Vaccine Efficacy of ALVAC-HIV and Bivalent Subtype C gp120-MF59 in Adults.

BACKGROUND: A safe, effective vaccine is essential to eradicating human immunodeficiency virus (HIV) infection. A canarypox-protein HIV vaccine regimen (ALVAC-HIV plus AIDSVAX B/E) showed modest efficacy in reducing infection in Thailand. An analogous regimen using HIV-1 subtype C virus showed potent humoral and cellular responses in a phase 1-2a trial in South Africa. Efficacy data and additional safety data were needed for this regimen in a larger population in South Africa. METHODS: In this phase 2b-3 trial, we randomly assigned 5404 adults without HIV-1 infection to receive the vaccine (2704 participants) or placebo (2700 participants). The vaccine regimen consisted of injections of ALVAC-HIV at months 0 and 1, followed by four booster injections of ALVAC-HIV plus bivalent subtype C gp120-MF59 adjuvant at months 3, 6, 12, and 18. The primary efficacy outcome was the occurrence of HIV-1 infection from randomization to 24 months. RESULTS: In January 2020, prespecified criteria for nonefficacy were met at an interim analysis; further vaccinations were subsequently halted. The median age of the trial participants was 24 years; 70% of the participants were women. The incidence of adverse events was similar in the vaccine and placebo groups. During the 24-month follow-up, HIV-1 infection was diagnosed in 138 participants in the vaccine group and in 133 in the placebo group (hazard ratio, 1.02; 95% confidence interval, 0.81 to 1.30; P = 0.84). CONCLUSIONS: The ALVAC-gp120 regimen did not prevent HIV-1 infection among participants in South Africa despite previous evidence of immunogenicity. (HVTN 702 ClinicalTrials.gov number, NCT02968849.).

Analysis of the HIV Vaccine Trials Network 702 Phase 2b-3 HIV-1 Vaccine Trial in South Africa Assessing RV144 Antibody and T-Cell Correlates of HIV-1 Acquisition Risk.

BACKGROUND: The ALVAC/gp120 + MF59 vaccines in the HIV Vaccine Trials Network (HVTN) 702 efficacy trial did not prevent human immunodeficiency virus-1 (HIV-1) acquisition. Vaccine-matched immunological endpoints that were correlates of HIV-1 acquisition risk in RV144 were measured in HVTN 702 and evaluated as correlates of HIV-1 acquisition. METHODS: Among 1893 HVTN 702 female vaccinees, 60 HIV-1-seropositive cases and 60 matched seronegative noncases were sampled. HIV-specific CD4+ T-cell and binding antibody responses were measured 2 weeks after fourth and fifth immunizations. Cox proportional hazards models assessed prespecified responses as predictors of HIV-1 acquisition. RESULTS: The HVTN 702 Env-specific CD4+ T-cell response rate was significantly higher than in RV144 (63% vs 40%, P = .03) with significantly lower IgG binding antibody response rate and magnitude to 1086.C V1V2 (67% vs 100%, P < .001; Pmag < .001). Although no significant univariate associations were observed between any T-cell or binding antibody response and HIV-1 acquisition, significant interactions were observed (multiplicity-adjusted P ≤.03). Among vaccinees with high IgG A244 V1V2 binding antibody responses, vaccine-matched CD4+ T-cell endpoints associated with decreased HIV-1 acquisition (estimated hazard ratios = 0.40-0.49 per 1-SD increase in CD4+ T-cell endpoint). CONCLUSIONS: HVTN 702 and RV144 had distinct immunogenicity profiles. However, both identified significant correlations (univariate or interaction) for IgG V1V2 and polyfunctional CD4+ T cells with HIV-1 acquisition. Clinical Trials Registration . NCT02968849.

Factors associated with reactogenicity to an investigational HIV vaccine regimen in HIV vaccine trials network 702.

BACKGROUND: Reactogenicity informs vaccine safety, and may influence vaccine uptake. We evaluated factors associated with reactogenicity in HVTN 702, a typical HIV vaccine efficacy trial with multiple doses and products. METHODS: HVTN 702, a phase 2b/3 double-blind placebo-controlled trial, randomized 5404 African participants aged 18-35 years without HIV to placebo, or ALVAC-HIV (vCP2438) at months 0, 1 and ALVAC-HIV (vCP2438) + Bivalent Subtype C gp120/MF59 at months 3, 6, 12 and 18. Using multivariate logistic regression, we evaluated associations between reactogenicity with clinical, sociodemographic and laboratory variables. RESULTS: More vaccine than placebo-recipients reported local symptoms (all p < 0.001), arthralgia (p = 0.008), chills (p = 0.012) and myalgia (p < 0.001). Reactogenicity was associated with female sex at birth (ORv = 2.50, ORp = 1.81, both p < 0.001) and geographic region. Amongst vaccine-recipients, each year of age was associated with 3 % increase in reactogenicity (OR = 1.03, p = 0.002). CONCLUSION: Vaccine receipt, female sex at birth, older age, and region may affect reactogenicity.

The Efficiency of TB LAM Antigen Test to Xpert MTB/RIF Ultra Test for the Diagnosis of Tuberculous Pericarditis Using Pericardial Fluid Samples.

Medical considerations for early diagnosis of tuberculous pericarditis (TBP) include Xpert MTB/RIF Ultra and TB lipoarabinomannan (LAM) antigen (Ag) tests, with immunological status influencing the performance of the latter. An evaluation of the efficiency of Xpert MTB/RIF Ultra and TB LAM Ag in detecting TBP was conducted using pericardial fluid samples from 46 patients with suspected TBP. Fifteen patients (34.1%) were diagnosed with TBP according to culture results. TB LAM Ag's sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were 33.3%, 100%, 100%, 74.4%, 0, and 0.67, respectively. The sensitivity, specificity, PLR, NLR, PPV, and NPV of Xpert MTB/RIF Ultra were 80%, 93.1%, 11.6, 0.21, 85.7%, and 90%, respectively. There was an association observed between a positive TB LAM Ag test and HIV status. When compared to the Xpert MTB/RIF Ultra test, TB LAM Ag has lower accuracy for the detection of microbiologically proven tuberculous pericarditis, yet its usage in HIV-positive populations may be worth exploring. The TB LAM Ag assay is not the best first-line test for the diagnosis of tuberculous pericarditis, and it should be used in conjunction with other diagnostic tests.

Case Report: Neuroleptic malignant syndrome in a HIV-positive patient.

We report a 29-year-old, HIV-positive woman being treated with antipsychotic medication for psychosis (Clopixol 200mg intramuscularly monthly, Risperidone 2mg orally daily Haloperidol 2.5mg twice a day), who presented with neuroleptic malignant syndrome. She was also receiving lorazepam and sodium valproate. The patient was referred to our department as she had developed involuntary upper limb movements and simple permanent focal seizure on the lower part of the left hemiface. Clinically the patient had altered consciousness, autonomic dysfunction, and rigidity. Her blood tests showed elevated creatine kinase (1467U/L) but no leucocytosis. We did a thorough workup for other causes of such a presentation. A comprehensive history was taken from the family to exclude other medications used. Her cerebrospinal fluid results were average. Blood tests did not show evidence of infection or other abnormalities. Computed tomography brain was normal. The patient died a few days after the beginning of the attack, which we have also observed  in other HIV-female patients. As far as we know, it is the first report about this comorbidity reported in the medical literature.

Association of Kidney Function and Waist Circumference with Uric Acid Levels in South Africans.

BACKGROUND: Recent evidence that hyperuricemia is associated with incident chronic kidney disease (CKD) provides a potential therapeutic target for CKD that has not been explored in Africans. With hyperuricemia and gout increasing globally, we sought to determine their prevalence in South Africans with varying kidney function levels. METHODS: This was a cross-sectional study of ambulatory adult patients presenting at a General Internal Medicine Outpatients Clinic between September 2012 and March 2014. Demographic, clinical, and laboratory data collected were analyzed using STATA11. Odds ratios (ORs) and 95% confidence intervals were determined using multivariable logistic regression with bootstrapping. RESULTS: There were 225/261 (86.2%) black/Africans, 31/261 (11.9%) Indian South Africans, 3/261 (1.1%) Caucasians, and 2/261 (<1%) mixed ancestry South Africans. Mean age was 51.3 ± 14.5 years. Median (interquartile range) estimated glomerular filtration rate (eGFR) was 71 (38) mL/min/1.73 m2 and 39.8% (104/261) of patients had CKD. Hyperuricemia prevalence was 43.7% (114/261) and increased from 16.7% in patients with eGFR ≥90 mL/min/1.73 m2 to 74.2% with eGFR <30 mL/min/1.73 m2 (P < 0.001). Gout prevalence was 5.4% (14/261), with equal distribution across eGFR categories (0.814). Factors independently associated with hyperuricemia were eGFR <90 [ORs 3.24 (1.15-9.14), 7.28 (2.26-23.49), and 7.88 (1.95-31.82) for eGFR 60-89.9, 30-60, and <30, respectively], albuminuria [2.32 (1.11-4.85)], and waist circumference [1.04 (1.01-1.06) per 1 cm increase]. In univariate and multivariable analysis, gout was positively associated with male gender and cardiovascular disease, while it was negatively associated with African ancestry, but none of these factors remained significant after bootstrapping; ORs 6.65 (0.64-69.24), 4.14 (0.61-28.07), and 0.18 (0.01-2.21), respectively. CONCLUSION: Hyperuricemia prevalence was high, with CKD and waist circumference being the strongest predictors. Gout was uncommon in black Africans. With population data lacking, screening high-risk individuals may provide insight into the burden of hyperuricemia and gout in South Africa.

Spectrum of infections and outcome among hospitalized South Africans with systemic lupus erythematosus.

Our aim was to determine reasons for admission, the prevalence and spectrum of infections, and the outcomes in a multiethnic cohort of hospitalized systemic lupus erythematosus (SLE) patients in Durban, South Africa. We reviewed the records of hospitalized SLE patients seen over a 79-month period; the demographic data, clinical manifestations, laboratory findings, reasons for admission, nature of infection, and outcome were recorded. Our 167 patients, comprising 59.3% Indians, 33.5% African Blacks, 5.4% Coloreds, and 1.8% Whites, had 327 admissions. Active disease and infections accounted for 218 (66.7%) and 115 (35.2%) admissions respectively, with 58 (17.7%) due to both active disease and infection. Features of active disease were mucocutaneous 33.0%, hematological 30.3%, renal 28.9%, and vasculitis 27.1%. Overall, 83 patients (49.7%) had 155 infections; pneumonia (36.8%), cutaneous sepsis (18.1%), tuberculosis (13.5%), urinary tract infections (12.9%), and septicemia (7.1%) were the most common. The organisms commonly isolated were Staphylococcus aureus 25.4%, Escherichia coli 20.3%, and Klebsiella species and Mycobacterium tuberculosis in 13.6% each. Serositis (odds ratio (OR) = 2.7, p = 0.005) and seizures (OR = 4.8, p = 0.007) were associated with increased risk of infection. Twenty-four (14.4%) patients died from infection and active disease; the patients who died had higher SLEDAI scores (p = 0.02) and longer duration of hospitalization (p = 0.03) but no significant associations on multiple logistic regression analysis. Bacterial infections, including tuberculosis, are common in SLE, and they are a major cause of mortality.

Concomitant systemic lupus erythematosus and HIV: case series and literature review.

OBJECTIVES: To determine the effect of systemic lupus erythematosus (SLE) and human immunodeficiency virus (HIV) infection on the course of each other and to review the published reports on concomitant SLE and HIV infection. METHODS: We performed a retrospective review of the records of patients with SLE and HIV seen in the Department of Rheumatology at the Inkosi Albert Luthuli Central Hospital, Durban, South Africa. We used the terms "systemic lupus erythematosus" and "HIV" or "AIDS" to identify patients with SLE and HIV infection reported in the English medical literature. RESULTS: We identified 13 patients with SLE and HIV infection. All the patients were females and there were 11 African blacks and 2 Indians. SLE and HIV infection were diagnosed together in 6 patients. In this group, there were 5 lupus flares in 4 patients, and 2 of the flares followed highly active anti-retroviral treatment (HAART). Five patients developed HIV after the diagnosis of SLE. The 3 patients in whom follow-up data was available had inactive SLE, one of whom was on HAART. Two HIV-positive patients developed SLE after receiving HAART for 30 and 35 mo. Seven of our patients also had tuberculosis. Our literature search identified 58 previously reported patients with HIV and SLE. CONCLUSION: Our case series and review of the literature show that there is a reduction in SLE disease activity in patients with concomitant SLE and HIV. However, when lupus flares occur in HIV-positive patients, they are unrelated to the use of HAART.

Predictive performance of eGFR equations in South Africans of African and Indian ancestry compared with 99mTc-DTPA imaging.

BACKGROUND: South African guidelines for early detection and management of chronic kidney disease (CKD) recommend using the Cockcroft-Gault (CG) or Modification of Diet in Renal Disease (MDRD) equations for calculating estimated glomerular filtration rate (eGFR) with the correction factor, 1.212, included for MDRD-eGFR in black patients. We compared eGFR against technetium-99m-diethylenetriaminepentaacetic acid ((99m)Tc-DTPA) imaging. METHODS: Using clinical records, we retrospectively recorded demographic, clinical, and laboratory data as well as (99m)Tc-DTPA-measured GFR (mGFR) results obtained from routine visits. Data from 148 patients of African (n = 91) and Indian (n = 57) ancestry were analyzed. RESULTS: Median (IQR) mGFR was 38.5 (44) ml/min/1.73 m(2), with no statistical difference between African and Indian patients (P = 0. 573). In African patients with stage 3 CKD, MDRD-eGFR (unadjusted for black ethnicity) overestimated mGFR by 5.3% [2.0 (16.0) ml/min/1.73 m(2)] compared to CG-eGFR and MDRD-eGFR (corrected for black ethnicity) that overestimated mGFR by 17.7% [6.0 (15.0) ml/min/1.73 m(2)] and 17.1% [6.0 (17.5) ml/min/1.73 m(2)], respectively. In stage 1-2, CKD eGFR overestimated mGFR by 52.5, 38.0, and 19.3% for CG, MDRD (ethnicity-corrected), and MDRD (without correction), respectively. In Indian stage 3 CKD patients, MDRD-eGFR underestimated mGFR by 35.6% [-21.0 (6.5) ml/min/1.73 m(2)] and CG-eGFR by 4.4% [-2.0 (27.0) ml/min/1.73 m(2)], while in stage 1-2 CKD, CG-eGFR and MDRD-eGFR overestimated mGFR by 13.8 and 6.3%, respectively. CONCLUSION: MDRD-eGFR calculated without the African-American correction factor improved GFR prediction in African CKD patients and using the MDRD correction factor of 1.0 in Indian patients as in Caucasians may be inappropriate.