Emergence of Drug Resistance in Human Immunodeficiency Virus Type 1 Infected Patients from Pune, India, at the End of 12 Months of First Line Antiretroviral Therapy Initiation

Introduction. In India, 4,86,173 HIV infected patients are on first line antiretroviral therapy (ART) as of January 2012. HIV drug resistance (HIVDR) is drug and regimen-specific and should be balanced against the benefits of providing a given ART regimen. Material & Methods. The emergence of HIVDR mutations in a cohort of 100 consecutive HIV-1 infected individuals attending ART centre, on first line ART for 12 months, was studied. CD4+ T-cell counts and plasma HIV-1 RNA level were determined. Result. Out of the 100 HIV-1 infected individuals, 81 showed HIVDR prevention (HIV-1 RNA level < 1000/mL), while the remaining 19 had HIV-1 viral RNA level > 1000/mL. HIVDR genotyping was carried out for individuals with evidence of virologic failure (HIV-1 RNA level > 1000/mL). The most frequent NRTI-associated mutation observed was M184V, while K103N/S was the commonest mutation at NNRTI resistance position. Conclusion. Our study has revealed the emergence of HIVDR in HIV-1 infected patients at the end of 12 months of first line ART initiation. For NRTIs, the prevalence of HIVDR mutations was 9% and 10% for NNRTIs. Our findings will contribute information in evidence-based decision making with reference to first and second line ART delivery and prevention of HIVDR emergence.

Understanding the Profile of Tuberculosis and Human Immunodeficiency Virus Coinfection: Insights from Expanded HIV Surveillance at a Tuberculosis Facility in Durban, South Africa

Background. Expanded HIV surveillance in TB patients forms part of the World Health Organization framework for strategic collaborative activity. Surveillance helps understand the epidemiology of the local dual epidemic and enables design of a tailored response to these challenges. Methods. We conducted an observational, cross-sectional study of anonymous unlinked HIV testing for 741 consecutive TB suspects attending an urban TB facility during a seven-week period in 2008. Results. A total of 512 patients were found to have TB. The mean age was 35.7 years, and 63% were male. The prevalence of HIV was 72.2% (95% CI: 68.2–75.9) in all TB cases, 69.8% (95% CI: 65.3–74.2) in pulmonary tuberculosis (PTB), 81.6% (95% CI: 72.9–90.3) in extrapulmonary disease, and 66.8% (95% CI: 60.7–72.9) in those without TB disease. HIV prevalence in TB patients was higher in females than males and in younger age groups (18–29 years). The sex ratio of PTB patients correlated with the sex ratio of the prevalence of HIV in the respective age groups P<0.05. Conclusion. The use of a rapid HIV test performed on sputum anonymously provides an opportunity for HIV surveillance in this high-burdened setting, which has the potential to lend valuable insight into the coepidemics.

Rapid Tests versus ELISA for Screening of HIV Infection: Our Experience from a Voluntary Counselling and Testing Facility of a Tertiary Care Centre in North India

Early and accurate diagnosis of human immunodeficiency virus (HIV) infection is essential for timely identification of patients needing antiretroviral therapy and for instituting HIV prevention strategies. The primary methodology for HIV testing has shifted from enzyme linked immunosorbent assay (ELISA) to rapid diagnostic tests (RDTs) in recent years, especially in resource limited settings. However, the diagnostic performance of RDTs is a matter of concern. In the present study the performance of an RDT being used as the initial test in serial testing based algorithm for HIV diagnosis was compared with ELISA. Seven hundred and eighty-seven sera, tested at the voluntary counselling and testing facility employing a serial testing algorithm (based on SD Bioline HIV-1/2 3.0 as the first test), were subsequently tested with Microlisa-HIV for anti-HIV antibodies. The first test missed 9 HIV reactive samples and also registered 5 false positives. The sensitivity, specificity, and negative and positive predictive values of the first test were 77.5%, 99.3%, and 98.8% and 86.1%, respectively, taking ELISA as the standard test. Our study highlights that RDTs fare poorly compared to ELISA as screening assays and that reactive results by RDTs need to be confirmed by western blot for a positive serodiagnosis of HIV infection.

Factors Determining Survival and Retention among HIV-Infected Children and Adolescents in a Community Home-Based Care and a Facility-Based Family-Centred Approach in Kampala, Uganda: A Cohort Study

We describe factors determining retention and survival among HIV-infected children and adolescents engaged in two health care delivery models in Kampala, Uganda: one is a community home-based care (CHBC) and the other is a facility-based family-centred approach (FBFCA). This retrospective cohort study reviewed records from children aged from 0 to 18 years engaged in the two models from 2003 to 2010 focussing on retention/loss to follow-up, mortality, use of antiretroviral therapy (ART), and clinical characteristics. Kaplan Meier survival curves with log rank tests were used to describe and compare retention and survival. Overall, 1,623 children were included, 90.0% (1460/1623) from the CHBC. Children completed an average of 4.2 years of follow-up (maximum 7.7 years). Median age was 53 (IQR: 11–109) months at enrolment. In the CHBC, retention differed significantly between patients on ART and those not (log-rank test, adjusted, P<0.001). Comparing ART patients in both models, there was no significant difference in long-term survival (log-rank test, P=0.308, adjusted, P=0.489), while retention was higher in the CHBC: 94.8% versus 84.7% in the FBFCA (log-rank test, P<0.001, adjusted P=0.006). Irrespective of model of care, children receiving ART had better retention in care and survival.

The Syndromic versus Laboratory Diagnosis of Sexually Transmitted Infections in Resource-Limited Settings

Sexually transmitted infections (STIs) are highly prevalent in sub-Saharan Africa, where there is a severe HIV epidemic. Thus, accurate recognition and diagnosis of STIs are essential for successful HIV prevention programs in the region. Due to lack of trained personnel and adequate laboratory infrastructure in the region, information regarding the profile of STIs relies essentially on self-reported or physician-diagnosed symptoms. The main objective of the study was to assess the effectiveness of the syndromic diagnosis of STIs, which is often used as a proxy for laboratory diagnosis of STIs in sub-Saharan Africa and other resource-limited settings. The study builds on previously collected data from a community-based survey in Northern Tanzania. We found no significant agreements between patient-reported STIs symptoms and laboratory-confirmed STIs tests. The reported STIs symptoms had high specificity (range = 85–99%) and poor sensitivity (range = 2–17%). Knowledge gained from our study will have significant public health implications, and can help improve the syndromic diagnosis of STIs.

Improvements in Immune Function and Activation with 48-Week Darunavir/Ritonavir-Based Therapy: GRACE Substudy

Objective. During the course of HIV infection, progressive immune deficiency occurs. The aim of this prospective substudy was to evaluate the recovery of functional immunity in a subset of patients from the GRACE (Gender, Race, And Clinical Experience) study treated with a DRV/r-based regimen. Methods. The recovery of functional immunity with a darunavir/ritonavir-based regimen was assessed in a subset of treatment-experienced, HIV-1 infected patients from the GRACE study. Results. 19/32 patients (59%) enrolled in the substudy were virologically suppressed (<50 copies/mL). In these patients, median (range) CD4+ cell count increased from 222 (2, 398) cells/mm3 at baseline to 398 (119, 812) cells/mm3 at Week 48. CD8+% decreased significantly from baseline to Week 48 (P=.03). Proliferation of CD4+ lymphocytes in response to CD3+/CD28+, phytohemagglutinin, and pokeweed was significantly increased (P<.01) by Week 12. Proliferation in response to Candida and tetanus was significantly increased by Week 48 (P<.01 and P=.014, resp.). Staphylococcal enterotoxin B-stimulated tumor necrosis factor-alpha and interleukin-2 in CD4+ cells was significantly increased by Week 12 (P=.046) and Week 48 (P<.01), respectively. Conclusions. Darunavir/ritonavir-based therapy demonstrated improvements in CD4+ cell recovery and association with progressive functional immune recovery over 48 weeks. This trial is registered with NCT00381303.

Predictors of Adherence to Antiretroviral Therapy among HIV/AIDS Patients in the Upper West Region of Ghana

Background. The effectiveness of ART interventions is only realized in maximal levels of adherence. A near perfect adherence level of >95% is required for the effective suppression of HIV/AIDS virus. The main objective of this study was to identify the sociodemographic and socioeconomic factors that facilitate adherence to antiretroviral therapy among HIV/AIDS patients. Methods. This descriptive cross-sectional study was conducted between March and May 2013 at the Upper West Regional Hospital, Wa. A total of 201 confirmed HIV 1 seropositive subjects (mean age 36.6±9.9 years) receiving antiretroviral therapy were interviewed using a structured questionnaire. The collected data was analyzed using GraphPad Prism version 5. A P value of <0.05 was considered statistically significant for all statistical analyses. Results. Overall lifetime adherence was found to be 62.2% while medication adherence in the last six months, last three months, last month, and last week were 73.6%, 87.1%, 91.0%, and 86.0%, respectively. The study revealed a positive association between adherence to ART and immunological success, with nonadherence increasing the risk (OR (95% CI): 9.2 (3.2–26.9)) of immunological failure. Univariate logistic regression analysis of the data showed that other ailments and side effects of drug were negatively associated with adherence to ART whereas self-perceived wellness, family support, and regular followup were positively associated with adherence to ART. Conclusion. Regular attendance at followup and family support are vital factors for 100% lifetime medication adherence. Effective counseling sessions on adherence for patients on antiretroviral therapy are paramount for the realization of the purpose of antiretroviral therapy programmes in Ghana.

The Age of Initiation of Drug Use and Sexual Behavior May Influence Subsequent HIV Risk Behavior: A Systematic Review

Researchers examining injection drug users (IDUs) in drug treatment have been trying for decades to determine the optimal way to intervene to prevent the transmission and spread of human immunodeficiency virus (HIV) in this population. Although efficacious HIV risk reduction interventions are widely available, questions remain about what specific factors are most related to HIV risk behavior and defined as unprotected sexual activity and/or high risk drug use. This review involved an evaluation of the research literature in order to better understand the association between drug use and sexual behavior debut on HIV risk behavior. Findings suggest that drug use debut and sexual behavior debut may be related to subsequent HIV risk behavior. Evidence to date implies that intervening at an earlier age to assist youth to avoid or delay these high risk behaviors may be an additional means of reducing subsequent HIV risk.

Early Atherosclerosis in HIV Infected Subjects on Suppressive Antiretroviral Treatment: Role of Osteoprotegerin

Cardiovascular disease is increased in HIV-infected patients. Cytokines such as osteoprotegerin are implicated in atherosclerosis. The aim of our study was to evaluate the role of osteoprotegerin in the development and progression of atherosclerosis in HIV infected subjects on suppressive antiretroviral treatment. We enrolled 76 patients; 35 HIV infected men on suppressive Highly Active Antiretroviral Therapy with Framingham score <10%; 21 HIV negative individuals matched for age, gender, and Framingham score, and 20 subjects with Framingham score >10% as control groups. HIV positive subjects underwent echocardiography, electrocardiography, and heart multidetector computed tomography, whereas in HIV negative subjects, tomography was only performed in case of any abnormalities either in echocardiography or electrocardiography. In HIV positive patients, computed tomography showed stenosis in 51.4% of the subjects. Osteoprotegerin plasma levels were higher in HIV-infected patients than those in healthy controls but lower than in HIV negative subjects with Framingham score >10%. Higher osteoprotegerin plasma levels were found in HIV positive patients with grade I stenosis than in patients with grade II/III stenosis. In conclusion, in HIV infected subjects with Framingham score <10%, osteoprotegerin plasma concentrations are associated with atherosclerosis, in particular at the early stage of the process.

Nonadherence Factors and Sociodemographic Characteristics of HIV-Infected Adults Receiving Antiretroviral Therapy in Nnamdi Azikiwe University Teaching Hospital, Nnewi, Nigeria

Adherence to treatment instructions with antiretroviral therapy (ART) is very crucial for successful treatment outcome. However, sticking to treatment instructions pose-great challenges to HIV/AIDS patients. This cross-sectional study was on HIV infected adults attending ART clinic in Nigeria to explore nonadherence factors in relation to their socioeconomic characteristics. Validated structured questionnaire was administered to 221 participants. Results showed a high nonadherence rate of 85.1%. The commonest occurring factors of non-adherence were forgetfulness (53.8%), busy schedule (38.8%), side effects of drugs (31.9%), and stigma (31.9%). Males were more likely to complain from busy schedule, feeling healthy, fear of partner disclosure, long waiting period, and long term regimen. Patients with no formal education were more likely to attribute non-adherence to poor communication, side effects of drugs, and stigma. Employed patients seemed to miss their drugs more than the unemployed and artisans. The high non-adherence rate has serious implications for the control of HIV in infected individuals and management of HIV in general. Nurses should intensify efforts on patient education and counseling.