Predictors of Self-repackaging of Antiretroviral Therapy in Northern Tanzania.

Objectives: In this study, we explored determinants of "researcher-observed" patient-initiated antiretroviral therapy (ART) repackaging practices among people living with HIV (PLHIV) in Northern Tanzania. Methods: We used a quasi-experimental design to describe the prevalence of ART self- repackaging; we conducted face-to-face surveys to determine factors associated with ART self- repackaging practices. Data collection sites included the Kilimanjaro Christian Medical Centre and the Mawenzi Referral Hospital. We used study-specific numerical identifiers assigned to ARTs packaging to determine self-repackaging behavior. Self-repackaging was defined as a binary variable where participants who discarded antiretroviral drugs packaging in at least 2 clinic visits were classified as self- repackagers. We used multivariable logistic regression to assess the determinants of patient-initiated repackaging practices. Results: Among 590 study participants, 57.6% self-repackaged based on researcher observation and 55.6% self-repackaged based on patient report. Researcher-observed self- repackaging was associated with gender (AOR = 1.590; 95% CI: 1.011, 2.502), employment status (AOR = 0.475: 95% CI; 0.239, 0.942), and study site (AOR = 0.218; 95% CI: 0.134, 0.355). Conclusions: A substantial proportion of patients self-repackage their ARTs for various reasons. Health system interventions should focus on addressing the attributes of repackaging among men and unemployed patients.

Correlates of Blood Pressure Awareness, Treatment, and Control Among Adults 50 Years or Older by HIV Status in Northwestern Tanzania.

PURPOSE OF REVIEW: The objective of this study was to describe the increasing incidence and risk of cardiovascular disease among persons living with HIV (PLWH) in Sub-Saharan Africa. We also used data to compare hypertension (a common NCD among PLWH) outcomes between PLWH and HIV-uninfected individuals among older adults in Northwestern Tanzania. RECENT FINDINGS: Hypertension is increasingly common in Sub-Saharan Africa and a leading cause of cardiovascular disease for PLWH. Among those with hypertension, PLWH have a 50% higher risk of incident myocardial infarction compared to the general population. In response to the rising incidence of these non-communicable diseases (NCDs) among PLWH, recently, the Joint United Nations Program on HIV/AIDS supported the integration of NCD care into routine clinical care for HIV. However, data are lacking on levels of awareness of hypertension status, diagnosis, and antihypertensive medication adherence. Given the higher likelihood of elevated blood pressure among PLWH, there is an urgent need to implement interventions to improve blood pressure control in this population. Researchers should evaluate treatment barriers at multiple levels including health system, healthcare providers, and patients' level and tailor evidence-based interventions to increase achievement of blood pressure control for PLWH.

Healthcare-seeking behaviour, barriers to care and predictors of symptom improvement among patients with cardiovascular disease in northern Tanzania.

BACKGROUND: Little is known about healthcare-seeking behaviour and barriers to care for cardiovascular disease (CVD) in sub-Saharan Africa. METHODS: Emergency department patients in Tanzania with acute CVD were prospectively enrolled. Questionnaires were administered at enrollment and 30 d later. RESULTS: Of 241 patients, 186 (77.2%) had visited another facility for the same illness episode (median symptom duration prior to presentation was 7 d) and 82 (34.0%) reported that they were initially unaware of the potential seriousness of their symptoms. Of the 208 (86.3%) patients completing follow-up, 16 (7.7%) had died, 38 (18.3%) had visited another facility for persistent symptoms, 99 (47.6%) felt they understood their diagnosis, 87 (41.8%) felt they understood their treatment and 11 (7.8%) could identify any of their medications. Predictors of 30 d survival with symptom improvement included medication compliance (p<0.001), understanding the diagnosis (p=0.007), understanding the treatment (p<0.001) and greater CVD knowledge (p=0.008). CONCLUSIONS: Patients with CVD in Tanzania usually visit multiple facilities for the same illness episode, typically after prolonged delays. Only a minority understand their diagnosis and treatment, and such understanding is correlated with survival with symptom improvement. Patient-centred interventions are needed to improve the quality of cardiovascular care in Tanzania.

Effect of a Triage-Based Screening Protocol on Diagnosis and Treatment of Acute Coronary Syndrome in a Tanzanian Emergency Department: A Prospective Pre-Post Study.

Background Evidence suggests that acute coronary syndrome (ACS) is underdiagnosed in sub-Saharan Africa. Triage-based interventions have improved ACS diagnosis and management in high-income settings but have not been evaluated in sub-Saharan African emergency departments (EDs). Our objective was to estimate the effect of a triage-based screening protocol on ACS diagnosis and care in a Tanzanian ED. Methods and Results All adults presenting to a Tanzanian ED with chest pain or shortness of breath were prospectively enrolled. Treatments and clinician-documented diagnoses were observed and recorded. In the preintervention phase (August 2018 through January 2019), ACS testing and treatment were dictated by physician discretion, as per usual care. A triage-based protocol was then introduced, and in the postintervention phase (January 2019 through October 2019), research assistants performed ECG and point-of-care troponin I testing on all patients with chest pain or shortness of breath upon ED arrival. Pre-post analyses compared ACS care between phases. Of 1020 total participants (339 preintervention phase, 681 postintervention phase), mean (SD) age was 58.9 (19.4) years. Six (1.8%) preintervention participants were diagnosed with ACS, versus 83 (12.2%) postintervention participants (odds ratio [OR], 7.51; 95% CI, 3.52-19.7; P<0.001). Among all participants, 3 (0.9%) preintervention participants received aspirin, compared with 50 (7.3%) postintervention participants (OR, 8.45; 95% CI, 3.07-36.13; P<0.001). Conclusions Introduction of a triage-based ACS screening protocol in a Tanzanian ED was associated with significant increases in ACS diagnoses and aspirin administration. Additional research is needed to determine the effect of ED-based interventions on ACS care and clinical end points in sub-Saharan Africa.

Acute myocardial infarction under-diagnosis and mortality in a Tanzanian emergency department: A prospective observational study.

BACKGROUND: Growing evidence suggests that under-diagnosis of acute myocardial infarction (AMI) may be common in sub-Saharan Africa. Prospective studies of routine AMI screening among patients presenting to emergency departments in sub-Saharan Africa are lacking. Our objective was to determine the prevalence of AMI among patients in a Tanzanian emergency department. METHODS: In a prospective observational study, consecutive adult patients presenting with chest pain or shortness of breath to a referral hospital emergency department in northern Tanzania were enrolled. Electrocardiogram (ECG) and troponin testing were performed for all participants to diagnose AMI types according to the Fourth Universal Definition. All ECGs were interpreted by two independent physician judges. ECGs suggesting ST-elevation myocardial infarction (STEMI) were further reviewed by additional judges. Mortality was assessed 30 days following enrollment. RESULTS: Of 681 enrolled participants, 152 (22.3%) had AMI, including 61 STEMIs and 91 non-STEMIS (NSTEMIs). Of AMI patients, 91 (59.9%) were male, mean (SD) age was 61.2 (18.5) years, and mean (SD) duration of symptoms prior to presentation was 6.6 (12.2) days. In the emergency department, 35 (23.0%) AMI patients received aspirin and none received thrombolytics. Of 150 (98.7%) AMI patients completing 30-day follow-up, 65 (43.3%) had died. CONCLUSIONS: In a northern Tanzanian emergency department, AMI is common, rarely treated with evidence-based therapies, and associated with high mortality. Interventions are needed to improve AMI diagnosis, care, and outcomes.

Does Antiretroviral Therapy Packaging Matter? Perceptions and Preferences of Antiretroviral Therapy Packaging for People Living with HIV in Northern Tanzania.

INTRODUCTION: Despite improvements in treatment (eg, reduction in pill intake), antiretroviral therapy (ART) is dispensed in socially inefficient and uneconomical packaging. To make pills less conspicuous and decrease the risk of being stigmatized, people living with HIV (PLWH) often engage in self-repackaging - the practice of transferring ART from original packaging to alternative containers. This behavior has been associated with ART nonadherence and failure to achieve viral load suppression. While much of the literature on ART packaging has centered around medication adherence, patients stated preferences for ART packaging and packaging attributes that influence the observed ART nonadherence are understudied. METHODS: We conducted a qualitative study to elucidate perceptions of ART packaging among PLWH at two large referral hospitals in Northern Tanzania. Interviews were conducted until thematic saturation was reached. Interviews were audio-recorded, transcribed and coded. RESULTS: Of the 16 participants whose data were used in the final analysis, a majority were between 36 and 55 years of age (Mean 45.5 years SD: 11.1), had primary-level education (n=11, 68.8%), were self-employed (n=9, 56.3%), reported that they had self-repacked ART (n=14, 88%), and were taking ART for more than 6 years (n=11, 68.8%). Participants identified three attributes of ART packaging that increased anticipated HIV stigma and prompted self-repackaging, including visual identification, bulkiness, and the rattling noise produced by ART pill bottles. CONCLUSION: Given the drastic reduction in the number of pills required for HIV treatment, there is an opportunity to not only assess the cost-effectiveness of innovative ART packaging but also evaluate the acceptability of such packaging among PLWH in order to address stigma and improve ART adherence.

The effect of HIV infection, antiretroviral therapy on carotid intima-media thickness: A systematic review and meta-analysis.

AIMS: We performed a systematic review and meta-analysis on the effect of HIV infection and antiretroviral therapy (ART) on carotid intima-media thickness (cIMT) to elucidate the role of HIV infection and ART. Also, an analysis on the role of ethnicity and gender on cIMT in HIV-infected populations was performed. MAIN METHODS: We searched the PubMed, Web of Science, the WHO websites and International AIDS Society for published observational studies were conducted by two independent reviewers for studies comparing HIV-infected antiretroviral-experienced patients and/or inexperienced with healthy controls on cIMT. The primary outcome was the standardized mean difference (SMD) of cIMT. FINDINGS: Twenty studies (five cohort, 15 cross-sectional, and two both cohort and cross-sectional studies) were identified comprising 7948 subjects (4656 HIV-infected; 3292 controls). In cohort studies, the standardized mean 1-year change in cIMT between HIV-infected patients and uninfected controls was not significantly different (0.16 mm/yr; 95% CI, -0.16, 0.49; p = 0.326). In 17 cross-sectional studies, the SMD in cIMT was significantly higher in HIV-infected than uninfected persons (0.27 mm; 95% CI, 0.04, 0.49; p = 0.027). HIV-infected patients on ART exhibited significantly higher SMD in cIMT compared to those not on ART (0.75 mm; 95% CI, 0.30, 1.19; p = 0.001). No confounding effect of gender and ethnicity could be established using meta-regression p > 0.05. SIGNIFICANCE: HIV infection itself and ART appear to influence the progression of cIMT and hence may be risk factors for cardiovascular events. No firm conclusions could be drawn on the effect of ethnic/race and gender differences on cIMT in HIV-infected populations.

Correction to: Association of HIV-infection, antiretroviral treatment and metabolic syndrome with large artery stiffness: a cross-sectional study.

Following publication of the original article [1], the authors reported that they have provided the wrong caption.

Cancer disparities in people with HIV: A systematic review of screening for non-AIDS-defining malignancies.

BACKGROUND: People with HIV (PWHIV) have improved survival because of the advent of antiretroviral therapy. Consequently, PWHIV experience higher rates of non-acquired immunodeficiency syndrome-defining malignancies (NADMs). Previous studies have demonstrated worsened cancer-specific survival in PWHIV, partly because of advanced cancer stage at diagnosis. The objective of the current systematic review was to evaluate screening disparities for NADMs among PWHIV. METHODS: The PubMed, Cochrane, EMBASE, and ClinicalTrials.gov databases were searched from January 1, 1996 through April 10, 2018 to identify studies related to screening disparities for NADMs among PWHIV. Eligibility criteria included any study performed in a high-income country that compared screening for NADMs by HIV status. After title/abstract screening and full-text review, articles that met eligibility criteria were analyzed. RESULTS: Of 613 unique articles identified through the search, 9 studies were analyzed. Three studies addressed breast cancer screening, 4 addressed colorectal cancer screening, and 2 addressed prostate cancer screening. Five of the reviewed studies demonstrated that PWHIV were less likely to receive indicated cancer screenings compared with the general population, whereas 3 indicated that screening proportions were higher among PWHIV, and 1 demonstrated that screening proportions were comparable. In most of the studies, PWHIV who had regular access to health care were more likely to undergo cancer screening. CONCLUSIONS: The available evidence does not uniformly confirm that PWHIV are less likely to receive cancer screening. Social determinants of health (insurance status, access to health care, education, income level) were associated with the receipt of appropriate cancer screening, suggesting that these barriers need to be addressed to improve cancer screening in PWHIV.

The burden of acute coronary syndrome, heart failure, and stroke among emergency department admissions in Tanzania: A retrospective observational study.

INTRODUCTION: The prevalence of cardiovascular disease in sub-Saharan Africa is substantial and growing. Much remains to be learned about the relative burden of acute coronary syndrome (ACS), heart failure, and stroke on emergency departments and hospital admissions. METHODS: A retrospective chart review of admissions from September 2017 through March 2018 was conducted at the emergency department of a tertiary care center in northern Tanzania. Stroke admission volume was compared to previously published data from the same hospital and adjusted for population growth. RESULTS: Of 2418 adult admissions, heart failure and stroke were the two most common admission diagnoses, accounting for 294 (12.2%) and 204 (8.4%) admissions, respectively. ACS was uncommon, accounting for 9 (0.3%) admissions. Of patients admitted for heart failure, uncontrolled hypertension was the most commonly identified etiology of heart failure, cited in 124 (42.2%) cases. Ischemic heart disease was cited as the etiology in only 1 (0.3%) case. Adjusting for population growth, the annual volume of stroke admissions increased 70-fold in 43 years, from 2.9 admissions per 100,000 population in 1974 to 202.2 admissions per 100,000 in 2017. CONCLUSIONS: The burden of heart failure and stroke on hospital admissions in Tanzania is substantial, and the volume of stroke admissions is rising precipitously. ACS is a rare diagnosis, and the distribution of cardiovascular disease phenotypes in Tanzania differs from what has been observed outside of Africa. Further research is needed to ascertain the reasons for these differences.

The burden of acute coronary syndrome, heart failure, and stroke among emergency department admissions in Tanzania: A retrospective observational study

Introduction The prevalence of cardiovascular disease in sub-Saharan Africa is substantial and growing. Much remains to be learned about the relative burden of acute coronary syndrome (ACS), heart failure, and stroke on emergency departments and hospital admissions.Methods A retrospective chart review of admissions from September 2017 through March 2018 was conducted at the emergency department of a tertiary care center in northern Tanzania. Stroke admission volume was compared to previously published data from the same hospital and adjusted for population growth. Results Of 2418 adult admissions, heart failure and stroke were the two most common admission diagnoses, accounting for 294 (12.2%) and 204 (8.4%) admissions, respectively.ACS was uncommon, accounting for 9 (0.3%) admissions. Of patients admitted for heart failure, uncontrolled hypertension was the most commonly identified etiology of heart failure, cited in 124 (42.2%) cases. Ischemic heart disease was cited as the etiology in only 1 (0.3%) case. Adjusting for population growth, the annual volume of stroke admissions increased 70-fold in 43 years, from 2.9 admissions per 100,000 population in 1974 to 202.2 admissions per 100,000 in 2017.Conclusions :The burden of heart failure and stroke on hospital admissions in Tanzania is substantial, and the volume of stroke admissions is rising precipitously. ACS is a rare diagnosis, and the distribution of cardiovascular disease phenotypes in Tanzania differs from what has been observed outside of Africa. Further research is needed to ascertain the reasons for these differences

Association of HIV-infection, antiretroviral treatment and metabolic syndrome with large artery stiffness: a cross-sectional study.

BACKGROUND: Effective combined antiretroviral therapy (cART) has improved life expectancy among people living with HIV-1 infection. Treated HIV-1infection increases the prevalence of metabolic syndrome (MS). Despite sub-Saharan Africa having among the highest rates of HIV-1 infection, the effects of MS in HIV-1-infected individuals on cardiovascular risk is poorly explored. The aim of the study was to assess whether MS and/or HIV-1 treatment correlates with large elastic artery stiffness in HIV-1-infected patients treated with first-line cART. METHODS: The study sample comprised of 102 subjects free of cardiovascular disease and major risk factors divided into two groups based on HIV-1 infection, treatment, and MS status: HIV-1+/cART+/MS+ (n = 12); HIV-1+/cART-/MS+ (n = 16); HIV-1-/ MS+ (n = 10); HIV-1+/cART+/MS- (n = 42); HIV-1+/cART-/MS- (n = 32); HIV-1-/ MS- (n = 39). MS was established according the International Diabetes Federation definition. Large artery stiffness was measured using applanation tonometry to assess aortic pulse wave velocity (aPWV) and aortic augmentation index at heart rate of 75 bpm (AIx@HR75). cART included lamivudine/zidovudine and nevirapine or efavirenz. RESULTS: The prevalence of MS in the HIV-1-infected patients was 28%. There were no significant differences in aPWV in the non-MS groups. However, in subjects with MS, aPWV was significantly higher in the HIV-1 cART patients (9.0 ± 1.9 m/s) compared with both controls (7.5 ± 1.8 m/s; P = 0.018) and untreated HIV-1 patients (7.7 ± 1.3 m/s; P = 0.023), and these differences remained after adjustment for blood pressure and sex. Aortic PWV was significantly elevated (P = 0.009) in HIV-1 cART patients with MS compared to their counterparts without MS. Untreated HIV-1 patients with MS also demonstrated increased aPWV compared to their counterparts without MS (P = 0.05). Aortic AIx@HR75 was, on average, ~ 5% higher in HIV-1 cART patients with MS (28.3 ± 62% compared with untreated HIV-1 patients with MS (23.5 ± 9%; P = 0.075). Sub-group multivariate analysis identified MS as an independent predictor of increased aPWV in HIV-1 cART patients. CONCLUSIONS: Our study established that presence of MS in HIV-1 patients on treatment was associated with increased aPWV and hence increased arterial stiffness in sub-Saharan African HIV-1 patients on first-line cART.

Patient-Initiated Repackaging of Antiretroviral Therapy, Viral Suppression and Drug Resistance.

Patient-initiated repackaging of antiretroviral therapy (ART) refers to removal of ART medications from their original manufacturer's containers, and putting them into alternative containers. This behavior may be triggered by stigma associated with HIV infection, and may impact patient outcomes. We assessed association between patient initiated repackaging of ART and failure to achieve viral suppression (FVS) in a sample of 450 HIV-infected adults (≥8 years) on first line ART for ≥6 months. FVS was defined as a plasma HIV RNA level ≥400 copies/mL. A total of 197 (43.7%) patients reported repackaging their ART medications. One hundred ninety-one patients (42.4%) failed to suppress and FVS was associated with medication repackaging [adjusted odds ratio (aOR), 2.2; 95% CI 1.4-3.3.] Adherence to ART was also associated with FVS (aOR; 0.4; 95% CI 0.2-0.6.). Benefits of retaining drugs in their original packaging along with adherence to ART should be emphasized to reduce the risk of FVS.

Predictors of non-adherence to antiretroviral therapy among HIV infected patients in northern Tanzania.

BACKGROUND: Antiretroviral therapy (ART) has been shown to reduce HIV-related morbidity and mortality amongst those living with HIV and reduce transmission of the virus to those who are yet to be infected. However, these outcomes depend on maximum ART adherence, and HIV programs around the world make efforts to ensure optimal adherence. Predictors of ART non-adherence vary considerably across populations and settings with respect to demographic, psychological, behavioral and economic factors. The objective of this study is to investigate risk factors that predict non-adherence to antiretroviral treatment among HIV-infected individuals in northern Tanzania. METHODS: At Kilimanjaro Christian Medical Centre (KCMC), a tertiary and referral hospital in northern Tanzania, we used an existing ART database to randomly select HIV-infected patients above 18 years of age who have been on triple ART for at least two years. We used interviewer administered structured questionnaires to cross-sectionally determine predictors of ART non-adherence. We determined non-adherence through retrospective review of pharmacy drug refill (PDR) records of the interviewed participants using a pharmacy database. RESULTS: Non-adherence was defined as collecting less than 95% of expected monthly refills in the previous 2 years. Multivariable logistic regression model was used to determine the predictors of non-adherence. Of the 256 patients enrolled mean age was 44 years (SD ± 11) and median CD4 count was 499 cells per microliter (IQR 332-690). Median PDR adherence was 71% (IQR 58%-75%). Non-adherence was associated with younger age and unemployment. CONCLUSION: In this setting, adherence strategies could be adapted to address issues facing young adults, and those with household challenges such as unemployment. Further research is required to better understand the potential roles of these factors in suboptimal adherence.

Partnership Conference.

BACKGROUND: The Duke Global Health Institute (DGHI) was founded in 2006 with a goal to foster interdisciplinary global health education and research across Duke University and Duke Medical Center. Critical to achieving this goal is the need to develop and sustain strong international partnerships. OBJECTIVE: To host a conference with multiple international partners and strengthen existing relationships. METHODS: After a deliberate year-long planning process, DGHI convened a Partnership Conference with its international partners on the Duke University campus in conjunction with its 10th Anniversary Celebration. The Partnership Conference sought to promote an exchange of novel ideas in support of global health education and research, explore new collaborations in South-South relationships, and identify and facilitate pursuit of new educational and research opportunities. FINDINGS: A total of 25 partners from 10 countries and 46 DGHI faculty members participated in the 3-day event in October 2016. Activities included workshops on preselected research topics, educational symposia on novel teaching methods and harnessing technological advances, introduction of the Health Humanities Laboratory to prepare students and trainees for fieldwork, and discussions of research infrastructure and training needs. Surveys from visiting partners revealed a high degree of satisfaction. Proposed action items include methods to realize improved communications, enhancement of mutual education opportunities, support and mentoring to build local research capacity, and more exchange of faculty and students between partnering institutions. CONCLUSIONS: With careful planning from all parties, a multilateral partnership conference including both university and medical center faculty can be a productive forum for exchange on global health education and research. Sustaining such partnerships is vital to the success of global health scholarship.

HIV Resistance and Prevention of Mother-to-Child Transmission Regimen in HIV-Infected Infants in Northern Tanzania.

Prevention of mother-to-child transmission (PMTCT) guidelines recommend that all HIV-infected pregnant women receive antiretroviral therapy (Option B) and HIV-infected infants should initiate therapy with a protease inhibitor-based regimen; however, implementation of these guidelines has lagged in many resource-limited settings. Tanzania only recently implemented these guidelines with little country-specific data to inform whether HIV non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance was present among infected infants under the Option A guidelines. This study aimed to identify primary resistance mutations in HIV-infected infants and to identify risk of nevirapine (NVP) resistance based on maternal and infant NVP exposure. Infant dried blood spots (DBSs) were sent to the zonal reference laboratory at Kilimanjaro Christian Medical Centre Clinical Laboratory and underwent DNA polymerase chain reaction testing for HIV as standard of care. Using the clinical laboratory registry, HIV-positive DBS cards, stored at ambient temperature, were identified and sent for further viral load testing, nucleotide sequencing, and analysis. Clinical information was obtained from the PMTCT clinical sites and the National PMTCT registry for information regarding maternal and infant demographics and PMTCT treatment regimen. Results demonstrated that infants exposed to NVP were more likely to have high level resistance mutations (HLRMs) to NVP than those infants not exposed to NVP (p = .002). The most common HLRMs to NVP were K103 N, Y181C, and Y188 L. HIV subtype A was most common, followed by subtype C. Approximately one-third of HIV-infected infants had documented referral to HIV care. This study demonstrated the ongoing need to scale up and strengthen points along the PMTCT continuum and supported the recommendation for all HIV-infected infants to initiate a lopinavir/ritonavir-based antiretroviral therapy regimen.

Association of knowledge on ART line of treatment, scarcity of treatment options and adherence.

BACKGROUND: Adherence to Antiretroviral Therapy (ART) is critical piece in the management of HIV infected patients. Despite the benefits of ART, non-adherence to ART persists. This study explores association between patient's knowledge of the ART line of treatment, availability of future treatment options and adherence. METHODS: A cross sectional survey of HIV infected adolescent and adults was conducted. Cumulative optimal and sub-optimal adherence was defined as percentage adherence of ≥ 95 % and < 95 %, respectively. Binomial regression models were used to assess the association of patient's knowledge of the ART line of treatment, availability of future treatment options and adherence. RESULTS: Of the 402 patients reviewed, 101 (25.1 %) patients knew their ART line of treatment and were aware that future treatment options are limited. Compared to those who were not aware of the ART line of treatment and/or scarcity of future treatment options, those who were aware were more likely to be adherent (adjusted prevalence ratio [APR], 1.1; 95 % CI, 1.0-1.3). CONCLUSION: The study reports knowledge of patient's ART line of treatment and future treatment options is important indicator of adherence to ART. Although majority of the patients did not have the knowledge, those who had the knowledge demonstrated to be more adherent. It is critical for the physicians/health care providers in these settings to clearly educate patients about ART line of treatment and limited availability of future treatment options as such information is likely to influence individual behavior and improve patient's adherence to ART.

Nonnucleoside Reverse-transcriptase Inhibitor- vs Ritonavir-boosted Protease Inhibitor-based Regimens for Initial Treatment of HIV Infection: A Systematic Review and Metaanalysis of Randomized Trials.

BACKGROUND: Previous studies suggest that nonnucleoside reverse-transcriptase inhibitors (NNRTIs) cause faster virologic suppression, while ritonavir-boosted protease inhibitors (PI/r) recover more CD4 cells. However, individual trials have not been powered to compare clinical outcomes. METHODS: We searched databases to identify randomized trials that compared NNRTI- vs PI/r-based initial therapy. A metaanalysis calculated risk ratios (RRs) or mean differences (MDs), as appropriate. Primary outcome was death or progression to AIDS. Secondary outcomes were death, progression to AIDS, and treatment discontinuation. We calculated RR of virologic suppression and MD for an increase in CD4 cells at week 48. RESULTS: We included 29 trials with 9047 participants. Death or progression to AIDS occurred in 226 participants in the NNRTI arm and in 221 in the PI/r arm (RR, 1.03; 95% confidence interval, .87-1.22; 12 trials; n = 3825), death in 205 participants in the NNRTI arm vs 198 in the PI/r arm (1.04; 0.86-1.25; 22 trials; n = 8311), and progression to AIDS in 140 participants in the NNRTI arm vs 144 in the PI/r arm (1.00; 0.80-1.25; 13 trials; n = 4740). Overall treatment discontinuation (1.12; 0.93-1.35; 24 trials; n = 8249) and from toxicity (1.21; 0.87-1.68; 21 trials; n = 6195) were comparable, but discontinuation due to virologic failure was more common with NNRTI (1.58; 0.91-2.74; 17 trials; n = 5371). At week 48, there was no difference between NNRTI and PI/r in virologic suppression (RR, 1.03; 0.98-1.09) or CD4(+) recovery (MD, -4.7 cells; -14.2 to 4.8). CONCLUSIONS: We found no difference in clinical and viro-immunologic outcomes between NNRTI- and PI/r-based therapy.

The Effect of Switching to Second-Line Antiretroviral Therapy on the Risk of Opportunistic Infections Among Patients Infected With Human Immunodeficiency Virus in Northern Tanzania.

Background. Due to the unintended potential misclassifications of the World Health Organization (WHO) immunological failure criteria in predicting virological failure, limited availability of treatment options, poor laboratory infrastructure, and healthcare providers' confidence in making switches, physicians delay switching patients to second-line antiretroviral therapy (ART). Evaluating whether timely switching and delayed switching are associated with the risk of opportunistic infections (OI) among patients with unrecognized treatment failure is critical to improve patient outcomes. Methods. A retrospective review of 637 adolescents and adults meeting WHO immunological failure criteria was conducted. Timely and delayed switching to second-line ART were defined when switching happened at <3 and ≥3 months, respectively, after failure diagnosis was made. Cox proportional hazard marginal structural models were used to assess the effect of switching to second-line ART on the risk of developing OI. Results. Of 637 patients meeting WHO immunological failure criteria, 396 (62.2%) switched to second-line ART. Of those switched, 230 (58.1%) were delayed. Switching to second-line ART reduced the risk of OI (adjusted hazards ratio [AHR], 0.4; 95% CI, .2-.6). Compared with patients who received timely switch after failure diagnosis was made, those who delayed switching were more likely to develop OI (AHR, 2.2; 95% CI, 1.1-4.3). Conclusion. Delayed switching to second-line ART after failure diagnosis may increase the risk of OI. Serial immunological assessment for switching patients to second-line ART is critical to improve their outcomes.