Mpox severity and associated hospitalizations among people with HIV and related immunosuppression in Brazil.

OBJECTIVES: This study aimed to analyze characteristics of mpox hospitalization in a Brazilian cohort, further exploring the impact of HIV on mpox-related outcomes and hospitalization. DESIGN: We conducted a descriptive analysis, comparing characteristics of individuals diagnosed with mpox according to hospitalization and HIV status, and described the mpox cases among those living with HIV. METHODS: This was a single-center, prospective cohort study conducted at a major infectious diseases referral center in Rio de Janeiro, Brazil, that enrolled participants older than 18 years of age diagnosed with mpox. Information was collected on standardized forms, including data on sociodemographic, behavioral, clinical and laboratory characteristics. For comparisons, we used chi-squared, Fisher's exact and the Moods median tests whenever appropriate. RESULTS: From June to December, 2022, we enrolled 418 individuals diagnosed with mpox, of whom 52% were people with HIV (PWH). PWH presented more frequently with fever, anogenital lesions and proctitis. The overall hospitalization rate was 10.5% ( n  = 43), especially for pain control. Among hospitalized participants, PWH had more proctitis and required invasive support. Mpox severity was related to poor HIV continuum of care outcomes and low CD4 + cell counts. All deaths ( n  = 2) occurred in PWH with CD4 + less than 50 cells/µl. CONCLUSION: HIV-related immunosuppression likely impacts mpox clinical outcomes. This is of special concern in settings of poor adherence and late presentation to care related to socioeconomic inequalities, such as Brazil. The HIV continuum of care must be taken into account when responding to the mpox outbreak.

Liver stiffness regression after sustained virological response by direct-acting antivirals reduces the risk of outcomes.

The role of liver stiffness measurement (LSM) after sustained virological response (SVR) in HCV patients treated by direct-acting antivirals (DAAs) remains unclear. We aimed to evaluate LSM regression value after SVR and to identify risk factors associated with liver related complications (LRC) or death. This retrospective study analyzed patients with LSM ≥ 10 kPa with LSM by transient elastography pre-DAAs and post-SVR. Patients with previous hepatic decompensation were excluded. Medical records were reviewed to identify primary outcomes. Kaplan-Meier curves and time-to-event Cox proportional-hazard models were performed. 456 patients [65% female, 62 years (IQR 57-68)] were included. During a follow-up of 2.3 years (IQR 1.6-2.7), 28 patients developed 37 outcomes [rate = 29.0 (95% CI 20.0-42.0) per 1000 person-years]. The cumulative incidence of outcomes was significantly lower in patients who regressed LSM ≥ 20% [3.4% (95% CI 1.8-7.0) vs. 9.0% (5.5-14.5), p = 0.028]. In a multivariate Cox-model [HR(95% CI)], male gender [HR = 3.00 (1.30-6.95), p = 0.010], baseline albumin < 3.5 mg/dL [HR = 4.49 (1.95-10.34), p < 0.001] and baseline unfavorable Baveno-VI [HR = 4.72 (1.32-16.83), p = 0.017] were independently associated and LSM regression ≥ 20% after SVR had a trend to reduce the risk of LRC or death [HR = 0.45 (0.21-1.02), p = 0.058]. The use of simple parameters before DAAs and repetition of LSM post-SVR can identify patients with different risks for severe outcome after HCV eradication.

Cryptococcal antigenemia prevalence and clinical data in HIV-infected patients from the reference centre at INI-FIOCRUZ, Rio de Janeiro, Southeast of Brazil.

Cryptococcal meningitis is a several disease common in late stage of HIV infection. Detection of cryptococcal antigen (CrAg) is an important for early diagnosis of this invasive mycosis. The pre-emptive treatment for isolated antigenemia prevents the onset of meningoencephalitis. Screening CrAg in patients with low CD4 count is cost-effective in countries with prevalence of antigenemia above 3%. However, in Brazil, the number of prevalence studies on cryptococcosis and HIV is insufficient. The objective of this study is to estimate the prevalence of CrAg and describe clinical characteristics from a cohort of patients followed at a reference center in Brazil. CrAg screening was performed in 89 inpatients with CD4 count ≤200 cells/mm3 or WHO stage III/IV from the National Institute of Infecttious Disease, Rio de Janeiro. Patients with isolated antigenemia received pre-emptive therapy with fluconazole and patients with meningoencephalitis were treated with Amphotericin B. Individuals were followed up for 12 months. Prevalence of serum CrAg was 11.23%, cryptococcal meningoencephalitis 6.74% and isolated antigenemia 4.81%. None of the patients with isolated antigenemia developed meningoencephalitis during the follow up. Signs and symptoms of meningoencephalitis were unspecific or absent. Our study suggests the need of CrAg screening in Brazil and highlights that lumbar puncture is mandatory in all individuals CrAg positive to exclude asymptomatic meningoencephalitis.

Resistance Mutations A30K and Y93N Associated with Treatment Failure with Sofosbuvir and Daclatasvir for Hepatitis C Virus Infection Non-Responder Patients: Case Reports.

In Brazil, hepatitis C treatment has been evolving significantly with the licensing of direct-acting antivirals (DAAs). However, viral determinants (amino acid substitutions in hepatitis C virus (HCV) genome and infective genotype) associated with host factors (hepatic condition and prior HCV therapy) might limit the achievement of sustained virologic response (SVR). Here, we described two case reports in which the occurrence of HCV NS5A mutations A30K (subtype 3a) and Y93N (subtype 1a) might have influenced daclatasvir (DCV)/sofosbuvir (SOF) combined therapy non-response. Despite high response rates for DAA combined therapies in Brazil, these case reports stated the importance of an investigation about how to manage a DAA treatment failure since a combination of factors, especially the occurrence of resistance substitutions, could impact a rescue therapy with new available antivirals in clinical routine.

Effectiveness of direct-acting agents for hepatitis C and liver stiffness changing after sustained virological response.

BACKGROUND AND AIM: Few studies have evaluated sustained virological response (SVR) rates by direct-acting agents (DAAs) and liver stiffness measurement (LSM) changing post-SVR in limited-resource settings. We aimed to describe the effectiveness of DAAs for hepatitis C virus treatment and to assess the changing of LSM post-SVR. METHODS: This retrospective study analyzed data of consecutive hepatitis C virus-infected patients treated by DAAs from 2015 to 2017 in two tertiary centers in Brazil. SVR rates were reported by intention-to-treat and per-protocol analyses. LSM by transient elastography performed before treatment and post-SVR was compared, and logistic regression models were performed. RESULTS: Six hundred seventy-one patients (63% female, 62 years [55-68], 89% genotype 1, 8% HIV co-infected, and 64% with cirrhosis) were included. Most patients were treated by sofosbuvir/daclatasvir ± ribavirin (74%) and sofosbuvir/simeprevir ± ribavirin (21%). SVR rates (95% confidence interval [CI]) were 94.6% (92.7-96.1) and 97.8% (96.4-98.7) for intention-to-treat and per-protocol analyses, respectively. The leading adverse event was anemia (9.6% [95% CI 7.6-12.1]). Pretreatment and post-SVR12 LSM were available in 400 patients. LSM had significantly decreased after SVR (13.6 kPa [interquartile range, 10.0-21.6] vs 10.2 kPa [7.0-17.6], P < 0.001). A total of 167 patients (42%) decreased at least 30% of LSM post-SVR. The absence of type 2 diabetes (odds ratio = 1.52 [95% CI 1.05-2.21], P = 0.028) and presence of platelet count ≥ 150 × 109 /mm3 (odds ratio = 1.75 [1.23-2.50], P = 0.002) were independently associated with a significant LSM regression (≥ 30%) post-SVR. CONCLUSION: DAAs were highly effective and safe, and LSM significantly decreased after SVR in a real-life cohort in Brazil. The absence of type 2 diabetes and presence of high platelet count were independently associated with LSM decrease post-SVR.

Treatment of chronic HCV infection with DAAs in Rio de Janeiro/Brazil: SVR rates and baseline resistance analyses in NS5A and NS5B genes.

The selection of viral strains with resistance-associated substitutions at hepatitis C virus (HCV) NS5A and NS5B genes is considered one of the limiting factors for achieving sustained virologic response (SVR) to combination of direct-acting antivirals daclatasvir (DCV) and sofosbuvir (SOF). Since 2015, this interferon-free regimen has been available in Brazilian clinical routine for treating mono- and HCV/HIV-coinfected patients chronically infected with genotypes 1 and 3. Our aim was to assess SVR rate for Brazilian patients chronically infected with genotypes 1 and 3 after DCV/SOF therapy and the frequency of baseline RASs in HCV NS5A and NS5B genes. Serum samples were collected from 107 monoinfected patients and 25 HCV/HIV co-infected patients before antiviral therapy with DCV/SOF. Genetic diversity of NS5A and NS5B genes was assessed by direct nucleotide sequencing. Overall, SVR rate was 95.4% (126/132), and treatment failure occurred in five monoinfected and one HCV/HIV co-infected patient. NS5A RASs frequency was higher for HCV/HIV patients (28%) than monoinfected patients (16.8%). No difference was evidenced between mono- and HCV/HIV-coinfected groups (15% vs. 16%) regarding NS5B gene. Genotype (GT) 1b strains had significantly more baseline substitutions in NS5A (31.6%) than GT 1a and 3a. At least one primary NS5A RAS described in literature at loci 28, 30, 31 or 93 was identified in HCV GTs 1 strains for both groups. As for NS5B, RASs at positions 159 and 316 was observed only in GT 1b strains. This study highlighted that SVR rate in clinical routine in Brazil was similar to randomized clinical trials (89-98%). Our research provided genetic data about the circulation of resistant variants in Brazil. Despite its presence, most of identified baseline mutations did not negatively impact treatment outcome. Genetic diversity of circulating strains suggested that most of the Brazilian HCV chronic carriers are susceptible to new therapeutic regimens including recently approved DAAs.

Predictive factors associated with liver fibrosis and steatosis by transient elastography in patients with HIV mono-infection under long-term combined antiretroviral therapy.

INTRODUCTION: Non-alcoholic fatty liver disease is characterized by the presence of hepatic steatosis and can be associated with fibrosis progression, development of cirrhosis and liver-related complications. Data on the prevalence of liver fibrosis and steatosis in HIV patients remain contradictory in resource-limited settings. We aimed to describe the prevalence and factors associated with liver fibrosis and steatosis in patients with HIV mono-infection under long-term antiretroviral therapy (ART) in Rio de Janeiro, Brazil. METHODS: Clinical assessment, fasting blood collection and liver stiffness measurement (LSM)/controlled attenuation parameter (CAP) by transient elastography were performed on the same day for this cross-sectional study (PROSPEC-HIV study; NCT02542020). Patients with viral hepatitis co-infection, ART-naïve or missing data were excluded. Liver fibrosis and steatosis were defined by LSM ≥ 8.0 kPa and CAP ≥ 248 dB/m respectively. HIV history, cumulative and current ART regimens were evaluated. Multivariate logistic regression models adjusted for age and gender were performed. RESULTS: In total, 395 patients (60% female; median age of 45 (IQR, 35 to 52) years, body mass index = 25.7 (23.2 to 29.4) kg/m2 , alanine aminotransferase = 30 (23 to 42) IU/L, duration of ART for 7 (4 to 14) years) were included. LSM and CAP were reliable in 93% (n = 367) and 87% (n = 344) respectively. The prevalence of fibrosis and steatosis were 9% (95% confidence interval (CI), 7 to 13) and 35% (95% CI, 30 to 40) respectively. The following factors were associated with fibrosis (odds ratio (OR) (95% CI)): older age (per 10 years; 1.80 (1.27 to 2.55); p = 0.001) and CD4+ count <200 cells/mm3 (7.80 (2.09 to 29.09), p = 0.002). Type 2 diabetes had a trend towards the presence of liver fibrosis (2.67 (0.96 to 7.46), p = 0.061). Central obesity (10.74 (4.40 to 26.20), p < 0.001), type 2 diabetes (9.74 (3.15 to 30.10), p < 0.001), dyslipidaemia (2.61 (1.35 to 5.05), p = 0.003) and metabolic syndrome (4.28 (2.45 to 7.46), p < 0.001) were associated with steatosis. A dominant backbone ART regimen of zidovudine (AZT), d4T, ddI or ddC was associated with steatosis (1.90 (1.07 to 3.38), p = 0.028) independently of metabolic features. CONCLUSION: Integrated strategies for preventing non-communicable diseases in people with HIV mono-infection are necessary to decrease the burden of liver diseases. Clinical Trial Number: NCT02542020.

Efficacy and Safety of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir ± Ribavirin for HCV in Brazilian Adults with Advanced Fibrosis.

INTRODUCTION AND AIM: Approximately 650,000 people in Brazil have chronic hepatitis C virus (HCV) infection. We evaluated the safety and efficacy of ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) plus dasabuvir (DSV) with/without ribavirin (RBV) in an openlabel multicenter phase 3b trial in treatment-naive or interferon (IFN) treatment-experienced Brazilian patients with advanced hepatic fibrosis (METAVIR F3/4) and HCV genotype (GT) 1 infection. MATERIAL AND METHODS: All patients received coformulated OBV/PTV/r daily + DSV twice daily (3-DAA). GT1a-infected patients received 3-DAA plus RBV for 12 weeks, except for prior pegIFN/RBV nonresponders with cirrhosis who were treated for 24 weeks. GT1b-infected patients received 3-DAA alone (F3) or in combination with RBV (F4) for 12 weeks. The primary endpoint was sustained virologic response (HCV RNA < 15 IU/mL) at post-treatment Week 12 (SVR12). RESULTS: The study enrolled 222 patients, 214 achieved an SVR12 (96.4%; 95% CI, 93.1-98.2%), one GT1a-infected patient experienced virologic breakthrough, six (5 GT1a) relapsed, and one was lost to follow-up. SVR12 was achieved in 111/ 112 (99.1%) GT1b-infected patients, including 42/43 (97.7%) noncirrhotic, and 69/69 (100%) cirrhotic patients; and in 103/110 (93.6%) GT1a-infected patients, including 44/46 (95.7%) noncirrhotic and 59/64 (92.2%) cirrhotic patients. Overall there was a low rate of serious adverse events (n = 6, 2.7%). One patient experienced a treatment-related serious adverse event and one patient discontinued treatment because of an adverse event. DISCUSSION: The results confirm that the 3-DAA regimen with/without RBV is well tolerated and had a favorable safety profile and is efficacious in GT1-infected patients with advanced fibrosis (METAVIR F3/4).

Diabetes Mellitus is Associated with Increased Death Rates Among HIV-Infected Patients in Rio de Janeiro, Brazil.

Diabetes mellitus (DM) is a major cause of morbidity worldwide and a known factor leading to increased risk of death, especially in conjunction with other risk factors. In this study, we evaluated the prevalence of DM among HIV-infected patients and its association with overall mortality. All HIV-infected patients 18 years or older who were followed in the Instituto Nacional de Infectologia Evandro Chagas (INI) cohort from January 1991 to December 2011 were included. Time-updated covariables included DM status, calendar year, combination antiretroviral therapy (cART), and CD4 cell counts. Fixed demographic covariables included gender and age at entry. Poisson models were used to calculate mortality rate ratios (RR) with robust variances. Among the 4,871 patients included, 1,192 (24.4%) died (mortality rate = 4.72/100 person-years [PY]; 95% confidence interval [CI] = 4.46-5.00). Death rates were significantly higher among those presenting with DM compared with those who did not (6.16/100 vs. 4.61/100 PY, respectively. p = 0.001). In the final model, DM was significantly associated with mortality (RR = 1.74; 95% CI = 1.57-1.94; p < 0.001). When the analysis was restricted to those on cART or the period post-1996, the association between DM and mortality was even stronger (RR = 2.17; 95% CI = 1.91-2.46; p < 0.001 and RR = 1.95; 95% CI = 1.75-2.18; p < 0.001, respectively). Among the major groups of cause of deaths (CODs), the proportion of AIDS-related conditions in patients with DM was lower (74.27% vs. 58.93%, respectively; p < 0.001); whereas in non-AIDS-related conditions, nonimmunodeficiency-related causes (22.44% vs. 34.82%, respectively; p = 0.004) were more common in patients with DM. In conclusion, DM was associated with increased mortality rates even after controlling for HIV-related variables associated to this outcome. Differences in the underlying CODs were identified, reinforcing the necessity to assess and treat comorbidities such as DM in HIV-infected patients.

Immunogenicity and sustainability of the immune response in Brazilian HIV-1-infected individuals vaccinated with inactivated triple influenza vaccine.

HIV-infected individuals have a higher risk of serious illnesses following infection by infection with influenza. Although anti-influenza vaccination is recommended, immunosuppression may limit their response to active immunization. We followed-up a cohort of HIV-infected individuals vaccinated against influenza to assess the immunogenicity and sustainability of the immune response to vaccination. Individuals were vaccinated 2011 with inactivated triple influenza vaccine (TIV), and they had received in 2010 the monovalent anti-A(H1N1)pdm09 vaccine. The sustainability of the immune response to A(H1N1)pdm09 at 12 months after monovalent vaccination fell, both in individuals given two single or two double doses. For these individuals, A(H1N1)pdm09 component from TIV acted as a booster, raising around 40% the number of seroprotected individuals. Almost 70% of the HIV-infected individuals were already seroprotected to A/H3N2 at baseline. Again, TIV boosted over 90% the seroprotection to A/H3N2. Anti-A/H3N2 titers dropped by 20% at 6 months after vaccination. Pre-vaccination seroprotection rate to influenza B (victoria lineage) was the lowest among those tested, seroconversion rates were higher after vaccination. Seroconversion/protection after TIV vaccination did not differ significantly across categories of clinical and demographic variables. Anti-influenza responses in Brazilian HIV-infected individuals reflected both the previous history of virus circulation in Brazil and vaccination.

Changing mortality profile among HIV-infected patients in Rio de Janeiro, Brazil: shifting from AIDS to non-AIDS related conditions in the HAART era.

INTRODUCTION: We describe temporal trends in the mortality rates and factors associated with AIDS and non-AIDS related mortality at the Evandro Chagas Clinical Research Institute (IPEC), Oswaldo Cruz Foundation (FIOCRUZ). METHODS: Adult patients enrolling from 1986 through 2009 with a minimum follow up of 60 days were included. Vital status was exhaustively checked using patients' medical charts, through active contact with individuals and family members and by linkage with the Rio de Janeiro Mortality database using a previously validated algorithm. The CoDe protocol was used to establish the cause of death. Extended Cox proportional hazards models were used for multivariate modeling. RESULTS: A total of 3530 individuals met the inclusion criteria, out of which 868 (24.6%) deceased; median follow up per patient was 3.9 years (interquartile range 1.7-9.2 years). The dramatic decrease in the overall mortality rates was driven by AIDS-related causes that decreased from 9.19 deaths/100PYs n 1986-1991 to 1.35/100PYs in 2007-2009. Non-AIDS related mortality rates remained stable overtime, at around 1 death/100PYs. Immunodeficiency significantly increased the hazard of both AIDS-related and non-AIDS-related causes of death, while HAART use was strongly associated with a lower hazard of death from either cause. CONCLUSIONS: Our results confirm the remarkable decrease in AIDS-related mortality as the HIV epidemic evolved and alerts to the conditions not traditionally related to HIV/AIDS which are now becoming more frequent, needing careful monitoring.

H1N1pdm09 adjuvanted vaccination in HIV-infected adults: a randomized trial of two single versus two double doses.

BACKGROUND: Since human immunodeficiency virus (HIV)-infected individuals are at increased risk of severe disease from pandemic influenza A (H1N1pdm09), vaccination was recommended as a prevention strategy. The aim of the present study was to evaluate the safety, immunogenicity and persistence of the immune response after vaccination against pandemic influenza A (H1N1pdm09) with an adjuvanted vaccine in human immunodeficiency virus (HIV)-infected adults using two single and two double doses. METHODOLOGY/PRINCIPAL FINDINGS: Open label, randomized trial to evaluate the immune response following H1N1pdm09 vaccination in HIV-infected participants compared to HIV-negative controls (NCT01155037). HIV-infected participants were randomized to receive 2 single (3.75 µg hemagglutinin) or 2 double (7.5 µg hemagglutinin) doses of the vaccine, 21 days apart. Controls received one dose of the vaccine. The primary endpoint was seroconversion as measured by hemagglutination inhibition assay. Two hundred fifty six HIV-infected participants (129 and 127 randomized to single and double doses, respectively) and 71 HIV-negative controls were enrolled. Among HIV-infected participants, seroconversion increased from 46.7% and 51.7% after the first dose to 77.2% and 83.8% after the second dose of the vaccine using single and double doses, respectively. Participants aged >40 years showed higher seroconversion compared to younger participants. Seroconversion among HIV-infected women and those with nadir CD4<200 cells/mm(3) was significantly higher with double doses. Persistence of protective antibodies six months after vaccination was achieved by 80% and 89.9% of the HIV-infected participants who received single and double doses, respectively. CONCLUSIONS/SIGNIFICANCE: Our results support the recommendation of two double doses of adjuvanted H1N1pdm09 vaccine for HIV-infected individuals, particularly women, and those aged >40 years or with nadir CD4<200 cells/mm(3), to achieve antibody levels that are both higher and more sustained. TRIAL REGISTRATION: ClinicalTrials.gov NCT01155037.

Sepsis is a major determinant of outcome in critically ill HIV/AIDS patients.

INTRODUCTION: New challenges have arisen for the management of critically ill HIV/AIDS patients. Severe sepsis has emerged as a common cause of intensive care unit (ICU) admission for those living with HIV/AIDS. Contrastingly, HIV/AIDS patients have been systematically excluded from sepsis studies, limiting the understanding of the impact of sepsis in this population. We prospectively followed up critically ill HIV/AIDS patients to evaluate the main risk factors for hospital mortality and the impact of severe sepsis on the short- and long-term survival. METHODS: All consecutive HIV-infected patients admitted to the ICU of an infectious diseases research center, from June 2006 to May 2008, were included. Severity of illness, time since AIDS diagnosis, CD4 cell count, antiretroviral treatment, incidence of severe sepsis, and organ dysfunctions were registered. The 28-day, hospital, and 6-month outcomes were obtained for all patients. Cox proportional hazards regression analysis measured the effect of potential factors on 28-day and 6-month mortality. RESULTS: During the 2-year study period, 88 HIV/AIDS critically ill patients were admitted to the ICU. Seventy percent of patients had opportunist infections, median CD4 count was 75 cells/mm3, and 45% were receiving antiretroviral therapy. Location on a ward before ICU admission, cardiovascular and respiratory dysfunctions on the first day after admission, and the presence of severe sepsis/septic shock were associated with reduced 28-day and 6-month survival on a univariate analysis. After a multivariate analysis, severe sepsis determined the highest hazard ratio (HR) for 28-day (adjusted HR, 3.13; 95% CI, 1.21-8.07) and 6-month (adjusted HR, 3.35; 95% CI, 1.42-7.86) mortality. Severe sepsis occurred in 44 (50%) patients, mainly because of lower respiratory tract infections. The survival of septic and nonseptic patients was significantly different at 28-day and 6-month follow-up times (log-rank and Peto test, P < 0.001). CONCLUSIONS: Severe sepsis has emerged as a major cause of admission and mortality for hospitalized HIV/AIDS patients, significantly affecting short- and longer-term survival of critically ill HIV/AIDS patients.

Temporal changes in causes of death among HIV-infected patients in the HAART era in Rio de Janeiro, Brazil.

BACKGROUND: The widespread use of highly active antiretroviral therapy (HAART) has led to marked decreases in death rates in Brazil in HIV-infected individuals. Nonetheless, there are scarce data on specific causes of death. METHODS: Death rates from a cohort of HIV-infected patients in Rio de Janeiro, Brazil, were analyzed in 2-year periods, from 1997 to 2006. Poisson models and survival models accounting for competing risks were used to assess association of covariables. A standardized validated algorithm was used to ascertain specific causes of death. RESULTS: Of the 1538 eligible patients, 226 (14.7%) died during the study period, corresponding to a mortality rate of 3.2 per 100 person-years. The median follow-up time was 4.61 years (interquartile range = 5.63 years) and the loss to follow-up rate was 2.4 per 100 person-years. Overall, 98 (43.4%) were classified as non-AIDS-related causes. Although opportunistic infections were the leading causes of death (37.6%), deaths due to AIDS-related causes declined significantly over time (P < 0.01). In the most recent period (2005-2006), the rate of non-AIDS-related causes of deaths was higher than that of AIDS-related causes of death. CONCLUSIONS: In the HAART era, there has been a significant change in causes of death among HIV-infected patients in Rio de Janeiro. As access to HAART improves, integration with other public programs will become critically important for the long-term success of HIV/AIDS programs in developing countries.

Monotherapy with Lopinavir/Ritonavir as maintenance after HIV-1 viral suppression: results of a 96-week randomized, controlled, open-label, pilot trial (KalMo study).

BACKGROUND: Long-term adverse events and expenses associated with HAART have led to an interest in simplified therapy. Lopinavir/ritonavir monotherapy is attractive due to its potency and high genetic barrier. METHODS: This is a 96-week, open-label, randomized study to assess the feasibility of using LPV/r monotherapy in patients with undetectable viral load after being on successful HAART for at least 6 months. Subjects were randomized (1:1) to either switch from HAART to LPV/r monotherapy or to maintain their previous regimen. RESULTS: 60 patients were enrolled. Baseline characteristics were similar in both groups. At Week 96, by intention-to-treat analysis, 24/30 (80.0%) subjects in monotherapy group and 26/30(86.6%) in the control group had a plasma viral load of <80 copies/mL. There was one virologic failure (defined as VL not greater-than 500 copies/mL) in each arm. Genotyping testing identified no resistance-associated mutations. The patient on the monotherapy arm was successfully resuppressed to <80 copies/mL after intensification with tenofovir and lamivudine. No statistically significant differences were found with regard to changes in CD4 counts. One subject in the monotherapy group discontinued due to diarrhea. Five subjects in the control group underwent regimen changes due to drug-related toxicities. Viral load from semen samples collected at the end of follow-up was undetectable on 14/15 patients randomized to monotherapy. CONCLUSIONS: Switching from various HAART regimens to LPV/r monotherapy in patients who were virologically suppressed and without a history of previous virologic failure was effective, safe, and well tolerated through 96 weeks.