Anal Dysplasia Screening in People Living with HIV: Long-Term Follow-Up in a Large Cohort from Northwest Spain.

Anal squamous cell carcinoma (SCC) is not a common disease in the general population, although its incidence is higher in people living with human immunodeficiency virus (PLWH). Anal SCC is caused by human papillomavirus (HPV) infection and arises from premalignant lesions termed squamous intraepithelial lesions (SILs). SIL surveillance programs are based on the early detection and treatment of SILs, especially those with a higher risk of transforming into cancer. An anal surveillance program has been under development in our institution since 2011. In this context, we performed a retrospective cohort study at the anal dysplasia unit of Álvaro-Cunqueiro Hospital (Spain). Epidemiological and clinical data were gathered from our Infectious Diseases Sample Collection (an open sample cohort including PLWH) from January 2011 to January 2022. A total of 493 PLWH were considered, 122 (24.7%) of whom were diagnosed with anal dysplasia at baseline, including 2 cases of anal SCC. Briefly, most of individuals were young men (median age, 38 years old) born in Spain (76%), whose vaccination rate before their inclusion in the program was scarce (<3%). Throughout the study period, 81 (16.4%) cases were diagnosed with high-grade squamous-intraepithelial lesions (HSILs) and 3 with anal SCC. At the baseline, severe immunosuppression (i.e., nadir CD4+ lymphocyte count below 200 cell/µL), and prior diagnosis of condyloma acuminata were more frequent within the group with SILs. Conversely, the baseline CD4+ lymphocyte count was similar among both groups. HPV-16 was related to a higher risk of HSILs (odds ratio: 2.76). At the end of the follow-up, 385 PLWH had been retained in care; one patient had died of anal cancer. Anal dysplasia was common (25% of cases), especially among patients infected by HPV-16, diagnosed with condyloma acuminata, and who were severely immunosuppressed. HPV-16 was the main risk factor for the presentation of HSILs.

Real-life cohort experience after implementing HIV pre-exposure prophylaxis for one year in northwest Spain.

Introduction: Pre-exposure prophylaxis (PrEP) has become a useful tool to reduce the transmission of human immunodeficiency virus (HIV) in key populations. In this article we assessed the effectiveness, safety, adherence, sexually transmitted infections (STIs) dynamics, and frequency of anal dysplasia among a real-life cohort of PrEP users in Northwest Spain. Methods: A retrospective cohort study was undertaken in the Alvaro-Cunqueiro Hospital, Vigo which included every individual who started daily emtricitabine/tenofovir-disoproxil-fumarate (FTC/TDF) between November-2019 and October-2021. Clinical and epidemiological data were obtained from the patient's medical records. The effectiveness and safety of FTC/TDF were assessed by HIV serology and renal function monitoring every 3 months. Anal, urethral, and oropharyngeal exudates were collected quarterly after the baseline visit. Results: A total of 126 individuals were considered eligible, most of the participants had previously been diagnosed with a STI (60.3%), 22% had consumed recreational drugs in the year prior, and 13% had engaged in chemsex. At the end of the follow-up, no cases of HIV infection were detected; 3 patients had discontinued FTC/TDF because of side effects but none of them had presented renal toxicity. In addition, the diagnosis of STIs during the follow-up was common (100 cases in 54 patients). Moreover, engagement in chemsex was more common within this latter group (22 vs. 6%, p = 0.013). Among the study population included in the anal screening programme, the frequency of dysplasia was 9%. Conclusions: FTC/TDF was effective, safe, and tolerable in a real-life cohort; adherence remained high throughout the study period (79%). However, a high number of STIs were diagnosed, especially among patients who engaged in chemsex.

Update on the Epidemiological Features and Clinical Implications of Human Papillomavirus Infection (HPV) and Human Immunodeficiency Virus (HIV) Coinfection.

Human papillomavirus (HPV) infection is the most common sexually transmitted infection (STI) worldwide. Although most HPV infections will spontaneously resolve, a considerable proportion of them will persist, increasing the risk of anogenital dysplasia, especially within certain populations, such as patients infected with human immunodeficiency virus (HIV). Furthermore, high-risk oncogenic HPV types (HR-HPV) are the main cause of cervix and other anogenital cancers, such as cancer of the vagina, vulva, penis, or anus. HIV and HPV coinfection is common among people living with HIV (PLWH) but disproportionally affects men who have sex with men (MSM) for whom the rate of persistent HPV infection and reinfection is noteworthy. The molecular interactions between HIV and HPV, as well as the interplay between both viruses and the immune system, are increasingly being understood. The immune dysfunction induced by HIV infection impairs the rate of HPV clearance and increases its oncogenic risk. Despite the availability of effective antiretroviral therapy (ART), the incidence of several HPV-related cancers is higher in PLWH, and the burden of persistent HPV-related disease has become a significant concern in an aging HIV population. Several public health strategies have been developed to reduce the transmission of HIV and HPV and mitigate the consequences of this type of coinfection. Universal HPV vaccination is the most effective preventive tool to reduce the incidence of HPV disease. In addition, screening programs for HPV-related cervical and vulvovaginal diseases in women are well-recognized strategies to prevent cervical cancer. Similarly, anal dysplasia screening programs are being implemented worldwide for the prevention of anal cancer among PLWH. Herein, the main epidemiological features and clinical implications of HIV and HPV coinfection are reviewed, focusing mainly on the relationship between HIV immune status and HPV-related diseases and the current strategies used to reduce the burden of HPV-related disease.

Long COVID in hospitalized and non-hospitalized patients in a large cohort in Northwest Spain, a prospective cohort study.

Survivors to COVID-19 have described long-term symptoms after acute disease. These signs constitute a heterogeneous group named long COVID or persistent COVID. The aim of this study is to describe persisting symptoms 6 months after COVID-19 diagnosis in a prospective cohort in the Northwest Spain. This is a prospective cohort study performed in the COHVID-GS. This cohort includes patients in clinical follow-up in a health area of 569,534 inhabitants after SARS-CoV-2/COVID-19 diagnosis. Clinical and epidemiological characteristics were collected during the follow up. A total of 248 patients completed 6 months follow-up, 176 (69.4%) required hospitalization and 29 (10.2%) of them needed critical care. At 6 months, 119 (48.0%) patients described one or more persisting symptoms. The most prevalent were: extra-thoracic symptoms (39.1%), chest symptoms (27%), dyspnoea (20.6%), and fatigue (16.1%). These symptoms were more common in hospitalized patients (52.3% vs. 38.2%) and in women (59.0% vs. 40.5%). The multivariate analysis identified COPD, women gender and tobacco consumption as risk factors for long COVID. Persisting symptoms are common after COVID-19 especially in hospitalized patients compared to outpatients (52.3% vs. 38.2%). Based on these findings, special attention and clinical follow-up after acute SARS-CoV-2 infection should be provided for hospitalized patients with previous lung diseases, tobacco consumption, and women.

Massive Release of CD9+ Microvesicles in Human Immunodeficiency Virus Infection, Regardless of Virologic Control.

BACKGROUND: The role of extracellular vesicles (EVs) in human immunodeficiency virus (HIV) pathogenesis is unknown. We examine the cellular origin of plasma microvesicles (MVs), a type of ectocytosis-derived EV, the presence of mitochondria in MVs, and their relationship to circulating cell-free mitochondrial deoxyribonucleic acid (ccf-mtDNA) in HIV-infected patients and controls. METHODS: Five participant groups were defined: 30 antiretroviral therapy (ART)-naive; 30 ART-treated with nondetectable viremia; 30 elite controllers; 30 viremic controllers; and 30 HIV-uninfected controls. Microvesicles were quantified and characterized from plasma samples by flow cytometry. MitoTrackerDeepRed identified MVs containing mitochondria and ccf-mtDNA was quantified by real-time polymerase chain reaction. RESULTS: Microvesicle numbers were expanded at least 10-fold in all HIV-infected groups compared with controls. More than 79% were platelet-derived MVs. Proportions of MVs containing mitochondria (22.3% vs 41.6%) and MV mitochondrial density (706 vs 1346) were significantly lower among HIV-infected subjects than controls, lowest levels for those on ART. Microvesicle numbers correlated with ccf-mtDNA levels that were higher among HIV-infected patients. CONCLUSIONS: A massive release of platelet-derived MVs occurs during HIV infection. Some MVs contain mitochondria, but their proportion and mitochondrial densities were lower in HIV infection than in controls. Platelet-derived MVs may be biomarkers of platelet activation, possibly reflecting pathogenesis even in absence of HIV replication.

Prevalence and factors associated with SARS-CoV-2 seropositivity in the Spanish HIV Research Network Cohort.

OBJECTIVES: We aimed to assess the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and factors associated with seropositivity and asymptomatic coronavirus disease 2019 (COVID-19) among people with HIV (PWH). METHODS: This was a cross-sectional study carried out within the cohort of the Spanish HIV Research Network. Participants were consecutive PWH with plasma collected from 1st April to 30th September 2020. We determined SARS-CoV-2 antibodies (Abs) in plasma. Illness severity (NIH criteria) was assessed by a review of medical records and, if needed, participant interviews. Multivariable logistic regression analysis was used to identify predictors of seropositivity among the following variables: sex, age, country of birth, education level, comorbidities (hypertension, chronic heart disease, diabetes mellitus, non-AIDS-related cancer, chronic kidney disease, cirrhosis), route of HIV acquisition, prior AIDS, CD4+ cell count, HIV viral load, nucleoside/nucleotide reverse transcriptase inhibitor (N [t]RTI) backbone, type of third antiretroviral drug, and month of sample collection. RESULTS: Of 1076 PWH (88.0% males, median age 43 years, 97.7% on antiretroviral therapy, median CD4+ 688 cells/mm3, 91.4% undetectable HIV viral load), SARS-CoV-2 Abs were detected in 91 PWH, a seroprevalence of 8.5% (95%CI 6.9-10.3%). Forty-five infections (45.0%) were asymptomatic. Variables independently associated with SARS-CoV-2 seropositivity were birth in Latin American countries versus Spain (adjusted odds ratio (aOR) 2.30, 95%CI 1.41-3.76, p 0.001), and therapy with tenofovir disoproxil fumarate plus emtricitabine (TDF/FTC) versus tenofovir alafenamide (TAF)/FTC as the N(t)RTI backbone (aOR 0.49, 95%CI 0.26-0.94, p 0.031). CONCLUSIONS: Many SARS-CoV-2 infections among PWH were asymptomatic, and birth in Latin American countries increased the risk of SARS-CoV-2 seropositivity. Our analysis, adjusted by comorbidities and other variables, suggests that TDF/FTC may prevent SARS-CoV-2 infection among PWH.

HIV/AIDS in Sierra Leone: Characterizing the Hidden Epidemic.

Sierra Leone is a low-income West African country that has dealt with waves of economic, political, and public health challenges in its recent past, including a decade-long brutal civil war and the Ebola epidemic of 2014-2016. The HIV/AIDS epidemic, which has raged on in the country since 1987, has long been characterized as stable. The latest UNAIDS report estimates a countrywide HIV prevalence rate of 1.7% in 2016 among adults aged 15-49 years. However, there are indications that the epidemic may be in fact escalating and unless arrested urgently, has the potential to deteriorate into a major public health emergency. Although there are high levels of HIV awareness among adults (over 94%), uptake in voluntary HIV testing has remained low (<30%), and under one-third (29%) of the country's 60,000 people living with HIV/AIDS were on antiretroviral therapy in 2015. This review attempts to address the paucity of scientific information on the subject by presenting the historical and epidemiological background to the HIV/AIDS epidemic in Sierra Leone. Other aspects of the HIV/AIDS epidemic in Sierra Leone are examined, including routine HIV screening and diagnosis, linkage to and retention in HIV care, clinical characteristics and molecular epidemiology, treatment coverage, and prevention strategies. Finally, we identify four key areas of challenge that are hampering current efforts attempting to bring the epidemic under control, and perspective is offered on the way forward.

Minimizing Next-Generation Sequencing Errors for HIV Drug Resistance Testing.

Next-generation sequencing prototypes for the routine diagnosis of resistance to antiretrovirals approved for the treatment of HIV infection are now being used in many clinical diagnostic laboratories. As some of the next-generation sequencing platforms may be a source of errors, it is necessary to improve the currently available protocols and implement bioinformatic tools that may help to correctly identify the presence of resistance mutations with clinical impact. Several studies have addressed these issues in recent years. Some of them are mainly focused on improving protocols for decreasing the magnitude of errors during the polymerase change reaction. Other studies propose specific bioinformatic tools, able to reach both a 93-98% reduction of indels (insertions/deletions) and a sensitivity and specificity close to 100% in single nucleotide polymorphism variant calling. The implementation of new protocols and bioinformatic tools improving the accuracy of next-generation sequencing results must be considered for a correct analysis of HIV resistance mutations for making clinical decisions. This review summarizes the most relevant data available for the optimization of next-generation sequencing applied to HIV resistance testing.

Increased incidence of cancer observed in HIV/hepatitis C virus-coinfected patients versus HIV-monoinfected.

BACKGROUND: Cancer is a growing problem in persons living with HIV infection (PLWH) and hepatitis C virus (HCV) coinfection could play an additional role in carcinogenesis. Herein, all cancers in an HIV-mono and HIV/HCV-coinfected cohort were evaluated and compared to identify any differences between these two populations. METHODS: A retrospective cohort study was conducted including all cancers in PLWH between 1993 and 2014. Cancers were classified in two groups: AIDS-defining cancer (ADC) and non-AIDS-defining cancer (NADC). Cancer incidence rates were calculated and compared with that observed in the Spanish general population (GLOBOCAN, 2012), computing the standardized incidence ratios (SIRs). A competing risk approach was used to estimate the probability of cancer after HIV diagnosis. Cumulative incidence in HIV-monoinfected and HIV/HCV-coinfected patients was also compared using multivariable analysis. RESULTS: A total of 185 patients (117 HIV-monoinfected and 68 HIV/HCV) developed cancer in the 26 580 patient-years cohort, with an incidence rate of 696 cancers per 100 000 person-years, higher than in the general population (SIR = 3.8). The incidence rate of NADC in HIV/HCV-coinfected patients was 415.0 (SIR = 3.4), significantly higher than in monoinfected (377.3; SIR = 1.8). After adjustments, HIV/HCV-coinfected patients had a higher cumulative incidence of NADC than HIV-monoinfected (adjusted hazard ratio = 1.80), even when excluding hepatocellular carcinomas (adjusted hazard ratio = 1.26). CONCLUSION: PLWH have a higher incidence of NADC than the general population and HCV-coinfection is associated with a higher incidence of NADC. These data justify the need for prevention strategies in these two populations and the importance of eradicating HCV.

HTLV infection in HCV-antibody positive patients in Spain.

Since hepatitis C virus (HCV) and human T-lymphotropic virus (HTLV) share transmission routes, dual infection could be frequent. In Spain, HTLV underdiagnosis is highlighted by the high proportion of patients presenting either with tropical spastic paraparesis (TSP) or adult T-cell leukemia (ATL) at first diagnosis. We examined whether the renewed efforts for expanding HCV testing may provide a sentinel population that might selectively be targeted to unveil asymptomatic HTLV carriers. The presence of anti-HTLV antibodies was examined in 3,838 consecutive individuals with reactive HCV serology attended during the last three years at 13 hospitals distributed across the Spanish geography. Overall 71% were male and the median age was 41-years old. Foreigners represented 9% of the study population. A total of 50 individuals (1.3%) were seroreactive for HTLV, being 30 confirmed as HTLV-2 and two as HTLV-1 (0.12%). The remaining 18 had indeterminate Western blot patterns. Most individuals with HTLV-2 and HTLV indeterminate serology were HIV-positive, former injection drug users and native Spaniards. In contrast, the two HTLV-1 infections were found in men coming from Brazil and the Dominican Republic, respectively. In summary, the overall prevalence of HTLV infection in individuals living in Spain seropositive for HCV is 1.3%, more than 10-fold greater than in general outclinics in Spain. However, immigrants from HTLV-1 endemic regions and former injection drug users with HTLV-2 infection are by far the major contributory groups in HCV patients. Therefore, testing for HTLV in newly diagnosed HCV individuals would not contribute much to improve late HTLV diagnosis in Spain.

Characterization of chronic HCV infection in Northwest Spain: Impact of the treatment strategic plan of the Spanish National Health Service on HCV cure.

The aim of the study was to characterize HCV infection in Northwest Spain and assess the impact of the Spanish Strategic Plan to cure HCV infection. Overall, 387 patients were included (60.9% HIV/HCV coinfected and 28.2% cirrhotic). Of these, 72.9% of patients that were recognized as priority for HCV treatment according to the Spanish Strategic Plan (≥F2, transplant or extrahepatic manifestations), initiated treatment during 2015. Globally, SVR12 was achieved in 96.5% of patients. The implementation of the Spanish Strategic Plan has been critical to advance in HCV cure, but 27.1% of priority patients still remain awaiting HCV treatment initiation.

Trends in hospital admissions, re-admissions, and in-hospital mortality among HIV-infected patients between 1993 and 2013: Impact of hepatitis C co-infection.

BACKGROUND: New patterns in epidemiological characteristics of people living with HIV infection (PLWH) and the introduction of Highly Active Antiretroviral Therapy (HAART) have changed the profile of hospital admissions in this population. The aim of this study was to evaluate trends in hospital admissions, re-admissions, and mortality rates in HIV patients and to analyze the role of HCV co-infection. METHODS: A retrospective cohort study conducted on all hospital admissions of HIV patients between 1993 and 2013. The study time was divided in two periods (1993-2002 and 2003-2013) to be compared by conducting a comparative cross-sectional analysis. RESULTS: A total of 22,901 patient-years were included in the analysis, with 6917 hospital admissions, corresponding to 1937 subjects (75% male, mean age 36±11 years, 37% HIV/HCV co-infected patients). The median length of hospital stay was 8 days (5-16), and the 30-day hospital re-admission rate was 20.1%. A significant decrease in hospital admissions related with infectious and psychiatric diseases was observed in the last period (2003-2013), but there was an increase in those related with malignancies, cardiovascular, gastrointestinal, and chronic respiratory diseases. In-hospital mortality remained high (6.8% in the first period vs. 6.3% in the second one), with a progressive increase of non-AIDS-defining illness deaths (37.9% vs. 68.3%, P<.001). The admission rate significantly dropped after 1996 (4.9% yearly), but it was less pronounced in HCV co-infected patients (1.7% yearly). CONCLUSIONS: Hospital admissions due to infectious and psychiatric disorders have decreased, with a significant increase in non-AIDS-defining malignancies, cardiovascular, and chronic respiratory diseases. In-hospital mortality is currently still high, but mainly because of non-AIDS-defining illnesses. HCV co-infection increased the hospital stay and re-admissions during the study period.

New Strategies for a Comprehensive Fight Against HIV Infection using Monoclonal Antibody Therapy.

Highly active antiretroviral therapy (ART) has allowed a long-term control of viral replication and HIV infection has been transformed into a chronic disease. However, ART is not able to eradicate the virus, and high levels of inflammation and immune-activation are observed despite prolonged ART. Consequently, a number of comorbidities, such as cardiovascular diseases and cancer, are gaining relevance in patients living with HIV. Moreover, the toxicities associated with continued exposure to ART cause several metabolic disturbances with clinical relevance, and the cost of treatment is a heavy burden for the national health systems. In this scenario, new therapeutic strategies aiming at viral eradication are being actively pursued.

Seroprevalence of HCV and HIV infections by year of birth in Spain: impact of US CDC and USPSTF recommendations for HCV and HIV testing.

BACKGROUND: The US Centers for Disease Control and Prevention (CDC) recently add the advice of one-time testing of HCV infection in persons born during 1945-1965. Moreover, the US Preventive Services Task Force (USPSTF) newly recommended one-time HIV testing for persons aged 15-65. Herein, we evaluate the potential impact of these recommendations in a reference medical area of Spain. METHODS: All assays results entries for HCV and HIV serological markers ordered at a reference lab from primary care and specialized physicians between 2008 and 2012 were recorded in a medical area which covers 501,526 citizens in Northern Spain. The year of birth were also documented. RESULTS: A total of 108,159 anti-HCV-Ab results were generated during the study period. The global rate of anti-HCV-Ab+ was 7.7% (95% CI: 7.6%-7.9%), being more prevalent in men than women (8.6% vs. 4.5%). By year of birth, the highest prevalence was found in persons born between 1955 and 1970. HCV genotype 1 was the most prevalent (59.7%) followed by genotype 3 (22.7%). Regard HIV infection, among 65,279 anti-HIV results generated the prevalence of anti-HIV+ was 1.1% (95% CI: 1.0%-1.2%), being more frequent in men (2% vs 0.5%). The years of birth with highest rates of HIV infection exactly match with those for HCV infection. CONCLUSIONS: The highest rates of HCV and HIV infections are found between 1960 and 1965. Different historical and social circumstances such as the huge intravenous drug use epidemic in the eighties in Spain, might explain it. Therefore, each country needs to determine its own HCV and HIV seroprevalences by year of birth to establish the proper recommendations for the screening of both infections.

Genotypic tropism testing in proviral DNA to guide maraviroc initiation in aviremic subjects: 48-week analysis of the PROTEST study.

INTRODUCTION: In a previous interim 24-week virological safety analysis of the PROTEST study (1), initiation of Maraviroc (MVC) plus 2 nucleoside reverse-transcriptase inhibitors (NRTIs) in aviremic subjects based on genotypic tropism testing of proviral HIV-1 DNA was associated with low rates of virological failure. Here we present the final 48-week analysis of the study. METHODS: PROTEST was a phase 4, prospective, single-arm clinical trial (ID: NCT01378910) carried on in 24 HIV care centres in Spain. Maraviroc-naïve HIV-1-positive adults with HIV-1 RNA (VL) <50 c/mL on stable ART during the previous 6 months, requiring an ART change due to toxicity, with no antiretroviral resistance to the ART started, and R5 HIV by proviral DNA genotypic tropism testing (defined as a G2P FPR >10% in a singleton), initiated MVC with 2 NRTIs and were followed for 48 weeks. Virological failure was defined as two consecutive VL>50 c/mL. Recent adherence was calculated as: (# pills taken/# pills prescribed during the previous week)*100. RESULTS: Tropism results were available from 141/175 (80.6%) subjects screened: 87/141 (60%) were R5 and 74/87 (85%) were finally included in the study. Their median age was 48 years, 16% were women, 31% were MSM, 36% had CDC category C at study entry, 62% were HCV+ and 10% were HBV+. Median CD4+ counts were 616 cells/mm(3) at screening, and median nadir CD4+ counts were 143 cells/mm(3). Previous ART included PIs in 46 (62%) subjects, NNRTIs in 27 (36%) and integrase inhibitors (INIs) in 1 (2%). The main reasons for treatment change were dyslipidemia (42%), gastrointestinal symptoms (22%), and liver toxicity (15%). MVC was given alongside TDF/FTC in 40 (54%) subjects, ABC/3TC in 30 (40%), AZT/3TC in 2 (3%) and ABC/TDF in 2 (3%). Sixty-two (84%) subjects maintained VL<50 c/mL through week 48, whereas 12 (16%) discontinued treatment: two (3%) withdrew informed consent, one (1%) had a R5→X4 shift in HIV tropism between the screening and baseline visits, one (1%) was lost to follow-up, one (1%) developed an ART-related adverse event (rash), two (3%) died due to non-study-related causes (1 myocardial infarction at week 0 and 1 lung cancer at week 36), and five (7%) developed protocol-defined virological failure, although two of them regained VL<50 c/mL with the same MVC regimen (Table 1). CONCLUSIONS: Initiation of MVC plus 2 NRTIs in aviremic subjects based on genotypic tropism testing of proviral HIV-1 DNA is associated with low rates of virological failure up to one year.

Hepatitis B in HIV-infected patients.

Chronic hepatitis B virus (HBV) infection is common in HIV-positive individuals. Although HBV vaccination is mandatory for HIV-positive individuals with negative-HBV markers, lower rates of protection are achieved. HIV infection accelerates the course of liver disease caused by chronic HBV infection, leading to end-stage hepatic illness and increasing the risk of hepatocellular carcinoma. Anti-HBV active agents, especially tenofovir, improve outcomes. Lamivudine alone should be limited to patients with low serum HBV-DNA levels, since selection of drug resistance often compromises long-term benefits, leads to cross-resistance with other antivirals, and favors the potential emergence of HBV-vaccine escape mutants.

Longitudinal changes in viral RNA concentration in patients with chronic hepatitis C and/or HIV infection in the absence of antiviral therapy.

BACKGROUND: The concentration of circulating viral RNA at baseline and during antiviral therapy predicts response in both HIV infection and chronic hepatitis C. METHODS: Retrospective review of longitudinal plasma HCV-RNA determinations in untreated chronic hepatitis C patients. As comparison, longitudinal plasma HIV-RNA measurements were performed in untreated HIV individuals. RESULTS: A total of 3169 HCV-RNA determinations over 43.0±31.6 months were available for 818 chronic hepatitis C patients. For 333 HIV individuals, 1998 HIV-RNA measurements were examined over 27.3±17.5 months. Overall 44% consecutive specimens had >0.5 log variation in HCV-RNA values compared to 23% for HIV-RNA (p<0.001). These rates were 15% and 4%, respectively, for variations >1 log (p<0.001). In multivariate analysis (odds ratio, 95% confidence interval, p), the likelihood of experiencing HCV-RNA variations >0.5 log IU/mL was greater in patients with lower HCV-RNA (0.35 per log[0.26-0.47], 0.001), HIV coinfection (2.57[91.56-4.23], <0.001) and IL28B-CC (1.87[1.28-2.74], 0.001). CONCLUSIONS: Fluctuation in circulating HCV-RNA may be clinically meaningful in a substantial proportion of chronic hepatitis C patients. It may influence the best time to prescribe antiviral therapy. Moreover, decisions based on early viral kinetics, such as early stopping rules, may require testing of baseline specimens the closest to treatment initiation.

Hepatitis B virus and HIV infection.

Approximately 5 to 10% of human immunodeficiency virus- (HIV-) infected persons worldwide have chronic hepatitis B virus (HBV). The management of these patients merits special attention. They experience a faster progression to cirrhosis and more frequent liver-related death than HBV-monoinfected individuals. For this reason, therapy for both HIV and HBV is a priority in most cases. Some antivirals (i.e., tenofovir, lamivudine, emtricitabine) are active against both viruses and should be part of the antiretroviral treatment choice. However, drugs such as entecavir, telbivudine, or adefovir are active against HBV and may display some residual activity against HIV, occasionally leading to the selection of resistance mutations in the HIV polymerase, as is clearly shown with entecavir. Thus, they should be used only in the context of potent antiretroviral treatment. In this review, the authors will provide updated information on the natural history of HIV/HBV coinfected patients, when and which drugs should be used in treatment, and the concern about selection of drug resistance and vaccine escape mutants.