HIV Co-infected Patients Research Articles

Model-Based Assessment of Variability in Isoniazid Pharmacokinetics and Metabolism in Patients Co-Infected With Tuberculosis and HIV: Implications for a Novel Dosing Strategy.

Tuberculosis is the most common cause of death in HIV-infected patients. Isoniazid is used as a first-line drug to treat tuberculosis infection. However, variability in isoniazid pharmacokinetics can result in hepatotoxicity or treatment failure. Determination of clinical factors affecting isoniazid pharmacokinetics and metabolic pathways in HIV co-infected patients is therefore critical. Plasma levels of isoniazid, acetyl-isoniazid, and isonicotinic acid from 63 patients co-infected with tuberculosis and HIV were analyzed by liquid chromatography with tandem mass spectrometry followed by nonlinear mixed-effects modeling. Patients were genotyped to determine acetylator status. Patients were either on concomitant efavirenz-based antiretroviral therapy or HIV treatment naïve. Clearances of isoniazid were 1.3-fold and 2.3-fold higher in intermediate and rapid acetylators, respectively, compared with slow acetylators. Patients on concomitant efavirenz-based antiretroviral therapy had 64% and 80% higher population predicted clearances of acetyl-isoniazid and isonicotinic acid, respectively, compared with patients who were HIV treatment naïve. Both sex and CD4 cell count affected the bioavailability of isoniazid. Variability in isoniazid exposure could be reduced by dose adaptions based on acetylator type and sex in addition to the currently used weight bands. A novel dosing strategy that has the potential to reduce isoniazid-related toxicity and treatment failure is presented.

Examination of using alcohol to cope, depressive symptoms, and perceived social support in persons with HIV and Hepatitis C

ABSTRACT Depression is common among people living with HIV (PLWH) and some likely turn to alcohol to cope with this emotional distress. Using alcohol to cope is associated with increased alcohol use, persistent longitudinal alcohol use, and alcohol-related problems. This association is particularly concerning among PLWH who are co-infected with Hepatitis C (HCV) because alcohol adds to the damage already caused by HCV. Despite data showing the associated risks of using alcohol to cope, scant research has examined factors that might contribute to coping-based alcohol use in HIV-HCV patients, such as limited social support. Baseline data from a randomized trial of strategies to reduce alcohol use in co-infected HIV and HCV adult patients (n=110) were analyzed. Multiple linear regression models were used to estimate the association between using alcohol to cope, depression, and four aspects of social support, controlling for demographic variables. Results showed that using alcohol to cope was not significantly correlated with social support but was significantly correlated with depressive symptoms. In fact, depressive symptoms and severity of alcohol consumption accounted for nearly 45% of the variance related to coping-based alcohol use. These data highlight the central role of depression in the coping motives-alcohol use relationship among co-infected patients.

Determination of anti-leishmanial drugs efficacy against Leishmania martiniquensis using a colorimetric assay

Autochthonous leishmaniasis caused by Leishmania martiniquensis cases in Thailand have dramatically increased in the recent years. L. martiniquensis infection primarily occurs in immunocompromised patients, especially AIDS patients. In Thailand, amphotericin B is the only drug available for leishmaniasis treatment, and some patients relapse after amphotericin B therapy. Moreover, the efficacy of anti-leishmanial drugs against L. martiniquensis has not been evaluated to date. In this study, we determined the efficacy of various anti-leishmanial drugs against the promastigote and intracellular amastigote stages of L. martiniquensis using a colorimetric assay. Two strains (CU1 and CU1R1) were isolated from leishmaniasis HIV co-infected patient from Songkhla province, southern Thailand. The CU1 strain was isolated from the patient in 2011, and CU1R1 was isolated from the same patient in 2013, when he was diagnosed as relapse leishmaniasis. The third strain (LSCM1) used in this study has been isolated from immunocompetent patient from Lamphun province, northern Thailand. All strains were identified as L. martiniquensis by sequencing of ribosomal RNA ITS-1 and large subunit of RNA polymerase II gene. Bioassays have been conducted both with promastigote and intracellular amastigote stages of the parasite. All L. martiniquensis strains have been tested against amphotericin B, miltefosine and pentamidine to determine the efficacy of the drugs against the parasite by using a PrestoBlue. The efficacy of miltefosine and pentamidine exhibit no significant difference between each stage of L. martiniquensis among all strains. Surprisingly, the promastigote and intracellular amastigote of the CU1R1 isolate, which was isolated from a relapsed patient after amphotericin B treatment, exhibited a two-fold increased inhibitory concentration (IC50) against amphotericin B compared with other strains, and the difference was statistically significant (p < 0.05). Moreover, intracellular amastigotes isolated from CU1R1 exhibited slightly increased susceptibility to amphotericin B compared with the promastigote (p < 0.05). The result of this experiment is a scientific evident to support that in case of relapsed leishmaniasis caused by L. martiniquensis, increasing dosage of amphotericin B is essential. Moreover, this study also determined efficacy of other anti-leishmanial drugs for treatment the leishmaniasis in Thailand in case of these drugs are available in the country and the clinicians should have alternative drugs for treatment leishmaniasis in Thailand apart from amphotericin B.

Evaluating the Effect of Standard of Care Treatment on Burden of Chronic HepatitisB: A Retrospective Analysis of the United States Veterans Population.

IntroductionThis study aimed to characterize chronic hepatitis B (CHB)-infected patients and estimate the association between nucleos(t)ide analogue (NA) persistence and economic outcomes using data from the Veterans Health Administration (VHA) database.MethodsPatients (at least 18 years of age) with two or more claims for CHB and at least one pharmacy claim for NA were identified using VHA data from 1 April 2013 to 31 March 2018. The index date was the first NA prescription fill date during 1 October 2014 to 31 March 2017. Persistence and non-persistence to NA treatment were assessed during the first 2 years post index date. Non-persistence was defined as at least one failure to refill medication within 30 days from the run-out date. Generalized linear models were used to compare health care utilization and costs between persistent and non-persistent patients.ResultsAmong patients treated with NAs (N = 2368), 1428 (60%) were CHB mono-infected and 748 (32%) were HIV co-infected. Total costs per patient per year (PPPY) were $39,240, $29,957, and $55,220 PPPY for NA-treated, mono-infected, and HIV co-infected patients, respectively. An inception cohort of 564 patients (24%), without a NA prescription in the 6 months pre-index period and at least 2 years of follow-up, was created. Persistence among the inception cohort was 29% for first year and 14% for first 2 years. After adjustment for baseline differences, persistent patients had lower cumulative overall health care costs compared to non-persistent patients, with a net cost saving of $851 (p > 0.05) in the first 2 years.ConclusionCHB is associated with considerable economic burden. We observed suboptimal persistence to NAs which decreased over time. Short-term savings could be generated for CHB-infected patients when they remain persistent to NAs.Electronic supplementary materialThe online version of this article (10.1007/s12325-020-01240-1) contains supplementary material, which is available to authorized users.

Micro-elimination of hepatitis C virus.

HCV affects about 71 million people worldwide with 1.75million new infections a year, mainly associated with healthcare, blood transfusion before screening of donors and drug use. Hepatitis C is a systemic disease with hepatic and extrahepatic manifestations resulting in increased morbidity and mortality in HCV-infected patients compared to cured or uninfected individuals. The goal of eliminating hepatitis C by 2030 is based on the following three main actions: strengthening and increasing outreach screening; increasing access to treatment; and improving prevention. Although the tools and the targets of HCV elimination have now been well established, micro-elimination, a cure in high-risk populations, is possible, but has not been achieved. These populations are mainly migrants, prisoners, drug users, HIV co-infected patients and psychiatric patients. New tools must be developed to achieve micro-elimination, in particular, rapid diagnostic orientation tests for better screening, delocalization of healthcare services to improve access to care, and training physicians to raise awareness of the disease, increase understanding of its pathogenesis and provide information on the availability of safe and effective treatment to cure chronic infection and reverse hepatic and extrahepatic manifestations. Thus, while the goal of complete elimination of hepatitis C virus was feasible in Western countries, it was more difficult in high-prevalence countries where improvement in the detection of chronic infection (with rapid serological and virological diagnostic tests), outsourcing of diagnostic and therapeutic care and access to direct oral antivirals are urgently needed.

Xpert MTB/RIF Ultra versus Xpert MTB/RIF for the diagnosis of tuberculous meningitis: a prospective, randomised, diagnostic accuracy study

SummaryBackgroundXpert MTB/RIF Ultra (Xpert Ultra) might have higher sensitivity than its predecessor, Xpert MTB/RIF (Xpert), but its role in tuberculous meningitis diagnosis is uncertain. We aimed to compare Xpert Ultra with Xpert for the diagnosis of tuberculous meningitis in HIV-uninfected and HIV-infected adults.MethodsIn this prospective, randomised, diagnostic accuracy study, adults (≥16 years) with suspected tuberculous meningitis from a single centre in Vietnam were randomly assigned to cerebrospinal fluid testing by either Xpert Ultra or Xpert at baseline and, if treated for tuberculous meningitis, after 3–4 weeks of treatment. Test performance (sensitivity, specificity, and positive and negative predictive values) was calculated for Xpert Ultra and Xpert and compared against clinical and mycobacterial culture reference standards. Analyses were done for all patients and by HIV status.FindingsBetween Oct 16, 2017, and Feb 10, 2019, 205 patients were randomly assigned to Xpert Ultra (n=103) or Xpert (n=102). The sensitivities of Xpert Ultra and Xpert for tuberculous meningitis diagnosis against a reference standard of definite, probable, and possible tuberculous meningitis were 47·2% (95% CI 34·4–60·3; 25 of 53 patients) for Xpert Ultra and 39·6% (27·6–53·1; 21 of 53) for Xpert (p=0·56); specificities were 100·0% (95% CI 92·0–100·0; 44 of 44) and 100·0% (92·6–100·0; 48 of 48), respectively. In HIV-negative patients, the sensitivity of Xpert Ultra was 38·9% (24·8–55·1; 14 of 36) versus 22·9% (12·1–39·0; eight of 35) by Xpert (p=0·23). In HIV co-infected patients, the sensitivities were 64·3% (38·8–83·7; nine of 14) for Xpert Ultra and 76·9% (49·7–91·8; ten of 13) for Xpert (p=0·77). Negative predictive values were 61·1% (49·6–71·5) for Xpert Ultra and 60·0% (49·0–70·0) for Xpert. Against a reference standard of mycobacterial culture, sensitivities were 90·9% (72·2–97·5; 20 of 22 patients) for Xpert Ultra and 81·8% (61·5–92·7; 18 of 22) for Xpert (p=0·66); specificities were 93·9% (85·4–97·6; 62 of 66) and 96·9% (89·5–91·2; 63 of 65), respectively. Six (22%) of 27 patients had a positive test by Xpert Ultra after 4 weeks of treatment versus two (9%) of 22 patients by Xpert.InterpretationXpert Ultra was not statistically superior to Xpert for the diagnosis of tuberculous meningitis in HIV-uninfected and HIV-infected adults. A negative Xpert Ultra or Xpert test does not rule out tuberculous meningitis. New diagnostic strategies are urgently required.FundingWellcome Trust and the Foundation for Innovative New Diagnostics.

SLC11A1 (rs3731865) polymorphism and susceptibility to visceral leishmaniasis in HIV-coinfected patients from Northeastern Brazil.

Following the emergence of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), the number of visceral leishmaniasis-HIV (VL-HIV) coinfections has increased worldwide, mainly in Brazil. The development of clinical forms of VL can be influenced by nutritional status, age, and host genetic factors, which are important variables determining susceptibility to disease. There are no studies with a candidate gene approach assayed directly in the VL-HIV-coinfected population. Herein, we determined and analyzed the associations of SLC11A1, LECT2, CCL1, CCL16, and IL4 genetic polymorphisms with susceptibility to VL-HIV coinfection in Northeastern Brazil. We analyzed 309 DNA samples extracted from the peripheral blood of HIV patients, and clinical and hematological data were collected from medical records. The diagnosis of VL was confirmed in 110 out of 309 patients; genotyping was carried out by TaqMan assays afterwards. Our results confirmed the association between the SLC11A1 polymorphism (rs3731865) and VL-HIV coinfection (p = 0.0206, OR 1.8126, 95% CI 1.1050-2.9727). In addition, the SLC11A1 genotype GG (p= 0.0050, OR 3.0395, 95% CI 1.4065-6.5789) and CD4+ T lymphocyte count (p= 0.0030, OR 0.9980, 95% CI 0.9970-0.9990) were associated with VL-HIV coinfection in a multivariate model. The polymorphism of the SLC11A1 gene (rs3731865) was associated with VL-HIV coinfection, suggesting a possible genetic mechanism involved in the susceptibility to VL in HIV patients. This finding can suggest new therapeutic targets and genetic markers for the VL-HIV-coinfected population.

Multiple Relapses of Visceral Leishmaniasis in HIV Co-Infected Patients: A Case Series from Ethiopia

BackgroundHuman visceral leishmaniasis (VL) is a life-threatening protozoan disease caused by parasites belonging to the Leishmania donovani complex. Ethiopia has the highest VL-HIV co-infection rate in the world, with several of these patients presenting with repeated episodes of VL disease (ie, relapse). However, we lack data on how HIV patients with multiple VL relapse present clinically, and whether they continue to respond to currently available medicines. MethodsThe medical records of VL-HIV co-infected patients with multiple VL relapses at the Leishmaniasis Treatment and Research Center in Gondar, Ethiopia, between June 2012 and June 2016 were retrieved. Variables on their clinical and laboratory profiles were collected. Descriptive analysis was done to show the characteristics of the VL episodes. ResultA total of 48 VL episodes in 12 patients were identified, the median number of episodes per patient was 5 (interquartile range, 4–8 episodes). The median time to relapse was 5 months (interquartile range, 3–5.5 months). Splenomegaly was present in 47 of the episodes (98%), fever or other accompanying symptoms were present in only 66% (32 out of 48). The median tissue parasite grade at VL diagnosis was 6+ (interquartile range, 5+– 6+). All patients were on antiretroviral therapy. The median duration of treatment per episode was 2 months (interquartile range, 2–2 months). All patients achieved parasitological cure at discharge at each episode. ConclusionsMultiple recurrences of VL diseases were observed in HIV co-infected patients. With recurrent episodes, splenomegaly was found to be the main manifestation, whereas fever was less common. These patients came with recurrence of diseases in <6 months and required prolonged treatment to achieve cure.Further research on prediction, prevention, and better management options for recurrent VL is needed. ORCID ID: https://orcid.org/0000-0002-1410-0454. (Curr Ther Res Clin Exp. 2020; 81:XXX–XXX)

Impact of HIV co-infection in patients presenting with hepatic hydatid disease

Background: HIV and echinococcus granulosis (EG) co-infection, whilst rare globally, still affects communities in Southern Africa and appears to be increasing. In this, the first comparative study between patients with hepatic hydatid disease (HHD) with and without HIV co-infection in the same population, the hypothesis from case studies that co-infection-associated immune modulation may lead to a more severe clinical presentation of HHD was assessed. Material & Methods: Patients presenting at the Surgical Gastroenterology unit, Groote Schuur Hospital, South Africa with HHD between 2012 and 2018, and for whom the HIV status was known, were included. Demographic characteristics, clinical parameters and serological and laboratory tests were compared in patients, with and without HIV co-infection. Results: HIV prevalence in the study population (n=38) was 50%. Females predominated in both groups (16/19 HIV+ and 14/19 HIV-). HIV+ patients tended to be younger (median age 32 vs. 39; p=0.181) with a lower BMI (median 23.6 vs. 25.4; p=0.126). No significant clinical differences were found. Abdominal pain was the most common symptom (15/19 in both groups) and abdominal tenderness the most common clinical finding (9/19 HIV+ and 10/19 HIV- patients). EG serology was positive in only 10/19 HIV+ patients, compared to 16/19 HIV- patients (p<0.060). Laboratory findings were similar, however conjugated bilirubin was more often raised in HIV+ patients (p<0.064). Conclusion: Whilst supporting previous reports of an impaired EG antibody response in HIV+ patients, this study refutes the hypothesis of a more severe clinical presentation. The HIV co-infection rate was higher than the prevalence in the general South African population of 12.6%, indicating that HIV is an important factor in HHD infection. Most patients were controlled on anti-retrovirals, suggesting disease severity might be contained by HIV suppression. Urgent surgery should be dictated by disease severity rather than the presence of HIV co-infection.

Men and Women Have an Equal Oropharyngeal and Anorectal Chlamydia trachomatis Bacterial Load: A Comparison of 3 Anatomic Sites.

The Chlamydia trachomatis bacterial load could have impact on transmission and sequelae. This is the first study providing comparison of C. trachomatis load at 3 anatomic sites estimated by cycle quantification (Cq) values. Data from 7900 C. trachomatis-positive samples were included (2012-2018). Cq value was used as an inversely proportional measure for C. trachomatis load. Multivariable linear regression analyses assessed differences in mean Cq values. Vaginal swabs had the lowest Cq values (31.0) followed by urine (32.5), anorectal swabs (34.0), and oropharyngeal swabs (36.8) (P < .001). Men and women had similar oropharyngeal (36.4 vs 37.3; P = .13) and anorectal (34.2 vs 33.9; P = .19) Cq values. Men (32.2) and women (30.7) aged <25 years had lower urogenital Cq values than men (32.8) and women (31.9) aged ≥25 years (P < .001). HIV-positive patients had higher urogenital Cq values than HIV-negative patients (33.8 vs 32.6; P < .03). Men and women have a similar C. trachomatis load at extragenital locations arguing for similar transmission potential and clinical relevance. Older patients and HIV-coinfected patients had lower C. trachomatis load, suggesting exposure to previous C. trachomatis infections potentially leading to partial immunity reducing load.

Genital Kaposi sarcoma in a HIV and syphilis co-infected patient: case presentation

BackgroundKaposi sarcoma, as an epidemiological factor, is associated with acquired immunodeficiency syndrome (AIDS) and it is related to human herpes virus (HHV-8), as well as a higher prevalence in males and non-genital involvement. Vulvar localization is quite infrequent; therefore it may be considered in the differential diagnosis of genital lesions, especially in HIV patients.Case presentationWe describe the atypical presentation of a female HIV patient with multiple comorbidities, with the clinical manifestation of Kaposi sarcoma (KS) in a vulvar region that was initially diagnosed as a syphilitic gumma. The patient underwent a biopsy of the lesion, and histopathology revealed a Kaposi sarcoma.DiscussionThis case reinforces that the pathogenesis of Kaposi sarcoma is still unclear and that probably multiple factors, regarding both the virus and the patient characteristics may lead to carcinogenesis. Conclusion: It is imperative to seek more excellent knowledge about this disease, to facilitate the diagnosis, to warrant the appropriate treatment and to improve the prognosis of the patient, especially the genital lesions.

Determinants of mortality among patients with drug-resistant tuberculosis in northern Nigeria

BackgroundDrug-Resistant tuberculosis (DR-TB) is estimated to cause about 10% of all TB related deaths. There is dearth of data on determinants of DR-TB mortality in Nigeria. Death among DR-TB treated cohorts in Nigeria from 2010 to 2013 was 30%, 29%, 15% and 13% respectively. Our objective was to identify factors affecting survival among DR-TB patients in northern Nigeria.MethodsDemographic and clinical data of all DR-TB patients enrolled in Kano, Katsina and Bauchi states of Nigeria between 1st February 2015 and 30th November 2016 was used. Survival analysis was done using Kaplan-Meier and multiple regression with Cox proportional hazard modeling.ResultsMean time to death during treatment is 19.2 weeks and 3.9 weeks among those awaiting treatment. Death was recorded among 38 of the 147 DR-TB patients assessed. HIV co-infection significantly increased probability of mortality, with an adjusted hazard ratio (aHR) of 2.35, 95% CI: 1.05–5.29, p = 0.038. Treatment delay showed significant negative association with survival (p = 0.000), not starting treatment significantly reduced probability of survival with an aHR of 7.98, 95% CI: 2.83–22.51, p = 0.000. Adjusted hazard ratios for patients started on treatment more than eight weeks after detection or within two to four weeks after detection, was beneficial though not statistically significant with respective p-values of 0.056 and 0.092. The model of care (facility vs. community-based) did not significantly influence survival.ConclusionBoth HIV co-infected DR-TB patients and DR-TB patients that fail to start treatment immediately after diagnosis are at significant risk of mortality. Our study showed no significant difference in mortality based on models of care. The study highlights the need to address programmatic and operational issues pertaining to treatment delays and strengthening DR-TB/HIV co-management as key strategies to reduce mortality.

Sustained virological response at week 12 after interferon-free therapy as criterion for HCV cure definition: Validation in a real-life cohort of HIV-coinfected patients

IntroductionSustained virological response (SVR) 12 weeks after the end-of-therapy (EOT) has been correlated with SVR24 for HCV-monoinfection. We aim to validate SVR12 as criterion for definition of HCV cure in HIV-coinfected patients treated with all-oral direct-acting antivirals (DAA). MethodsProspectively observational study including HIV/HCV-coinfected subjects who received DAA and had HCV-RNA measures at weeks 12 and 24 after EOT. Every patient who took ≥1 drug dose was analyzed. ResultsDAA were prescribed to 423 patients, of whom 387 had HCV-RNA measures both at weeks 12 and 24 after EOT. SVR12 was confirmed in 379/387 patients, while SVR24 was confirmed in 377/387 subjects. The positive-predictive-value (PPV) of SVR12 for SVR24 was 99.5% (95%CI: 98.1–99.9). One of the recurrences was clinically suspected to be a late relapse. ConclusionsSVR12 has a high PPV for HCV cure in HIV/HCV-coinfection, though further follow-up could be necessary for those with deeper immunosuppression.

361. Residual Lamivudine-Resistant Hepatitis B Virus Detected on Next-Generation Sequencing of Treatment-Experienced HIV Patients Failing Antiretrovirals

BackgroundHepatitis B is highly prevalent in the Philippines, with 17% of the population infected. With the fastest-growing HIV epidemic in the Asia-Pacific, 12% of HIV patients are HBsAg reactive. With the use of lamivudine and tenofovir-based antiretrovirals (ARVs), hepatitis B virus (HBV) treatment in co-infected HIV patients is not usually an issue. However, there is a potential to develop HBV resistance when patients are switched off tenofovir when antiretroviral resistance develops. With high rates of acquired K65R tenofovir resistance, the potential for inadvertently causing re-emergence of lamivudine-resistant HBV is present. We report two HIV patients with residual whole-genome HBV with lamivudine and telbivudine resistance mutations.MethodsAs part of a surveillance study on acquired drug resistance in the Philippines, samples with an HIV viral load >1,000 copies underwent Sanger sequencing of RT and PR for genotyping and HIV drug-resistance testing. Near-whole-genome next-generation sequencing (NGS) for HIV using Illumina HiSeq was also performed on these samples.ResultsTwo patients had coincidental whole-genome amplification of HBV on NGS (Table 1). HBV serology for both showed reactive anti-HBsAg and non-reactive HBsAg and Anti-HBc. The two HBV samples were genotype A and were resistant to lamivudine and telbivudine, with intermediate resistance to entecavir.ConclusionResidual HBV may be present in patients on ARVs. Antibody responses for HBV serology may not be very reliable in highly immunosuppressed patients. The potential of lamivudine-resistant HBV to emerge when HIV patients are shifted off tenofovir due to resistance in patients should be considered when deciding on second-line ARVs. Disclosures All authors: No reported disclosures.

1342. Impact of HIV Infection on Treatment Outcome of New Tuberculosis Patients Attending Tuberculosis and Antiretroviral Treatment Services in the Community-Based Hospital, Thailand: A Retrospective Cohort Study

BackgroundTuberculosis (TB) and HIV are one of the significant public health problems in Thailand, and an estimated 15,000 individuals have a dual infection. Both HIV and TB each disease speeds up the progression of each other. TB is the leading cause of death in HIV-infected individuals, and HIV coinfected TB patients have disease-specific, and treatment affected their treatment outcomes. There is insufficient evidence on issues of TB and HIV co-infection patients received treatment. This study aimed to assess the impact of HIV status on treatment outcome of TB patients.MethodsWe conducted a retrospective cohort study among TB patients who registered to service at Chaophraya Abhaibhubejhr Hospital, Prachin Buri, Thailand from October 1, 2017 to October 31, 2018. All patients’ demographic data, diagnosis, and treatment were retrieved. Clinical characteristics, treatment outcome, and factors associated with treatment outcome were analyzed.ResultsThere were 49 (10.65%) HIV among 460 TB patients with a median (IQR) age of 44 (32–61) years old and 65.2% were males. Disseminated TB and extrapulmonary TB were higher in HIV coinfected group (P < 0.001). All pulmonary TB patients’ lower lobe involvement was higher in HIV coinfected group (62.50 vs. 36.00, P = 0.001). In HIV coinfected group median CD4 was 134 cell/mm3 (IQR 19–294), 66.67% were diagnosed HIV infection after TB diagnosis, the median time from TB diagnosed to antiretroviral was 29 days (IQR 21–48). The overall treatment success rate was 93.04%; the treatment success rate was similar in HIV coinfected TB patients (89.80%) and non- HIV-infected patients (93.43%) (P = 0.66).Adverse drug reactions were higher in HIV coinfected group (44.89% vs 12.41%) (P < 0.001). By multiple stepwise logistic regression, factors associated with anti-TB drug adverse reactions were having HIV infection (OR 7.99; 95% CI 3.73–17.10, P < 0.001), Age >60 years (OR 2.64; 95% CI 1.43–4.87, P = 0.002) and female sex (OR 1.97; 95% CI 1.11–3.52, P = 0.02).ConclusionThere is a high TB treatment success rate among patients who have treated for TB, but adverse drug events in HIV co-infected TB patients is higher than that observed in non-HIV-infected patients. Disclosures All authors: No reported disclosures.

PROFILE OF HCV GENOTYPES AND HIV-SUBTYPES AMONG HIV-COINFECTED PATIENTS IN SOUTHERN BRAZIL.

Hepatitis B and C virus (HBV and HCV) are the two most common infections among human immunodeficiency virus (HIV)-infected patients. To identify the frequency of HIV subtypes and HCV genotypes in HIV-coinfected patients. A cross-sectional and retrospective study was carried out into two reference centers in Southern Brazil between January 1, 2002 and June 30, 2016. The Abbott Real Time HCV Genotype II system was used for routine diagnostics to determine the HCV genotype based on dual-target real-time PCR. Proviral HIV-1 RNA was extracted from serum samples and fragments of the pol gene were generated by PCR. The HIV-1 PT and RT gene sequences were submitted to Maximum Likelihood Phylogenetic analysis by collecting reference sequences from the HIV-1 group M subtype of the Los Alamos database. During the study period, 3340 patients with HIV were diagnosed at both referral centers, of which 4.97% (166/3340) had HBV and/or HCV coinfection. Seroprevalence of HIV-HBV, HIV-HCV and HIV-HBV-HCV was 37.4%, 58.4%, and 4.2%, respectively. HIV-HCV-coinfected patients had a lower median nadir CD4+ T-cell count when compared to HIV-HBV-coinfected patients (P=0.01). Among those coinfected with HCV, HCV-1 (HCV-1) and HCV-3 (HCV-3) genotypes were the most prevalent, being detected in 73.8% and 21.4%, respectively. Among the HCV-1 coinfected patients, 79.3% and 20.1% had subtypes 1a and 1b, respectively. HIV subtype B was the most prevalent in HIV-coinfected patients. There was no significant difference regarding nadir CD4+ T-cell count and HIV viral load when compared to coinfected with HCV-1 with HCV-3, as well as those co-infected with HCV-1a with HCV-1b. In the present study, a higher frequency of subtype B of HIV and HCV-1 were found in HIV-coinfected patients. Further larger-scale and long-term studies are needed to better understand the effect of HCV genotypes in HIV-infected patients.

1996 Rectal Syphilis Presenting as Painless Hematochezia

INTRODUCTION: Diagnosing syphilis is challenging and rectal syphilis is a rare presentation. Patients with rectal syphilis can be asymptomatic or have anal pruritus, tenesmus, urgency of defecation, or anal discharge. We describe a case of rectal syphilis presenting with painless hematochezia. CASE DESCRIPTION/METHODS: A 40-year-old man with a history of HIV not on antiretroviral therapy and multiple sexually transmitted diseases presented with 7 days of painless hematochezia. He reported that 17 years ago he was infected with Chlamydia, gonorrhea and syphilis, which were all treated. He last had anal intercourse one-year prior. Starting 8 months ago, the patient had daily 7–10 non-bloody formed bowel movements that decreased the week prior to presentation to 3–5 bowel movements daily when his hematochezia began. Over the past month he has had progressive fatigue limiting his functional capacity and a 10-lb weight loss. He did not have nausea, vomiting, abdominal pain, constipation, or fever. Upon presentation, vital signs were within normal limits. He was well-developed and well-nourished with unremarkable abdominal, perianal and digital rectal examinations. CBC showed normocytic anemia. CD4 count was 204 with HIV viral load of 1.5 million copies/mL. CMV viral load was undetectable. Testing for Chlamydia and gonorrhea were negative. Notably his rapid plasma regain (RPR) was non-reactive. Stool studies including culture, ova and parasites were unremarkable. CT scan of the abdomen and pelvis showed mild asymmetric rectal thickening. A colonoscopy was performed which was significant for a 4-mm rectal submucosal nodule with ulceration and surrounding erythematous tissue. Hematoxylin and eosin stain of the biopsy was negative for malignancy, but Warthin-Steiner (silver) stain was positive for spirochetes. There was concern for rectal syphilis and the patient was referred for treatment. DISCUSSION: The differential diagnosis of spirochetes in the intestines include Treponema and Brachyspira. Patients with successfully treated syphilis can have reactive non-treponemal and treponema serum testing, but the titers wane over time. In HIV and syphilis co-infected patients serum testing has a lower sensitivity and specificity. Therefore despite the findings of blood testing, direct visualization helps with diagnosis. If there is any concern for syphilis, such as in this patient, treatment with penicillin is used to prevent sequelae of the disease (e.g. neurosyphilis or gummas).

Evaluation of hepatitis C viral RNA persistence in HIV-infected patients with long-term sustained virological response by droplet digital PCR

Several studies have reported the persistence of HCV RNA in liver and/or peripheral blood mononuclear cells (PBMCs) in spite of undetectable viremia in patients who have achieved sustained virological response (SVR). This event, defined as occult HCV infection, remains controversial and low titers of persistent virus may be underestimated because it has not yet been analyzed by a highly sensitive test such as droplet digital PCR (ddPCR). This method provides an alternate ultra-sensitive detection technique for very low numbers of copies of viral RNA or DNA. The aim of this study was to evaluate the persistence of HCV in HIV-coinfected patients with long-term SVR using ddPCR. For each patient, the presence of HCV RNA in serum and PBMCs at baseline was determined by nested RT-ddPCR. Patients with HCV RNA in PBMCs at baseline were followed until the end of the study. One hundred and twenty-three patients were analyzed for persistence of HCV RNA in serum and PBMCs. Persistence of HCV was not found in serum in any patient. HCV RNA was detected in PBMCs in one patient (0.81%; 95% CI: 0.04–3.94) and resolved spontaneously during follow-up. Persistence of HCV RNA in PBMCs is not a common event in HIV/HCV co-infected patients with long-term SVR evaluated by RT-ddPCR.

Epidemiology of HIV-assosiated tuberculosis in the Far Eastern Federal District

Aim. To determine epidemiologic manifestations of HIV-infection associated with tuberculosis in the Far Eastern Federal District (FEFD). Materials and methods. The retrospective epidemiologic analysis was performed based on the official statistical data form № 61 «Data on HIV infected population» in reference to clinically registered HIV and tuberculosis co-infected patients. Results. The research revealed a growth trend of general tuberculosis prevalence against the background of stabilization of the tuberculosis incidence in HIV-positive patients in the FEFD during 2006-2015. High tuberculosis-burden was registered in the most of the Far Eastern federal district constituent entities (Khabarovsk and Primorsky regions, Jewish and Chukotka autonomous districts, Amursk oblast, and Republic Sakha (Yakutia). A statistically significant positive correlation (r=0,66, p=0,003) between percentage of active tuberculosis in HIV-positive patients and percentage of patients with AIDS was identified. The percentage of active tuberculosis in HIV-positive people on average over 10 years equaled to 65.0%. The prevalence rate of tuberculosis was higher by 19.2% in HIV-positive inmates compared with HIV-positive civilians. Conclusion. Тhe FEFD is a constituent entity of the Russian Federation with high and unstable levels of tuberculosis prevalence in people living with HIV.

Treatment outcomes and antiretroviral uptake in multidrug-resistant tuberculosis and HIV co-infected patients in Sub Saharan Africa: a systematic review and meta-analysis

BackgroundMultidrug-resistant tuberculosis (MDR-TB) in HIV endemic settings is a major threat to public health. MDR-TB is a substantial and underreported problem in Sub-Saharan Africa (SSA), with recognised cases projected to increase with advancement in diagnostic technology. There is paucity of review evidence on treatment outcomes and antiretroviral (ART) uptake among MDR-TB patients with HIV in SSA. To address this gap a review of treatment outcomes in HIV patients co-infected with MDR-TB in the SSA region was undertaken.MethodsThree databases (Medline, Web of Science, CINHAL), Union on Lung Heath conference proceedings and grey literature were searched for publications between January 2004 and May 2018. Records were assessed for eligibility and data extracted. Random effect meta-analysis was conducted using STATA and Cochrane’s review manager.ResultsA total of 271 publications were identified of which nine fulfilled the inclusion criteria. Data was collected from 3368 MDR-TB and HIV co-infected patients from four SSA countries; South Africa (6), Lesotho (1), Botswana (1) and Ethiopia (1). The most common outcome was cure (34.9% cured in the pooled analysis), this was followed by death (18.1% in pooled analysis). ART uptake was high, at 83% in the pooled analysis. Cure ranged from 28.6 to 54.7% among patients on ART and from 22.2 to 57.7% among those not on ART medication. MDR-TB and HIV co-infected patients were less likely to be successfully treated than HIV negative MDR-TB patients (Risk Ratio = 0.87, 95% CI 0.97, 0.96).ConclusionTreatment outcomes for MDR-TB and HIV co-infected patients do not vary widely from those reported globally. However, treatment success was lower among HIV positive MDR-TB patients compared to HIV negative MDR-TB patients. Prompt antiretroviral initiation and interventions to improve treatment adherence are necessary.