Since the discovery of CCR5 as a coreceptor for HIV entry, there has been interest in blockade of the receptor for treatment and prevention of HIV infection. Although several CCR5 antagonists have been evaluated in clinical trials, only maraviroc has been approved for clinical use in the treatment of HIV-infected patients. The efficacy, safety and resistance profile of CCR5 antagonists with a focus on maraviroc are reviewed here along with their usage in special and emerging clinical situations. Despite being approved for use since 2007, the optimal use of maraviroc has yet to be well-defined in HIV and potentially in other diseases. Maraviroc and other CCR5 antagonists have the potential for use in a variety of other clinical situations such as the prevention of HIV transmission, intensification of HIV treatment and prevention of rejection in organ transplantation. The use of CCR5 antagonists may be potentiated by other agents such as rapamycin which downregulate CCR5 receptors thus decreasing CCR5 density. There may even be a role for their use in combination with other entry inhibitors. However, clinical use of CCR5 antagonists may have negative consequences in diseases such as West Nile and Tick-borne encephalitis virus infections. In summary, CCR5 antagonists have great therapeutic potential in the treatment and prevention of HIV as well as future use in novel situations such as organ transplantation. Their optimal use either alone or in combination with other agents will be defined by further investigation.
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). 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. 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]). 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.
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. 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. 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. 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.
1 February 2012 in JAIDS Journal of Acquired Immune Deficiency Syndromes
Background: Monitoring and evaluation of antiretroviral treatment (ART) scale-up has been challenging in resource-limited settings. We describe an innovative cell-phone-based and internet-based reporting system (TRACnet) utilized in Rwanda. Methods: From January 2004 to June 30, 2010, all health facilities with ART services submitted standardized monthly aggregate reports of key indicators. National cohort data were analyzed to examine trends in characteristics of patients initiating ART and cumulative cohort outcomes. Estimates of HIV-infected patients eligible for ART were obtained from Joint United Nations Program on HIV/AIDS (Estimation and Projection Package-Spectrum, 2010). Results: By June 30, 2010, 295 (65%) of 451 health centers, District and referral hospitals provided ART services; of these, 255 (86%) were located outside Kigali, the capital. Cell phone–based and internet-based reporting was used by 253 (86%) and 42 (14%), respectively. As of June 30, 2010, 83,041 patients were alive on ART, 6171 (6%) had died, and 9621 (10%) were lost-to-follow-up. Of those alive on ART, 7111 (8.6%) were children, 50,971 (61.4%) were female, and 1823 (2.2%) were on a second-line regimen. The proportion of all patients initiating ART at World Health Organization clinical stages 3 and 4 declined from 65% in 2005 to 27% in 2010. National ART coverage of eligible patients increased from 13% in 2005 to 79% in 2010. Conclusions: Rwanda has successfully expanded ART access and achieved high national ART coverage among eligible patients. TRACnet captured essential data about the ART program during rapid scale-up. Cell phone-based and internet-based reporting may be useful for monitoring and evaluation of similar public health initiatives in other resource-limited settings.
24 September 2021 in Open Forum Infectious Diseases
Human herpesvirus 6 (HHV-6) reactivation can occur in patients who are highly immunosuppressed, including those who have undergone hematopoietic stem cell transplantation (HSCT). HHV-6 encephalitis is a severe manifestation that is well described in the HSCT population. Chimeric antigen receptor T-cell (CAR-T) therapy is a novel cancer-directed immunotherapy that results in severe immunosuppression. Patients undergoing CAR-T therapy may be at risk for HHV-6 encephalitis, which can be difficult to distinguish from a common adverse effect of CAR-T therapy, neurotoxicity. Herein, we describe 2 patients diagnosed with HHV-6 encephalitis after CAR-T therapy and discuss the diagnostic approach and differential diagnosis for altered mental status after CAR-T therapy. Diagnosing HHV-6 encephalitis can be difficult in this patient population as altered mental status is common after CAR-T therapy and may be attributed to CAR-T-associated neurotoxicity.
Objective: To determine mortality associated with a new cancer diagnosis in an urban, predominantly African–American, HIV-infected population. Design: Retrospective cohort study. Methods: All HIV-infected patients diagnosed with cancer between 1 January 2000 and 30 June 2010 were reviewed. Mortality was examined using Kaplan–Meier estimates and Cox proportional hazards models. Results: There were 470 cases of cancer among 447 patients. Patients were predominantly African–American (85%) and male (79%). Non-AIDS-defining cancers (NADCs, 69%) were more common than AIDS-defining cancers (ADCs, 31%). Cumulative cancer incidence increased significantly over the study period. The majority (55.9%) was taking antiretroviral therapy (ART) at cancer diagnosis or started afterward (26.9%); 17.2% never received ART. Stage 3 or 4 cancer was diagnosed in 67%. There were 226 deaths during 1096 person years of follow-up, yielding an overall mortality rate of 206 per 1000 person years. The cumulative mortality rate at 30 days, 1 year, and 2 years was 6.5, 32.2, and 41.4%, respectively. Mortality was similar between patients on ART whether they started before or after the cancer diagnosis but was higher in patients who never received ART. In patients with a known cause of death, 68% were related to progression of the underlying cancer. Conclusion: In a large cohort of urban, predominantly African–American patients with HIV and cancer, many patients presented with late-stage cancer. There was substantial 30-day and 2-year mortality, although ART had a significant mortality benefit. Deaths were most often caused by progression of cancer and not from another HIV-related or AIDS-related event.