were common in HIV-infected participants, geographically variable, and largely consistent with metabolic complications of first-line ART. [ABSTRACT FROM AUTHOR]

Background: In high-income countries, inflammation has been associated with increased morbidity and mortality in human immunodeficiency virus (HIV)-infected individuals despite treatment with antiretroviral therapy (ART). However, these findings may not be generalizable to low-income settings.Methods: In this cross-sectional study, multivariable linear regression was used to compare 28 inflammatory biomarker levels in HIV-infected and -uninfected participants. Correlations between biomarkers and Veterans Aging Cohort Study (VACS) index, Fibrosis-4 (FIB-4) score, and Framingham risk score were assessed.Results: Plasma samples from 304 Kenyans were analyzed. Compared to HIV-uninfected controls, virologically suppressed HIV-infected participants had higher levels of CCL5, CXCL10, fatty acid binding protein (FABP) 2, fas ligand (FASLG), matrix metalloproteinase (MMP) 1, MMP7, soluble CD14 (sCD14), and soluble CD163 (sCD163) and lower MMP9 (P < .01). CD4+/HLA-DR+CD38+ (ρ = 0.32; P < .001), sCD14 (ρ = 0.25; P = .004), and sCD163 (ρ = 0.24; P = .006) were correlated with the VACS index. FABP2 was positively correlated (ρ = 0.29; P = .002), whereas MMP1 (ρ = -.32; P < .001) and MMP2 (ρ = -0.28; P = .002) were inversely correlated with the FIB-4 score.Conclusions: Differences in biomarker levels exist between well-controlled HIV-infected participants on ART and uninfected controls. Some biomarkers are correlated to scoring indices predictive of morbidity and mortality. These biomarkers could serve as prognostic indicators and inform therapeutic development. [ABSTRACT FROM AUTHOR]

Background. Many individuals with acute human immunodeficiency virus infection (AHI) experience acute retroviral syndrome (ARS), which is associated with adverse long-term clinical outcomes. Methods. Participants presenting for voluntary human immunodeficiency virus (HIV) testing were enrolled during AHI in Bangkok, Thailand. ARS was defined by ≥3 qualifying signs/symptoms. HIV burden, immunophenotypes, and biomarkers were stratified by ARS diagnosis at enrollment and after up to 96 weeks of antiretroviral therapy (ART). Results. From 212 382 samples screened, 430 participants were enrolled during AHI, including 335 (78%) with ARS. Median age was 26 years and 416 (97%) were men. Sixty (14%) underwent sigmoid biopsy and 105 (24%) underwent lumbar puncture during AHI. Common symptoms included fever (93%), fatigue (79%), pharyngitis (67%), and headache (64%). Compared to those without ARS, participants with ARS were in later Fiebig stages with higher HIV RNA in blood, colon, and cerebrospinal fluid; higher total HIV DNA in blood; CD4 depletion in blood and colon; and elevated plasma tumor necrosis factor alpha (TNF-α), C-reactive protein, and D-dimer (all P < .05). Subgroup analyses of Fiebig I/II participants (95 with ARS, 69 without) demonstrated similar findings. After 96 weeks of ART, TNF-α and interleukin 6 were elevated in the ARS group (P < .05) but other biomarkers equilibrated. Conclusions. ARS was associated with high viral burden, CD4 depletion, and immune activation across multiple body compartments during AHI and prior to ART. Persistent inflammation despite suppressive ART could contribute to increased morbidity in individuals who experience ARS. [ABSTRACT FROM AUTHOR]

Background. Elite controllers spontaneously suppress human immunodeficiency virus (HIV) viremia but also demonstrate chronic inflammation that may increase risk of comorbid conditions. We compared hospitalization rates and causes among elite controllers to those of immunologically intact persons with medically controlled HIV. Methods. For adults in care at 11 sites from 2005 to 2011, person-years with CD4 T-cell counts ⩾350 cells/mm2 were categorized as medical control, elite control, low viremia, or high viremia. All-cause and diagnostic categoryspecific hospitalization rates were compared between groups using negative binomial regression. Results. We identified 149 elite controllers (0.4%) among 34 354 persons in care. Unadjusted hospitalization rates among the medical control, elite control, low-viremia, and high-viremia groups were 10.5, 23.3, 12.6, and 16.9 per 100 person-years, respectively. After adjustment for demographic and clinical factors, elite control was associated with higher rates of all-cause (adjusted incidence rate ratio, 1.77 [95% confidence interval, 1.21-2.60]), cardiovascular (3.19 [1.50-6.79]) and psychiatric (3.98 [1.54-10.28]) hospitalization than was medical control. Non- AIDS-defining infections were the most common reason for admission overall (24.1% of hospitalizations) but were rare among elite controllers (2.7%), in whom cardiovascular hospitalizations were most common (31.1%). Conclusions. Elite controllers are hospitalized more frequently than persons with medically controlled HIV and cardiovascular hospitalizations are an important contributor. [ABSTRACT FROM AUTHOR]

Background Immune non-response (INR) for people living with HIV (PLWH) is the inability to regain healthy CD4 counts despite viral suppression (VS) on antiretroviral therapy (ART). We identified factors associated with INR in two methodologically similar but demographically diverse cohorts with open access to care and assessed the relationship between INR and incident serious non-AIDS event (SNAE). Methods The US Military HIV Natural History Study (NHS) and the African Cohort Study (AFRICOS) are multisite, open cohort studies enrolling PLWH. Participants with 2 years of VS < 400 copies/mL on ART were evaluated for INR, defined as CD4 < 350 cells/µL at 2 years VS. Logistic regression was used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for factors associated with INR. Cox proportional hazards regression produced adjusted hazard ratios (aHR) and 95% CIs for factors associated with incident SNAE (first non-AIDS cancer, cardiovascular, gastrointestinal, genitourinary, liver, musculoskeletal or respiratory event) after 2 years of VS. Results 10.8% of the 1,784 NHS and 25.8% of the 984 AFRICOS subjects had INR. The AFRICOS cohort was older and had a higher proportion of females. In both cohorts, immune non-responders were significantly older and had a significantly lower CD4 at ART initiation. Those with INR also took longer to reach 2 years of VS since starting ART. Odds of INR decreased by over 60% for every 100 cell increase in baseline CD4 in both cohorts (NHS aOR = 0.31 [95% CI 0.26, 0.37]; AFRICOS aOR = 0.36 [95% CI 0.21, 0.86]). In the NHS, hazard of incident SNAE was 61% higher for those with INR (aHR = 1.61 [95% CI 1.12, 2.33]). Probability of SNAE-free survival at 15 years since 2 years of VS was approximately 20% lower comparing those with and without INR; nearly equal to the differences observed by 15-year age groups. Conclusion INR was common in two diverse cohorts with open access to care and treatment. The association with SNAEs suggests early identification of and interventions to prevent or reverse INR may improve clinical outcomes, but further study is needed. The clinical relevance of INR highlights the value of early HIV identification and treatment, and suggests CD4 monitoring at ART initiation and post-VS is important in settings where INR is prevalent. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background In Sub-Saharan African (SSA) women living with HIV, pregnancy creates unique stressors that may induce or exacerbate depression. We described the prevalence of depression during the perinatal period among women living with HIV that became pregnant (P-WLWH) as compared with those that did not (NP-WLWH). Methods We analyzed data from WLWH, age < 45 years, across 11 HIV clinics in Kenya, Nigeria, Uganda, and Tanzania, within the African Cohort Study (AFRICOS). Depression screening was performed via the Center for Epidemiological Studies-Depression (CESD) scale at enrollment and every 6 months in the study. For these analyses, the CESD score was assessed during three periods in time. For P-WLWH, these periods were: (1) enrollment, (2) during pregnancy and (3) the study visit following delivery. For NP-WLWH, three sequential evaluations were analyzed, with visit 1 being enrollment. We compared the prevalence of depression between groups at each period using χ 2 analysis and calculated adjusted odds ratios (OR) using logistic regression for variables associated with positive depression screening (CESD score ≥16). Results There were 764 WLWH selected for analysis, including 164 P-WLWH and 600 NP-WLWH. At enrollment, P-WLWH tended to be younger than NP-WLWH (mean age=30 vs. 34, P < 0.01). Neither group differed significantly with respect to marital status, employment, education, viral load, or duration of HIV. The crude prevalence of depression during periods 1 thru 3 for P-WLWH and NP-WLWH was: 20% (in both groups, P = 0.99), 10% and 13% (P = 0.26), and 4% and 10% (P = 0.01), respectively (figure). P-WLWH had 74% lower odds [OR = 0.26 [0.09–0.75], P = 0.01] of positive depression screening during period 3 than NP-WLWH, when controlling for age, marital status, educational level, viral load, and duration of HIV. Conclusion Surprisingly, our analyses demonstrate P-WLWH were less likely to have positive screening for depression following their pregnancies. These findings may highlight the strength of comprehensive maternal health initiatives in SSA. Additionally, these women will be followed further longitudinally to evaluate patterns of depression in the months following pregnancy. Disclosures All authors: No reported disclosures.