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1.  HIV Drug Resistance Early Warning Indicators in Namibia with Updated World Health Organization Guidance 
PLoS ONE  2014;9(7):e100539.
In response to concerns about the emergence of HIV drug resistance (HIVDR), the World Health Organization (WHO) has developed a comprehensive set of early warning indicators (EWIs) to monitor HIV drug resistance and good programme practice at antiretroviral therapy (ART) sites.
In 2012, Namibia utilized the updated WHO EWI guidance and abstracted data from adult and pediatric patients from 50 ART sites for the following EWIs: 1. On-time Pill Pick-up, 2. Retention in Care, 3. Pharmacy Stock-outs, 4. Dispensing Practices, and 5. Virological Suppression.
Data for EWIs one through four were abstracted and validated. EWI 5 – Virological Suppression was not included due to poor data entry at many sites. On-time Pill Pick-up national estimate was 87.9% (87.2–88.7) of patients picking up pills on time for adults and 90.0% (88.9–90.9) picking up pills on time for pediatrics. Retention in Care national estimate was 82% of patients retained on ART after 12 months for adults and 83% for pediatrics. Pharmacy Stock-outs national estimate was 99% of months without a stock-out for adults and 97% for pediatrics. Dispensing Practices national estimate was 0.01% (0.003–0.064) of patients dispensed mono- or dual-therapy for adults and 0.25% (0.092–0.653) for pediatrics.
The successful 2012 EWI exercise provides Namibia a solid evidence base, which can be used to make national statements about programmatic functioning and possible HIVDR. This evidence base will serve to contextualize results from Namibia's surveys of HIVDR, which involves genotype testing. EWI abstraction has prompted the national program and its counterparts to engage sites in dialogue regarding the need to strengthen adherence and retention of patients on ART. The EWI collection process and EWI results will serve to optimize patient care and support Namibia in making evidence-based recommendations and take action to minimize the emergence of preventable HIVDR.
PMCID: PMC4079656  PMID: 24988387
2.  Clinical Mentorship of Nurse Initiated Antiretroviral Therapy in Khayelitsha, South Africa: A Quality of Care Assessment 
PLoS ONE  2014;9(6):e98389.
To combat the AIDS epidemic and increase HIV treatment access, the South African government implemented a nurse-based, doctor-supported model of care that decentralizes administration of antiretroviral treatment (ART) for HIV positive patients through nurse initiated and managed ART. Médecins Sans Frontières (MSF) implemented a mentorship programme to ensure successful task-shifting, subsequently assessing the quality of clinical care provided by nurses.
A before-after cross-sectional study was conducted on nurses completing the mentorship programme in Khayelitsha, South Africa, from February 2011-September 2012. Routine clinical data from 229 patient folders and 21 self-assessment questionnaires was collected to determine the number of patients initiated on ART by nurses; quality of ART management before-after mentorship; patient characteristics for doctor and nurse ART initiations; and nurse self-assessments after mentorship.
Twenty one nurses were authorized by one nurse mentor with one part-time medical officer's support, resulting in nurses initiating 77% of ART eligible patients. Improvements in ART management were found for drawing required bloods (91% vs 99%, p = 0.03), assessing adherence (50% vs 78%, p<0.001) and WHO staging (63% vs 91%, p<0.001). Nurse ART initiation indicators were successfully completed at 95–100% for 11 of 16 indicators: clinical presentation; patient weight; baseline blood work (CD4, creatinine, haemoglobin); STI screening; WHO stage, correlating medical history; medications prescribed appropriately; ART start date; and documented return date. Doctors initiated more patients with TB/HIV co-infection and WHO Stage 3 and 4 disease than nurses. Nurse confidence improved for managing HIV-infected children and pregnant women, blood result interpretation and long-term side effects.
Implementation of a clinical mentorship programme in Khayelitsha led to nurse initiation of a majority of eligible patients, enabling medical officers to manage complex cases. As mentorship can increase clinical confidence and enhance professional development, it should be considered essential for universal ART access in resource limited settings.
PMCID: PMC4041881  PMID: 24887260
3.  Patient–provider perceptions on engagement in HIV care in Argentina 
AIDS care  2013;26(5):602-607.
Approximately 30% of patients participating in the national antiretroviral therapy (ART) program in Argentina fail to achieve an undetectable viral load, and approximately 25% are not retained in care. This qualitative study was designed to explore and identify factors associated with engagement and retention in public and private health care in Buenos Aires, Argentina. Qualitative data from key informants (n = 12) and focus groups (n = 4 groups) of patients and providers from private and public HIV treatment facilities were recorded and transcribed. Predetermined and arising themes related to adherence, engagement, and retention in care were coded and analyzed using qualitative data analysis software. Reasons identified for patients’ lack of adherence or engagement in care differed between patients and providers, and patients attributed limitations to low self-efficacy, fear and concerns about HIV, and lack of provider involvement in treatment. In contrast, providers viewed themselves as decision-makers in patient care and patients as responsible for their own nonadherence due to lack of commitment to their own health or due to medication side effects. Patients reported health care system limitations and HIV concerns contributed to a lack of engagement, and providers identified limited HIV literacy and stigma as additional problems. Both agreed that chronic illness and substance addiction impacted adherence and retention, and agreed on the importance of trust, honesty, and communication in the patient–provider relationship. Results support the incorporation of system-, provider-, and patient-focused components into interventions to facilitate patient engagement, adherence, and retention in public and private settings in Argentina.
PMCID: PMC3966648  PMID: 24138788
HIV; adherence; engagement; communication; Argentina
4.  Incidence and Predictors of First Line Antiretroviral Regimen Modification in Western Kenya 
PLoS ONE  2014;9(4):e93106.
Limited antiretroviral treatment regimens in resource-limited settings require long-term sustainability of patients on the few available options. We evaluated the incidence and predictors of combined antiretroviral treatment (cART) modifications, in an outpatient cohort of 955 patients who initiated cART between January 2009 and January 2011 in western Kenya.
cART modification was defined as either first time single drug substitution or switch. Incidence rates were determined by Poisson regression and risk factor analysis assessed using multivariate Cox regression modeling.
Over a median follow-up period of 10.7 months, 178 (18.7%) patients modified regimens (incidence rate (IR); 18.6 per 100 person years [95% CI: 16.2–21.8]). Toxicity was the most common cited reason (66.3%). In adjusted multivariate Cox piecewise regression model, WHO disease stage III/IV (aHR; 1.82, 95%CI: 1.25–2.66), stavudine (d4T) use (aHR; 2.21 95%CI: 1.49–3.30) and increase in age (aHR; 1.02, 95%CI: 1.0–1.04) were associated with increased risk of treatment modification within the first year post-cART. Zidovudine (AZT) and tenofovir (TDF) use had a reduced risk for modification (aHR; 0.60 95%CI: 0.38–0.96 and aHR; 0.51 95%CI: 0.29–0.91 respectively). Beyond one year of treatment, d4T use (aHR; 2.75, 95% CI: 1.25–6.05), baseline CD4 counts ≤350 cells/mm3 (aHR; 2.45, 95%CI: 1.14–5.26), increase in age (aHR; 1.05 95%CI: 1.02–1.07) and high baseline weight >60kg aHR; 2.69 95% CI: 1.58–4.59) were associated with risk of cART modification.
Early treatment initiation at higher CD4 counts and avoiding d4T use may reduce treatment modification and subsequently improve sustainability of patients on the available limited options.
PMCID: PMC3973699  PMID: 24695108
5.  Risk Behaviors and Risk Factors for HIV Infection among Participants in the Bangkok Tenofovir Study, an HIV Pre-Exposure Prophylaxis Trial among People Who Inject Drugs 
PLoS ONE  2014;9(3):e92809.
HIV spread rapidly among people who inject drugs in Bangkok in the late 1980s. In recent years, changes in drug use and HIV-associated risk behaviors have been reported. We examined data from the Bangkok Tenofovir Study, an HIV pre-exposure prophylaxis trial conducted among people who inject drugs, to assess participant risk behavior and drug use, and to identify risk factors for HIV infection.
The Bangkok Tenofovir Study was a randomized, double-blind, placebo-controlled trial. HIV status was assessed monthly and risk behavior every 3 months. We used generalized estimating equations logistic regression to model trends of injecting, needle sharing, drugs injected, incarceration, and sexual activity reported at follow-up visits; and proportional hazards models to evaluate demographic characteristics, sexual activities, incarceration, drug injection practices, and drugs injected during follow-up as predictors of HIV infection.
The proportion of participants injecting drugs, sharing needles, and reporting sex with more than one partner declined during follow-up (p<0.001). Among participants who reported injecting at enrollment, 801 (53.2%) injected methamphetamine, 559 (37.1%) midazolam, and 527 (35.0%) heroin. In multivariable analysis, young age (i.e., 20–29 years) (p = 0.02), sharing needles (p<0.001), and incarceration in prison (p = 0.002) were associated with incident HIV infection. Participants reporting sex with an opposite sex partner, live-in partner, casual partner, or men reporting sex with male partners were not at a significantly higher risk of HIV infection compared to those who did not report these behaviors.
Reports of HIV-associated risk behavior declined significantly during the trial. Young age, needle sharing, and incarceration were independently associated with HIV infection. Sexual activity was not associated with HIV infection, suggesting that the reduction in HIV incidence among participants taking daily oral tenofovir compared to those taking placebo was due to a decrease in parenteral HIV transmission.
PMCID: PMC3965466  PMID: 24667938
6.  Field Evaluation of PIMA Point-of-Care CD4 Testing in Rakai, Uganda 
PLoS ONE  2014;9(3):e88928.
To assess the accuracy of PIMA Point-of-Care (POC) CD4 testing in rural Rakai, Uganda.
903 HIV positive persons attending field clinics provided a venous blood sample assessed on site using PIMA analyzers per manufacturer's specifications. The venous samples were then run on FACSCalibur flow cytometry at a central facility. The Bland–Altman method was used to estimate mean bias and 95% limits of agreement (LOA). Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were calculated for a CD4 threshold of <350 and <500 cells/uL for antiretroviral eligibility.
There was a high correlation between PIMA and FACSCalibur CD4 counts (r = 0.943, p<0.001). Relative to FACSCalibur, the PIMA POC CD4 had negative mean bias of −34.6 cells/uL (95% LOA: −219.8 to 150.6) overall. The dispersion at CD4<350 cells/uL was 5.1 cells/uL (95% LOA: −126.6 to 136.8). For a threshold of CD4<350 cells/uL, PIMA venous blood had a sensitivity of 88.6% (95%CI 84.8–92.4%), specificity of 87.5% (95%CI 84.9–90.1%), NPV of 94.9% (95%CI 93.1–96.7%), and PPV of 74.4% (95%CI 69.6–79.2%). PIMA sensitivity and PPV significantly increased to 96.1% and 88.3% respectively with increased threshold of 500 cells/uL.
Overall, PIMA POC CD4 counts demonstrated negative bias compared to FACSCalibur. PIMA POC sensitivity improved significantly at a higher CD4 threshold of 500 than a 350 cells/uL threshold.
PMCID: PMC3948619  PMID: 24614083
7.  Clinical and Radiographic Characteristics of Pulmonary Nocardiosis: Clues to Earlier Diagnosis 
PLoS ONE  2014;9(3):e90724.
Background and objectives
Pulmonary nocardiosis (PN) is a rare but life-threatening disease that is caused by Nocardia spp. The aim of this study was to characterize the common risk factors, clinical features, imaging findings, treatment and outcomes of PN, which are useful for an early diagnosis and patient management.
From January 2009 to June 2013, a retrospective study was performed on all PN cases that were diagnosed at our hospital.
The study included 17 patients who were diagnosed with PN. Of these patients, 4 developed concomitant disseminated disease. A male predominance was observed among the patients with PN (76.47%). The most common risk factors were corticosteroid therapy (64.71%), diabetes mellitus (29.41) and chronic lung disease (23.53%). Cough and fever were the most common symptoms (94% and 71%, respectively). One or more nodules or masses (82.35%) and consolidations (58.82%) were the most frequent radiologic abnormalities, and cavitation mostly occurred within two weeks. The median time to diagnosis was 25 days. Overall, the mortality rate was 18.75% for PN, and death was most frequent among patients who received immunosuppressive drugs. For the patients with central nervous system involvement, the mortality rate was 50%.
PN remains a rare opportunistic infection that mainly affects immunocompromised patients. A high clinical index of suspicion is necessary for an early diagnosis and timely treatment in immunocompromised patients who present with new nodules or masses evolving into cavitation in a short amount of time.
PMCID: PMC3940923  PMID: 24594890
8.  HIV Screening among TB Patients and Co-Trimoxazole Preventive Therapy for TB/HIV Patients in Addis Ababa: Facility Based Descriptive Study 
PLoS ONE  2014;9(2):e86614.
Collaborative TB/HIV management is essential to ensure that HIV positive TB patients are identified and treated appropriately, and to prevent tuberculosis (TB) in HIV positive patients. The purpose of this study was to assess HIV case finding among TB patients and Co-trimoxazole Preventive Therapy (CPT) for HIV/TB patients in Addis Ababa.
A descriptive cross-sectional, facility-based survey was conducted between June and July 2011. Data was collected by interviewing 834 TB patients from ten health facilities in Addis Ababa. Both descriptive and inferential statistics were used to summarize and analyze findings.
The proportion of TB patients who (self reported) were offered for HIV test, tested for HIV and tested HIV positive during their anti-TB treatment follow-up were; 87.4%, 69.4% and 20.2%; respectively. Eighty seven HIV positive patients were identified, who knew their status before diagnosed for the current TB disease, bringing the cumulative prevalence of HIV among TB patients to 24.5%. Hence, the proportion of TB patients who knew their HIV status becomes 79.9%. The study revealed that 43.6% of those newly identified HIV positives during anti-TB treatment follow-up were actually treated with CPT. However, the commutative proportion of HIV positive TB patients who were ever treated with CPT was 54.4%; both those treated before the current TB disease and during anti-TB treatment follow-up.
HIV case finding among TB patients and provision of CPT for TB/HIV co-infected patients needs boosting. Hence, routine offering of HIV test and provision of CPT for PLHIV should be strengthened in-line with the national guidelines.
PMCID: PMC3911916  PMID: 24498278
9.  Predictors of Mortality among Patients Enrolled on Antiretroviral Therapy in Aksum Hospital, Northern Ethiopia: A Retrospective Cohort Study 
PLoS ONE  2014;9(1):e87392.
Since launching of antiretroviral (ART) treatment, the numbers of patients enrolled in to ART are increasing in many developing countries. But many studies done across Africa including Ethiopia on antiretroviral therapy programs have shown higher mortality at the first six months of treatment initiation. But the factors associated with this high mortality are poorly characterized. So this study aims to determine mortality and identify predictors of it among patients on ART.
Retrospective cohort study was employed among a total of 520 records of patients who were enrolled on antiretroviral therapy in Aksum hospital from September 2006 to August 2011. Baseline patient records were extracted from electronic and paper based medical records database and analysed using Kaplan Meier survival and Cox proportional hazard model to identify the independent predictors of mortality of patients on ART.
A total of 46 (8.85%) deaths was observed giving an overall mortality rate of 3.2 per 100 person-years. The independent predictor of mortality identified for this cohort were haemoglobin level <11 mg/dl (Hazard Ratio (HR) = 1.9, 95%-CI = 1.01, 3.52), CD4 cell counts lower than 50 cells/µl (HR = 2.1, 95%- CI = 1.13,3.89), Male gender (HR = 1.9, 95%-CI = 1.01,3.52), Weight <40 kg (HR = 2.3,95% CI = 1.24,4.55), primary level of education and lower (HR = 2.6, 95%- CI = 1.29,5.55).
The over all mortality of adults patients on ART was low but higher in the early months of ART initiation. low levels of haemoglobin <11 gm/dl, lower CD4 cell count, male gender, weight <40 Kg and individuals who have primary level of education and lower were indentified as the independent predictors of mortality. For this reason, early initiation of ART despite the CD4 count and method of HIV diagnosis, nutritional support and close monitoring of patients in the early periods of ART treatment initiation is very crucial to improve patient survival.
PMCID: PMC3909114  PMID: 24498093
10.  Experience of Offering HIV Rapid Testing to At-Risk Patients in Community Health Centers in Eight Chinese Cities 
PLoS ONE  2014;9(1):e86609.
To explore the feasibility of offering HIV counseling and testing in community health centers (CHCs) and to provide evidence for the HIV/AIDS response in China.
Forty-two CHCs were selected from the eight cities that participated in the study. Rapid testing was mainly provided to: clients seeking HIV testing and counseling (HTC); outpatients with high-risk behavior of contracting HIV; inpatients and outpatients of key departments. Aggregate administrative data were collected in CHCs and general hospitals and differences between the two categories were compared.
There were 23,609 patients who underwent HIV testing, accounting for 0.37% of all estimated clinic visits at the 42 sites (0.03%–4.35% by site). Overall, positive screening prevalence was 0.41% (95% confidence interval [CI] 0.33%–0.49%, range 0.00%–0.98%), which is higher than in general hospitals (0.17%). The identification efficiency was 0.22% (95% CI: 0.16%–0.27%) in pilot CHCs, 3.5 times higher than in general hospitals (0.06%) (Chi square test = 95.196, p<0.001). The percentage of those receiving confirmatory tests among those who screened positive was slightly lower in CHCs (73.7%) than in general hospitals (80.1%) (Chi-square test = 17.472, p<0.001). Composition of clients mobilized for testing was consistent with the usage of basic public health and medical services in CHCs. The rate of patients testing HIV positive was higher among patients from key CHC departments (0.68%) than among high-risk Voluntary Counseling and Testing (VCT) clients (0.56%), those participating in outreach activities (0.41%), pregnant women (0.05%), and surgical patients (0.00%).
This project demonstrates that providing HIV testing services for patients who exhibit high risk behavior has a high HIV case detection rate and that CHCs have the capacity to integrate HTC into routine work. It provides concrete evidence supporting the involvement of CHCs in the expansion of HIV/AIDS testing and case finding.
PMCID: PMC3904922  PMID: 24489750
11.  Food Insecurity Is Associated with Increased Risk of Non-Adherence to Antiretroviral Therapy among HIV-Infected Adults in the Democratic Republic of Congo: A Cross-Sectional Study 
PLoS ONE  2014;9(1):e85327.
Food insecurity is increasingly reported as an important barrier of patient adherence to antiretroviral therapy (ART) in both resource-poor and rich settings. However, unlike in resource rich-settings, very few quantitative studies to date have investigated the association of food insecurity with patient adherence to ART in Sub-Saharan Africa. The current study examines the association between food insecurity and adherence to ART among HIV-infected adults in the Democratic Republic of Congo (DRC).
Methods and Findings
This is a cross-sectional quantitative study of patients receiving ART at three private and one public health facilities in Kinshasa, DRC. Participants were consecutively recruited into the study between April and November 2012. Adherence was measured using a combined method coupling pharmacy refill and self-reported adherence. Food insecurity was the primary predictor, and was assessed using the Household Food Insecurity Access Scale (HFIAS). Of the 898 participants recruited into the study, 512 (57%) were food insecure, and 188 (20.9%) were not adherent to ART. Food insecurity was significantly associated with non-adherence to ART (AOR, 2.06; CI, 1.38–3.09). We also found that perceived harmfulness of ART and psychological distress were associated respectively with increased (AOR, 1.95; CI, 1.15–3.32) and decreased (AOR, 0.31; CI, 0.11–0.83) odds of non-adherence to ART.
Food insecurity is prevalent and a significant risk factor for non-adherence to ART among HIV-infected individuals in the DRC. Our findings highlight the urgent need for strategies to improve food access among HIV-infected on ART in order to ensure patient adherence to ART and ultimately the long-term success of HIV treatment in Sub-Saharan Africa.
PMCID: PMC3893174  PMID: 24454841
12.  Early Gag Immunodominance of the HIV-Specific T-Cell Response during Acute/Early Infection Is Associated with Higher CD8+ T-Cell Antiviral Activity and Correlates with Preservation of the CD4+ T-Cell Compartment 
Journal of Virology  2013;87(13):7445-7462.
The important role of the CD8+ T-cell response on HIV control is well established. Moreover, the acute phase of infection represents a proper scenario to delineate the antiviral cellular functions that best correlate with control. Here, multiple functional aspects (specificity, ex vivo viral inhibitory activity [VIA] and polyfunctionality) of the HIV-specific CD8+ T-cell subset arising early after infection, and their association with disease progression markers, were examined. Blood samples from 44 subjects recruited within 6 months from infection (primary HIV infection [PHI] group), 16 chronically infected subjects, 11 elite controllers (EC), and 10 healthy donors were obtained. Results indicated that, although Nef dominated the anti-HIV response during acute/early infection, a higher proportion of early anti-Gag T cells correlated with delayed progression. Polyfunctional HIV-specific CD8+ T cells were detected at early time points but did not associate with virus control. Conversely, higher CD4+ T-cell set points were observed in PHI subjects with higher HIV-specific CD8+ T-cell VIA at baseline. Importantly, VIA levels correlated with the magnitude of the anti-Gag cellular response. The advantage of Gag-specific cells may result from their enhanced ability to mediate lysis of infected cells (evidenced by a higher capacity to degranulate and to mediate VIA) and to simultaneously produce IFN-γ. Finally, Gag immunodominance was associated with elevated plasma levels of interleukin 2 (IL-2) and macrophage inflammatory protein 1β (MIP-1β). All together, this study underscores the importance of CD8+ T-cell specificity in the improved control of disease progression, which was related to the capacity of Gag-specific cells to mediate both lytic and nonlytic antiviral mechanisms at early time points postinfection.
PMCID: PMC3700299  PMID: 23616666
13.  A Genetic Association Study of CCL5 -28 C>G (rs2280788) Polymorphism with Risk of Tuberculosis: A Meta-Analysis 
PLoS ONE  2013;8(12):e83422.
The CC chemokine ligand 5 (CCL5), plays a key role in the inflammatory response by recruiting mononuclear cells during tuberculosis (TB) infection. Association studies of CCL5 -28 C>G (rs2280788) polymorphism and TB risk have shown inconsistent and contradictory results among different ethnic populations. The aim of this meta-analysis is to investigate the association between CCL5 -28 C>G polymorphism and TB susceptibility.
We performed quantitative synthesis for published studies based upon association between CCL5 -28 C>G polymorphism and TB risk from PubMed (Medline), EMBASE web databases. The meta-analysis was performed and pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for all genetic models.
A total of six studies including 1324 TB cases and 1407 controls were involved in this meta-analysis. Variant allele (G vs. C: p = 0.257; OR = 1.809, 95% CI = 0.649 to 5.043), heterozygous (CG vs. CC: p = 0.443; OR = 1.440, 95% CI = 0.567 to 3.658) and homozygous (GG vs. CC: p = 0.160; OR = 5.140, 95% CI = 0.524 to 50.404) carriers did not show increased risk compare with those individual with the CC genotype. Similarly, no associations were found in the dominant (GG+CG vs. CC: p = 0.295; OR = 1.802, 95% CI = 0.599 to 5.412) and recessive (GG vs. CC+CG: p = 0.188; OR = 3.533, 95% CI = 0.541 to 23.085) models.
Overall findings of this meta-analysis suggest that genetic polymorphism -28 C>G in CCL5 is not associated with increased TB risk. However, future larger studies with group of populations will be needed to analyze the relationship between the CCL5 -28 C>G polymorphism and risk of TB.
PMCID: PMC3871615  PMID: 24376699
14.  HIV Sexual Transmission Is Predominantly Driven by Single Individuals Rather than Discordant Couples: A Model-Based Approach 
PLoS ONE  2013;8(12):e82906.
Understanding the relative contribution to HIV transmission from different social groups is important for public-health policy. Information about the importance of stable serodiscordant couples (when one partner is infected but not the other) relative to contacts outside of stable partnerships in spreading disease can aid in designing and targeting interventions. However, the overall importance of within-couple transmission, and the determinants and correlates of this importance, are not well understood. Here, we explore how mechanistic factors – like partnership dynamics and rates of extra-couple transmission – affect various routes of transmission, using a compartmental model with parameters based on estimates from Sub-Saharan Africa. Under our assumptions, when sampling model parameters within a realistic range, we find that infection of uncoupled individuals is usually the predominant route (median 0.62, 2.5%–97.5% quantiles: 0.26–0.88), while transmission within discordant couples is usually important, but rarely represents the majority of transmissions (median 0.33, 2.5%–97.5% quantiles: 0.10–0.67). We find a strong correlation between long-term HIV prevalence and the contact rate of uncoupled individuals, implying that this rate may be a key driver of HIV prevalence. For a given level of prevalence, we find a negative correlation between the proportion of discordant couples and the within-couple transmission rate, indicating that low discordance in a population may reflect a relatively high rate of within-couple transmission. Transmission within or outside couples and among uncoupled individuals are all likely to be important in sustaining heterosexual HIV transmission in Sub-Saharan Africa. Hence, intervention policies should be broadly targeted when practical.
PMCID: PMC3869741  PMID: 24376602
15.  Feasibility of Performing Multiple Point of Care Testing for HIV Anti-Retroviral Treatment Initiation and Monitoring from Multiple or Single Fingersticks 
PLoS ONE  2013;8(12):e85265.
Point of Care testing (POCT) provides on-site, rapid, accessible results. With current South African anti-retroviral treatment guidelines, up to 4 fingersticks /patient/clinic visit could be required if utilizing POC. We determined the feasibility and accuracy of a nurse performing multiple POCT on multiple fingersticks followed by simplification of the process by performance of multiple POC on a single fingerstick.
Method and Findings
Random HIV positive adult patients presenting at a HIV treatment clinic in South Africa, for ART initiation/ monitoring, were approached to participate in the study between April-June 2012. Phase I: n=150 patients approached for multiple POCT on multiple fingersticks. Phase II: n=150 patients approached for multiple POCT on a single fingerstick. The following POC tests were performed by a dedicated nurse: PIMA (CD4), HemoCue (hemoglobin), Reflotron (alanine aminotransferase, creatinine). A venepuncture specimen was taken for predicate laboratory methodology. Normal laboratory ranges and Royal College of Pathologists Australasia (RCPA) allowable differences were used as guidelines for comparison. In 67% of participants, ≥3 tests were requested per visit. All POCT were accurate but ranged in variability. Phase I: Hemoglobin was accurate (3.2%CV) while CD4, alanine aminotransferase and creatinine showed increased variability (16.3%CV; 9.3%CV; 12.9%CV respectively). PIMA generated a misclassification of 12.4%. Phase II: Hemoglobin, alanine aminotransferase and creatinine showed good accuracy (3.2%CV, 8.7%CV, 6.4%CV respectively) with increased variability on CD4 (12.4%CV) but low clinical misclassification (4.1%). No trends were observed for the sequence in which POC was performed on a single fingerstick. Overall, PIMA CD4 generated the highest error rate (16-19%).
Multiple POCT for ART initiation and/or monitoring can be performed practically by a dedicated nurse on multiple fingersticks. The process is as accurate as predicate methodology and can be simplified using a single fingerstick.
PMCID: PMC3869909  PMID: 24376873
16.  Type 2 Diabetes : An Independent Risk Factor for Tuberculosis: A Nationwide Population-Based Study 
PLoS ONE  2013;8(11):e78924.
Tuberculosis continues to be a major global health problem. We wanted to investigate whether Type 2 diabetes was a risk factor for tuberculosis in an Asian population.
From Taiwan’s National Health Insurance Research Database, we collected data from 31,237 female patients with type 2 diabetes and 92,642 female controls and 32,493 male patients with type 2 diabetes and 96,977 male controls. Cox proportional hazard regression was performed to evaluate independent risk factors for tuberculosis in all patients and to identify risk factors in patients with type 2 diabetes.
During the study period, both female (standardized incidence ratio (SIR): 1.40, p<0.01) and male (SIR: 1.48, p<0.01) patients with type 2 diabetes were found to have a significantly higher rate of incident tuberculosis than the control group. Type 2 diabetes (HR:1.31, 1.23–1.39, p<0.001) was significantly associated with tuberculosis after adjusting sex, age, bronchiectasis, asthma and chronic obstructive lung disease.
Patients with type 2 diabetes have a higher risk of tuberculosis compared to control subjects after adjusting for confounding factors. The current diabetes epidemic may lead to a resurgence of tuberculosis in endemic regions. Therefore, preventive measures, including addressing the possibility that type 2 diabetes increase the individual’s susceptibility for incident TB, should be taken to further reduce the incidence of tuberculosis.
PMCID: PMC3827305  PMID: 24236069
17.  Spectrums of Opportunistic Infections and Malignancies in HIV-Infected Patients in Tertiary Care Hospital, China 
PLoS ONE  2013;8(10):e75915.
HIV-related opportunistic infections (OIs) and malignancies continued to cause morbidity and mortality in Chinese HIV-infected individuals. The objective for this study is to elucidate the prevalence and spectrums of OIs and malignancies in HIV-infected patients in the Beijing Ditan Hospital.
The evaluation of the prevalence and spectrums of OIs and malignancies was conducted by using the clinical data of 834 HIV-infected patients admitted in the Beijing Ditan hospital from January 1, 2009, to November 30, 2012.
The prevalence and spectrums of OIs and malignancies varied contingent on geographic region, transmission routes, and CD4 levels. We found that tuberculosis was most common OI and prevalence was 32.5%, followed by candidiasis(29.3%), Pneumocystis pneumonia(PCP)(22.4%), cytomegalovirus(CMV) infection(21.7%), other fungal infections(16.2%), mycobacterium avium complex(MAC)(11.3%), cryptococcosis(8.0%), progressive multifocal leukoencephalopathy(PML)(4.4%), Cerebral Toxoplasmosis(3.5%) and Penicillium marneffei infection(1.4%); while Lymphoma(2.9%), Kaposi’s sarcoma(0.8%) and cervix carcinoma(0.3%) were emerged as common AIDS-defining malignancies. Pulmonary OI infections were the most prevalent morbidity and mortality in patients in the AIDS stage including pulmonary tuberculosis (26.6%) and PCP (22.4%). CMV infection(21.7%) was most common viral infection; Fungal OIs were one of most prevalent morbidity in patients in the AIDS stage, including oral candidiasis (29.3%), other fungal infection (16.2%), Cryptococcosis (8.0%) and Penicillium marneffei infection (1.4%). We found the low prevalence of AIDS-defining illnesses in central neural system in this study, including progressive multifocal leukoencephalopathy (4.4%), cerebral toxoplasmosis (3.5%), tuberculosis meningitis (3.2%), cryptococcal meningitis (2.4%) and CMV encephalitis (1.1%). In-hospital mortality rate was 4.3 per 100 person-years due to severe OIs, malignancies, and medical cost constraints.
The prevalence and spectrums of OIs, malignancies and co-infections were discussed in this study. It would help increase the awareness for physicians to make a diagnosis and empirical treatment sooner and plan good management strategies, especially in resource limited regions.
PMCID: PMC3808390  PMID: 24204583
18.  Male, Mobile, and Moneyed: Loss to Follow-Up vs. Transfer of Care in an Urban African Antiretroviral Treatment Clinic 
PLoS ONE  2013;8(10):e78900.
The purpose of this study was to analyze characteristics, reasons for transferring, and reasons for discontinuing care among patients defined as lost to follow-up (LTFU) from an antiretroviral therapy (ART) clinic in Nairobi, Kenya.
The study used a prospective cohort of patients who participated in a randomized, controlled ART adherence trial between 2006 and 2008.
Participants were followed from pre-ART clinic enrollment to 18 months after ART initiation, and were defined as LTFU if they failed to return to clinic 4 weeks after their last scheduled visit. Reasons for loss were captured through phone call or home visit. Characteristics of LTFU who transferred care and LTFU who did not transfer were compared to those who remained in clinic using log-binomial regression to estimate risk ratios.
Of 393 enrolled participants, total attrition was 83 (21%), of whom 75 (90%) were successfully traced. Thirty-seven (49%) were alive at tracing and 22 (59%) of these reported having transferred their antiretroviral care. In the final model, transfers were more likely to have salaried employment [Risk Ratio (RR), 2.7; 95% confidence interval (CI), 1.2-6.1; p=0.020)] and pay a higher monthly rent (RR, 5.8; 95% CI, 1.3-25.0; p=0.018) compared to those retained in clinic. LTFU who did not transfer care were three times as likely to be men (RR, 3.1; 95% CI, 1.1-8.1; p=0.028) and nearly 4 times as likely to have a primary education or less (RR, 3.8; 95% CI, 1.3-10.6; p=0.013). Overall, the most common reason for LTFU was moving residence, predominantly due to job loss or change in employment.
A broad definition of LTFU may include those who have transferred their antiretroviral care and thereby overestimate negative effects on ART continuation. Interventions targeting men and considering mobility due to employment may improve retention in urban African ART clinics.
Clinical Trials
The study’s identifier is NCT00273780.
PMCID: PMC3812001  PMID: 24205345
19.  Tuberculosis in Antiretroviral Treatment Programs in Lower Income Countries: Availability and Use of Diagnostics and Screening 
PLoS ONE  2013;8(10):e77697.
In resource-constrained settings, tuberculosis (TB) is a common opportunistic infection and cause of death in HIV-infected persons. TB may be present at the start of antiretroviral therapy (ART), but it is often under-diagnosed. We describe approaches to TB diagnosis and screening of TB in ART programs in low- and middle-income countries.
Methods and findings
We surveyed ART programs treating HIV-infected adults in sub-Saharan Africa, Asia and Latin America in 2012 using online questionnaires to collect program-level and patient-level data. Forty-seven sites from 26 countries participated. Patient-level data were collected on 987 adult TB patients from 40 sites (median age 34.7 years; 54% female). Sputum smear microscopy and chest radiograph were available in 47 (100%) sites, TB culture in 44 (94%), and Xpert MTB/RIF in 23 (49%). Xpert MTB/RIF was rarely available in Central Africa and South America. In sites with access to these diagnostics, microscopy was used in 745 (76%) patients diagnosed with TB, culture in 220 (24%), and chest X-ray in 688 (70%) patients. When free of charge culture was done in 27% of patients, compared to 21% when there was a fee (p = 0.033). Corresponding percentages for Xpert MTB/RIF were 26% and 15% of patients (p = 0.001). Screening practices for active disease before starting ART included symptom screening (46 sites, 98%), chest X-ray (38, 81%), sputum microscopy (37, 79%), culture (16, 34%), and Xpert MTB/RIF (5, 11%).
Mycobacterial culture was infrequently used despite its availability at most sites, while Xpert MTB/RIF was not generally available. Use of available diagnostics was higher when offered free of charge.
PMCID: PMC3798412  PMID: 24147059
20.  The Effect of Tuberculosis Treatment at Combination Antiretroviral Therapy Initiation on Subsequent Mortality: A Systematic Review and Meta-Analysis 
PLoS ONE  2013;8(10):e78073.
We aimed to perform a systematic review and meta-analysis examining the impact of TB treatment at the time of combination antiretroviral therapy (cART) initiation on subsequent mortality.
We searched PubMed, EMBASE, and selected conference proceedings for studies that report adult mortality on cART, stratified by TB treatment status at cART initiation. Stratified random-effects and meta-regression analyses were used to examine the influence of study and population characteristics.
22 eligible cohort studies reported data on 98,350 (range 74-15,225) adults, of whom 14,779 (15%) were receiving TB treatment at cART initiation. Studies of those receiving vs. not receiving TB treatment had an average mortality relative risk of 1.10 (95% confidence interval 0.87-1.40) at 1-3 months (based upon 8 estimates), 1.15 (0.94-1.41) at 6-12 months (11 estimates), and 1.33 (1.02-1.75) at 18-98 months (10 estimates) following cART initiation. However, there was a wide range of estimates and those at later time points were markedly heterogeneous. Meta-regression identified factors associated with elevated average risk estimates: lower median baseline CD4 counts and adjustment for baseline hemoglobin at 1-3 months; longer length of follow-up and women-only studies at 6-12 months; and not adjusting for BMI/weight at 18-98 months.
Patients receiving TB treatment at cART initiation did not have a statistically significant estimated increase in short-term risk of all-cause mortality as compared to those not receiving TB treatment. TB treatment was significantly associated with increased mortality after about a year of cART, suggesting that patients with concurrent TB treatment at cART initiation may benefit from continued support after TB treatment completion.
PMCID: PMC3797056  PMID: 24143260
21.  Prevalence and Correlates of Alcohol Dependence Disorder among TB and HIV Infected Patients in Zambia 
PLoS ONE  2013;8(9):e74406.
To determine the prevalence and correlates of alcohol dependence disorders in persons receiving treatment for HIV and Tuberculosis (TB) at 16 Primary Health Care centres (PHC) across Zambia.
649 adult patients receiving treatment for HIV and/or TB at PHCs in Zambia (363 males, 286 females) were recruited between 1st December 2009 and 31st January 2010. Data on socio-demographic variables, clinical disease features (TB and HIV), and psychopathological status were collected. The Mini International Neuropsychiatric Interview (MINI) was used to diagnose alcohol dependence disorder. Correlates of alcohol dependence were analyzed for men only, due to low prevalence in women. Univariable and multivariable logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI), using general estimating equations to allow for within-PHC clustering.
The prevalence of alcohol dependence was 27.2% (95%CI: 17.7-39.5%) for men and 3.9% (95%CI: 1.4-0.1%) for women. Factors associated with alcohol dependence disorder in men included being single, divorced or widowed compared with married (adjusted OR = 1.47, 95%CI: 1.00-2.14) and being unemployed (adjusted OR=1.30, 95%CI: 1.01-1.67). The highest prevalence of alcohol dependence was among HIV-test unknown TB patients (34.7%), and lowest was among HIV positive patients on treatment but without TB (14.1%), although the difference was not statistically significant (p=0.38).
Male TB/HIV patients in this population have high prevalence of alcohol dependence disorder, and prevalence differs by HIV/TB status. Further work is needed to explore interventions to reduce harmful drinking in this population.
PMCID: PMC3775777  PMID: 24069309
22.  Pregnancy in HIV Clinical Trials in Sub Saharan Africa: Failure of Consent or Contraception? 
PLoS ONE  2013;8(9):e73556.
Higher than expected pregnancy rates have been observed in HIV related clinical trials in Sub-Saharan Africa. We designed a qualitative study to explore the factors contributing to high pregnancy rates among participants in two HIV clinical trials in Sub-Saharan Africa.
Female and male participants enrolled in one of two clinical HIV trials in south-west Uganda were approached. The trials were a phase III microbicide efficacy trial among HIV negative women using vaginal gel (MDP); and a trial of primary prevention prophylaxis for invasive cryptococcal disease using fluconazole among HIV infected men and women in Uganda (CRYPTOPRO). 14 focus group discussions and 8 in-depth interviews were conducted with HIV positive and negative women and their male partners over a six month period. Areas explored were their experiences about why and when one should get pregnant, factors affecting use of contraceptives, HIV status disclosure and trial product use.
All respondents acknowledged being advised of the importance of avoiding pregnancy during the trial. Factors reported to contribute to pregnancy included; trust that the investigational product (oral capsules/vaginal gel) would not harm the baby, need for children, side effects that led to inconsistent contraceptive use, low acceptance of condom use among male partners. Attitudes towards getting pregnant are fluid within couples over time and the trials often last for more than a year. Researchers need to account for high pregnancy rates in their sample size calculations, and consider lesser used female initiated contraceptive options e.g. diaphragm or female condoms. In long clinical trials where there is a high fetal or maternal risk due to investigational product, researchers and ethics committees should consider a review of participants contraceptive needs/pregnancy desire review after a fixed period, as need for children, partners and health status of participants may alter over time.
PMCID: PMC3769278  PMID: 24039981
23.  A Qualitative Analysis of Factors Influencing HPV Vaccine Uptake in Soweto, South Africa among Adolescents and Their Caregivers 
PLoS ONE  2013;8(8):e72094.
In South Africa, the prevalence of oncogenic Human Papillomavirus (HPV) may be as high as 64%, and cervical cancer is the leading cause of cancer-related death among women. The development of efficacious prophylactic vaccines has provided an opportunity for primary prevention. Given the importance of psycho-social forces in vaccine uptake, we sought to elucidate factors influencing HPV vaccination among a sample of low-income South African adolescents receiving the vaccine for the first time in Soweto.
The HPV vaccine was introduced to adolescents in low-income townships throughout South Africa as part of a nationwide trial to understand adolescent involvement in future vaccine research targeting human immunodeficiency virus (HIV). We performed in-depth semi-structured interviews with purposively-sampled adolescents and their care providers to understand what forces shaped HPV vaccine uptake. Interviews were recorded, transcribed, translated, and examined using thematic analysis.
Of 224 adolescents recruited, 201 initiated the vaccine; 192 (95.5%) received a second immunization; and 164 (81.6%) completed three doses. In our qualitative study of 39 adolescent-caregiver dyads, we found that factors driving vaccine uptake reflected a socio-cultural backdrop of high HIV endemnicity, sexual violence, poverty, and an abundance of female-headed households. Adolescents exercised a high level of autonomy and often initiated decision-making. Healthcare providers and peers provided support and guidance that was absent at home. The impact of the HIV epidemic on decision-making was substantial, leading participants to mistakenly conflate HPV and HIV.
In a setting of perceived rampant sexual violence and epidemic levels of HIV, adolescents and caregivers sought to decrease harm by seeking a vaccine targeting a sexually transmitted infection (STI). Despite careful consenting, there was confusion regarding the vaccine’s target. Future interventions promoting STI vaccines will need to provide substantial information for participants, particularly adolescents who may exercise a significant level of autonomy in decision-making.
PMCID: PMC3758285  PMID: 24023613
24.  New Insights of Microsporidial Infection among Asymptomatic Aboriginal Population in Malaysia 
PLoS ONE  2013;8(8):e71870.
Studies on microsporidial infection mostly focus on immunodeficiency or immunosuppressive individuals. Therefore, this cross-sectional study describes the prevalence and risk factors of microsporidiosis among asymptomatic individuals in Malaysia.
Four hundred and forty seven stool samples were collected and examined for microsporidia after staining with Gram-chromotrope Kinyoun. Demographic, socioeconomic, environmental, and behavioral information were collected by using a pre-tested questionnaire. Overall, 67 (15%) samples were positive for microsporidia. The prevalence of infection was significantly higher among individuals aged more than 15 years compared to those aged <15 years (OR = 1.97, 95% CI = 1.08, 3.62; P = 0.028). Furthermore, logistic regression analysis confirmed that the presence of other family members infected with microsporidia (OR = 8.45; 95% CI = 4.30, 16.62; P<0.001) and being a consumer of raw vegetables (OR = 2.05; 95% CI = 1.15, 3.66; P = 0.016) were the significant risk factors of this infection.
These findings clearly show that exposure to microsporidia is common among Aboriginal population. Further studies using molecular approach on microsporidia isolates from asymptomatic individuals is needed to determine species-specific. The risk factors associated with microsporidiosis will help in identifying more clearly the sources of the infection in the environment that pose a risk for transmission so that preventive strategies can be implemented.
PMCID: PMC3754962  PMID: 24014078
25.  Patient Perspectives on the Experience of Being Newly Diagnosed with HIV in the Emergency Department/Urgent Care Clinic of a Public Hospital 
PLoS ONE  2013;8(8):e74199.
We sought to understand patient perceptions of the emergency department/urgent care (ED/UC) HIV diagnosis experience as well as factors that may promote or discourage linkage to HIV care. We conducted in-depth interviews with patients (n=24) whose HIV infection was diagnosed in the ED/UC of a public hospital in San Francisco at least six months prior and who linked to HIV care at the hospital HIV clinic. Key diagnosis experience themes included physical discomfort and limited functionality, presence of comorbid diagnoses, a wide spectrum of HIV risk perception, and feelings of isolation and anxiety. Patients diagnosed with HIV in the ED/UC may not have their desired emotional supports with them, either because they are alone or they are with family members or friends to whom they do not want to immediately disclose. Other patients may have no one they can rely on for immediate support. Nearly all participants described compassionate disclosure of test results by ED/UC providers, although several noted logistical issues that complicated the disclosure experience. Key linkage to care themes included the importance of continuity between the testing site and HIV care, hospital admission as an opportunity for support and HIV education, and thoughtful matching by linkage staff to a primary care provider. ED/UC clinicians and testing programs should be sensitive to the unique roles of sickness, risk perception, and isolation in the ED/UC diagnosis experience, as these things may delay acceptance of HIV diagnosis. The disclosure and linkage to care experience is crucial in forming patient attitudes towards HIV and HIV care, thus staff involved in disclosure and linkage activities should be trained to deliver compassionate, informed, and thoughtful care that bridges HIV testing and treatment sites.
PMCID: PMC3753265  PMID: 23991214

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