High Human Immunodeficiency Virus Load Research Articles

Mental Health, Self-Care, and Engagement in Care among Black Women Living with HIV.

Due to sociostructural factors, Black women living with human immunodeficiency virus (HIV) in the United States represent the highest percentage of women with HIV and experience mental health struggles that impact health behaviors. This study examines associations between mental health, self-care, medication adherence, engagement with healthcare, HIV-related healthcare visits, and hospitalization. One hundred and nineteen Black women living with HIV in the Southeastern United States completed measures on scheduled visits (general and HIV-related healthcare), visits attended/missed/rescheduled, mental healthcare engagement (therapy and support groups), hospital visits (emergency room and overnight stays), medication adherence, and a clinician-administered interview assessing mental health. Higher self-care was associated with fewer emergency room visits (β=-0.31, P<.001) and hospitalizations (β=-0.22, P<.05). Higher post-traumatic stress disorder symptoms were associated with hospitalization (β=0.23, P<.05) and missed HIV-related visits (β=0.20, P<.05) but higher outpatient mental healthcare visits for group psychotherapy (β=0.20, P< .05). Higher suicidality was associated with lower HIV-related healthcare visits scheduled (β=-0.26, P<.01). Higher HIV load was associated with higher HIV-related healthcare visits scheduled (β=0.45, P<.001) and hospitalization (β=0.41, P<.001). Higher Wisepill medication adherence (β=-0.28, P<.01) and self-reported adherence (β=-0.33, P<.001) were associated with fewer HIV missed visits. Higher self-reported adherence was associated with fewer emergency room visits (β=-0.38, P<.001) and hospitalizations (β=-0.27, P<.001). Our findings highlight the need for treating mental health symptoms and enhancing self-care among Black women living with HIV to improve engagement in care and health behaviors and decrease emergency room visits and hospitalization.

Successful Treatment of HIV-Associated Kaposi Sarcoma with Immune Checkpoint Blockade.

Kaposi sarcoma (KS) is an incurable, human immunodeficiency virus (HIV)-associated malignancy. We reviewed 320 immunotherapy-treated patient records. Seventeen had HIV-associated malignancies, including nine men with KS. Median viral load was 20 copies/mL (range, undetectable to 549,704) and median CD4 count was 256 cells/μL (range, 10-603). Eight patients received nivolumab and one received pembrolizumab. Six patients (67%) achieved partial (N = 5) or complete remission (N = 1). No drug-related grade >2 toxicities occurred. In seven patients, CD4 counts increased (P = 0.09). Tissue and/or blood-derived circulating tumor DNA (ctDNA) was evaluated by next-generation sequencing. Four evaluable patients each showed anomalies in distinct genes: TP53, KRAS, TLL2, PTPN6 (tissue and/or ctDNA), and NF1 (ctDNA). Tumor mutational burden was low, and PD-L1 immunohistochemistry was negative (three and four assessable patients, respectively). Responders included patients with low CD4 counts, high HIV load, and/or visceral disease. In summary, checkpoint blockade demonstrated significant antitumor activity and low toxicity in patients with HIV-associated KS. Cancer Immunol Res; 6(10); 1129-35. ©2018 AACR.

Neoplasms and infections as the main causes of death in patients in complete response to HIV‐related non‐Hodgkin lymphoma in the combination antiretroviral therapy era: a study out of a series of 146 patients

Neoplasms and infections as the main causes of death in patients in complete response to HIV‐related non‐Hodgkin lymphoma in the combination antiretroviral therapy era: a study out of a series of 146 patients

Presentation of HIV-associated nephropathy and outcome in HAART-treated patients

Among the numerous renal diseases observed in human immunodeficiency virus (HIV) patients, HIV-associated nephropathy (HIVAN) is a major cause of end-stage renal disease (ESRD). The purpose of our study was to describe the presentation and outcome of HIVAN in the era of highly active antiretroviral therapy (HAART). We analysed clinical features and outcome of 57 patients with histologically proven HIVAN diagnosed between 2000 and 2009 in four teaching hospitals in Paris, France. This series was characterized by median age of 41 years (18-58), frequent African origin (87%), severe renal dysfunction [estimated glomerular filtration rate (eGFR) 20 mL/min/1.73m(2) (1-68)], high-grade proteinuria [4.1 g/day (0.6-16.8)], high proportion of sclerotic glomeruli [31.5% (0-95)], high HIV load [4.5 log copies/mL (0-6.7)] and low CD4+ count [127/mm(3) (3-713)]. Nevertheless, a non-negligible proportion of patients did not present with these typical features. Follow-up data were available for 51 patients. ESRD occurred in 30 patients (58.8%). Median renal survival was 40 months. Baseline characteristics significantly associated with ESRD were as follows: severity of renal dysfunction, percentage of sclerotic glomeruli, time from HIV infection to HIVAN diagnosis longer than 1 year and prior exposure to antiretroviral drugs. There was an insignificant trend towards better renal outcome being associated with viral suppression during follow-up. Use of renin-angiotensin system (RAS) blockers was associated with higher renal survival (P < 0.05). Despite HAART, HIVAN led to ESRD in more than half of the cases. Early recognition of the disease is crucial to start HAART and RAS blockers before irreversible renal injury.

Impact of Hepatitis B Virus Infection on Human Immunodeficiency Virus Response to Antiretroviral Therapy in Nigeria

As highly active antiretroviral therapy (ART) is introduced into areas of the world in which hepatitis B virus (HBV) infection is highly endemic, it is important to determine the influence of HBV on persons with human immunodeficiency virus (HIV) and HBV coinfection who are receiving ART. We studied 1564 HIV-infected patients in Jos, Nigeria, who initiated ART. Participants with HIV-HBV coinfection had hepatitis B e antigen (HBeAg) and HBV DNA status determined. CD4+ T cell count and HIV load at ART initiation were compared between individuals with HIV monoinfection and those with HIV-HBV coinfection with use of univariate methods. Regression analyses were used to determine if HBeAg status or HBV DNA at ART initiation were associated with baseline HIV parameters or ART response. The median CD4+ T cell count of the 262 participants with HIV-HBV coinfection (16.7%) was 107 cells/mL, compared with 130 cells/mL for participants with HIV monoinfection at ART initiation (P = .001). Participants with HIV-HBV coinfection also had higher HIV loads than did patients with HIV monoinfection (4.96 vs 4.75 log10 copies/mL; p = .02 ). Higher HBV DNA and detectable HBeAg levels were independently associated with lower CD4+ T cell counts at ART initiation but not with higher HIV loads. In a multivariable model, HBeAg-positive patients were less likely than HBeAg-negative patients to suppress HIV replication to <or= 400 copies/mL (odds ratio, 0.54; P = .03 ) at 24 weeks, but they had similar CD4+ T cell increases. At 48 weeks, there was no significant effect of HBeAg status on ART response. Among HIV-infected Nigerian individuals, HBV coinfection, especially among those with high levels of HBV replication, was associated with lower CD4+ T cell counts at ART initiation, independent of HIV RNA level. Patients with HBeAg-positive status had a slower virological response to ART, compared with HBeAg-negative patients. Further work is needed to understand the effects of HBV on CD4+ T cells.

Breast-feeding, mastitis, and HIV transmission: nutritional implications.

In many developing countries, transmission of the human immunodeficiency virus (HIV) from mother to infant occurs through breast-feeding. Mastitis, an inflammatory process in the breast, may be common in lactating women in Africa and is associated with both higher HIV load in breast milk and mother-to-child transmission of HIV. Antioxidant micronutrient deficiencies may increase the risk of mastitis. Whether prevention, early diagnosis, and prompt treatment of mastitis will help reduce mother-to-child transmission of HIV in breast-feeding women needs further study.

Preventing Sexual Transmission of HIV

The risk of human immunodeficiency virus (HIV) transmission during sexual activity is dependent on the infectivity of the HIV-positive individual and the susceptibility of the uninfected partner. HIV is most often transmitted during periods of high HIV load, but factors such as the type of sexual activity and the innate and genetic defenses of the uninfected partner exert a strong influence on the risk of transmission. Certain factors, such as coinfection with other sexually transmitted diseases or the presence of genital lesions in either sexual partner, amplify the risk of transmission that is predicted on the basis of sexual contact alone. In the absence of more-reliable options, such as a vaccine, factors that define HIV infectivity and susceptibility and factors that amplify the risk of HIV transmission, may serve as critical targets for containment of the HIV epidemic.

Rates of HIV‐1 Transmission per Coital Act, by Stage of HIV‐1 Infection, in Rakai, Uganda

We estimated rates of human immunodeficiency virus (HIV)-1 transmission per coital act in HIV-discordant couples by stage of infection in the index partner. We retrospectively identified 235 monogamous, HIV-discordant couples in a Ugandan population-based cohort. HIV transmission within pairs was confirmed by sequence analysis. Rates of transmission per coital act were estimated by the index partner's stage of infection (recent seroconversion or prevalent or late-stage infection). The adjusted rate ratio of transmission per coital act was estimated by multivariate Poisson regression. The average rate of HIV transmission was 0.0082/coital act (95% confidence interval [CI], 0.0039-0.0150) within approximately 2.5 months after seroconversion of the index partner; 0.0015/coital act within 6-15 months after seroconversion of the index partner (95% CI, 0.0002-0.0055); 0.0007/coital act (95% CI, 0.0005-0.0010) among HIV-prevalent index partners; and 0.0028/coital act (95% CI, 0.0015-0.0041) 6-25 months before the death of the index partner. In adjusted models, early- and late-stage infection, higher HIV load, genital ulcer disease, and younger age of the index partner were significantly associated with higher rates of transmission. The rate of HIV transmission per coital act was highest during early-stage infection. This has implications for HIV prevention and for projecting the effects of antiretroviral treatment on HIV transmission.

Low plasma selenium concentrations, high plasma human immunodeficiency virus load and high interleukin-6 concentrations are risk factors associated with anemia in adults presenting with pulmonary tuberculosis in Zomba district, Malawi

Although anemia is common among adults with pulmonary tuberculosis and human immunodeficiency virus (HIV) infection in sub-Saharan Africa, the factors contributing to its pathogenesis have not been well characterized. To characterize the antioxidant micronutrient status, interleukin-6 (IL-6) concentrations, and HIV load in relationship with anemia in adults with pulmonary tuberculosis. Zomba district, Malawi. Erythropoietin, IL-6, plasma HIV load, and markers of micronutrient status (hemoglobin (Hb), plasma concentrations of retinol, alpha-tocopherol, carotenoids, ferritin, zinc, and selenium) were measured in 500 adults who presented with pulmonary tuberculosis in Zomba Central Hospital, Malawi. Among 370 HIV-positive and 130 HIV-negative adults, the prevalence of anemia was 88 and 77%, respectively (P = 0.002), and moderate to severe anemia (Hb < 80 g/l) occurred in 30 and 15%, respectively (P = 0.001). Geometric mean IL-6 concentration was 21.1 pg/ml, with no difference between HIV-positive and -negative adults. The erythropoietin response to anemia was not different between adults with elevated IL-6 and those with lower IL-6 concentrations. In a multivariate logistic regression model, HIV load, and lower plasma selenium concentrations were associated with moderate to severe anemia. In a final multivariate linear regression model, IL-6, plasma HIV load, and plasma selenium concentrations were associated with Hb concentrations. This study suggests that low selenium concentrations, high HIV load, and high IL-6 concentrations are associated with anemia in adults with pulmonary tuberculosis in sub-Saharan Africa.

Micronutrient malnutrition and wasting in adults with pulmonary tuberculosis with and without HIV co-infection in Malawi.

BackgroundWasting and micronutrient malnutrition have not been well characterized in adults with pulmonary tuberculosis. We hypothesized that micronutrient malnutrition is associated with wasting and higher plasma human immunodeficiency virus (HIV) load in adults with pulmonary tuberculosis.MethodsIn a cross-sectional study involving 579 HIV-positive and 222 HIV-negative adults with pulmonary tuberculosis in Zomba, Malawi, anthropometry, plasma HIV load and plasma micronutrient concentrations (retinol, α-tocopherol, carotenoids, zinc, and selenium) were measured. The risk of micronutrient deficiencies was examined at different severity levels of wasting.ResultsBody mass index (BMI), plasma retinol, carotenoid and selenium concentrations significantly decreased by increasing tertile of plasma HIV load. There were no significant differences in plasma micronutrient concentrations between HIV-negative individuals and HIV-positive individuals who were in the lowest tertile of plasma HIV load. Plasma vitamin A concentrations <0.70 μmol/L occurred in 61%, and zinc and selenium deficiency occurred in 85% and 87% respectively. Wasting, defined as BMI<18.5 was present in 59% of study participants and was independently associated with a higher risk of low carotenoids, and vitamin A and selenium deficiency. Severe wasting, defined as BMI<16.0 showed the strongest associations with deficiencies in vitamin A, selenium and plasma carotenoids.ConclusionsThese data demonstrate that wasting and higher HIV load in pulmonary tuberculosis are associated with micronutrient malnutrition.

Does tuberculosis increase HIV load?

The effect that tuberculosis (TB) has on human immunodeficiency virus (HIV) disease progression is not clearly understood. In an observational cohort study of HIV-infected adults in South Africa, baseline and final HIV load were compared between individuals who experienced an episode of TB (n=30) during follow-up and control subjects (n=56) matched by baseline CD4 cell count and follow-up time; linear regression modeling was used to control for confounding. Mean HIV load was higher in the TB group than in the non-TB control group for both baseline (4.73 vs. 4.24 log(10) copies/mL; P=.003) and final values (5.02 vs. 4.34 log(10) copies/mL; P<.001). After adjustment for baseline HIV load and World Health Organization HIV stage, the difference in final HIV load was 0.24 log(10) copies/mL (95% confidence interval, -0.01 to 0.50 log(10) copies/mL; P=.06). Poor prognosis for HIV-infected individuals after TB may be due to preexisting high HIV load rather than to the TB event itself. An episode of TB was associated with a small adjusted increase in HIV load at the end of the study--an increase that would not be regarded as clinically significant in an individual but could have some effect on HIV disease progression or HIV transmission at the population level. Prevention of TB is important for the reduction of HIV-related morbidity and mortality; however, antiretroviral therapy is required to have a major effect on survival in individuals with HIV disease.

Determinants of HIV-1 load in subjects with early and later HIV infections, in a general-population cohort of Rakai, Uganda.

Human immunodeficiency virus (HIV) type 1 RNA loads were determined for 256 subjects with early (incident) HIV infection and for 1293 subjects with later (prevalent) HIV infection, in a Ugandan cohort. Prevalent infections were classified as latent (0-1 symptoms) and midstage disease (>/=2 symptoms), and deaths were ascribed to acquired immunodeficiency syndrome. Among subjects with incident HIV infection, HIV load did not differ by sex, but, among subjects with prevalent HIV infection, it was higher in males than in females. HIV load was highest in subjects (25-29 years old) with incident HIV infection but increased with age in subjects with prevalent HIV infection. Viremia was higher after serconversion than in latency and increased with more advanced disease. Viremia was increased with genital ulcer disease (GUD) in both subjects with incident infection and in those with prevalent infection, and with herpes simplex virus type 2 seropositivity in subjects with incident HIV infection. GUD was consistently associated with higher HIV loads in subjects with incident and those with prevalent HIV infection, suggesting that treatment of GUD might reduce HIV viremia.

Longitudinal study of mucosal Candida species colonization and candidiasis among human immunodeficiency virus (HIV)-seropositive and at-risk HIV-seronegative women.

Acquisition and loss rates and estimates of duration of oral and vaginal Candida species colonization and candidiasis were examined among 868 human immunodeficiency virus (HIV)-seropositive and 437 at-risk HIV-seronegative women monitored prospectively during 1993-1999. Colonization and candidiasis acquisition rates, both oral and vaginal, were significantly higher among HIV-seropositive women; the magnitude of increase in candidiasis outcomes for HIV-seropositive women was greater for oral candidiasis than for vaginal candidiasis. Loss rates and estimates of duration of incident outcomes indicated that persistent mucosal colonization was more likely among HIV-seropositive women. However, results did not suggest persistent mucosal candidiasis. Higher HIV loads were significantly associated with increased odds of incident or persistent oral and vaginal colonization and candidiasis, an effect significantly reduced by highly active antiretroviral therapy for the incident outcomes of oral candidiasis and vaginal colonization. Cell-mediated immunodeficiency (CD4(+) lymphocyte count <500 cells/mm(3)) was significantly associated with increased odds of oral colonization or candidiasis, but not with vaginal colonization or candidiasis. In HIV-seropositive women, mucosal candidiasis is the consequence of multiple interacting factors.

Longitudinal study of cervical squamous intraepithelial lesions in human immunodeficiency virus (HIV)-seropositive and at-risk HIV-seronegative women.

We examined incidence and correlates of progression and regression of abnormal cervical cytologic test results, defined as at least low-grade squamous intraepithelial lesions (SILs), in 774 human immunodeficiency virus (HIV)-seropositive and 391 HIV-seronegative women monitored semiannually for up to 5.5 years. During follow-up, 224 (35%) HIV-seropositive women and 34 (9%) HIV-seronegative women had incident SILs detected by Pap test; 47 (7%) HIV-seropositive women developed high-grade lesions. The incidence of SILs was 11.5 cases among HIV-seropositive and 2.6 cases among HIV-seronegative women per 100 person-years of observation (rate ratio, 4.5; 95% confidence interval, 3.1-6.4; P<.001). Risk of incident SILs and likelihood of Pap test progression were increased among HIV-seropositive women with CD4(+) lymphocyte counts <500 cells/mm(3) and among women with human papillomavirus (HPV) infection, with risk-ordering from low- to high-risk HPV type. SIL regression was less likely among HIV-seropositive women with higher HIV loads. No beneficial effect of highly active antiretroviral therapy was demonstrated.

Prevalence of high-grade dysplasia and cancer in the anal canal in human papillomavirus-infected individuals.

The incidence of anal cancer is higher in patients with anal canal condyloma, a sexually transmitted disease, than in the general population. We determined the prevalence of anal dysplasia and cancer in patients with anal canal condyloma with respect to human immunodeficiency virus (HIV) status, immunity status, and human papillomavirus types. In 174 consecutive patients (114 HIV positive, 60 HIV negative) with anal canal condyloma, lesions were cured, and the patients were then followed up prospectively. Langerhans cells (LCs) in normal anal mucosa were quantified, and viruses (Epstein-Barr virus, cytomegalovirus, human simplex virus 1, and various human papillomavirus [HPV] types) were characterized on inclusion. During follow-up (median 26 months), relapsed condylomas were resected and examined histologically. HIV load and CD4 T-lymphocyte counts in serum were determined at each visit. Several factors differed significantly between HIV-positive and HIV-negative patients: LCs/mm anal tissue (15 vs. 30), oncogenic HPV (27% vs. 13%), other current anal infections (44% vs. 0%), and sex ratio (93% vs. 73% male). During follow-up, condylomas relapsed in 75% of the HIV-positive patients, with 19 high-grade dysplasias (HGDs) and 1 invasive carcinoma, but in only 6% of HIV-negative patients, with 1 HGD. Male sex, HIV positivity, and <15 LCs/mm tissue were independent risk factors for condyloma relapse. HIV positivity, HGD before inclusion, and condyloma relapse were independent risk factors for HGD and cancer. Serum HIV load was associated with relapse, whereas CD4 T-lymphocyte counts were not. The prevalence of HGD and carcinoma is higher in HIV-positive than in HIV-negative patients, probably because of HPV activity. HIV-positive patients with high serum HIV load and/or a history of anal dysplasia should be examined by anoscopy, and condylomas should be analyzed histologically.

Virus load and risk of heterosexual transmission of human immunodeficiency virus and hepatitis C virus by men with hemophilia. The Multicenter Hemophilia Cohort Study.

A high human immunodeficiency virus (HIV) load may increase the probability of HIV transmission by sexual contact, but the association of virus load of hepatitis C virus (HCV) with risk of HCV transmission is uncertain. HIV and HCV virus loads were examined in hemophilic men, as were risks of HIV and HCV transmission to their female partners in a hemophilia cohort in which most subjects are dually infected. A higher HIV load was associated with an increased risk of HIV transmission (odds ratio [OR], 1.31 per log10 increase in virus load). A higher HCV load was associated, although not significantly, with an increased risk of HCV transmission (OR, 1. 42 per log10). HCV load was higher among dually infected men than in those infected with HCV alone (P=.001). However, much larger studies are needed to clearly show whether HIV/HCV coinfection significantly increases the risk of HCV transmission to female partners.

Mastitis and immunological factors in breast milk of human immunodeficiency virus-infected women.

Human milk contains important immunological factors that protect the breast from infection and are thought to protect infants from infection, including human immunodeficiency virus (HIV) infection. Human milk immunological factors have not been well characterized in HIV-infected lactating women. Lysozyme, secretory leukocyte protease inhibitor (SLPI), sodium (an indicator of mastitis), and HIV were measured in breast milk of 334 HIV-infected women at 6 weeks postpartum. Women with mastitis, as indicated by elevated breast milk sodium concentrations, had higher median levels lysozyme (290 vs 221 mg/L, p < 0.04), SLPI (38 vs 19 mg/L, p < 0.0001) and HIV (920 copies/mL vs undetectable, p < 0.0001) compared with women without mastitis. Lower total plasma carotenoid levels (p < 0.02) and higher maternal HIV load (p < 0.006) by quartile were risk factors for mastitis. Mastitis, as indicated by elevated breast milk sodium levels, is associated with high concentrations of immunological factors and higher HIV load in breast milk.