Gina R. Kruse

Single-dose tenofovir and emtricitabine for reduction of viral resistance to non-nucleoside reverse transcriptase inhibitor drugs in women given intrapartum nevirapine for perinatal HIV prevention: an open-label randomised trial

BACKGROUND Intrapartum and neonatal single-dose nevirapine are essential components of perinatal HIV prevention in resource-constrained settings, but can induce resistance to other non-nucleoside reverse transcriptase inhibitor drugs. We aimed to investigate whether this complication would be reduced with a single peripartum intervention of tenofovir and emtricitabine. METHODS We randomly assigned 400 HIV-infected pregnant women who sought care at two public-sector primary health facilities in Lusaka, Zambia. One was excluded, 200 were assigned to receive a single oral dose of 300 mg tenofovir disoproxil fumarate with 200 mg emtricitabine under direct observation, and 199 to receive no study drug. Short-course zidovudine and intrapartum nevirapine were offered to all HIV-infected women, according to the local standard of care. Women who met national criteria for antiretroviral therapy were referred for care and not enrolled. Our primary study outcome was resistance to non-nucleoside reverse transcriptase inhibitors at 6 weeks after delivery. We used standard population sequencing to determine HIV genotypes. Analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00204308. FINDINGS Of the 200 women who were randomly assigned to the intervention, 14 were lost to follow-up or withdrew from the study, two did not take study drug according to protocol, and one specimen was lost; 23 of 199 controls were lost to follow-up or withdrew from the study, and three specimens were lost. Women given the intervention were 53% less likely than controls to have a mutation that conferred resistance to non-nucleoside reverse transcriptase inhibitors at 6 weeks after delivery (20/173 [12%] vs 41/166 [25%]; risk ratio [RR] 0.47, 95% CI 0.29-0.76). We noted postpartum anaemia, the most common serious adverse event in mothers, in four women in each group. 20 of 198 (10%) infants in the intervention group and 23 of 199 (12%) controls had a serious adverse event, mostly due to septicaemia (n=22) or pneumonia (n=8); these events did not differ between groups, and none were judged to be caused by the study intervention. INTERPRETATION A single dose of tenofovir and emtricitabine at delivery reduced resistance to non-nucleoside reverse transcriptase inhibitors at 6 weeks after delivery by half; therefore this treatment should be considered as an adjuvant to intrapartum nevirapine.

Baseline renal insufficiency and risk of death among HIV-infected adults on antiretroviral therapy in Lusaka, Zambia

Objective:To examine the association between baseline renal insufficiency and mortality among adults initiating antiretroviral therapy (ART) in an urban African setting. Design:Open cohort evaluation. Methods:We examined mortality according to baseline renal function among adults initiating ART in Lusaka, Zambia. Renal function was assessed by the Cockcroft–Gault method, the Modification of Diet in Renal Disease equation, and serum creatinine. Results:From April 2004 to September 2007, 25 779 individuals started ART with an available creatinine measurement at baseline. When creatinine clearance was calculated by the Cockcroft–Gault method, 8456 (33.5%) had renal insufficiency: 73.5% were mild (60–89 ml/min), 23.4% moderate (30–59 ml/min), and 3.1% severe (<30 ml/min). Risk for mortality at or before 90 days was elevated for those with mildly [adjusted hazard ratio (AHR) = 1.7; 95% confidence interval (95% CI) = 1.5–1.9], moderately (AHR = 2.3; 95% CI = 2.0–2.7), and severely (AHR = 4.3; 95% CI = 3.1–5.5) reduced creatinine clearance. Mild (AHR = 1.4; 95% CI = 1.2–1.6), moderate (AHR = 1.9; 95% CI = 1.5–2.3), and severe (AHR = 3.6; 95% CI = 2.4–5.5) insufficiency were also associated with increased mortality after 90 days, when compared with those with normal renal function. Trends were similar when renal function was estimated with Modification of Diet in Renal Disease or serum creatinine. Conclusion:Renal insufficiency at time of ART initiation was prevalent and associated with increased mortality risk among adults in this population. These results have particular relevance for settings like Zambia, where tenofovir – a drug with known nephrotoxicity – has been adopted as part of first-line therapy. This emphasizes the need for resource-appropriate screening algorithms for renal disease, both as part of ART eligibility and pretreatment assessment.

Burnout and use of HIV services among health care workers in Lusaka District, Zambia: a cross-sectional study

BackgroundWell-documented shortages of health care workers in sub-Saharan Africa are exacerbated by the increased human resource demands of rapidly expanding HIV care and treatment programmes. The successful continuation of existing programmes is threatened by health care worker burnout and HIV-related illness.MethodsFrom March to June 2007, we studied occupational burnout and utilization of HIV services among health providers in the Lusaka public health sector. Providers from 13 public clinics were given a 36-item, self-administered questionnaire and invited for focus group discussions and key-informant interviews.ResultsSome 483 active clinical staff completed the questionnaire (84% response rate), 50 staff participated in six focus groups, and four individuals gave interviews. Focus group participants described burnout as feeling overworked, stressed and tired. In the survey, 51% reported occupational burnout. Risk factors were having another job (RR 1.4 95% CI 1.2–1.6) and knowing a co-worker who left in the last year (RR 1.6 95% CI 1.3–2.2). Reasons for co-worker attrition included: better pay (40%), feeling overworked or stressed (21%), moving away (16%), death (8%) and illness (5%). When asked about HIV testing, 370 of 456 (81%) reported having tested; 240 (50%) tested in the last year. In contrast, discussion groups perceived low testing rates. Both discussion groups and survey respondents identified confidentiality as the prime reason for not undergoing HIV testing.ConclusionIn Lusaka primary care clinics, overwork, illness and death were common reasons for attrition. Programmes to improve access, acceptability and confidentiality of health care services for clinical providers and to reduce workplace stress could substantially affect workforce stability.

Drug choice, spatial distribution, HIV risk, and HIV prevalence among injection drug users in St. Petersburg, Russia.

BackgroundThe HIV epidemic in Russia has been driven by the unsafe injection of drugs, predominantly heroin and the ephedrine derived psychostimulants. Understanding differences in HIV risk behaviors among injectors associated with different substances has important implications for prevention programs.MethodsWe examined behaviors associated with HIV risk among 900 IDUs who inject heroin, psychostimulants, or multiple substances in 2002. Study participants completed screening questionnaires that provided data on sociodemographics, drug use, place of residence and injection- and sex-related HIV risk behaviors. HIV testing was performed and prevalence was modeled using general estimating equation (GEE) analysis. Individuals were clustered by neighborhood and disaggregated into three drug use categories: Heroin Only Users, Stimulant Only Users, and Mixed Drug Users.ResultsAmong Heroin Only Users, younger age, front/backloading of syringes, sharing cotton and cookers were all significant predictors of HIV infection. In contrast, sharing needles and rinse water were significant among the Stimulant Only Users. The Mixed Drug Use group was similar to the Heroin Only Users with age, front/back loading, and sharing cotton significantly associated with HIV infection. These differences became apparent only when neighborhood of residence was included in models run using GEE.ConclusionThe type of drug injected was associated with distinct behavioral risks. Risks specific to Stimulant Only Users appeared related to direct syringe sharing. The risks specific to the other two groups are common to the process of sharing drugs in preparation to injecting. Across the board, IDUs could profit from prevention education that emphasizes both access to clean syringes and preparing and apportioning drug with these clean syringes. However, attention to neighborhood differences might improve the intervention impact for injectors who favor different drugs.

Addition of single-dose tenofovir and emtricitabine to intrapartum nevirapine to reduce perinatal HIV transmission

Objective:To determine the impact of adjuvant single-dose peripartum tenofovir/emtricitabine (TDF/FTC) on intrapartum/early postpartum HIV transmission. Methods:In the setting of routine short-course zidovudine (ZDV) and peripartum nevirapine (NVP) for perinatal HIV prevention, participants were randomized to single-dose TDF (300 mg)/FTC (200 mg) or to no intervention in labor. Six-week infant HIV infection was compared according to actual-use drug regimens. Results:Of 397 women randomized, 355 (89%) had infants who were alive and active at 6 weeks postpartum. Of these, 18 (5.1%) were infected in utero and 6 (1.8%) were infected intrapartum/early postpartum. Among the 243 who used ZDV and NVP, intrapartum/early postpartum transmission was not reduced among infants whose mothers received TDF/FTC compared with those who did not (2 of 123 [1.6%] vs. 3 of 109 [2.8%]; P = 0.67). Among the 49 infants whose mothers did not receive antenatal ZDV but who had confirmed NVP ingestion, transmission similarly did not differ (0 of 19 [0%] vs. 1 of 26 [3.4%]). TDF/FTC was not significantly associated with reduced overall transmission (odds ratio [OR] = 0.7, 95% confidence interval [CI]: 0.3 to 1.6), even when other antiretroviral drugs were considered (adjusted OR = 0.8, 95% CI: 0.3 to 1.8). Conclusions:Adjuvant peripartum single-dose TDF/FTC did not reduce perinatal transmission. Whether a higher dose might be effective remains unknown but should be studied in settings in which NVP is used without antenatal ZDV.

Patient involvement in medical decision-making and pain among elders: physician or patient-driven?

BackgroundPain is highly prevalent among older adults, but little is known about how patient involvement in medical decision-making may play a role in limiting its occurrence or severity. The purpose of this study was to evaluate whether physician-driven and patient-driven participation in decision-making were associated with the odds of frequent and severe pain.MethodsA cross-sectional population-based survey of 3,135 persons age 65 and older was conducted in the 108-county region comprising West Texas. The survey included self-reports of frequent pain and, among those with frequent pain, the severity of pain.ResultsFindings from multivariate logistic regression analyses showed that higher patient-driven participation in decision-making was associated with lower odds (OR, 0.82; 95% CI, 0.75–0.89) of frequent pain, but was not significantly associated with severe pain. Physician-driven participation was not significantly associated with frequent or severe pain.ConclusionsThe findings suggest that patients may need to initiate involvement in medical decision-making to reduce their chances of experiencing frequent pain. Changes to other modifiable health care characteristics, including access to a personal doctor and health insurance coverage, may be more conducive to limiting the risk of severe pain.

Use of Electronic Cigarettes Among U.S. Adults With Medical Comorbidities

INTRODUCTION Electronic cigarette (e-cigarette) use is rising in the U.S. Smokers with comorbidities may increasingly use e-cigarettes if they believe e-cigarettes reduce smoking-related harm. This study examined e-cigarette use among adults with medical comorbidities. METHODS In 2016, this study analyzed 68,136 U.S. adults in the 2014 and 2015 National Health Interview Survey. Prevalent e-cigarette use by medical comorbidities and adjusted odds of e-cigarette use were calculated. RESULTS Among current cigarette smokers, ever use of e-cigarettes was more often reported by adults with one or more medical comorbidity versus those without comorbidity (18-24 years: 73.5% vs 61.4%; 25-44 years: 60.6% vs 54.3%; 45-64 years: 46.5% vs 40.3%; ≥65 years: 35.2% vs 19.4%; all p<0.05). Current smokers aged 25-64 years with one or more comorbidity reported current e-cigarette use more often than those without comorbidity (25-44 years, 17.8% vs 14.3%, p=0.03; 45-64 years, 15.9% vs 11.5%, p=0.02). Current smokers with chronic obstructive pulmonary disease, asthma, and cardiovascular disease had higher odds of ever e-cigarette use versus those without comorbidity. Current smokers with asthma and cardiovascular disease had higher odds of current e-cigarette use. Former smokers with chronic obstructive pulmonary disease had higher odds of ever and current e-cigarette use and former smokers with cancer had lower odds of current e-cigarette use. CONCLUSIONS E-cigarette use by current and former smokers with medical comorbidities is substantial, especially among individuals with chronic lung or cardiovascular disease. Clinicians should routinely ask these patients about e-cigarette use, actively consider all pathways to help their patients quit combustible cigarettes, and recommend evidence-based treatments.

Hispanic ethnicity, rural residence, and regular source of care.

This study assessed whether Hispanic ethnicity and rural residence were related to usual source-of-care. We studied 3,689 persons over age 65 who lived in their own homes in a 108-county area in West Texas. A telephone interview in two waves was used to collect information. Usual source-of-care was measured in two ways: by asking if the subject had a usual place to go and by asking if the subject had a personal physician or nurse. In a logistic regression analysis, Hispanic ethnicity was independently associated with both having a usual place of care (OR = .511, CI = .32–.82) and a usual provider (OR = .629, CI = .45–.88). Rural residence was not associated with either measure. Efforts to promote usual source-of-care should be targeted at Hispanic seniors in this region of the southwestern United States.

Tobacco Dependence Treatment Training Programs: An International Survey

INTRODUCTION In line with Article 14 guidelines for the WHO Framework Convention on Tobacco Control, we aimed to assess the progress in training individuals to deliver tobacco cessation treatment. METHODS Cross-sectional web-based survey in May-September 2013 among 122 experts in tobacco control and training from 84 countries (73% response rate among 115 countries surveyed). We measured training program prevalence, participants, and challenges faced. RESULTS Overall, 21% (n = 18/84) of countries, mostly low and middle-income countries (LMICs; P = .002), reported no training program. Among 66 countries reporting at least one training program, most (84%) trained healthcare professionals but 54% also trained other individuals including community health workers, teachers, and religious leaders. Most programs (54%) cited funding challenges, although stability of funding varied by income level. Government funding was more commonly reported in higher income countries (high 56%, upper middle 50%, lower middle 27%, low 25%; P = .03) while programs in LMICs relied more on nongovernmental organizations (high 11%, upper middle 37%, lower middle 27%, low 38%; P = .02). CONCLUSIONS One in five countries reported having no tobacco treatment training program representing little progress in terms of training individuals to deliver tobacco treatment in LMICs. Without more trained tobacco treatment providers, one of the tenets of Article 14 is not yet being met and health inequalities are likely to widen. More effort and resources are needed to ensure that healthcare worker educational programs include training to assess tobacco use and deliver brief advice and that training is available for individuals outside the healthcare system in areas with limited healthcare access.

Smoking-Cessation Efforts by US Adult Smokers with Medical Comorbidities

BACKGROUND Continued cigarette smoking by individuals with chronic medical diseases can adversely affect their symptoms, disease progression, and mortality. We assessed the association between medical comorbidities and smoking-cessation efforts among US adult smokers. METHODS We analyzed cross-sectional data from 12,494 past-year cigarette smokers aged ≥18 years from Wave 1 (2013-2014) of the nationally representative Population Assessment of Tobacco and Health study. We assessed the association between self-reported medical comorbidities and past-year quit attempts, use of evidence-based smoking-cessation treatment or electronic cigarettes, and successful smoking cessation using logistic regression, adjusting for sociodemographics, insurance status, geographic region, and having a past-year doctor visit. RESULTS In the study sample, 39% were aged 18 to 34 years, 45% were female, 70% were non-Hispanic white, and 48% reported ≥1 comorbidity. Smokers with any comorbidity, compared with those without comorbidities, had higher odds of trying to quit (adjusted odds ratio, 1.19; 95% confidence interval, 1.08-1.30), but no higher likelihood of quitting success. Having more medical comorbidities was associated with increased odds of trying to quit. Smokers with a comorbidity used evidence-based treatment more often than smokers without comorbidities (43% vs 26%); use of e-cigarettes to quit was similar between smokers with and without comorbidities (27% vs 28%). CONCLUSIONS Adult smokers with chronic medical diseases try to quit and use evidence-based tobacco-cessation treatment more often than smokers without comorbidities, but they are no more likely to quit, suggesting that their quit attempts are less likely to succeed. Smokers with medical comorbidities may require more intensive, prolonged, and repeated treatment to stop smoking.