Disease Control Human Immunodeficiency Virus Research Articles

Immune checkpoint blockade effect on immunologic and virologic profile of five cancer patients living with human immunodeficiency virus (HIV) infection.

Immune checkpoint inhibitors (ICI) have changed the prognostic outlook for several malignancies. Despite the unprecedented durable responses and improvement in survival outcomes with ICIs, exclusion of oncology patients living with human immunodeficiency virus (HIV) from most ICI-related trials has limited utility of these agents. Clinical outcomes related to concomitant use of antiretroviral therapy and ICI remain unclear. We present a case series based on our institution's experience to address this unmet need of clinical outcomes with ICI in oncology patients living with HIV. Electronic medical records were queried to identify patients living with HIV who were also diagnosed with cancer and treated with ICI from May 2019 to September 2022. A total of five patients were on concurrent antiretroviral therapy and immunotherapy. From an efficacy perspective, three patients were observed to have a response (one complete response, one partial response, and one stable disease). There were three patients with known cluster of differentiation (CD4 + ) levels who had an increase in CD4 + cell count with ICI treatment. The HIV viral load remained undetected in most of the patients on ICI treatment. No confirmed immune-related adverse effects were documented for any patients in this review. Immune checkpoint inhibitors may be efficacious and tolerable for treatment of cancer in patients living with HIV. Upward trends in CD4 + cell counts observed in this case series suggest that immune checkpoint inhibitors may enhance HIV disease control. Further research is needed for this patient population to supply more robust evidence for clinical practice.

Clinical Characteristics of Peripheral Neuropathy in Kenyan Patients with HIV Infection Compared with Patients with Concurrent HIV Infection and Diabetes Mellitus.

IntroductionPersons living with human immunodeficiency virus (HIV) are living longer and at risk of non-communicable diseases, including diabetes mellitus (DM). Both HIV and DM place patients at risk of peripheral neuropathy (PN). Our aim was to demonstrate the prevalence and characteristics of PN in our population of patients with HIV infection compared with concomitant HIV and DM.MethodsA prospective cross-sectional study was performed at the Aga Khan Hospital in Nairobi, Kenya. Data were collected on demographics and characteristics of DM and HIV. Symptoms and signs of PN were evaluated by Neuropathy Symptom Score, Neuropathy Disability Score, and 10 g monofilament testing.ResultsTwo groups were recruited, each consisting of 68 patients: (1) HIV only, (2) HIV and DM. The median age of patients was 51 years (IQR 42.8–58.6) and 55% were male. Median duration for HIV was 10 years (IQR 5–12) with a median CD4 count of 524 cells/mm3 (IQR 369–731). Median duration for DM was 1 year with a median glycosylated hemoglobin of 6.7% (IQR 6.6–7.6). Sixty-nine percent of patients with HIV had suppressed viral loads, and 9 patients (6.6%) had a history neurotoxic antiretroviral therapy use. PN was detected in 11 (16%) HIV-only patients, and in 17 (25%) participants who had both HIV and DM (Fisher exact test chi-square = 0.4). Univariate analysis demonstrated older age, high body mass index, and long duration of HIV were associated with an OR of 1.07 (95% CI 1.02–1.11), 1.21 (95% CI 0.46–3.11), and 1.07 (95% CI 0.99–1.15) in the overall group, respectively.ConclusionOur study demonstrates a higher but non-significant prevalence of PN in patients with both HIV and DM when compared to HIV alone. HIV disease control had no association with PN presence.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-022-01205-3.

Early Use of the Palliative Approach to Improve Patient Outcomes in HIV Disease: Insights and Findings From the Care and Support Access (CASA) Study 2013-2019

Young men of color who have sex with men (yMSM) living with human immunodeficiency virus (HIV) in syndemic environments have been difficult-to-retain in care resulting in their being at-risk for poor health outcomes despite availability of effective once-daily antiretroviral treatment (ART). Multiple methods have been implemented to improve outcomes for this cohort; none with sustainable results. Outpatient HIV staff themselves may be a contributing factor. We introduced multidisciplinary staff to the concept of using a palliative approach early (ePA) in outpatient HIV care management to enable them to consider the patient-level complexity of these young men. Young MSM (18-35 years of age) enrolled in and cared for at the intervention site of the Care and Support Access Study (CASA), completed serial surveys over 18 months. Patients' Global and Summary quality of life (QoL) increased during the study at the intervention site (IS) where staff learned about ePA, compared with patients attending the control site (CS) (p=.021 and p=.018, respectively). Using serial surveys of staff members, we found that in the era of HIV disease control, outpatient staff are stressed more by environmental factors than by patients' disease status seen historically in the HIV epidemic. A Community Advisory Panel of HIV stakeholders contributed to all phases of this study and altered language used in educational activities with staff members to describe the patient cohort.

Retinal nerve fiber layer changes based on historic CD4 nadir among HIV positive patients undergoing glaucoma evaluation.

To determine relationships between retinal nerve fiber layer (RNFL) thickness and nadir CD4 cell count in human immunodeficiency virus (HIV) positive patients evaluated for glaucoma suspicion. Data were reviewed for 329 HIV positive patients evaluated for glaucoma suspicion. High-definition optical coherence tomography (OCT) RNFL measurements were obtained at least 6mo apart. Analyses were performed to identify relationships between nadir CD4 count and RNFL thickness. Totally 110 eyes of 55 patients met inclusion criteria, of which 46 eyes were from subjects with nadir CD4<200 cells/mm3 and 64 had nadir CD4≥200 cells/mm3. Patients with nadir CD4<200 cells/mm3 had significantly thicker superior (119.7±18.6 µm) and temporal (63.8±11.7 µm) quadrants at time of initial OCT compared to the superior (112.8±16.8 µm, P=0.048) and temporal (57.1±11.9 µm, P=0.004) quadrants of patients with higher nadir CD4. This trend toward thicker RNFL among subjects with lower nadir CD4 cell counts persisted at the time of follow up OCT where participants with nadir CD4<200 cells/mm3 showed average RNFL thickness in the superior and temporal quadrants of 117.9±18.3 µm and 63.8±12.8 µm, respectively, compared to a superior thickness of 110.5±16.9 µm (P=0.034) and temporal thickness of 57.3±11.6 µm (P=0.007) among those with higher nadir CD4. Patients with lower nadir CD4 cell counts have thicker RNFL in the superior and temporal quadrants compared to those with higher nadir CD4 counts. RNFL thickness in HIV positive patients may be affected by historic HIV disease control and should be considered when evaluating HIV positive patients for glaucoma.

Incidence of cardiovascular diseases in a nationwide HIV/AIDS patient cohort in Taiwan from 2000 to 2014.

The purpose of the study was to determine the incidence of cardiovascular disease (CVD) among people living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (PLWHA) in Taiwan. PLWHA were identified from the Taiwan Centers for Disease Control HIV Surveillance System between 2000 and 2014. To examine the effect of active antiretroviral therapy (HAART) on CVD incidence, incidence densities and standardised incidence rates (SIRs) of CVD were calculated after stratifying PLWHA by HAART. Of 26 272 PLWHA (mean age, 32.3 years) identified, 73.4% received HAART. Compared with general population, SIRs (95% confidence interval) were higher for incident coronary artery disease (1.11 (1.04-1.19)), percutaneous coronary intervention (1.32 (1.18-1.47)), coronary artery bypass surgery (1.47 (1.29-1.66)), sudden cardiac death (3.01 (2.39-3.73)), heart failure (1.50 (1.31-1.70)) and chronic kidney disease (1.95 (1.81-2.10)), but was lower for incident atrial fibrillation (0.53 (0.37-0.73)). Considering the effect of HAART on incident CVD, the SIRs for all-cause, ischaemic and haemorrhagic stroke were higher in PLWHA who did not receive HAART, but were lower in PLWHA who received HAART. PLWHA had higher risks of incident coronary artery disease, percutaneous coronary intervention, coronary artery bypass surgery, sudden cardiac death, heart failure and chronic kidney disease. HAART reduces risks of incident CVD in PLWHA.

O11 - Two diseases, same person: moving towards a combined HIV and TB continuum of care

The human immunodeficiency virus (HIV) and Mycobacterium tuberculosis syndemic remains a global public health threat. Separate HIV and tuberculosis (TB) global targets have been set; however, success will depend on achieving combined disease control objectives and care continua. The objective of this study was to review available policy, budgets, and data to reconceptualize TB and HIV disease control objectives by combining HIV and TB care continua. For 22 World Health Organization (WHO) TB and TB/HIV priority countries, we used 2015 data from the HIV90-90-90watch website, UNAIDS AIDSinfo, and WHO 2016 and 2017 Global TB Reports. Global resources available in TB and HIV/TB activities for 2003-2017 were collected from publicly available sources. In 22 high-burden countries, people living with HIV on antiretroviral therapy ranged from 9 to 70%; viral suppression was 38-63%. TB treatment success ranged from 71 to 94% with 14 (81% HIV/TB burden) countries above 80% TB treatment success. From 2003 to 2017, reported global international and domestic resources for HIV-associated TB and TB averaged $2.85 billion per year; the total for 2003-2017 was 43 billion dollars. Reviewing combined HIV and TB targets demonstrate disease control progress and challenges. Using an integrated HIV and TB continuum supports HIV and TB disease control efforts focused on improving both individual and public health.

Two diseases, same person: moving toward a combined HIV and tuberculosis continuum of care

The human immunodeficiency virus (HIV) and Mycobacterium tuberculosis syndemic remains a global public health threat. Separate HIV and tuberculosis (TB) global targets have been set; however, success will depend on achieving combined disease control objectives and care continua. The objective of this study was to review available policy, budgets, and data to reconceptualize TB and HIV disease control objectives by combining HIV and TB care continua. For 22 World Health Organization (WHO) TB and TB/HIV priority countries, we used 2015 data from the HIV90-90-90watch website, UNAIDS AIDSinfo, and WHO 2016 and 2017 Global TB Reports. Global resources available in TB and HIV/TB activities for 2003-2017 were collected from publicly available sources. In 22 high-burden countries, people living with HIV on antiretroviral therapy ranged from 9 to 70%; viral suppression was 38-63%. TB treatment success ranged from 71 to 94% with 14 (81% HIV/TB burden) countries above 80% TB treatment success. From 2003 to 2017, reported global international and domestic resources for HIV-associated TB and TB averaged $2.85 billion per year; the total for 2003-2017 was 43 billion dollars. Reviewing combined HIV and TB targets demonstrate disease control progress and challenges. Using an integrated HIV and TB continuum supports HIV and TB disease control efforts focused on improving both individual and public health.

Human Immunodeficiency Virus Infection Increases the Risk of Incident Autoimmune Hemolytic Anemia: A Population-Based Cohort Study in Taiwan.

Currently, the association between human immunodeficiency virus (HIV) infection and subsequent development of autoimmune hemolytic anemia (AIHA) remains unclear. This nationwide population-based cohort study aimed to determine the association between incident AIHA and HIV infection in Taiwan. During 2000-2012, we identified people aged ≧15 years living with HIV (PLWH) from the Taiwan Centers for Disease Control HIV Surveillance System. Individuals were considered to be infected with HIV on the basis of positive results of an HIV type 1 Western blot. Age- and sex-matched controls without HIV infection were selected from the Taiwan National Health Insurance Research Database for comparison. All patients were followed until 31 December 2012 and observed for occurrence of AIHA. Of 171468 subjects (19052 PLWH and 152416 controls), 30 (0.02%) had incident AIHA during a mean follow-up of 5.45 years, including 23 PLWH (0.12%) and 7 controls (0.01%). After adjustment for age, sex, and comorbidities, HIV infection was found to be an independent risk factor of incident AIHA (adjusted hazard ratio, 20.9; 95% confidence interval, 8.34-52.3). Moreover, PLWH who were receiving highly active antiretroviral therapy were more likely to develop AIHA than those who were not receiving these drugs (adjusted hazard ratio, 16.2; 95% confidence interval, 3.52-74.2). Our study suggests that HIV infection is an independent risk factor for incident AIHA.

Impact of the Centers for Disease Control's HIV Preexposure Prophylaxis Guidelines for Men Who Have Sex With Men in the United States.

Preexposure prophylaxis (PrEP) is effective for preventing human immunodeficiency virus (HIV) infection among men who have sex with men (MSM) within trial settings. Population impact will depend on clinical indications for PrEP initiation, coverage levels, and drug adherence. No modeling studies have estimated the impact of clinical practice guidelines for PrEP issued by the Centers for Disease Control and Prevention (CDC). Mathematical models of HIV transmission among MSM were used to estimate the percentage of infections averted (PIA) and the number needed to treat (NNT) under behavioral indications of the CDC's PrEP guidelines. We modeled the contribution of these indications while varying treatment coverage and adherence. At 40% coverage of indicated MSM over the next decade, application of CDC guidelines would avert 1162 infections per 100 000 person-years, 33.0% of expected infections. The predicted NNT for the guidelines would be 25. Increasing coverage and adherence jointly raise the PIA, but reductions to the NNT were associated with better adherence only. Implementation of CDC PrEP guidelines would result in strong and sustained reductions in HIV incidence among MSM in the United States. The guidelines strike a good balance between epidemiological impact (PIA) and efficiency (NNT) at plausible scale-up levels. Adherence counseling could maximize public health investment in PrEP by decreasing the NNT.

Human Immunodeficiency Virus Disease Control in a Cohort of Pregnant Women Delivering in Birmingham, Alabama [304

Human Immunodeficiency Virus Disease Control in a Cohort of Pregnant Women Delivering in Birmingham, Alabama [304

Assessment of Second-Line Antiretroviral Regimens for HIV Therapy in Africa

BackgroundThe efficacy and toxic effects of nucleoside reverse-transcriptase inhibitors (NRTIs) are uncertain when these agents are used with a protease inhibitor in second-line therapy for human immunodeficiency virus (HIV) infection in resource-limited settings. Removing the NRTIs or replacing them with raltegravir may provide a benefit.MethodsIn this open-label trial in sub-Saharan Africa, we randomly assigned 1277 adults and adolescents with HIV infection and first-line treatment failure to receive a ritonavir-boosted protease inhibitor (lopinavir–ritonavir) plus clinician-selected NRTIs (NRTI group, 426 patients), a protease inhibitor plus raltegravir in a superiority comparison (raltegravir group, 433 patients), or protease-inhibitor monotherapy after 12 weeks of induction therapy with raltegravir in a noninferiority comparison (monotherapy group, 418 patients). The primary composite end point, good HIV disease control, was defined as survival with no new World Health Organization stage 4 events, a CD4+ count of more than 250 cells per cubic millimeter, and a viral load of less than 10,000 copies per milliliter or 10,000 copies or more with no protease resistance mutations at week 96 and was analyzed with the use of imputation of data (≤4%).ResultsGood HIV disease control was achieved in 60% of the patients (mean, 255 patients) in the NRTI group, 64% of the patients (mean, 277) in the raltegravir group (P=0.21 for the comparison with the NRTI group; superiority of raltegravir not shown), and 55% of the patients (mean, 232) in the monotherapy group (noninferiority of monotherapy not shown, based on a 10-percentage-point margin). There was no significant difference in rates of grade 3 or 4 adverse events among the three groups (P=0.82). The viral load was less than 400 copies per milliliter in 86% of patients in the NRTI group, 86% in the raltegravir group (P=0.97), and 61% in the monotherapy group (P<0.001).ConclusionsWhen given with a protease inhibitor in second-line therapy, NRTIs retained substantial virologic activity without evidence of increased toxicity, and there was no advantage to replacing them with raltegravir. Virologic control was inferior with protease-inhibitor monotherapy. (Funded by European and Developing Countries Clinical Trials Partnership and others; EARNEST Current Controlled Trials number, ISRCTN37737787, and ClinicalTrials.gov number, NCT00988039.)

Benefit of interpregnancy HIV viral load suppression on subsequent maternal and infant outcomes

The objective of the study was to determine whether interpregnancy human immunodeficiency virus (HIV) viral load suppression affects outcomes in subsequent pregnancies. This is a retrospective review of all women who delivered 2 consecutive pregnancies while diagnosed with HIV from Jan. 1, 1984, until Jan. 1, 2012. Medical records were reviewed for maternal, infant, and delivery data. Pregnancies were divided into index and subsequent pregnancy and analyzed for outcomes. During the study period, 172 HIV-infected women who delivered 2 pregnancies at our institution were identified. There was no difference in median HIV viral load at presentation or delivery between the index and subsequent pregnancies. During the subsequent pregnancy, more women presented on antiretroviral therapy (ART) and more often remained compliant with ART; however, there was no difference in vertical transmission risk between the pregnancies. Of those with a viral load less than 1000 copies/mL at the end of their index pregnancy (n= 103), 57 (55%) presented for their subsequent pregnancy with a viral load still less than 1000 copies/mL. Those women who maintained the viral load suppression between pregnancies were more likely to present for their subsequent pregnancy on ART, maintained a greater viral load suppression and CD4 counts during the pregnancy, and had fewer vertical transmissions compared with those who presented with higher viral loads in their subsequent pregnancy (0% vs 9%, P= .02). Maintaining an HIV viral load suppression between pregnancies is associated with improved HIV disease status at delivery in subsequent pregnancies. Interpregnancy HIV viral load suppression is associated with less vertical transmission, emphasizing the importance of maintaining HIV disease control between pregnancies.

N-acetyltransferase 2 polymorphism in patients infected with human immunodeficiency virus.

To evaluate the prevalence of slow acetylation of hepatic N-acetyltransferase 2 (NAT2) in patients with different stages of human immunodeficiency virus (HIV) infection, to assess the relationship between acetylation capacity and the degree of immunosuppression, and to study the concordance between NAT2 phenotype and genotype. This prospective study in a consecutive sample of HIV-infected patients was performed in the outpatient department of a university hospital that provides primary and tertiary care. The NAT2 genotype was assessed by polymerase chain reaction and restriction fragment length polymorphism, the NAT2 phenotype was determined by caffeine test (urinary metabolic ratio of the caffeine metabolites 5-acetylamino-6-formylamino-3-methyluracil and 1-methylxanthine). Fifty patients with Centers for Disease Control HIV infection stages A (10 patients), B (20 patients), and C (20 patients) were included in the study after each gave informed consent. According to genotyping and phenotyping, 32 (64%) patients were slow acetylators, with a concordance of the two methods of 96%. The overall distribution was similar to distributions reported in other white populations. The slow acetylator phenotype was found in seven, 16, and nine patients with stage A, B, and C, respectively. Eight of the 10 patients with previous adverse reactions to sulfonamides had slow acetylator phenotypes. Acetylation capacity was independent of CD4 cell counts. This study revealed an excellent agreement between genotypes and phenotypes of NAT2 in patients with HIV infection. There was no increase in prevalence of slow acetylation in patients with advanced stages of the disease. This apparent discrepancy to an earlier study may be the result of differences in co-medication of the patients studied and may point to the relevance of drug interactions in the treatment of patients with HIV infection.

Cyotkines as Potential Therapies for Human Immunodeficiency Virus Infections

Cytokines are attracting increased interest as potential therapies for human immunodeficiency virus (HIV) infections. This attraction has particularly arisen as these cytokines have become more commercially available through recombinant technologies. This review focuses on the effects of these biological response modifiers on preclinical HIV and related retrovirus infections. Cytokines that have particularly been considered for HIV disease control include: interferons ‐α , ‐β and ‐γ, interleukins‐2. ‐3. ‐4. ‐6 and ‐7; tumour necrosis factors ‐α and ‐β; and the colony stimulating factors. Efficacy has especially been seen when these cytokines have been used in combination with the more conventional antiviral agents. Due to the many biological functions exerted by cytokines and their interweaving of biological effects with other cytokines, they appear to have the potential to both inhibit as well as enhance viral infections, depending upon how they are used, and caution is therefore urged in their use.

Summary of the Centers for Disease Control human immunodeficiency virus (HIV) performance evaluation surveys for 1985 and 1986.

During 1985 and 1986, the Centers for Disease Control conducted eight surveys to evaluate laboratory performance in testing for antibody to human immunodeficiency virus (HIV). (Other names for this virus include "human T-lymphotropic virus type III" and "lymphadenopathy associated virus.") The first survey was conducted with ten samples and 50 laboratories; the remaining surveys used six samples, but enrollment increased to as many as 475 laboratories. The purpose of these surveys was to measure test performance by the laboratories under the actual conditions of use. The surveys contained duplicate samples to permit measurement of within- and between-survey reproducibility. One survey included positive and negative reference materials as evaluation samples. Results of the Western blot (WB) test were not always positive on samples that were positive by enzyme immunoassay (EIA), and sometimes they were positive on samples that had negative results by EIA. The percentage of positive results reported by laboratories using Electronucleonics tests was lower than that reported by users of Abbott and of Litton tests. positive results on the negative reference material were reported by 13.7% of the Abbott EIA test users. The tests do not seem to be calibrated against an equivalent standard. Within-survey reproducibility was usually above 95% for EIA and WB methods and for the major manufacturers of EIA tests. Between-survey reproducibility was usually above 90%. Reproducibility was below 75% for some combinations of samples, method, and manufacturer. The test performance observed in these surveys may be lower than is actually achieved on patient samples because the samples were selected to measure technical competence and contain a higher frequency of samples with low reactivity than would be encountered with clinical samples. Stratification and weighting of the results in these surveys to estimate performance parameters for a blood bank population indicate that the tests are performing well in this application. If single EIA tests at the performance levels achieved in these surveys were used (no repeat and no confirmation), about 1 sample with positive results in every 50,000 samples tested would be missed and about 2.5% would be false positive results. Because tests are duplicated and confirmed in blood banks, better performance would be expected. Testing for antibody to HIV virus continues to undergo rapid change because of the introduction of new tests, changes in technical aspects of existing tests, and application of testing to changing populations. Such dynamic factors necessitate an ongoing, comprehensive monitoring of test performance.