Immune correlates of Mycobacterium Tuberculosis patients in Zambia stratified by HIV serostatus and level of immunity-a cross-sectional analytical laboratory based study

Background People living with HIV (PLHIV) co-infected with tuberculosis (TB) have a distinct clinical presentation and poorer treatment outcomes compared to HIV-seronegative TB patients. Excluding low CD4 count, innate immune factors associated with TB are not fully elucidated. We, therefore, characterised and compared the expression of IL-6, TNF-α, IFN-γ, and IL-10 in whole blood of treatment naïve TB patients stimulated with heat-killed Mycobacterium tuberculosis stratified by HIV status and the level of CD4 count. Results We recruited 39 HIV seropositive and 31 HIV seronegative TB patients. Median (IQR) age was 35(28–42) years and 31(25–36) years respectively, and a majority had pulmonary tuberculosis i.e. 38(95%) and 30(97%), respectively. The two groups were significantly different in the distribution of CD4 count, 563 [465–702.5 cells/mm3] vs 345 [157–483 cell/mm3] in HIV negative vs HIV positive respectively p = <0.001. Post stimulation, the expression of IL-6 in HIV negative TB patients was significantly higher than in the HIV positive 16,757366 [8,827–23,686 pg/ml] vs. 9,508 [5,514–15,008 pg/ml], respectively; p = 0.0360. TNF-α and IFN-γ were highly expressed in HIV negative TB patients compared to the HIV positive though not statistically significant. We only observed higher expression of IL-6 in HIV negative patients in comparison to the HIV positive when stratified by level of CD4 counts as < 500 and ≥ 500 cell/mm3 for both cohorts. 21,953 [8,990–24,206 pg/ml] vs 9,505 [5,400–15,313 pg/ml], p value = 0.0585 in patients with CD4 count < 500 cell/mm3 and 13,168 [7,087–22,584 pg/ml] vs 10,413 [7,397–14,806 pg/ml], p value = 0.3744 for patients with CD4 count of ≥ 500 cell/mm3 respectively. We found a positive pairwise correlation between TNF-α -alpha and IL-6 in both HIV positive and HIV negative patients, r = 0.61 (95% CI 0.36–0.72; p < 0.0001) and r = 0.48 (95% CI 0.15–0.68; p = 0.005) respectively. The IFNγ/IL-10 ratio was higher in HIV negative when compared to HIV positive individuals, 0.052 [0.0–0.28] vs 0.007 [0–0.32] respectively; p = 0.05759. IL-6 independently reduced the probability of TB/HIV, Adjusted odds ratio 0.99, p value 0.007. Conclusions This study suggests that HIV seronegative TB patients have a higher pro-inflammatory response to MTB than HIV seropositive TB patients. Further, it also shows that the level of CD4 influences immunomodulation. The findings suggest that the difference in cytokine expression may be responsible for the distinct patterns of TB presentation between HIV positive and HIV negative patient.

Decreased MIP-3α Production from Antigen-Activated PBMCs in Symptomatic HIV-Infected Subjects

CD4+ CCR6+ T cells are highly susceptible to HIV infection, and a high cytokine producing CCR6+ T cell subset is selectively lost during HIV infection. The CCR6 chemokine MIP-3α (CCL20) is produced at sites of infection in SIV animal models. Recently, we have shown that MIP-3α inhibits HIV replication. This inhibition of HIV infection is mediated by CCR6 signaling and eventuates in increased APOBEC3G expression. Since there are no existing reports on the role of MIP-3α in health or disease, we studied its production by PBMCs from HIV-seronegative and HIV+ subjects. We evaluated the ability of PBMCs to produce MIP-3α in response to antigen stimulation using cells obtained from two groups: one composed of HIV-seronegative subjects (n = 16) and the other composed of HIV+ subjects (n = 58), some asymptomatic and some with clinically defined AIDS. Antigens included fragment C of the tetanus toxin, Candida albicans, whole-inactivated HIV, and HIV p24. MIP-3α was detected by ELISA in tissue culture supernatants of antigen-stimulated PBMCs. MIP-3α production by antigen-stimulated PBMCs was readily measured for HIV-negative subjects and for HIV-seropositive asymptomatic subjects, but not for patients with AIDS. These results suggest that subversion of the MIP-3α-CCR6 axis by HIV during the course of infection contributes to the loss of immune function that eventually leads to AIDS.

Living With a Stigmatized Identity; Perceptions of Disclosure, Coping, and Medication Adherence Among Adolescent Boys and Young Men in Chiredzi-Zimbabwe

There is limited research on adolescent boys and young men (ABYM)'s initial and onward HIV seropositive status disclosure, coping strategies and treatment adherence journeys especially in Zimbabwe. This qualitative exploratory study employed in-depth individual interviews at Chiredzi General Hospital in Zimbabwe to explore the dynamics of disclosure, coping and treatment adherence among ABYM. Twenty-one HIV positive ABYM with ages ranging from 14 to 21 were recruited from their scheduled visit to collect medication at the hospital. Findings indicate that ABYM disclosure journeys began with shock, confusion or misunderstanding and ended in a positive life outlook. Treatment adherence among ABYM was very poor due to poverty, erratic food supply, feeling sick after taking medication, forgetfulness and the public nature of medication collection centers. The study concluded that ABYM maintained secrecy in order to be accepted by their peers but also to protect themselves from stigma and isolation.

Prevalence of Human Papillomavirus (HPV) Genotypes in Cervicovaginal Secretions of Human Immunodeficiency Virus (HIV) Positive Indian Women and Correlation With Clinico-Virological Parameters

Introduction and Background: Both human papillomavirus (HPV) and the human immunodeficiency virus (HIV) are sexually transmitted. High-risk (HR) HPV types are a causal factor in cervical cancer. Persistent HPV infection in this subset of immunocompromised women results in faster disease progression. The study determined the prevalence of HPV genotypes in cervicovaginal secretions of HIV seropositive women and the correlation with CD4 counts and cytology.Method: One hundred, non-pregnant, HIV-positive women of 18 years of age and above were enrolled in this cross-sectional study following approval by the institutional ethical committee. A written consent, questionnaire, followed by sample collection including a Papanicolaou (Pap) smear for cytology was undertaken. Cervicovaginal secretion samples were collected in the Digene® specimen transport medium (STM) (Qiagen Gaithersburg Inc., MD, USA). HPV genotyping was carried out with PCR amplification of a 65-base pair (bp) fragment in the L1 region of the HPV genome using the short PCR fragment (SPF10) primers followed by reverse hybridization by line probe assay (LPA) using the INNOLiPA HPV Genotyping Extra kit (Fujirebio, Belgium). Quantitation of HPV-16 and−18 viral loads (VLs) was done by real-time PCR. Results of Pap smear cytology were correlated with CD4 counts and HPV-16 and−18 VLs.Results: Mean age of the subjects was 34.9 years ± 7.2 years (median 33.0 years, range 24–60 years). HPV was detected in 62 of 93 (66.6%) samples. Twenty (32.25%) of these 62 samples harbored a single HPV genotype. Multiple genotypes (more than two) were detected in 38 (61.3%) samples. HPV-16 was the commonest genotype detected in 26 (27.9%) of all samples and 41.9% of HPV positive samples. Pap smear cytology was reported for 93 women included in the study. Women who had normal cytology were reported as negative for intraepithelial malignancy or lesion (NILM; n = 62; 71.36%), two women had a high-grade squamous intraepithelial lesion (HSIL), low-grade squamous intraepithelial lesion (LSIL; n = 11), atypical squamous cells of undetermined significance (ASCUS; n = 12). Those smears with inadequate material were reported as scant (n = 6). The median CD4 count was 363/cu.mm (range 39–787) in HPV-positive women compared to 423/cu.mm (range 141–996) in those HPV-negative women. Quantitation of HPV-16 and−18 VL was done in duplicate for samples positive by PCR reverse hybridization (INNOLiPA). Of these 20 samples (65%), 12 samples were positive by real-time PCR. The normalized HPV-16 VL ranged between 18 and 240,000 copies/cell. The normalized HPV-18 VL in cervical samples ranged between ~24 and 60,000 copies/cell.Conclusion: HIV-positive women may be infected with multiple genotypes other than HPV-16 and−18. This may have implications on the vaccines available currently which target few specific genotypes only. Studies are required to determine the predictive role of HR HPV genotypes, in significant copy numbers especially in HIV seropositive women. It would be clinically relevant if the HPV VLs, cervical cytology, and CD4 counts are considered into cervical cancer screening programs for triage and follow-up of these women.

Vroegtijdige opsporing van voorstadia van een anaal carcinoom bij hiv-seropositieve patiënten

Early detection of precursor lesions of anal cancer in HIV-seropositive patients Although anal cancer is rare in the overall population, its incidence is increasing in the last decades. Especially HIV-seropositive patients have an increased risk of developing anal squamous cell carcinoma (SCC), mainly because of the high prevalence of high-grade anal intraepithelial neoplasia (AIN) among these patients. High-grade AIN is a precursor lesion for anal SCC associated with human papillomavirus (HPV) infection. Despite the lack of direct evidence demonstrating that AIN identification reduces the risk of anal cancer, experts think that screening and treatment of high-risk patients will prevent the disease. This article aims to review the current literature about AIN and discusses the screening options, including digital rectal examination, anal cytology and high-resolution anoscopy.

HIV-2 infections: a lesson in diagnostic test selection in Egypt

The first HIV-2 infection in an Egyptian national is documented in this report. Infection with HIV-2 was recognized only after a HIV-1 specific assay yielded negative results in an individual previously identified as being HIV-seropositive by a HIV-1/HIV-2 assay. This emphasizes the importance of using assays capable of detecting both HIV-1 and HIV-2 for testing blood supplies and diagnosis of HIV infections in regions where the prevalence of HIV-2 infections is extremely low.

Intestinal Parasite Infestation in HIV Infected Patients in Tertiary Care Center

Every year, the number of people living with HIV rises as a consequence of advanced infections and the positive effects of highly active antiretroviral therapy (HAART). Gastrointestinal involvement is common, with 90% of patients seeking treatment for gastrointestinal problems as their HIV infection progresses. Nonetheless, identifying and characterization of infectious agents is important for patient management by excluding a clinical diagnosis and determining appropriate treatment, as well as determining public healthcare policy for true pathogen prevalence and yielding epidemiological risk factors for specific infections. The aim of this study is to evaluate the prevalence of symptomatic or asymptomatic intestinal parasitic infection among HIV or AIDS patients. For this study with 80 HIV seropositive patients being recruited from various wards and the Integrated Counseling and Testing Center (ICTC) affiliated to the microbiology department. Patients with acute and chronic diarrhea with abdominal disorder were taken as symptomatic whereas patients without these clinical complaints and who came for routine investigations were taken as asymptomatic. Firstly stool samples were analyzed by macroscopically for the presence of mucus, blood, larvae, segments of tapeworm and adult worms. The consistencies of stool were also recorded such as formed, watery or soft or loose with odor and color. It was examined microscopically after macroscopically for protozoan cysts and trophozoites, helminthic ova and larvae, as wet mount preparation by saline and iodine preparation as well as formal ether concentrated. For the detection of intestinal coccidian parasites, smears were prepared from stool samples and a modified Ziel-Nelseen (MZN) stain was also performed. Stool samples with the detection of parasites were informed for treatment. The prevalence of intestinal parasite was 23.75% with asymptomatic and symptomatic groups having a prevalence of 16.98% and 37.04% respectively. Out of total patients, 56.25% were male and 43.75% were female. Among the male patients, 11 (13.75%) were positive for an intestinal parasitic infection and 8 (10%) were positive among females. The age distribution data revealed that the age group 21-40 years old had the highest number of intestinal parasites, followed by 41-60, 61-80, and 0-20 years old. The most intestinal parasites were found in the young and middle-aged patients, according to this study. Different parasites were identified as Entamoeba histolytica, Taenia species, Ascaris lumbricoides, Cryptosporidium parvum and Isospora with one protozoan, two coccidian parasites and two helminthes. The most common parasite was Taenia species 6 (7.5%) followed by Entamoeba histolytica 5 (6.3%) and Cryptosporidium parvum 5 (6.3%). Intestinal parasitic infection is not uncommon in HIV seropositive patients. This study underscores the need for early diagnosis and treatment of these intestinal parasites in both symptomatic and asymptomatic HIV patients.

Human immune deficiency virus among cervical cancer patients at Tikur Anbessa Specialized Hospital, Ethiopia: a cross sectional study

Background The discrepancy in cervical cancer incidence between women with HIV and women without HIV is highest in low and middle-income countries. In Africa, cervical cancer is the most common cause of cancer death. As a result, HIV-infected women are 6 times more likely to develop cervical cancer than uninfected women. In addition, HIV is associated with several triggering factors for cervical cancer, including multiple sexual partners, early sexual debut, economic status and substance use. Objective To assess the prevalence and associated factors of HIV among cervical cancer patients at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia. Methods A cross sectional study was conducted among 1057 cervical cancer patients registered from January 1, 2014 to December 31, 2018 at Oncology Center of Tikur Anbessa Specialized Hospital. A structured English version checklist was used to collect the data from patient charts. The pre coded data were entered in to EPI-data version 3.1 then exported to STATA version 14.0 for analysis. Both bivariable and multivariable regression analysis were carried out. Variables with p value < 0.05 in multivariable logistic regression were consider as significant predictors of the outcome variable. Result The prevalence of HIV among cervical cancer patients was 18.35%. HIV among cervical cancer patients was significantly associated with age group 30–39 [AOR = 2.83; 95%CI (1.27, 6.22)] and 40–49 [AOR = 2.39; 95%CI (1.07, 5.32)], employed [AOR = 2.23; 95%CI (1.46, 3.41)] and substance users [AOR = 3.92; 95%CI (2.04, 6.28)]. Conclusion This study revealed that about 18% of cervical cancer patients were HIV seropositive. HIV seropositivity was significantly increased with 30–49 age group, employed and substance users. Authors recommended that it is better to screen all HIV seropositive patients for cervical cancer and give greater attention for women with cervical cancer in the age groups of 30–49 years, employed and substance users.