Human Immunodefiency Virus Research Articles

Kaposi's sarcoma: epidemiologic aspects, the immune reconstitution inflammatory syndrome, and more along the Silk Road of cognition.

Kaposi's sarcoma remains enignmatic with many clinical and epidemiological patterns. We review them and describe the groove sign, an important association worthy of recognition. We also stress Kaposi's sarcoma (KS) without coexistent human immunodefiency virus infection, with recent data from China describing an extraordinarily high classical KS prevalence rate among Uygurs and Kazaks in the Xinjiang Uygur Autonomous Region in northwestern China, presumably derived from elderly men residing there. The possible travel of HHV-8 along the ancient silk road from Italy to the Xinjiang Uyghur region remains intriguing. If only one in 10,000 HHV-8-infected patients develops classical KS worldwide, then triggers for its overrepresentation in this population within China are of particular concern. The KS-related immune reconstitution inflammatory syndrome is also emphasized.

Rapid Slide Culture Technique for Mycobacterium Tuberculosis and Predictors of Poor Outcomes among Pulmonary Tuberculosis Patients

Tuberculosis (TB), a dreadful disease known to mankind continues to be a problem in a developing country likeIndia. The incidence of people getting infected with TB is on the rise due to compounding factors like coinfectionwith the human immunodefiency virus and multidrug-resistant strains. There is a definitive need for earlydiagnosis and treatment of TB to curb transmission of the infection. Direct smear microscopy, though cheap andrapid, lacks sensitivity. Isolation of Mycobacterium tuberculosis in culture requires a long time, because of whichthere is a need for a rapid method which has good sensitivity and specificity for the detection of M. tuberculosis.Hence the present study was undertaken to determine Performance of rapid slide culture method for confirmingpulmonary tuberculosis in clinically suspected and smear positive cases and also to assess the factors responsiblefor poor outcomes in the study population.

Human Immunodefiency Virus Infection in Tuberculosis Patients at Kotaraja Health Center of Papua

Human Immunodeficiency Virus (HIV) is a virus that attacks white blood cells and causes the human immune system to decrease. Tuberculosis in HIV patients is an opportunistic infection that will aggravate the disease infection in patients. Examination of HIV (Human Immunodeficiency Virus) in Tuberculosis Patients was carried out at the Kotaraja Health Center. This study was conducted for 1 month starting from May 17, 2019, to June 07, 2019. The purpose of this study was to determine HIV in tuberculosis patients at the Kotaraja Health Center. This type of research is descriptive with a laboratory test approach. The sample used is a serum sample with a diagnosis of HIV. The method used in this examination is the Rapid Test method. The results of HIV testing on tuberculosis patients, sample data obtained from HIV tuberculosis co-infected respondents amounted to 30 HIV respondents who took tuberculosis treatment >6-9 months, negative 6 patients (20%).

An Assessment of Perceived Stigmatization of Patients Infected with COVID-19 in the Nation's Epicenter of the Pandemic: A Cross-Sectional Study of Residents of Agege, Lagos, Nigeria

Background: In some parts of Africa, the patients and those who survived COVID-19 are stigmatized and this has impeded the response activities put in place to control the pandemic. In spite of this, most efforts in preventing COVID-19 were geared towards the use of non-pharmacologic measures without corresponding measures to dissipate stigmatization in the community. Therefore, this study assessed the factors associated with perceived stigmatization of patients with COVID-19 among residents of Agege local government, Lagos State, Nigeria.
 Methods: We conducted a cross-sectional survey among 333 consenting residents recruited from Agege local government area (LGA) using a multi-stage sampling technique. A semistructure, interviewer-administered questionnaire adapted from the People Living with Human Immunodefiency Virus (PLHIV) Stigma Index was used to collect data on socio-demographic characteristics, knowledge of COVID-19 and perceived stigmatization. Bivariate analysis was done using Chi-square and binary logistic regression was used to identify the determinants of perceived stigmatization at 5% level of significance.
 Results: The mean age of the respondents was 35.7 ± 13.6 years. Awareness about COVID-19 outbreak was 95.2%. Television (43.5%) and radio (36.9%) were the two major sources of information on COVID-19 infection and prevention. The proportions of the respondents who had poor knowledge and perceived stigmatization of COVID-19 patients were 50.0% and 47.7% respectively. A higher likelihood of perceived stigmatization was found among those aged 25 - 49 years (aOR= 3.1, 95% CI = 1.4 - 6.7), > 50 years (aOR= 2.1, 95% CI = 1.1 - 3.9) and married respondents (aOR= 1.8, 95% CI = 1.1 - 2.9).
 Conclusion: The study highlights the poor knowledge about COVID-19 and a high level of stigmatization. Hence, targeted health educational interventions are urgently needed for the residents of Agege, most especially among married respondents as well as the adults.
 Authors
 O A Babatunde 1 2, S A Owoicho 3, S T Sunday 3, A Akande 4, B M Yesufu 5, I M Akanbi 6, M D Dairo 7

Decolonising ‘man’, resituating pandemic: an intervention in the pathogenesis of colonial capitalism

This paper brings together fifth-wave public health theory and a decolonised approach to the human informed by the Caribbean thinker, Sylvia Wynter, and the primary exponent of African Humanism, Es’kia...

Bearing the Burden of Non-AIDS Comorbidities: This Is What Women Aging With Human Immunodefiency Virus Look Like.

Bearing the Burden of Non-AIDS Comorbidities: This Is What Women Aging With Human Immunodefiency Virus Look Like.

Incidence and Persistence of High-risk Anogenital Human Papillomavirus Infection Among Female Youth With and Without Perinatally Acquired Human Immunodefiency Virus Infection: A 3-year Observational Cohort Study.

Female youth with perinatally acquired human immunodeficiency virus (PHIV) may be at higher risk than uninfected youth for persistent anogenital human papillomavirus (HPV) infection, due to prolonged immunodeficiency. A 3-year cohort study was conducted between 2013 and 2017 among Thai and Vietnamese PHIV and HIV-uninfected females 12-24 years, matched by age group and number of lifetime sexual partners. For HPV genotyping, cervical and anal samples were obtained at baseline and annually. Vaginal samples were collected at baseline and every 6 months. Factors associated with high-risk HPV (HR-HPV) persistence and incidence were assessed. We enrolled 93 PHIV and 99 HIV-uninfected females. Median age was 19 (interquartile range [IQR] 18-20) years. For the 7 HR-HPV types (16, 18, 31, 33, 45, 52, 58) in the nonavalent HPV vaccine, PHIV had significantly higher incidence (P = .03) and persistence (P = .01) than HIV-uninfected youth over a 3-year period. Having HIV (adjusted hazard ratio [aHR] 2.1, 95% confidence interval [CI] 1.1-3.9) and ever using illegal substances (aHR 4.8, 95% CI 1.8-13.0) were associated with incident 7 HR-HPV infections. HIV-positive status (adjusted prevalence ratio [aPR] 2.2, 95% CI 1.5-3.2), recent alcohol use (aPR 1.75, 95% CI 1.2-2.5), and higher number of lifetime partners (aPR 2.0, 95% CI 1.4-3.1, for 3-5 partners; aPR 1.93, 95% CI 1.2-3.2, for ≥6 partners) were significantly associated with persistent 7 HR-HPV infections. Female PHIV were at higher risk of having anogenital HR-HPV acquisition and persistence. Primary and secondary prevention programs for HPV infection and HPV-related diseases should be prioritized for PHIV children and youth.

Implementation and Effectiveness of community-based resources to increase cervical cancer screening uptake among women living in sub-Saharan Africa: A protocol for systematic review

# Background Sub-Saharan Africa (SSA) accounts for about 70% of the global burden of cervical cancer; this is due to several factors including lack of access to cervical cancer screening, low knowledge of cervical cancer and screening services, poor-functioning health systems, insufficient and poorly trained health workers, and the high burden of human immunodefiency virus (HIV) infection. To date, to the best of our knowledge, there has been no systematic review of the literature on the role of community-based resources such as community health workers and community-based organisations in increasing the uptake and or continuing participation of women in cervical cancer screening, in the setting of high HIV burden, in sub-Saharan Africa. # Methods We will systematically search selected databases and websites from 1980 to date for published and grey literature including citation and reference list tracking, on studies with a community focus carried out in sub-Saharan Africa, without language restrictions. Randomised controlled trials (RCTs), observational studies, and qualitative and mixed methods studies of interventions (carried out with and without comparison groups) reporting impact on participation in cervical cancer screening in sub-Saharan Africa will be identified and assessed for methodological quality by two independent reviewers. We will use narrative synthesis and/or meta-analysis depending on the study selection. # Results Findings will be summarised into abstracts for presentation at conferences and submission to peer-reviewed journals in the field for wide-ranging dissemination to patients, researchers, healthcare professionals and policy makers on cervical cancer in sub-Saharan Africa. # Conclusion The review will address the gap in evidence for effective and implementable community-based strategies that encourages uptake of cervical cancer screening among women living in sub-Saharan Africa. The findings will have the potential to inform future screening practice and research with the hope of reducing the burden of cervical cancer in the region. # PROSPERO registration number -- CRD42018102539.

Outcomes of Immunocompromised Adults Hospitalized With Laboratory-confirmed Influenza in the United States, 2011-2015.

Hospitalized immunocompromised (IC) adults with influenza may have worse outcomes than hospitalized non-IC adults. We identified adults hospitalized with laboratory-confirmed influenza during 2011-2015 seasons through CDC's Influenza Hospitalization Surveillance Network. IC patients had human immunodefiency virus (HIV)/AIDS, cancer, stem cell or organ transplantation, nonsteroid immunosuppressive therapy, immunoglobulin deficiency, asplenia, and/or other rare conditions. We compared demographic and clinical characteristics of IC and non-IC adults using descriptive statistics. Multivariable logistic regression and Cox proportional hazards models controlled for confounding by patient demographic characteristics, pre-existing medical conditions, influenza vaccination, and other factors. Among 35 348 adults, 3633 (10%) were IC; cancer (44%), nonsteroid immunosuppressive therapy (44%), and HIV (18%) were most common. IC patients were more likely than non-IC patients to have received influenza vaccination (53% vs 46%; P < .001), and ~85% of both groups received antivirals. In multivariable analysis, IC adults had higher mortality (adjusted odds ratio [aOR], 1.46; 95% confidence interval [CI], 1.20-1.76). Intensive care was more likely among IC patients 65-79 years (aOR, 1.25; 95% CI, 1.06-1.48) and those >80 years (aOR, 1.35; 95% CI, 1.06-1.73) compared with non-IC patients in those age groups. IC patients were hospitalized longer (adjusted hazard ratio of discharge, 0.86; 95% CI, .83-.88) and more likely to require mechanical ventilation (aOR, 1.19; 95% CI, 1.05-1.36). Substantial morbidity and mortality occurred among IC adults hospitalized with influenza. Influenza vaccination and antiviral administration could be increased in both IC and non-IC adults.

Scientific rationale for traditional use of plants to treat tuberculosis in the eastern region of the OR Tambo district, South Africa

Ethnopharmacological relevanceTuberculosis (TB) remains a major health problem for humans worldwide, and was responsible for 1.4 million human deaths in 2015 alone. Although there is treatment for TB, emerging multi-drug, extensively drug and totally drug resistant forms of this disease, as well as co-infection with human immunodefiency virus (HIV) continue to worsen the situation. South Africa is among countries with reported traditional use and published documentation of such knowledge concerning the use of plants against TB. Based on a previous study where plants used traditionally for treating TB in the eastern region of OR Tambo district, South Africa, were documented, the present study aimed to determine the antimycobacterial effect, cytotoxicity and genotoxicity of plants selected from that list. Material and methodsAcetone, 70% ethanol, cold and hot water extracts were tested for antimycobacterial activity against saprophytic Mycobacterium species including M. aurum, M. bovis BCG, M. gordonae, M. fortuitum, and M. smegmatis using a microdilution method. Extracts with MIC values less than 1 mg/ml against at least three Mycobacterium strains were evaluated for antimycobacterial activity against pathogenic Mycobacterium strains including M. tuberculosis H37RV, M. tuberculosis and M. bovis, cytotoxicity (against Vero monkey kidney and bovine dermis cells), and genotoxicity (against Salmonella typhimurium TA98 and TA100). ResultsThe MIC values of the extracts ranged from 0.02 to 2.50 mg/ml, LC50 values of twenty-nine extracts ranged from 0.001 to > 1 mg/ml and the highest selectivity index was 79.50, an extremely promising value. Phymaspermum acerosum roots and leaves (ethanol and water) extracts had the best MIC value (0.02 mg/ml) against at least one Mycobacterium strain. It was interesting to note the lack of cytotoxicity of these extracts with the highest selectivity index value of 39.75. Pterocelastrus echinatus bark acetone and Protorhus longifolia leaf hot water extracts were the most cytotoxic with LC50 = 0.001 and 0.008 mg/ml, respectively, whereas Pittosporum viridiflorum bark water extract was genotoxic. Among non-pathogenic strains, M. gordonae, M. aurum, M. smegmatis showed good correlation of activity with pathogenic M. tuberculosis H37Rv, M. tuberculosis and M. bovis, however, M. aurum was the best predictor with Mycobacterium tuberculosis H37Rv (correlation coefficient value = 0.73). ConclusionThe results indicate that Heteromorpha trifoliata and Phymaspermum acerosum should be investigated further for antimycobacterial efficacy against drug resistant strains of Mycobacterium.

Missed hepatitis b/c or syphilis diagnosis among Kurdish, Russian, and Somali origin migrants in Finland: linking a population-based survey to the national infectious disease register

BackgroundMigrants are considered a key population at risk for sexually transmitted and blood-borne diseases in Europe. Prevalence data to support the design of infectious diseases screening protocols are scarce. We aimed to estimate the prevalence of hepatitis B and C, human immunodefiency virus (HIV) infection and syphilis in specific migrant groups in Finland and to assess risk factors for missed diagnosis.MethodsA random sample of 3000 Kurdish, Russian, or Somali origin migrants in Finland was invited to a migrant population-based health interview and examination survey during 2010–2012. Participants in the health examination were offered screening for hepatitis B and C, HIV and syphilis. Notification prevalence in the National Infectious Diseases Register (NIDR) was compared between participants and non-participants to assess non-participation. Missed diagnosis was defined as test-positive case in the survey without previous notification in NIDR. Inverse probability weighting was used to correct for non-participation.ResultsAltogether 1000 migrants were screened for infectious diseases. No difference in the notification prevalence among participants and non-participants was observed. Seroprevalence of hepatitis B surface antigen (HBsAg) was 2.3%, hepatitis C antibodies 1.7%, and Treponema pallidum antibodies 1.3%. No cases of HIV were identified. Of all test-positive cases, 61% (34/56) had no previous notification in NIDR. 48% of HBsAg, 62.5% of anti-HCV and 84.6% of anti-Trpa positive cases had been missed. Among the Somali population (n = 261), prevalence of missed hepatitis B diagnosis was 3.0%. Of the 324 Russian migrants, 3.0% had not been previously diagnosed with hepatitis C and 2.4% had a missed syphilis diagnosis. In multivariable regression model missed diagnosis was associated with migrant origin, living alone, poor self-perceived health, daily smoking, and previous diagnosis of another blood-borne infection.ConclusionsMore than half of chronic hepatitis and syphilis diagnoses had been missed among migrants in Finland. Undiagnosed hepatitis B among Somali migrants implies post-migration transmission that could be prevented by enhanced screening and vaccinations. Rate of missed diagnoses among Russian migrants supports implementation of targeted hepatitis and syphilis screening upon arrival and also in later health care contacts. Coverage and up-take of current screening among migrants should be evaluated.

Development and validation of a prognostic score during tuberculosis treatment

BackgroundDeath under care is a major challenge for tuberculosis (TB) treatment programs. We derived and validated a simple score to predict mortality during tuberculosis treatment in high endemicity areas.MethodsWe used data for patients aged ≥15 years, diagnosed and treated for tuberculosis at the Yaounde Jamot Hospital between January 2012 and December 2013. Baseline characteristics associated with mortality were investigated using logistic regressions. A simple prognosis score (CABI) was constructed with regression coefficients for predictors in the final model. Internal validation used bootstrap resampling procedures. Models discrimination was assessed using c-statistics and calibration assessed via calibration plots and the Hosmer and Lemeshwow (H-L) statistics. The optimal score was based on the Youden’s index.ResultsA total of 2250 patients (men 57.2%) with a mean age of 35.8 years were included; among whom 213 deaths (cumulative incidence 9.5%) were recorded. Clinical form of tuberculosis (C), age (A, years), adjusted body mass index (B, BMI, kg/m2) and status for HIV (Human immunodefiency virus) infection (I) were significant predictors in the final model (p < 0.0001) which was of the form Death risk = 1/(1 + e− (−1.3120 + 0.0474 ∗ age − 0.1866 ∗ BMI + 1.1637 (if smear negative TB) + 0.5418(if extra − pulmonary TB) + 1.3820(if HIV+))). The c-statistic was 0.812 in the derivation sample and 0.808 after correction for optimism. The calibration was good [H-Lχ2 = 6.44 (p = 0.60)]. The optimal absolute risk threshold was 4.8%, corresponding to a sensitivity of 81% and specificity of 67%.ConclusionsThe preliminary promising findings from this study require confirmation through independent external validation studies. If confirmed, the model derived could facilitate the stratification of TB patients for mortality risk and implementation of additional monitoring and management measures in vulnerable patients.

Chronic Hepatitis C Treatment : A Systematic Review

Background: Chronic hepatitis C (CHC) infection affects almost 3% of the global population and can lead to cirrhosis, liver failure, and hepatocellular carcinoma in a significant number of those infected. Thus, there is a complelling need to develop and introduce new therapeutics with a direct-acting antiviral effect in order to target various stages of the HCV lifecycle for HCV eradication without concomitant interferon. Study Objective: to provide treatment recommendations for chronic HCV for specialists and generalists based on published evidence. Methods: A literature search of Web of Science, Scopus, Embase, Agricola, Cochrane Library, Cinahl Plus, Google Scholar, and Oaister was conducted from 1990 to 2016, records were filtered according to the Inclusion criteria and 27 hits were yielded. Results: Hepatitis C virus genotype 1 is more difficult to cure than genotype 2 or genotype 3. Patients with HCV genotype 1 should receive treatment with sofosbuvir + pegylated interferon + ribavirin because of the shorter duration of therapy and high rates of SVR (89%-90%). Simeprevir + pegylated interferon + ribavirin is an alternative for patients with HCV genotype 1 (SVR, 79%-86%). Patients with HCV genotypes 2 and 3 should receive therapy with sofosbuvir + ribavirin alone (SVR for genotype 2, 12 weeks’ duration: 82%-93%; SVR for genotype 3, 24 weeks’ duration, 80%-95%). Patients with HIV-HCV coinfection and patients with compensated cirrhosis (ie, cirrhosis but preserved synthetic liver function) should receive the same treatment as HCV-monoinfected patients. Conclusion: A growing body of evidence suggests that recently developed HCV combined treatment modalities have transformed chronic HCV into a routinely curable disease being relatively available and well tolerated ,which can potentially reduce the need for liver transplantation and reduce HCV-related mortality. Treatment protocol for genotype1 is based on a combined regimen of Pegylated interferons with ribavirin and sofosbuvir or simeprevir while Sofosbuvir with ribavirin alone should be used to treat patients infected with HCV genotypes 2 and 3. Patients coinfected with human immunodefiency virus and HCV genotype 1 should be treated for HCV with pegylated interferons, ribavirin, and sofosbuvir by a physician with experience in treating this particular group of patients and familiar with potential drug interactions.

ENGLISH

Sensitivity analysis was performed on a mathematical model of Human Immunodefiency Virus (HIV) to determine the gauge and importance of each parameter to basic reproduction number in the dynamical spread of the disease. The threshold basic reproduction number , 0 R which is the average number of secondary infection generated by infected individuals in his or her infectious period was calculated using next generation matrix method, which shows that, the disease dies out when 1 0  R , and the disease will persist and spread when 1 0  R.The relative sensitivity analysis was computed for all the parameters in the basic reproduction number, which shows the influence of each parameter in the dynamical spread of the disease. Numerical sensitivity reveals that effective contact rate and progressor rate are the most sensitive parameters in the basic reproduction number. This analysis will help the medical practitioners and policy health makers to know the best control intervention strategies to be adopted in order to reduce dynamical spread of Human Immunodefiency Virus (HIV) in the community.

Recurrent Nasal Sebaceous Carcinoma in Human Immunodefiency Virus/ Hepatitis B Virus (HIV/HBV) Coinfection Patient: A Case Report

Background: Human Immunodefiency Virus (HIV) since the first case was reported is recognized as a major risk factor for development of different types of malignancies, Sebaceous carcinoma is a rare and aggressive form of cutaneous carcinoma and very rare in HIV Patients. Method: A case report and literature review of 46 years old male, known to have HIV/HBV coinfection presented with a history of four months of gradual growth Nasal mass. Result: Excisional biopsy performed for the nasal mass and histopathology examination showed sebaceous cell carcinoma, Surgical removal of the nasal mass was done and nasal reconstruction with right paramedian forehead flap plus full thickness skin graft taken from the abdomen for reconstruction of the inner nose also was done, after two years patient came back with recurrent at same site. Conclusion: sebaceous cell carcinoma is an extremely rare in HIV patients, but should be considers for any skin tumor in HIV patient, follow up also needed for the risk of recurrent.

High-Dose Rifapentine with Moxifloxacin for Pulmonary Tuberculosis

BackgroundTuberculosis regimens that are shorter and simpler than the current 6-month daily regimen are needed.MethodsWe randomly assigned patients with newly diagnosed, smear-positive, drug-sensitive tuberculosis to one of three regimens: a control regimen that included 2 months of ethambutol, isoniazid, rifampicin, and pyrazinamide administered daily followed by 4 months of daily isoniazid and rifampicin; a 4-month regimen in which the isoniazid in the control regimen was replaced by moxifloxacin administered daily for 2 months followed by moxifloxacin and 900 mg of rifapentine administered twice weekly for 2 months; or a 6-month regimen in which isoniazid was replaced by daily moxifloxacin for 2 months followed by one weekly dose of both moxifloxacin and 1200 mg of rifapentine for 4 months. Sputum specimens were examined on microscopy and after culture at regular intervals. The primary end point was a composite treatment failure and relapse, with noninferiority based on a margin of 6 percentage points and 90% confidence intervals.ResultsWe enrolled a total of 827 patients from South Africa, Zimbabwe, Botswana, and Zambia; 28% of patients were coinfected with the human immunodefiency virus. In the per-protocol analysis, the proportion of patients with an unfavorable response was 4.9% in the control group, 3.2% in the 6-month group (adjusted difference from control, −1.8 percentage points; 90% confidence interval [CI], −6.1 to 2.4), and 18.2% in the 4-month group (adjusted difference from control, 13.6 percentage points; 90% CI, 8.1 to 19.1). In the modified intention-to-treat analysis these proportions were 14.4% in the control group, 13.7% in the 6-month group (adjusted difference from control, 0.4 percentage points; 90% CI, −4.7 to 5.6), and 26.9% in the 4-month group (adjusted difference from control, 13.1 percentage points; 90% CI, 6.8 to 19.4).ConclusionsThe 6-month regimen that included weekly administration of high-dose rifapentine and moxifloxacin was as effective as the control regimen. The 4-month regimen was not noninferior to the control regimen. (Funded by the European and Developing Countries Clinical Trials Partnership and the Wellcome Trust; RIFAQUIN Current Controlled Trials number, ISRCTN44153044.)

Screening for diabetes mellitus and human immunodefiency virus infection in persons with tuberculosis.

Nigeria is a country saddled with a high tuberculosis (TB) and human immunodeficiency virus (HIV) burden but the possible combination of these communicable diseases with diabetes mellitus (DM) has been overlooked. We undertook to determine the burden of HIV and DM in persons with TB by documenting the prevalence rates of these disorders. This is a cross-sectional Study that was conducted within 54TB/DOT centers in Lagos State. A total of 3,376 persons with TB who were on antiTB drugs were screened for HIV and DM using standardized tests. Statistical analysis was performed using Students t test and chi square. The frequency of occurrence of DM in TB and that of HIV in TB were comparable (4.8% Vs 3.5%). The Study subjects with DM were older, had higher waist circumference measurements and had higher proportions of hypertension compared to the subjects without DM. The combination of HIV and DM in TB was found in (0.3%). We also noted that DM in TB and HIV in TB occurred more frequently in the third and fourth decades of life. This study demonstrated the potential co existence of HIV, DM and Tuberculosis. It is therefore important that these two diseases are sought for in patients with TB considering the changing epidemiology of these diseases particularly in developing countries like Nigeria.

HIV-Associated tuberculosis: A sub-saharan african perspective

The sub-Saharan Africa bears the brunt of being the region with the highest burden of both Human Immunodefiency Virus (HIV) infection and of tuberculosis (TB). While only 10% of immunocompetent individuals infected with M.tuberculosis go on to develop active disease in their lifetime, 50% of those co-infected with HIV develop active TB. Qualitative and quantitative defects of CD4+ T-lymphocytes explain the inability of HIV-infected individuals to contain mycobacterial proliferation. Similarly, TB also accelerates the progression of HIV infection. The clinical and radiological presentation of TB in patients infected with the HIV virus may be different and atypical posing significant diagnostic challenges. This is compounded by the dearth of diagnostic facilities in sub-Saharan Africa. The initiation of antiretroviral therapy (ART) during anti-TB therapy (ATT) significantly improves survival of TB/HIV co-infected persons. There are challenges in treatment of HIV associated TB because of overlapping drug toxicities, pill burden and suboptimal adherence, drug-drug interactions between ART and ATT as well as timing of ART. Of particular importance are the immune reconstitution inflammatory syndrome (IRIS) and the emergence of multi-drug resistant (MD-R) and extensively drug resistant (X-DR) TB. Centre's for tuberculosis diagnosis and treatment and for HIV care and treatment need to be integrated. This has not been so successful in sub-Saharan Africa. In spite of sustained support by donor organizations, a substantial number of HIV-TB co-infected individuals remain undiagnosed and are poorly managed. This review focuses on the epidemiology and pathogenesis of HIV-TB co-infection and the special areas of difficulty in the diagnosis and treatment of the dual infection. Emphasis is placed on the peculiarities of management in sub-Saharan Africa, the region with the highest burden of both infections.

A quarter-century of HIV prevention intervention efforts among children and adolescents across the globe

In 1988 a group of pediatricians, developmental, clinical, child and social psychologists, anthropologists and health educators began researching in Baltimore, Maryland, on an Human Immunodefiency Virus (HIV) prevention intervention, Focus on Youth (FOY). Over the next 25 years, the questions being addressed by FOY reflected those of the global HIV research experience. During the first phase, the questions being addressed by the broader research community included: Can HIV risk behaviors be purposefully impacted by behavioral interventions? If so, how do successful interventions differ from those that are not effective? Are theory-based interventions more likely to be effective than information-only-based interventions? Can theories be translated into culturally and developmentally appropriate interventions including those that are appropriate for children and adolescents? Should parents be involved – and if so, how? During its next phase, the FOY team increasingly became concerned with a disturbing reality. A large number of interventions had been developed and some had been shown to have evidence of impact. But virtually all of these interventions had been conducted in the USA or Europe. The questions facing researchers included: With the global burden of HIV disproportionately impacting low- and middle-income countries (LMIC), especially those in southern Africa, the Caribbean and parts of Asia, what is known about the effectiveness of western-based interventions in these culturally, racially and economically disparate settings? With the exciting proliferation of interventions, federal agencies in the USA and international agencies including Joint United Nations Programme on HIV/AIDS realized the importance of assessing the research portfolio and developing metrics of effectiveness. The questions during this phase included: What is an “effective” intervention? How are effective interventions implemented in a new setting? This phase merged with the next phase as researchers and public health workers realized that the dissemination to a new community of an intervention developed and found to be effective in one community requires change. The central questions during this time included: What changes or kinds of changes can be made to an intervention without undermining its effectiveness? What aspects of an intervention cannot be changed without potentially undermining its effectiveness? What constitutes a “change”? Who should be involved in this decision-making? These efforts culminated in our current phase, one focused on implementation. We must learn more about the factors that allow an intervention to survive and thrive and selectively target these critical factors. The main objective of this paper is to review our experiences and lessons learned in developing, implementing and evaluating FOY in a wide range of socio-cultural settings over the past quarter of century.

Protective effects of alanyl-glutamine supplementation against nelfinavir-induced epithelial impairment in IEC-6 cells and in mouse intestinal mucosa

Purpose: Human Immunodefiency Virus (HIV) protease inhibitors (PI) remain a crucial component of highly active therapy (HAART) and recently have been demonstrated to have potent antitumor effect on a wide variety of tumor cell lines. However, discontinuation of therapy is an important issue, which may be related to various side-effects, especially diarrhea. The aim of this study was to evaluate the effects of nelfinavir (NFV), an HIV PI, and of alanyl-glutamine (AQ) supplementation, on intestinal cell migration, proliferation, apoptosis and necrosis, using IEC-6 cells and on intestinal crypt depth, villus length, villus area, mitotic index and apoptosis in Swiss mice. Methods: Migration was evaluated at 12 and 24 h after injury using a wound healing assay. Cellular proliferation was measured indirectly at 24 and 48 h using tetrazolium salt WST-1. Apoptosis and necrosis were measured by flow cytometry using the Annexin V assay. Intestinal morphometry and mitotic index in vivo were assessed following a seven-day treatment with 100 mg/kg of NFV, given orally. In vivo proliferation and apoptosis were evaluated by intestinal crypt mitotic index and immunohistochemistry, respectively. Results: In vitro, AQ supplementation enhanced IEC-6 cell migration and proliferation, following challenge with NFV. In vivo, AQ increased intestinal villus length, villus area, crypt depth and cell proliferation and cell migration, following treatment with NFV. AQ did not decrease cell death induced by NFV both in vivo and in vitro. Conclusions: AQ supplementation is potentially beneficial in preventing the effects of PIs, such as NFV, in the intestinal tract.