Re-Engagement into HIV Care: A Systematic Review.

Identifying evidence-based interventions that can optimize the re-engagement into care of people living with HIV is necessary to achieve and sustain HIV epidemic control. We conducted a systematic review of interventions for re-engagement into HIV care to examine the accumulated evidence and to identify similarities and differences across studies. Between January and March 2020, we searched MEDLINE, Embase, CINAHL, and PsycINFO databases for publications from 1996 to 2020. We screened 765 references and selected 125 publications for full-text review. For the nine included studies, the intervention centered on (1) integration of clinic and HIV surveillance data; (2) additional or different levels of support provided by healthcare workers; or (3) multi-component intervention. Irrespective of the interventions, mixed results were found for re-engagement into care or ART re-initiation. None of the studies led to an improvement in viral suppression. Re-engagement in HIV care is critical for longitudinal HIV and national program success. Standardizing definitions for out-of-care and re-engagement would facilitate the comparison of interventions. Rigorous study designs to assess strategies to enhance HIV re-engagement are warranted.

Epidemiology of sexually transmitted infections: trends among patients screened for sexually transmitted infections in rwandan health facilities 2014-2020.

BACKGROUND: Sexually Transmitted Infections (STIs) are of great global health concern. Currently, there are limited epidemiological data characterizing STIs in the general population in Rwanda. We assessed the national and regional epidemiology of STIs in Rwanda from 2014-2020 among patients syndromically screened for STIs in all health facilities in Rwanda. METHODS: This is a retrospective analysis of the trend of STIs epidemiology among screened patients at all health facilities in Rwanda using data from the Health Management Information System (HMIS) reporting. Adult patients (15 years and over) screened for STIs between July 2014 and June 2020 were included in the analysis. Outcomes of interest were the number of individuals screened for STIs and individuals diagnosed with at least one STI with a syndromic approach only or plus a test together. RESULTS: Overall, the number of individuals screened for STIs over the study period was 5.3 million (M) in 2014-2015, 6.6 M in 2015-2016, 6.3 M in 2016-2017, 6.7 M in 2017-2018, 6.2 M in 2018-2019, and 4.9 M in 2019-2020. There was a modest increase in the number of individuals diagnosed and treated for STIs from 139,357 in 2014-15 to 202,294 (45% increase) in 2019-2020. At the national level, the prevalence of STI syndromes amongst individuals screened at health facilities in Rwanda varied between 2.37% to 4.16% during the study period. Among the provinces, Kigali city had the highest prevalence for the whole 6 years ranging from 3.46% (95%CI: 3.41, 3.51) in 2014-2015 to 8.23% (95%CI: 8.15, 8.31) in 2019-2020. CONCLUSION: From 2014 to 2020, the number of patients screened for STI syndromes in Rwanda varied between 4.9 M and 6.7 M. However, the prevalence of STIs among screened patients increased considerably over time, which could be associated with public awareness and improved data recording. The highest prevalence of all STIs was observed in urban areas and near borders, and private clinics reported more cases, suggesting the need to improve awareness in these settings and increase confidentiality and trust in public health clinics.

Nosocomial disseminated fusariosis in a hematopoietic stem cell transplant recipient.

We report a case of nosocomial disseminated Fusarium in a stem cell transplant recipient. Identification of hospital fungal water reservoirs with routine surveillance cultures could potentially decrease rates of invasive infection.

Towards elimination of mother-to-child transmission of HIV in Rwanda: a nested case-control study of risk factors for transmission.

BACKGROUND: Mother-to-child HIV transmission (MTCT) has substantially declined since the scale-up of prevention programs around the world, including Rwanda. To achieve full elimination of MTCT, it is important to understand the risk factors associated with residual HIV transmission, defined as MTCT at the population-level that still occurs despite universal access to PMTCT. METHODS: We performed a case control study of children born from mothers with HIV with known vital status at 18 months from birth, who were followed in three national cohorts between October and December 2013, 2014, and 2015 in Rwanda. Children with HIV were matched in a ratio of 1:2 with HIV-uninfected children and a conditional logistic regression model was used to investigate risk factors for MTCT. RESULTS: In total, 84 children with HIV were identified and matched with 164 non-infected children. The median age of mothers from both groups was 29 years (interquartile range (IQR): 24-33). Of these mothers, 126 (51.4 %) initiated antiretroviral therapy (ART) before their pregnancy on record. In a multivariable regression analysis, initiation of ART in the third trimester (Adjusted Odds Ratio [aOR]: 9.25; 95 % Confidence Interval [95 % CI]: 2.12-40.38) and during labour or post-partum (aOR: 8.87; 95 % CI: 1.92-40.88), compared to initiation of ART before pregnancy, increased the risk of MTCT. Similarly, offspring of single mothers (aOR: 7.15; 95 % CI: 1.15-44.21), and absence of postpartum neonatal ART prophylaxis (aOR: 7.26; 95 % CI: 1.66-31.59) were factors significantly associated with MTCT. CONCLUSIONS: Late ART initiation for PMTCT and lack of postpartum infant prophylaxis are still the most important risk factors to explain MTCT in the era of universal access. Improved early attendance at antenatal care, early ART initiation, and enhancing the continuum of care especially for single mothers is crucial for MTCT elimination in Rwanda.

Intravesicular Cidofovir in the Treatment of BK Virus-Associated Hemorrhagic Cystitis Following Hematopoietic Stem Cell Transplantation.

Background: BK virus hemorrhagic cystitis (BKV-HC) is a common complication following hematopoietic stem cell transplant (HSCT); optimal management remains uncertain. Supportive care (bladder irrigation and blood transfusions) and intravenous and intravesicular cidofovir have all been used with varying success. Objective: The purpose of this study was to determine the safety and effectiveness of intravesicular cidofovir for BKV-HC following HSCT. Methods: A retrospective analysis of all HSCT patients with BKV-HC prescribed intravesicular cidofovir from 2012 to 2017. Results: 33 patients were treated for BKV-HC. The median age was 50 years (range 23-73), and 18 (55%) were male. The median HC symptom severity was 2, with a median BK urine viral load pretreatment of 100,000,000 IU/mL. Patients received a median of 2 intravesicular treatments (range 1-7) at a dosage of 5 mg/kg per instillation. In all, 19 (59%) patients demonstrated complete clinical resolution of symptoms; 9 (28%) had a partial response; and 4 (13%) had no change in symptoms. Patients with a high pretreatment BK viral load (>100 million) and high HC grade (2-4) had a lower frequency of complete remission. The main side effect of intravesicular instillation was severe bladder spasms in 4 patients (12%). Conclusion and Relevance: This is the largest study of intravesicular cidofovir treatment of BKV HC reported to date; 88% of patients with BVK-HC achieved clinical improvement of symptoms with minimal side effects. Clinical trials of intravesicular cidofovir could provide further evidence for this treatment for BKV-HC.

Prevalence of hepatitis B surface antigen (HBsAg) positivity and its associated factors in Rwanda.

BACKGROUND: The epidemiology of hepatitis B virus (HBV) infection in the general population in Rwanda is not well known. This study examined the prevalence of HBV surface antigen (HBsAg) positivity and associated risk factors among people aged 25 years and over in an organized national screening campaign. METHODS: This is a cross-sectional study using data from a nationwide HBV screening campaign organized by the Rwanda Biomedical Centre from March to October 2018. This campaign targeted individuals aged > 25 years old from 24 of 30 districts of Rwanda. Sensitization was done through multimedia announcements, community health workers and local church leaders. During the campaign, a structured interview was administered by trained healthcare workers to collect information on socio-demographic, clinical and behavioral characteristics of participants; HBV screening was performed with HBsAg using enzyme-linked immunosorbent assays (ELISA) testing. Bivariate and multivariate logistic regressions were used to assess factors associated with HBsAg positivity in the screened participants. RESULTS: A total of 327,360 individuals were screened during the campaign. Overall 12,865(3.9%) were HBsAg positive. The highest prevalence (4.2%) was found in the 35-44-year-old group, but the difference from other groups was not significant (Odds Ratio [OR = 1.057, 95% Confidence Interval(CI) (0.904-1.235)]. Being male [OR = 1.348, 95% CI (1.30,1.40)]; being single [OR = 1.092, 95% CI (1.10-1.16)] compared to married; a previous positive TB screening test [OR = 2.352, 95% CI (1.63-3.39)]; history of surgical operation [OR = 1.082, 95% CI (1.00,1.17)]; exposure to traditional operational practices and scarification [OR = 1.187, 95% CI (1.13, 1.24)]; and having a person in the family with viral hepatitis [OR = 1.367, 95% CI (1.21, 1.53)] were significantly associated with HBV infection. CONCLUSIONS: These data provide the first national estimate of the prevalence of HBsAg seropositivity and its associated factors in Rwanda. The study identified people with the highest risk of HBV infection who should be the priority of future prevention efforts in Rwanda and in similar settings.

Implementation of a unique hepatitis C care continuum model in Rwanda.

BACKGROUND: There has been an evolution in the treatment of chronic hepatitis C (HCV) due to highly effective direct-acting antivirals, however, restriction of treatment to medical specialists hinders escalation of HCV treatment. This is particularly true in resource-limited settings (RLS), which disproportionately represent the burden of HCV worldwide. The ASCEND study in Washington, DC, demonstrated that complete task-shifting can safely and effectively overcome a low provider-to-patient ratio and expand HCV treatment. However, this model has not been applied internationally to RLS. METHOD: The validated ASCEND model was translated to an international clinical program in Kigali, Rwanda, aimed at training general medicine providers on HCV management and obtaining HCV prevalence data. RESULTS: The didactic training program administered to 11 new HCV providers in Rwanda increased provider's knowledge about HCV management. Through the training program, 26% of patients seen during the follow-up period were screened for HCV and a prevalence estimate of 2% was ascertained. Of these patients, 30% were co-infected with hepatitis B. CONCLUSION: The ASCEND paradigm can be successfully implemented in RLS to escalate HCV care, in a self-sustaining fashion that educates more providers about HCV management, while increasing the public's awareness of HCV and access to treatment.

Syphilis and HIV prevalence and associated factors to their co-infection, hepatitis B and hepatitis C viruses prevalence among female sex workers in Rwanda.

BACKGROUND: Human Immunodeficiency Virus (HIV), syphilis, Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are sexually transmitted infections (STIs) and share modes of transmission. These infections are generally more prevalent among female sex workers (FSWs). METHODS: This is a cross-sectional study conducted among female sex workers (FSWs) in Rwanda in 2015. Venue-Day-Time (VDT) sampling method was used in recruiting participants. HIV, syphilis, HBV, and HCV testing were performed. Descriptive analyses and logistic regression models were computed. RESULTS: In total, 1978 FSWs were recruited. The majority (58.5%) was aged between 20 and 29 years old. Up to 63.9% of FSWs were single, 62.3% attained primary school, and 68.0% had no additional occupation beside sex work. Almost all FSWs (81.2%) had children. The majority of FSWs (68.4%) were venue-based, and most (53.5%) had spent less than five years in sex work. The overall prevalence of syphilis was 51.1%; it was 2.5% for HBV, 1.4% for HCV, 42.9% for HIV and 27.4% for syphilis/HIV co-infection. The prevalence of syphilis, HIV, and syphilis + HIV co-infection was increasing with age and decreasing with the level of education. A positive association with syphilis/HIV co-infection was found in: 25 years and older (aOR = 1.82 [95% CI:1.33-2.50]), having had a genital sore in the last 12 months (aOR = 1.34 [95% CI:1.05-1.71]), and having HBsAg-positive test (aOR = 2.09 [1.08-4.08]). CONCLUSION: The prevalence of HIV and syphilis infections and HIV/syphilis co-infection are very high among FSWs in Rwanda. A strong, specific prevention program for FSWs and to avert HIV infection and other STIs transmission to their clients is needed.

Hepatitis C virus and HIV co-infection among pregnant women in Rwanda.

BACKGROUND: Hepatitis C virus (HCV) infection is a pandemic causing disease; more than 185 million people are infected worldwide. An HCV antibody (Ab) prevalence of 6.0% was estimated in Central African countries. The study aimed at providing HCV prevalence estimates among pregnant women in Rwanda. METHODS: HCV surveillance through antibody screening test among pregnant women attending antenatal clinics was performed in 30 HIV sentinel surveillance sites in Rwanda. RESULTS: Among 12,903 pregnant women tested at antenatal clinics, 335 (2.6% [95% Confidence Interval 2.32-2.87]) tested positive for HCV Ab. The prevalence of HCV Ab in women aged 25-49 years was 2.8% compared to 2.4% in women aged 15-24 years (aOR = 1.3; [1.05-1.59]); This proportion was 2.7% [2.37-2.94] in pregnant women in engaged in non-salaried employment compared to 1.2% [0.24-2.14] in those engaged in salaried employment (aOR = 3.2; [1.60-6.58]). The proportion of HCV Ab-positive co-infected with HIV was estimated at 3.9% (13 cases). Women in urban residence were more likely to be associated with HCV-infection (OR = 1.3; 95%CI [1.0-1.6]) compared to those living in rural setting. CONCLUSION: HCV is a public health problem in pregnant women in Rwanda. Few pregnant women were co-infected with HCV and HIV. Living in urban setting was more likely to associate pregnant women with HCV infection.

Hepatitis B virus and HIV co-infection among pregnant women in Rwanda.

BACKGROUND: Hepatitis B virus (HBV) affects people worldwide but the local burden especially in pregnant women and their new born babies is unknown. In Rwanda HIV-infected individuals who are also infected with HBV are supposed to be initiated on ART immediately. HBV is easily transmitted from mother to child during delivery. We sought to estimate the prevalence of chronic HBV infection among pregnant women attending ante-natal clinic (ANC) in Rwanda and to determine factors associated with HBV and HIV co-infection. METHODS: This study used a cross-sectional survey, targeting pregnant women in sentinel sites. Pregnant women were tested for hepatitis B surface antigen (HBsAg) and HIV infection. A series of tests were done to ensure high sensitivity. Multivariable logistic regression was used to identify independent predictors of HBV-HIV co-infection among those collected during ANC sentinel surveillance, these included: age, marital status, education level, occupation, residence, pregnancy and syphilis infection. RESULTS: The prevalence of HBsAg among 13,121 pregnant women was 3.7% (95% CI: 3.4-4.0%) and was similar among different socio-demographic characteristics that were assessed. The proportion of HIV-infection among HBsAg-positive pregnant women was 4.1% [95% CI: 2.5-6.3%]. The prevalence of HBV-HIV co-infection was higher among women aged 15-24 years compared to those women aged 25-49 years [aOR = 6.9 (95% CI: 1.8-27.0)]. Women residing in urban areas seemed having HBV-HIV co-infection compared with women residing in rural areas [aOR = 4.3 (95% CI: 1.2-16.4)]. Women with more than two pregnancies were potentially having the co-infection compared to those with two or less (aOR = 6.9 (95% CI: 1.7-27.8). Women with RPR-positive test were seemed associated with HBV-HIV co-infection (aOR = 24.9 (95% CI: 5.0-122.9). CONCLUSION: Chronic HBV infection is a public health problem among pregnant women in Rwanda. Understanding that HBV-HIV co-infection may be more prominent in younger women from urban residences will help inform and strengthen HBV prevention and treatment programmes among HIV-infected pregnant women, which is crucial to this population.

Drug resistance mutations after the first 12 months on antiretroviral therapy and determinants of virological failure in Rwanda.

OBJECTIVE: To evaluate HIV drug resistance (HIVDR) and determinants of virological failure in a large cohort of patients receiving first-line tenofovir-based antiretroviral therapy (ART) regimens. METHODS: A nationwide retrospective cohort from 42 health facilities was assessed for virological failure and development of HIVDR mutations. Data were collected at ART initiation and at 12 months of ART on patients with available HIV-1 viral load (VL) and ART adherence measurements. HIV resistance genotyping was performed on patients with VL ≥1000 copies/ml. Multiple logistic regression was used to determine factors associated with treatment failure. RESULTS: Of 828 patients, 66% were women, and the median age was 37 years. Of the 597 patients from whom blood samples were collected, 86.9% were virologically suppressed, while 11.9% were not. Virological failure was strongly associated with age <25 years (adjusted odds ratio [aOR]: 6.4; 95% confidence interval [CI]: 3.2-12.9), low adherence (aOR: 2.87; 95% CI: 1.5-5.0) and baseline CD4 counts <200 cells/µl (aOR 3.4; 95% CI: 1.9-6.2). Overall, 9.1% of all patients on ART had drug resistance mutations after 1 year of ART; 27% of the patients who failed treatment had no evidence of HIVDR mutations. HIVDR mutations were not observed in patients on the recommended second-line ART regimen in Rwanda. CONCLUSIONS: The last step of the UNAIDS 90-90-90 target appears within grasp, with some viral failures still due to non-adherence. Nonetheless, youth and late initiators are at higher risk of virological failure. Youth-focused programmes could help prevent further drug HIVDR development.

Cryptococcus neoformans infection in malignancy.

Cryptococcosis is an opportunistic invasive fungal infection that is well described and easily recognised when it occurs as meningitis in HIV-infected persons. Malignancy and its treatment may also confer a higher risk of infection with Cryptococcus neoformans, but this association has not been as well described. A case of cryptococcosis in a cancer patient is presented, and all cases of coincident C. neoformans infection and malignancy in adults published in the literature in English between 1970 and 2014 are reviewed. Data from these cases were aggregated in order to describe the demographics, type of malignancy, site of infection, clinical manifestations, treatment and outcomes of cryptococcosis in patients with cancer. Haematologic malignancies accounted for 82% of cases, with lymphomas over-represented compared to US population data (66% vs. 53% respectively). Cryptococcosis was reported rarely in patients with solid tumours. Haematologic malignancy patients were more likely to have central nervous system (P < 0.001) or disseminated disease (P < 0.001), receive Amphotericin B as part of initial therapy (P = 0.023), and had higher reported mortality rates than those with solid tumours (P = 0.222). Providers should have heightened awareness of the possibility of cryptococcosis in patients with haematologic malignancy presenting with infection.

The role of viral co-infection in HIV-associated non-AIDS-related cancers.

HIV-infected individuals are at increased risk for most types of cancer, including those typically classified as non-AIDS-defining cancers (NADCs). This increased risk is likely multifactorial, but a prominent risk factor for the increased rate of some cancers is co-infection with oncogenic viruses. Anal cancer, hepatocellular carcinoma, and Hodgkin lymphoma are three of the most common NADCs, and they are associated with co-infection with human papillomavirus, hepatitis B and C, and Epstein Barr virus, respectively. This review will examine the epidemiology, pathogenesis, and future trends around these virally associated NADCs frequently found in HIV-infected individuals.

Cancer Knowledge and Opportunities for Education Among HIV-Infected Patients in an Urban Academic Medical Center.

HIV-infected patients frequently present with advanced stage cancer. It is possible that late stage presentation may be related to lack of cancer knowledge and/or barriers to care. Questionnaires were administered to 285 adult HIV-infected patients to evaluate knowledge of cancer risk factors and symptoms and barriers to care between 2011 and 2012. Differences in mean and percent scores by group were assessed using a t test for independent samples and chi-square analysis, respectively. Respondents were predominantly male (64%), African-American (86%), and low income (60% < $10,000/year). Thirty-four (12%) had been diagnosed with cancer, and 169 (59%) had a family history of cancer. The mean knowledge score was 17.5 out of 24 questions (73%). Mean scores were not significantly different by sex, age, race, or income. Respondents with a college education scored significantly higher than those with less than a high school education (p < 0.01). In unadjusted analysis, a higher proportion of patients with a personal/family history of cancer (74%) scored in the highest quartile (>70% correct) compared to those without any personal history of cancer (62%) (p = 0.03). There was a higher level of cancer knowledge in this population compared to studies that have evaluated the HIV-uninfected population. Nevertheless, there were knowledge deficits, suggesting the need for further education about cancer to improve earlier detection rates and, ultimately, outcomes.

Do HIV Care Outcomes Differ by Provider Type?

BACKGROUND: We compared HIV care outcomes by HIV provider type to inform efforts to strengthen the HIV provider workforce. SETTING: United States. METHODS: We analyzed data from Center for Disease Control and Prevention's Medical Monitoring Project collected during June, 2019-May, 2021 from 6323 adults receiving HIV medical care. Provider types include infectious disease physicians only (ID physicians), non-ID physicians only, nurse practitioners only, physician assistants only, and ID physicians plus nurse practitioners and/or physician assistants (mixed providers). We measured patient characteristics, social determinants of health, and clinical outcomes, including retention in care; antiretroviral therapy prescription; antiretroviral therapy adherence; viral suppression; gonorrhea, chlamydia, and syphilis testing; satisfaction with HIV care; and HIV provider trust. RESULTS: Compared with patients of ID physicians, higher percentages of patients of other provider types had characteristics and social determinants of health associated with poor health outcomes and received HIV care at Ryan White HIV/AIDS Program-funded facilities. After accounting for these differences, most outcomes were not meaningfully different; however, higher percentages of patients of non-ID physicians, nurse practitioners, and mixed providers were retained in care (6.5, 5.6, and 12.7 percentage points, respectively) and had sexually transmitted infection testing in the past 12 months, if sexually active (6.9, 7.4, and 13.5 percentage points, respectively). CONCLUSION: Most HIV outcomes were equivalent across provider types. However, patients of non-ID physicians, nurse practitioners, and mixed providers were more likely to be retained in care and have recommended sexually transmitted infection testing. Increasing delivery of comprehensive primary care by ID physicians and including primary care providers in ID practices could improve HIV primary care outcomes.

Unmet Needs for Ancillary Services by Provider Type Among People With Diagnosed Human Immunodeficiency Virus.

Background: Unmet needs for ancillary services are substantial among people with human immunodeficiency virus (PWH), and provider type could influence the prevalence of unmet needs for these services. Methods: Data from a national probability sample of PWH were analyzed from the Centers for Disease Control and Prevention's Medical Monitoring Project. We analyzed 2019 data on people who had ≥1 encounter with a human immunodeficiency virus (HIV) care provider (N = 3413) and their care facilities. We assessed the proportion of needs that were unmet for individual ancillary services, overall and by HIV care provider type, including infectious disease (ID) physicians, non-ID physicians, nurse practitioners, and physician assistants. We calculated prevalence differences (PDs) with predicted marginal means to assess differences between groups. Results: An estimated 98.2% of patients reported ≥1 need for an ancillary service, and of those 46% had ≥1 unmet need. Compared with patients of ID physicians, needs for many ancillary services were higher among patients of other provider types. However, even after adjustment, patients of non-ID physicians had lower unmet needs for dental care (adjusted PD, -5.6 [95% confidence interval {CI}, -9.9 to -1.3]), and patients of nurse practitioners had lower unmet needs for HIV case management services (adjusted PD, -5.4 [95% CI, -9.4 to -1.4]), compared with patients of ID physicians. Conclusions: Although needs were greater among patients of providers other than ID physicians, many of these needs may be met by existing support systems at HIV care facilities. However, additional resources may be needed to address unmet needs for dental care and HIV case management among patients of ID physicians.

Cefazolin-induced hemolytic anemia in septic arthritis: A case report.

A 50-year-old woman living with untreated HIV and injection drug use presented with right shoulder pain. The shoulder exam and computed tomography (CT) scan were concerning for septic arthritis. She was started on empiric vancomycin and cefepime and underwent right shoulder debridement and humeral head resection. Bone cultures grew methicillin sensitive Staphylococcus aureus (MSSA); empiric broad-spectrum antibiotics were changed to cefazolin. The patient subsequently developed severe anemia refractory to blood transfusions approximately 6 days later. Further evaluation disclosed hemolytic anemia attributable to cefazolin. Antibiotic therapy was switched from cefazolin to daptomycin, and the patient was started on prednisone. She had sustained improvement in hemoglobin values above 6 g/dL without requiring further transfusions prior to hospital discharge. Drug-induced immune hemolytic anemia from cefazolin is rare but has been reported primarily in the perioperative setting. Here, we present a case following initiation of treatment for septic arthritis.

Fulminant Hepatic Failure as the Initial Presentation of Hodgkin Lymphoma in 4 Patients With Human Immunodeficiency Virus.

In the era of antiretroviral therapy (ART), Hodgkin Lymphoma (HL) is a common non-AIDS-defining cancer with increasing incidence in people with human immunodeficiency virus (PWH). Through review of these cases, we identify clinical patterns such as declining CD4 count despite ART, hyperbilirubinemia and recurrent fever, which preceded diagnosis. Identifying these important signs and symptoms may lead to earlier diagnosis and initiation of therapy. Fulminant hepatic failure limits the ability to give standard of care chemotherapy, likely jeopardizing outcomes in this patient population. Alternative bridging therapies should be considered until hepatic function improves.