Screening for Hepatocellular Carcinoma among adults with HIV/Hepatitis B coinfection in Zambia: A Pilot Study

Background & aims: Chronic hepatitis B virus (HBV) infection is the main cause of hepatocellular carcinoma (HCC) in sub-Saharan Africa (SSA). In an established cohort of HIV/HBV-coinfected individuals on antiretroviral therapy (ART), we piloted an HCC screening initiative at two outpatient clinics in Lusaka, Zambia. Methods: We performed abdominal ultrasound (AUS) and transient elastography in all patients. Results: Among 279 HIV/HBV-coinfected patients, 165 (59.1%) were men, median age was 34 years (interquartile range 28-39) and median CD4 count 246 cells/µl (112-355). While 102 (36.6%) individuals had elevated transaminases, 114 (40.9%) had HBV levels >2000 IU/mL and 59 (24.6%) significant fibrosis. On AUS, 75 (26.9%) participants had hepatomegaly and 69 (24.7%) peri-portal fibrosis. Five patients had a liver lesion >1cm, an indication for confirmatory imaging. Conclusions: In one of the first HCC screening initiatives in SSA, 2% of HIV/HBV-coinfected adults had significant liver lesions, and a quarter had findings suggestive of schistosomiasis-induced liver damage

Alcohol reduction outcomes following brief counseling among adults with HIV in Zambia: A sequential mixed methods study

Data from sub-Saharan Africa on the impact of alcohol on the HIV epidemic in sub-Saharan Africa is limited. In this region, it is not well understood how people with HIV (PLWHA) respond to alcohol reduction counseling while they are linked to HIV clinical care. We conducted an explanatory sequential mixed-methods study to understand patterns of alcohol use among adults (18+ years) within a prospective HIV cohort at two urban public-sector clinics in Zambia. At antiretroviral therapy (ART) start and one year later, we measured alcohol use with Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) and those reporting any alcohol use were provided brief counseling. We conducted focus groups at 1 year with participants who had any alcohol use and 20 in-depth interviews among the subgroup with unhealthy use pre-ART and who either reduced or did not reduce their use by 1 year to moderate levels or abstinence. Focus group Discussions (FGDs) (n = 2) were also held with HIV clinic staff. Qualitative data were analyzed using thematic analysis. The data obtained from 693 participants was analyzed (median age 34 years, 45% men), it revealed that unhealthy alcohol use (AUDIT-C >3 for men; >2 for women) was reported among 280 (40.4%) at baseline and 205 (29.6%) at 1 year on ART. Reduction from unhealthy to moderate use or abstinence was more common with older age, female, non-smoking, and at Clinic B (all P<0.05). Qualitative data revealed ineffective alcohol support at clinics, social pressures in the community to consume alcohol, and unaddressed drivers of alcohol use including poverty, poor health status, depression, and HIV stigma. Healthcare workers reported a lack of training in alcohol screening and treatment, which led to mixed messages provided to patients ('reduce to safe levels' versus 'abstain'). In summary, interventions to reduce unhealthy alcohol use are needed within HIV clinics in Zambia as a substantial population have persistent unhealthy use despite current HIV clinical care. A better understanding is needed regarding the implementation challenges related to screening for unhealthy alcohol use integrated with HIV services

Identifying barriers to ART initiation and adherence: An exploratory qualitative study on PMTCT in Zambia

Background Though antiretroviral therapy (ART) is widely available, HIV positive pregnant women in Zambia are less likely to start and remain on therapy throughout pregnancy and after delivery. This study sought to understand readiness to start ART among HIV pregnant women from the perspectives of both women and men in order to suggest more holistic programs to support women to continue life-long ART after delivery. Methods We conducted a qualitative study with HIV positive pregnant women before and after ART initiation, and men with female partners, to understand readiness to start lifelong ART. We conducted 28 in-depth interviews among women and 2 focus group discussions among male partners. Data were transcribed verbatim and analyzed in NVivo 12 using thematic analysis. Emerging themes from the data were organized using the social ecological framework. Results Men thought of their female partners as young and needing their supervision to initiate and stay on ART. Women agreed that disclosure and partner support were necessary preconditions to ART initiation and adherence and, expressed fear of divorce as a prominent barrier to disclosure. Maternal love and desire to look after one’s children instilled a sense of responsibility among women which motivated them to overcome individual, interpersonal and health system level barriers to initiation and adherence. Women preferred adherence strategies that were discrete, the effectiveness of which, depended on women’s intrinsic motivation. Conclusion The results support current policies in Zambia to encourage male engagement in ART care. To appeal to male partners, messaging on ART should be centered on emphasizing the importance of male involvement to ensure women remain engaged in ART care. Programs aimed at supporting postpartum ART adherence should design messages that appeal to both men’s role in couples’ joint decision-making and women’s maternal love as motivators for adherence

Short Communication: Late Refills During the First Year of Antiretroviral Therapy Predict Mortality and Program Failure Among HIV-Infected Adults in Urban Zambia

We evaluated the association of the number of late antiretroviral therapy (ART) refills with patient outcomes in a large public-sector human immunodeficiency virus treatment program in Lusaka, Zambia. Using pharmacy data routinely collected during 2004–2010, we calculated the number of late refills during the initial year of ART. We used multivariable Cox proportional hazard regression to examine the association between the number of late refills and death or program failure (i.e., death, loss to follow-up, or program withdrawal) >12 months after ART initiation, with and without stratification by the medication possession ratio (MPR) during the initial year of ART. Of 53,015 adults who received ART for ≥12 months (median follow-up duration, 86.1 months; interquartile range, 53.2–128.2 months), 26,847 (50.6%) had 0 late refills, 16,762 (31.6%) had 1, 6,505 (12.3%) had 2, and 2,901 (5.5%) had ≥3. Kaplan–Meier analysis revealed that ≥3 late refills was associated with a greater mortality risk than 1 and 2 late refills (p<0.001, by the log-rank test). The mortality risk was greater for patients with 2 late refills [adjusted hazard ratio (HR), 1.17; 95% confidence interval (CI), 0.99–1.38] or ≥3 late refills (adjusted HR, 1.51; 95% CI, 1.23–1.87), compared with that for patients with 0–1 late refills. Program failure was associated with ≥2 late refills. An MPR of <80% was associated with similar increases in mortality risk across late-refill strata. Monitoring late refills during the initial period of ART may help resource- and time-constrained clinics identify patients at risk for program failure

Validation of Medicaid Claims-based Diagnosis of Myocardial Infarction Using an HIV Clinical Cohort

In non-experimental comparative effectiveness research using healthcare databases, outcome measurements must be validated to evaluate and potentially adjust for misclassification bias. We aimed to validate claims-based myocardial infarction algorithms in a Medicaid population using an HIV clinical cohort as the gold standard

Age at Antiretroviral Therapy Initiation Predicts Immune Recovery, Death, and Loss to Follow-Up Among HIV-Infected Adults in Urban Zambia

We analyzed the association of age at antiretroviral therapy (ART) initiation with CD4+ T cell count recovery, death, and loss to follow-up (LTFU) among HIV-infected adults in Zambia. We compared baseline characteristics of patients by sex and age at ART initiation [categorized as 16–29 years, 30–39 years, 40–49 years, 50–59 years, and 60 years and older]. We used the medication possession ratio to assess adherence and analysis of covariance to measure the adjusted change in CD4+ T cell count during ART. Using Cox proportional hazard regression, we examined the association of age with death and LTFU. In a secondary analysis, we repeated models with age as a continuous variable. Among 92,130 HIV-infected adults who initiated ART, the median age was 34 years and 6,281 (6.8%) were aged ≥50 years. Compared with 16–29 year olds, 40–49 year olds (–46 cells/mm3), 50–59 year olds (–53 cells/mm3), and 60+ year olds (–60 cells/mm3) had reduced CD4+ T cell gains during ART. The adjusted hazard ratio (AHR) for death was increased for individuals aged ≥40 years (AHR 1.25 for 40–49 year olds, 1.56 for 50–59 year olds, and 2.97 for 60+ year olds). Adherence and retention in care were poorest among 16–29 year olds but similar in other groups. As a continuous variable, a 5-year increase in age predicted reduced CD4+ T cell count recovery and increased risk of death. Increased age at ART initiation was associated with poorer clinical outcomes, while age <30 years was associated with a higher likelihood of being lost to follow-up. HIV treatment guidelines should consider age-specific recommendations

Temporal trends in co-trimoxazole use among children on antiretroviral therapy and the impact of co-trimoxazole on mortality rates in children without severe immunodeficiency

Background: Co-trimoxazole is recommended for all children with human immunodeficiency virus. In this analysis, we evaluate trends in pediatric co-trimoxazole use and survival on co-trimoxazole in children using antiretroviral therapy (ART). Methods: We used data collected between January 1, 2006, and March 31, 2016, from the International Epidemiology Databases to Evaluate AIDS. Logistic regression was used to evaluate factors associated with using co-trimoxazole at ART initiation. Competing risk regression was used to assess factors associated with death. Results: A total of 54113 children were included in this study. The prevalence of co-trimoxazole use at ART initiation increased from 66.5% in 2006 to a peak of 85.6% in 2010 and then declined to 48.5% in 2015-2016. A similar trend was observed among children who started ART with severe immunodeficiency. After adjusting for year of ART initiation, younger age (odds ratio [OR], 1.18 for <1 vs 1 to <5 years of age [95% confidence interval (CI), 1.09-1.28]), lower height-for-age z score (OR, 1.15 for less than -3 vs greater than -2 [95% CI, 1.08-1.22]), anemia (OR, 1.08 [95% CI, 1.02-1.15]), severe immunodeficiency (OR, 1.25 [95% CI, 1.18-1.32]), and receiving care in East Africa (OR, 8.97 vs Southern Africa [95% CI, 8.17-9.85]) were associated with a high prevalence of co-trimoxazole use. Survival did not differ according to co-trimoxazole use in children without severe immunodeficiency (hazard ratio, 1.01 for nonusers versus users [95% CI, 0.77-1.34]). Conclusions: Recent declines in co-trimoxazole use may not be linked to the current shift toward early ART initiation. Randomized trial data might be needed to establish the survival benefit of co-trimoxazole in children without severe immunodeficiency

Chronic hepatitis B virus monoinfection at a university hospital in Zambia.

AIM: To characterize antiviral therapy eligibility among hepatitis B virus (HBV)-infected adults at a university hospital in Zambia. METHODS: Hepatitis B surface antigen-positive adults (n = 160) who were HIV-negative and referred to the hospital after a routine or clinically-driven HBV test were enrolled. Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), platelet count, hepatitis B e-antigen, and HBV DNA were measured. Liver fibrosis/cirrhosis was assessed by physical examination, AST-to-platelet ratio index, and transient elastography. In antiviral therapy-naïve individuals, we described HBV stages and antiviral therapy eligibility per World Health Organization (WHO) and by HBV test (routine vs clinical). Elevated ALT was > 19 in women and > 30 U/L in men. Among treatment-experienced individuals, we described medication side effects, adherence, and viral suppression. RESULTS: The median age was 33 years, 71.9% were men, and 30.9% were diagnosed with HBV through a clinically-driven test with the remainder identified via routine testing (at the blood bank, community events, etc.). Among 120 treatment-naïve individuals, 2.5% were categorized as immune tolerant, 11.7% were immune active, 35.6% were inactive carriers, and 46.7% had an indeterminate phenotype. Per WHO guidelines, 13 (10.8%) were eligible for immediate antiviral therapy. The odds of eligibility were eight times higher for those diagnosed at clinical vs routine settings (adjusted odds ratio, 8.33; 95%CI: 2.26-29.41). Among 40 treatment-experienced HBV patients, virtually all took tenofovir, and a history of mild side effects was reported in 20%. Though reported adherence was good, 12 of 29 (41.4%) had HBV DNA > 20 IU/mL. CONCLUSION: Approximately one in ten HBV-monoinfected Zambians were eligible for antivirals. Many had indeterminate phenotype and needed clinical follow-up.School of Medicine at University of Alabama at Birmingham; Fogarty International Center, No. K01TW009998; National Institute of Allergy and Infectious Diseases, U.S. National Institutes of Health, No. U01AI069924; and Swiss National Science Foundation (to Wandeler G), No. PZ0093_154730

Antiretroviral Therapy Initiated During Acute HIV Infection Fails to Prevent Persistent T-Cell Activation

Initiation of ART during acute HIV-1 infection may prevent persistent immune activation. We analyzed longitudinal CD38+HLA-DR+ CD8+ T cell percentages in 31 acutely infected individuals who started early (median 43 days since infection) and successful ART, and maintained viral suppression through 96 weeks. Pre-therapy a median of 72.6% CD8+ T cells were CD38+HLA-DR+, and while this decreased to 15.6% by 96 weeks, it remained substantially higher than seronegative controls (median 8.9%, p=0.008). Shorter time to suppression predicted lower activation at 96 weeks. These results support the hypothesis that very early events in HIV-1 pathogenesis may result in prolonged immune dysfunction

Area-level poverty and preterm birth risk: A population-based multilevel analysis

<p>Abstract</p> <p>Background</p> <p>Preterm birth is a complex disease with etiologic influences from a variety of social, environmental, hormonal, genetic, and other factors. The purpose of this study was to utilize a large population-based birth registry to estimate the independent effect of county-level poverty on preterm birth risk. To accomplish this, we used a multilevel logistic regression approach to account for multiple co-existent individual-level variables and county-level poverty rate.</p> <p>Methods</p> <p>Population-based study utilizing Missouri's birth certificate database (1989–1997). We conducted a multilevel logistic regression analysis to estimate the effect of county-level poverty on PTB risk. Of 634,994 births nested within 115 counties in Missouri, two levels were considered. Individual-level variables included demographics factors, prenatal care, health-related behavioral risk factors, and medical risk factors. The area-level variable included the percentage of the population within each county living below the poverty line (US census data, 1990). Counties were divided into quartiles of poverty; the first quartile (lowest rate of poverty) was the reference group.</p> <p>Results</p> <p>PTB < 35 weeks occurred in 24,490 pregnancies (3.9%). The rate of PTB < 35 weeks was 2.8% in counties within the lowest quartile of poverty and increased through the 4^thquartile (4.9%), p < 0.0001. High county-level poverty was significantly associated with PTB risk. PTB risk (< 35 weeks) was increased for women who resided in counties within the highest quartile of poverty, adjusted odds ratio (_adjOR) 1.18 (95% CI 1.03, 1.35), with a similar effect at earlier gestational ages (< 32 weeks), _adjOR 1.27 (95% CI 1.06, 1.52).</p> <p>Conclusion</p> <p>Women residing in socioeconomically deprived areas are at increased risk of preterm birth, above other underlying risk factors. Although the risk increase is modest, it affects a large number of pregnancies.</p