Journal of AIDS & Clinical Research

A workshop entitled: “What type of HIV Vaccine research should be promoted” took place during a virology conference held in Baltimore in November 2013 (www.omicsgroup.com/conferences/virology-2013/). The purpose of this workshop was to discuss new paradigms that better fit our increased knowledge of HIV immunopathology and which could possibly be more helpful in guiding future vaccine research than did past unsuccessful approaches. Panelists were asked to respond to four questions regarding possible novel paradigms that could guide future HIV vaccine research and their responses are summarized.

Objective: HLA polymorphisms within the peptide binding pocket have been associated with rapid and slowprogression to AIDS, suggesting that the capability to present efficiently HIV-1 epitopes is crucial for the infection control. To minimize the effects of genetic background due to population coming from different geographic area and viral strain variability in the cohort, an analysis of all the polymorphisms associated with the HLA-A, -B and -DR alleles has been performed in a cohort of children with a monophyletic HIV-1 infection (CRF02_AG) during an outbreak in Libya.

Methods: High-resolution HLA-typing has been performed in 58 children infected with a monophyletic strain of HIV-1: 26 Long-Term Non-Progressors (LTNP), 9 Slow-Progressors (SP) and 23 Fast-Progressors (FP). HLA amino acid polymorphism frequency has been compared in the in FP respect to LTNP.

Results: HLA-B resulted the most interesting locus of the study; 10 positions located in B- and F-pocket for peptidebinding have been found significant after Bonferroni’s correction: 11S (LTNP=7.69% FP=34.78% OR=0.156 P<0.05), 74D (LTNP=15.38%, FP=52.17%, OR=0.167; p<0.015) and 94T (LTNP=15.38%, FP=52.17%, OR=0.045; p<0.001), resulted associated with AIDS progression; 66N (LTNP=42.31% FP=8.7% OR=7.7; p<0.02), 80I (LTNP=80.77%, FP=34.78%, OR=7.86; p<0.036), 81A (LTNP=84.61%, FP=47.83%, OR=6; p<0.015), 82L (LTNP=88.46%, FP=47.83%, OR=7.86; p<0.006) and 83R (LTNP=88.46%, FP=47.83%, OR=7.86; p<0.006), has been associated with non-progression. Further, carrying Bw4-epitope resulted associated with LTNP (phenotype-frequency: LTNP=88.46%, FP=47.83%, OR=8.36; p<0.006), with homozygosis for Bw4 (LTNP=30.8%, FP=8.7%, p<0.05) associated with delayed progression and homozygosis for Bw6 (LTNP=11.5%, FP=52.1%, p<0.05) associated with fast progression to AIDS.

Conclusion: The progression to AIDS might be in part determined by the binding capability of B-pocket and F-pocket of HLA-B and in part by the interaction of NK’s inhibitory receptor with HLA-B Bw4-epitope which regulate innate immune response and might have important implications for a better disease control.

HIV is now a chronic treatable disease, with a life expectancy approaching the general population. However, treatments with anti-retroviral medications are associated with metabolic abnormalities and an increased risk of coronary artery disease, leading to a greater incidence of cardiac morbidity and mortality. A contemporary approach to the management of patients with HIV must therefore include aggressive management of cardiovascular risk factors and appropriate screening of cardiovascular disease. This review outlines the pathogenesis of coronary disease in patients with HIV and a modern approach for screening and management.

Objectives: The increased cardiovascular risk historically associated with protease inhibitor (PI) use in HIVinfected individuals is only partly attributable to fasting dyslipidaemia, and may not apply to the currently recommended PI drugs - atazanavir and darunavir. In this prospective pilot study, we aimed to describe the isolated metabolic differences between atazanavir/ritonavir and darunavir/ritonavir on circulating fasting and post-prandial lipids (primary objective), and arterial stiffness, glycaemic and inflammatory markers (secondary objectives) by administering them as monotherapy to healthy, HIV-uninfected adults.

Methods: Participants were randomised 1:1 to receive open-label atazanavir (300 mg/day) or darunavir (800 mg/day), both boosted with ritonavir (100 mg/day), for 4 weeks. A standardised high-energy meal was consumed at weeks 0 and 4, with hourly post-prandial blood samples and arterial stiffness assessed for 4 hours. Mean fasting and post-prandial measurements were compared, the latter as the change in mean post-prandial incremental area under the curve.

Results: Twenty participants (10 atazanavir/ritonavir, 10 darunavir/ritonavir; 50% male, mean age 38 years, mean blood pressure 113/72 mmHg, mean total cholesterol 4.4 mmol/L, mean triglycerides 0.9 mmol/L) completed the study. After four weeks, fasting total cholesterol rose more with darunavir/ritonavir than atazanavir/ritonavir (+0.8 mmol/L vs. +0.3 mmol/L, respectively; p=0.041), as did low-density lipoprotein cholesterol (+0.1 mmol/L vs. +0.7 mmol/L, respectively; p=0.017). Between-group differences in post-prandial lipid changes were non-significant. Postprandial decline in arterial stiffness was greater with atazanavir/ritonavir than darunavir/ritonavir (-27.6 h% vs. +0.1 h%, respectively; p=0.041). Bilirubin rose significantly with atazanavir/ritonavir but not darunavir/ritonavir (+29 μmol/L vs. -0.6 μmol/L, respectively; p=0.001). Changes in other parameters were similar.

Conclusion: Atazanavir/ritonavir has modestly, but significant, favourable metabolic and haemodynamic profiles over darunavir/ritonavir, evident even after short-term monotherapy. Post-prandial lipid effects were similar, however. Further study of treatment-emergent cardiovascular event incidence with darunavir/ritonavir therapy is required to determine the clinical relevance of this between-group difference.

Background: This study assesses among 200 HIV-infected outpatients the prevalence of positive alcohol use disorder (AUD) and its correlations with socio-demographic characteristics, life habits, sexual behavior and (hypo) manic symptoms. Methods: Between December 2009 and June 2011, patients were interviewed at the specialized clinic for HIV care located in Walter Cantídio’s University Hospital, Fortaleza, Ceará, Brazil. Screening for AUD was performed with the Alcohol Use Disorders Identification Test (AUDIT). A socio-demographic questionnaire based on WHO’s Behavioral Surveillance Surveys was used to track risky sexual behaviors. The Mood Disorder Questionnaire (MDQ) was used to screen for symptoms of mania and hypomania. Results: One hundred thirty-three patients (66.5%) were male, mean age of 37.4 years (standard deviation, SD=10.9) and mean years of study of 9.5(SD=3.5). Ninety nine patients (49.5%) had AUD: 80 (40%) had hazardous drinking and 19 (9.5%) had alcohol dependence. AUD patients had higher rates of male gender (OR=2.8; 95%CI=1.5, 5.2), living alone (OR=4.5; 95%CI=1.6, 12.7), use of tobacco (OR=3.0; 95%CI=1.4, 6.6), use of illicit drugs (OR=3.5; 95%CI=1.7, 7.1) and (hypo)manic symptoms (OR=6.4; 95%CI=2.3, 17.7). Regarding sexual behavior, AUD was associated with lower age at first sex (OR=1.1; 95%CI=1.05, 1.2) and higher prevalence of commercial (OR=2.7; 95%CI=1.3, 5.8) and non-regular sex partners (OR=4.3; 95%CI=2.1, 8.6). In multivariate analysis, independent associations between AUD and the following variables were found: manic symptoms (adjusted Odds Ratio [aOR]=10.1; 95%CI=2.3, 44.7), living alone (aOR=7.8; 95%CI=1.5, 39.0), tobacco use (aOR=3.9; 95%CI=1.2, 12.2), male gender (aOR=3.4; 95%CI=1.4, 8.3), sex with non-regular partners (aOR=2.7; 95%CI=1.1, 6.6), lower education (aOR=1.1; 95%CI=1.03, 1.2) and lower age (aOR=1.03; 95%CI=1.002, 1.076). Conclusion: Therefore, there is a significantly high prevalence of AUD among HIV-infected patients. AUD showed the following profile: young males, living alone, with lower education, higher rates of (hypo) manic symptoms and drug and sexual risk behaviors. A better understanding of AUD comorbidity and its implications on behavioral aspects of HIV-positive individuals may help in providing better long term outcomes of these patients.

Background: Human immune deficiency virus (HIV), the causative agent of Acquired Immune Deficiency Syndrome (AIDS) has remained a global cankerworm, with more impact in the sub-Saharan Africa. This virus destroys and depletes the human CD4 cells, leading to immune deficiency state and making the individual susceptible to opportunistic infections. Fungal opportunistic infections are among the common pathogens seen earlier in HIV positive individuals and may present as respiratory diseases like Pneumocystis jiroveci pneumonia and pulmonary cryptococcosis. This study aimed at understanding the pattern of fungal opportunists in the sputa of HIV positive individuals in our locality, to understand the demographics among those with the fungal isolates and to correlate CD4 level of the patients with the isolated opportunistic fungal pathogens.

Methods: This was a prospective study in design, study area was Federal Medical Centre Owerri, Imo state, Nigeria, and study population included HIV positive individuals who were older than fifteen (15) years who developed cough lasting for more than fourteen (14) days). The hospital is the largest in the state and serves some neighbouring states like Rivers, Anambra and Abia state. The sample size was seventy three (73). Samples were collected, processed and organisms identified and results tabulated.

Results: Out of the seventy three (73) sputa sample, 50 (68.5%) showed positive growth while twenty three 23 (31.5%) did not show any growth. Males with opportunistic fungal infections had a lower frequency (40%) than females (60%). 40/50 (80%) of the grown organisms were Candida organism and 23/40 (57.5%) of them were albicans. Candida albican had the highest incidence 23/50 (46%) and seen more in the age bracket (25-34). It was also rarely seen when the CD4 cell count was more than 500 cell/mm3 but very common when count was <400 cells/ mm3. Cryptococcus neoformans had 5/50 (10%) and isolated in individual with CD4 count<100 cells/mm3, Aspergillus flavus and A. fumigatus were isolated at 56 and 367 cells/mm3 with incidences of 2.0% respectively (Figure 1). The Penicillium marneffi reported as the emerging fungal infection among HIV clients in Southeast Asia was not seen in our series.

Conclusions: Most pulmonary fungal opportunistic infection in the setting of HIV often mimics pulmonary tuberculosis. Candida albicans has the highest incidence in our study. However, knowledge of fungal opportunistic infections pattern in HIV patients will help clinicians in the appropriate management of the clients—in terms of prophylaxis and therapeutics.

Purpose: In recent years, some authors have reported a high prevalence of cervical cancer in HIV depressed patients. As our unit also aims to protect HIV-positive patients of all diseases or all opportunist infections it was found appropriate to conduct this study in order to contribute to the early detection of precancerous lesions of the cervix (LPC) using the VIA technique with our patients.

Methods: This study which is a longitudinal prospective one was conducted in a descriptive and analytical perspective. It was carried out within the voluntary testing centre (VTC) of the Department of Dermato-Venereology of the University Hospital of Treichville and in collaboration with the Department of Gynecology. The recruitment of patients was done within a 4-month-period using a survey form. The study included 150 women screened HIV+ under anti-retroviral treatment (ARV) within the VTC. They were followed up at 4-month intervals. They were aged 18 or upper. They agreed to participate in this study on a verbal consent basis. None of them were commercial sex workers.

Results: Demographics of PLWHA in our study were similar to those observed in the literature;

• 16/150 women had a positive VIA test (10.6%);

• The factors favoring the occurrence of cervical PCL in our study were:

- Age of the first sexual intercourse;

- The existence of vulvar warts, genital herpes and a cervicovaginitis;

- CD4 level <200/mm3.

Conclusion: The cancer of the cervix as a concern for any woman is also a concern for those living with HIV. Its real extent in women infected with HIV is still unknown in our country because large scale screening is not conducted given financial difficulties. We believe that the method of detection of PCL using VIA technique should be encouraged because of its affordability in a limited resource countries of ours.

Background: Hepatotoxicity is one of the most frequent adverse events induced by anti-tuberculosis chemotherapy and remains one of the main causes of treatment interruption during TB treatment leading to hospitalization and life threatening events. Despite the high prevalence of TB/HIV co-infection in sub-Sahara Africa, paucity of data still exists on anti-TB drugs induced hepatotoxicity in HIV patients. Therefore, this study was aimed to determine the incidence and risk factors of hepatotoxicity induced by anti-tuberculosis drugs in HIV patients.

Methods: From March to September 2013, we conducted a nested case-control study by retrospectively following up TB/HIV co-infected patients on anti-TB treatment at the Buea and Limbe Regional Hospitals. Patients who developed hepatotoxicity due to increased liver enzymes (ALAT and ASAT) after anti-TB treatment initiation were labelled as “cases” while those without hepatotoxicity were “controls”. Each case was compared with 3 randomly selected controls.

Results: From the 191 TB/HIV patients recruited in the study, 26 developed hepatotoxicity. These 26 were labelled as cases and were compared to 78 randomly selected controls. WHO HIV/AIDS clinical stage 4, BMI<18.5 Kg/m2, CD4 count<50 cells/mm3, hepatitis B co-infection, and extra pulmonary TB were significantly associated with the development of anti-TB drug induced hepatotoxicity. These variables were then analysed using multivariate logistic regression and BMI<18.5 Kg/m2 [P=0.033; AOR=3.7] and hepatitis B co-infection [P=0.019; AOR=6.6] were identified as independent predictors of anti-TB induced hepatotoxicity.

Conclusion: The incidence of anti-TB drug induced hepatotoxicity was 13.61%. The findings suggest that TB/ HIV co-infected patients presenting with poor nutritional status as defined by BMI<18.5 Kg/m2 andhepatitis B should be closely monitored by clinicians especially during the intensive phase of anti-tuberculosis chemotherapy for better patient management and for the prevention of morbidity and mortality

Background: The aim of this study is to explore factors affecting survival of children living with HIV/AIDS after initiation of ART. In which it highlights the need for local evidence to promote interventions that optimize survival among HIV-infected children on ART in Ethiopia.

Methods: Institution based retrospective cohort study was employed on 560 children enrolled on ART from January, 2006-December, 2010. Information on relevant variables was collected from patients` medical cards and registries. Univariate analysis was used to describe the baseline characteristics of the patients`. Life table was used to estimate survival after initiation of ART. Log rank test was used to compare survival between different categories of independent variables. Multivariable Cox proportional model was fitted to identify factors affecting survival after initiation of ART.

Results: Children on ART were followed for a median follow up period of 47 months (IQR=29, 62). At the end of follow up, 364 (65%) were alive and 43 (7.6%) were reported dead. More than three fourth of the deaths occurred within the first sixth months of starting ART. The estimated cumulative survival probabilities were 0.939, 0.928, 0.926, 0.923, 0.920, and 0.916 at 6, 12, 18, 36, 48, and 60 months, respectively. Anemia (hemoglobin level<10 gm/dl) (AHR=2.60, 95% CI=1.41, 4.84), absolute CD4 cell count below the threshold for severe immunodeficiency (AHR=3.55, 95% CI 1.48, 8.46), advanced WHO staging (stage IV) (AHR=3.08, 95% CI=1.27, 7.47), and underweight (AHR=2.49, 95% CI 1.27, 4.88) have found to be predictors of mortality after ART initiation.

Conclusions: Mortality was high especially during the first sixth months following ART initiation. Therefore, close follow up of HIV exposed children to make early diagnosis and treatment initiation before the development of severe immune deficiency and advanced clinical stage is important.

Introduction: AIDS is a disease of human immune system caused by Human Immunodeficiency Virus. Immunologically it is defined as the condition characterized by CD4 cell count less than 200 cells/mm3. In developing countries the resource are limited so that CD4 count is not easily available in every parts of the country and is too expensive to afford. The Total lymphocyte count (TLC) has been found to be an inexpensive and useful surrogate marker of CD4 count for staging disease, timing of initiation of Antiretroviral Therapy (ART) and response to ART.

Objective: To study the relationship between the T-cell subsets (CD3 and CD4) in HIV patient and to evaluate TLC as a surrogate marker of CD4 T-cell count. Methods: A total of 303 samples were evaluated from July 2010 to September 2010 at NPHL for this study. The blood sample were analyzed by FACS count and the result were analyzed by SPSS 16.0 to determine sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) to find out the relationship between the T cells subsets and evaluate TLC as a surrogate marker of CD4 T cell count for the diagnosis of CD4 count<200 cell/ mm3 and <350 cell/mm3.

Results: There is a strong co-relation between CD4 count and TLC (r=0.714, p<0.01) and CD4 count and CD3 count (r=0.707, p<0.01). A threshold value of 1,400 cell/mm3, we found a maximal combination of sensitivity (70.1%), specificity (81.4%) and NPV (88.9%), but PPV is only 56.2% for a CD4+ T cell count<200 cell/mm3. A CD3 count of <1000 cell/mm3 would have a maximum combination of sensitivity (72.7%), specificity (81%) and NPV (89.7%) but PPV is only 56.6% for CD4 T-cell count<200 cell/mm3.

Conclusion: Total lymphocyte count may provide a simple and cost effective alternative for prioritizing therapy initiation in resources-limited settings. Our study showed a good co-relation (Pearson) of CD4 count with CD3 and TLC, result suggest that, if appropriately validated, judicious application of total lymphocyte counts could overcome one of the practical obstacles to more widespread provision of ART in resource-poor settings.