Antiretroviral Therapy In Patients Research Articles

Iatrogenic cushing syndrome secondary to ritonavir-epidural triamcinolone interaction: an illustrative case and review.

HIV positive patients on ritonavir-containing antiretroviral therapy (ART) can develop iatrogenic Cushing syndrome (IACS) and adrenal insufficiency as a result of drug-drug interactions with inhaled or intranasal glucocorticoid therapy. Reports related to epidural triamcinolone injections are relatively uncommon but increasingly reported. We describe a 48-year-old woman with immunologically and virologically well-controlled HIV on ritonavir-based ART, who developed headache, dizziness, and candida and herpes simplex virus (HSV) ulcerative esophagitis 7 days after receiving an epidural triamcinolone injection for cervical radicular pain. Iatrogenic Cushing syndrome and relative adrenal insufficiency were suspected and proven. The patient's ART was changed to a non-HIV protease inhibitor- (PI-) containing program, her symptoms improved, and she did not require hydrocortisone replacement. In this paper, we review the literature on IACS and relative secondary adrenal insufficiency from epidural triamcinolone injections in HIV patients on ritonavir-containing ART regimens. A high index of clinical suspicion is needed for diagnosis. Prevention of drug-drug interactions by taking a thorough medication history for patients on ritonavir-containing ART regimens before prescribing any form of corticosteroid is crucial and effective and sustained interdisciplinary communication in the care of such patients.

Stevens Johnson syndrome due to nevirapine

Adverse drug reactions continue to be among the important cause of morbidity and at times mortality among hospital admissions. The severity of cutaneous adverse drug reaction may vary from mild rashes to severe Stevens Johnson syndrome (SJS). Nevirapine (NVP) is an important component of antiretroviral therapy for patients having acquired immunodeficiency syndrome. It usually cause mild rash in some of these patients. This report describes a case of NVP induced SJS that was reversible on withdrawal of the drug. Possible mechanisms of NVP induced SJS and its clinical implications are also briefly discussed.

The Clinical Impact of Continuing to Prescribe Antiretroviral Therapy in Patients with Advanced AIDS Who Manifest No Virologic or Immunologic Benefit

IntroductionDespite the efficacy and tolerability of modern antiretroviral therapy (ART), many patients with advanced AIDS prescribed these regimens do not achieve viral suppression or immune reconstitution as a result of poor adherence, drug resistance, or both. The clinical outcomes of continued ART prescription for such patients have not been well characterized.MethodsWe examined the causes and predictors of all-cause mortality, AIDS-defining conditions, and serious non-AIDS-defining events among a cohort of participants in a clinical trial of pre-emptive therapy for CMV disease. We focused on participants who, despite ART had failed to achieve virologic suppression and substantive immune reconstitution.Results233 ART-receiving participants entered with a median baseline CD4+ T cell count of 30/mm3 and plasma HIV RNA of 5 log10 copies/mL. During a median 96 weeks of follow-up, 24.0% died (a mortality rate of 10.7/100 patient-years); 27.5% reported a new AIDS-defining condition, and 22.3% a new serious non-AIDS event. Of the deaths, 42.8% were due to an AIDS-defining condition, 44.6% were due to a non-AIDS-defining condition, and 12.5% were of unknown etiology. Decreased risk of mortality was associated with baseline CD4+ T cell count ≥25/mm3 and lower baseline HIV RNA.ConclusionsAmong patients with advanced AIDS prescribed modern ART who achieve neither virologic suppression nor immune reconstitution, crude mortality percentages appear to be lower than reported in cohorts of patients studied a decade earlier. Also, in contrast to the era before modern ART became available, nearly half of the deaths in our modern-era study were caused by serious non-AIDS-defining events. Even among the most advanced AIDS patients who were not obtaining apparent immunologic and virologic benefit from ART, continued prescription of these medications appears to alter the natural history of AIDS—improving survival and shifting the causes of death from AIDS- to non-AIDS-defining conditions.

Acceptability and challenges of rapid ART initiation among pregnant women in a pilot programme, Cape Town, South Africa

Maternal antiretroviral therapy (ART) is a critical intervention in the prevention-of-mother-to child transmission (PMTCT) of HIV. In South Africa, many HIV-infected pregnant women commence ART late in pregnancy, and as a result, the duration of ART prior to delivery is often insufficient to prevent vertical transmission. To address this, we designed an intervention for the rapid initiation of ART in pregnancy (RAP), where patient's ART preparation occurred during rather than before treatment commencement. Here we report on the acceptability and the challenges of the RAP programme. We conducted 7 key informant and 27 semi-structured interviews with RAP participants. Participants were purposefully selected based on ART-eligibility and stage in the pregnancy to post-partum continuum. Interviews were conducted in participants' home language by trained fieldworkers, with key informant interviews conducted by the study investigators. The data were analysed using a framework analysis approach. Rapid initiation in pregnancy was acceptable to the majority of programme participants and protection of the woman's unborn child was the primary motivation for starting treatment. The key barrier was the limited time to accept the dual challenges of being diagnosed HIV-positive and eligible for life-long ART. Truncated time also limited the opportunity for disclosure to others. Despite these and other barriers, most women found the benefits of rapid ART commencement outweighed the challenges, with 91% of women initiated onto ART starting the same day treatment eligibility was determined. Many participants and key informants identified the importance of counseling and the need to make an informed, independent choice on the timing of ART initiation, based on individual circumstances. Acceptance of ART-eligibility improved with time on the programme, however, as women's principal reason for initiating ART was protection of the unborn child, monitoring and supporting adherence during the post-partum period will be critical.

British HIV Association guidelines for the management of hepatitis viruses in adults infected with HIV 2013

British <scp>HIV A</scp>ssociation guidelines for the management of hepatitis viruses in adults infected with <scp>HIV</scp> 2013

Predictors of Raised Viral Load during Antiretroviral Therapy in Patients with and without Prior Antiretroviral Use: A Cross-Sectional Study

ObjectivesIn Lagos, Nigeria, Médecins Sans Frontières (MSF) and the Ministry of Health (MoH) commenced free antiretroviral treatment (ART) in a hospital-based clinic. We performed a cross-sectional study to compare factors associated with raised viral load between patients with (“experienced”) and without (“naïve”) prior antiretroviral (ARV) exposure at commencement of ART at the clinic. We also examined factors influencing ARV adherence in experienced patients prior to clinic entry.MethodsWe included adult patients receiving ART from MSF who answered a questionnaire about previous antiretroviral use. Multivariate logistic regression was used to estimate odds ratios (OR) for raised viral load (≥1000 copies/mL).Results1246 (96%) patients answered: 1075 (86%) reported no, and 171 (14%) some, prior ARV exposure. ARV-naïve patients were more immunosuppressed at baseline: 65% vs 37% (p<0.001) had CD4<200; 17% vs 9% (p = 0.013) were WHO stage 4. Proportionately more experienced than naïve patients had raised viral loads (20% vs 9%, p<0.001) on ART in the MSF/MoH clinic. Raised viral load was associated with prior ARV experience (adjusted OR = 3.74, 95%CI 2.09–6.70, p<0.001) and complete interruption of current ART (adjusted OR = 3.71, 95%CI 2.06–6.68, p<0.001). Higher CD4 at time of VL and a higher self-rated score of recent adherence were associated with lower OR of a raised viral load. Among experienced patients who missed pills before joining MSF/MoH, most common reasons were because ARVS were not affordable (58%) or available (33%), with raised viral load associated with being unsure how to take them (OR = 3.16, 95%CI 1.10–9.12, p = 0.033).ConclusionsPatients previously exposed to ARVs had increased OR of raised viral load. The cost and availability of ARVs were common reasons for missing ARVs before joining the MSF/MoH clinic, and inadequate patient knowledge was associated with raised viral load.

Treatment outcomes after early initiation of antiretroviral therapy for human immunodeficiency virus–associated tuberculosis

To evaluate the optimal timing for initiating antiretroviral therapy in patients with human immunodeficiency virus (HIV)-associated tuberculosis in Hong Kong. Historical cohort. SETTING. Tuberculosis and Chest Service and Special Preventive Programme, Public Health Service Branch, Centre for Health Protection, Department of Health, Hong Kong. Consecutive patients with HIV-associated tuberculosis in a territory-wide TB-HIV registry encountered from 1996 to 2009. Of the 260 antiretroviral therapy-naïve patients with HIV-associated tuberculosis, 32 (12%) had antiretroviral therapy initiated within 2 months after starting anti-tuberculosis treatment (early antiretroviral therapy). Early antiretroviral therapy was associated with a more favourable outcome (cure or treatment completion without relapse) at 24 months (91% vs 67%; P=0.007) than those with antiretroviral therapy started later or not initiated, and remained an independent predictor of a favourable outcome after adjustment for potential confounders. Adverse effects from anti-tuberculosis drugs tended to occur more frequently in patients with early antiretroviral therapy (13/32 or 41%) compared with the remainder (59/228 or 26%; P=0.08). A significantly higher proportion of patients in the former group experienced immune reconstitution inflammatory syndrome than in the latter group (7/32 or 22% vs 9/228 or 4%; P<0.001). There was no death attributable to immune reconstitution inflammatory syndrome. Early initiation of antiretroviral therapy is associated with more favourable tuberculosis treatment outcomes in patients with HIV-associated tuberculosis with a low CD4 count (<200/µL). Drug co-toxicity and immune reconstitution inflammatory syndrome that may be increased by earlier initiation of antiretroviral therapy does not undermine tuberculosis treatment outcomes to a significant extent.

Features of kidney affection in the conditions of highly active antiretroviral therapy in patients with HIV/AIDS

Features of kidney affection in the conditions of highly active antiretroviral therapy in patients with HIV/AIDS

Positive selection of mC46-expressing CD4+ T cells and maintenance of virus specific immunity in a primate AIDS model

AbstractDespite continued progress in the development of novel antiretroviral therapies, it has become increasingly evident that drug-based treatments will not lead to a functional or sterilizing cure for HIV+ patients. In 2009, an HIV+ patient was effectively cured of HIV following allogeneic transplantation of hematopoietic stem cells (HSCs) from a CCR5−/− donor. The utility of this approach, however, is severely limited because of the difficulty in finding matched donors. Hence, we studied the potential of HIV-resistant stem cells in the autologous setting in a nonhuman primate AIDS model and incorporated a fusion inhibitor (mC46) as the means for developing infection-resistant cells. Pigtail macaques underwent identical transplants and Simian-Human Immunodeficiency Virus (SHIV) challenge procedures with the only variation between control and mC46 macaques being the inclusion of a fusion-inhibitor expression cassette. Following SHIV challenge, mC46 macaques, but not control macaques, showed a positive selection of gene-modified CD4+ T cells in peripheral blood, gastrointestinal tract, and lymph nodes, accounting for >90% of the total CD4+ T-cell population. mC46 macaques also maintained high frequencies of SHIV-specific, gene-modified CD4+ T cells, an increase in nonmodified CD4+ T cells, enhanced cytotoxic T lymphocyte function, and antibody responses. These data suggest that HSC protection may be a potential alternative to conventional antiretroviral therapy in patients with HIV/AIDS.

P5.076 Deep Mycoses in Patients Infected with Human Immunodeficiency Virus (HIV) in Montevideo, Uruguay

BackgroundDeep fungal infections have been a major cause of morbidity and mortality in HIV-infected host, gaining importance due to their severity and poor prognosis. Because instituted antiretroviral therapy in patients...

Virological and immunological response to highly active antiretroviral therapy in patients over 50 years of age in a cohort of patients in Mexico

Virological and immunological response to highly active antiretroviral therapy in patients over 50 years of age in a cohort of patients in Mexico

Recomendaciones de GESIDA/Secretaría del Plan Nacional sobre el Sida para el tratamiento de la tuberculosis en adultos infectados por el virus de la inmunodeficiencia humana (actualización enero de 2013)

This consensus document was prepared by an expert panel of the Grupo de Estudio de Sida (GESIDA [Spanish AIDS Study Group]) and the Plan Nacional sobre el Sida (PNS [Spanish National AIDS Plan]). The document updates current guidelines on the treatment of tuberculosis (TB) in HIV-infected individuals contained in the guidelines on the treatment of opportunistic infections published by GESIDA and PNS in 2008. The document aims to facilitate the management and treatment of HIV-infected patients with TB in Spain, and includes specific sections and recommendations on the treatment of drug-sensitive TB, multidrug-resistant TB, and extensively drug-resistant TB, in this population. The consensus guidelines also make recommendations on the treatment of HIV-infected patients with TB in special situations, such as chronic liver disease, pregnancy, kidney failure, and transplantation. Recommendations are made on the timing and initial regimens of antiretroviral therapy in patients with TB, and on immune reconstitution syndrome in HIV-infected patients with TB who are receiving antiretroviral therapy. The document does not cover the diagnosis of TB, diagnosis/treatment of latent TB, or treatment of TB in children. The quality of the evidence was evaluated and the recommendations graded using the approach of the Grading of Recommendations Assessment, Development and Evaluation Working Group.

Impact of health care payer type on HIV stage of illness at time of initiation of antiretroviral therapy in the USA

There is evidence that earlier initiation of HIV antiretroviral therapy (ART) is associated with better outcomes, including lower morbidity and mortality. Based on recent studies indicating that Medicaid enrollees are more likely to have suboptimal access to medical care, we hypothesized that HIV severity at time of ART initiation is worse for Medicaid patients than patients with other health care coverage. We conducted a US retrospective analysis of GE Centricity Outpatient Electronic Medical Records spanning 1 January 1997 through 30 September 2009. Subjects included all adult HIV patients initiating first-line ART who had CD4+ results within 90 days pre-initiation. HIV stage was defined using CD4 ranges: >500 (n=520), 351–500 (n=379), 201–350 (n=580), or ≤200 (n=406) cells/mm3, with lower CD4 count being indicative of increased disease severity. Payer type was defined as the patient's primary payer: Medicaid, Medicare, commercial insurance, self-pay or other/unknown. After controlling for demographic and clinical covariates, cumulative logit models assessed the effect of payer type on HIV stage at ART initiation. The study included 1885 subjects with the primary payer being Medicaid (n=218), Medicare (n=330), commercial insurance (n=538), self-pay (n=159) or other/unknown (n=640). Final logit models demonstrated that, compared to patients on Medicaid, the odds of initiating ART at a higher CD4 range were significantly greater for those commercially insured (odds ratio [OR]=1.53; P=0.005), self-paying (OR=1.56; P=0.023) and other/unknown (OR=1.79; P<0.001) and similar for patients enrolled in Medicare (OR=1.11; P=0.521). Medicaid patients initiated ART at a more advanced stage of HIV than patients who were commercially insured, self-paying, or had other/unknown coverage. With HIV treatment guidelines now supporting ART initiation in patients with higher CD4 counts, these findings underscore the need for mitigating barriers, particularly in the Medicaid population, that may delay treatment initiation.

Optimal timing for antiretroviral therapy initiation in patients with HIV infection and concurrent cryptococcal meningitis

Currently, initiation of antiretroviral therapy (ART) in most patients with human immunodeficiency virus (HIV) infection is based on the CD4-positive-t-lymphocyte count. However, the point during the course of HIV infection at which ART should be initiated in patients with concurrent cryptococcal meningitis remains unclear. The aim of this systematic review was to summarise the evidence on the optimal timing of ART initiation in patients with cryptococcal meningitis for use in clinical practice and guideline development. To compare the clinical and immunologic outcomes for early initiation ART (less than four weeks after starting antifungal treatment) versus later initiation of HAART (four weeks or more after starting antifungal treatment) in HIV-positive patients with concurrent cryptococcal meningitis. We searched the following databases from January 1980 to February 2011: PubMed, EMBASE, and WHO International Clinical Trials Registry Platform, AEGIS database for conference abstracts, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews. A total of 35 full text articles were identified and supplemented by a bibliographic search. We contacted researchers and relevant organizations and checked reference lists of all included studies. Randomized controlled trials that compared the effect of ART (consisting of three drug combinations) initiated early or delayed in HIV patients with cryptococcal meningitis. Two review authors independently assessed study eligibility, extracted data, and graded methodological quality. Data extraction and methodological quality were checked by a third author who resolved differences when these arose. Where clinically meaningful, we performed a meta-analysis of dichotomous outcomes using the relative risk (RR) and report the 95% confidence intervals (95% CIs). Two eligible randomized controlled trials were included (N = 89). In our pooled analysis, we combined the clinical data for both trials comparing early initiation ART versus delayed initiation of ART. There was no statistically significant difference in mortality (RR=1.40, 95% CI [0.42, 4.68]) in the group with early initiation of ART compared to the group with delayed initiation of ART. This systematic review shows that there is insufficient evidence in support of either early or late initiation of ART. For the moment, because of the high risk of immune reconstitution syndrome in patients with cryptococcal meningitis, we recommend that ART initiation should be delayed until there is evidence of a sustained clinical response to antifungal therapy. However, large studies with appropriate comparison groups, and adequate follow-up are warranted to provide the evidence base for effective decision making.

Clinical aspects of visceral leishmaniasis in HIV infection

HIV infection profoundly impairs the immune mechanisms needed to control and clear Leishmania infection, and outcomes in patients with HIV-associated visceral leishmaniasis are poor. This review summarizes recent work describing the epidemiology, presentation and outcomes of HIV-associated visceral leishmaniasis and discusses advances in diagnosis and management. Studies have shown that serological tests can effectively diagnose HIV-associated visceral leishmaniasis, with a sensitivity of 98% if direct agglutination test and rK39 assays are used in combination. Few data exist to guide treatment recommendations. Observational data show high rates of toxicity and treatment failure with pentavalent antimonials, and their use is no longer recommended. Liposomal amphotericin B (L-AmB) is better tolerated, but outcomes are suboptimal, with mortality rates of 7-12%, and parasitological failure rates of up to 32%. Initial reports suggest that L-AmB and miltefosine in combination may be effective in HIV-associated visceral leishmaniasis; however, clinical trial data are lacking. Secondary prophylaxis reduces the rate of relapse, but optimal regimens have not been defined, and optimal timing of antiretroviral therapy initiation in patients with visceral leishmaniasis is unknown. Recent studies have demonstrated the inadequacy of current treatments for HIV-associated visceral leishmaniasis. Clinical trials are needed to improve early diagnosis, develop combination therapies and define effective secondary prophylaxis regimens.

The Clinical Impact of Continuing to Prescribe Antiretroviral Therapy in Patients with Advanced AIDS Who Manifest No Virologic or Immunologic Benefit

The Clinical Impact of Continuing to Prescribe Antiretroviral Therapy in Patients with Advanced AIDS Who Manifest No Virologic or Immunologic Benefit

A report from the 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (June 30-July 3, 2013 - Kuala Lumpur, Malaysia)

Effective antiretroviral drugs have been developed that, if continuously administered (although with simplification strategies once a patient's viral titer is suppressed) allow for a functional cure resulting in an almost normal life despite the presence of viral reservoirs. In that sense, observations that combination antiretroviral therapy has an untoward suppressive effect on antibody-dependent cellular cytotoxicity against T cells permitting the establishment of such viral reservoirs were discussed for its implications in the use of vaccines and/or modulators of the immune function to clear latent infections and the risk for reactivation (Madhavi, V. et al., Abst MOLBPE05). In addition to latent viral reservoirs, individual patient characteristics may also influence response to antiretroviral therapy, as exemplified by the increased likelihood of highly active antiretroviral therapy in patients carrying certain polymorphic variants (rs2229109, rs6961419) of the P-glycoprotein 1 gene (Dias, J. et al., Abst MOPE034). These, and many other important news derived from research into novel approaches to fight HIV infection were discussed during the International AIDS Society (IAS) meeting in Kuala Lumpur, as summarized in the following report.

HIV‐1 drug resistance‐associated mutations among antiretroviral‐naive thai patients with chronic HIV‐1 infection

Antiretroviral therapy (ART) has increased in resource-limited settings. This study determined the prevalence of HIV-1 drug resistance-associated mutations (DRAMs) among patients with chronic HIV-1 infections and compare DRAMs between CRF01_AE and B subtypes. ART-naive Thai patients who had ART initiation between 2010 and 2011 were enrolled prospectively. Genotypic assays were performed on viral reverse transcriptase and protease genes within 4 weeks before starting ART. DRAMs were assessed using the International AIDS Society-USA 2011 list. A total of 330 patients were included. HIV-1 subtypes included CRF01_AE (73%), B (23.9%), and others (3.1%). Median (IQR) CD4+ was 66 (23-172) cells/mm(3) and median (IQR) HIV-1 RNA was 5.2 (4.6-5.8) log copies/ml. The prevalence of patients with ≥1 DRAMs for any antiretroviral agents was 17.6%. DRAM prevalence was 17% for non-nucleoside reverse transcriptase inhibitors (NNRTIs), 0.6% for NRTIs, and 0.6% for protease inhibitors (PIs). DRAMs to NNRTIs were V106I (7%), V179D (4.2%), V179T (1.8%), E138A (1.5%), V90I (1.2%), K103N (0.9%), Y181C (0.9%), and P225H (0.3%). DRAMs to NRTIs were M184V (0.3%) and T215S (0.3%). The only major DRAM for PIs was M46L (0.6%). Minor DRAMs to PIs including I13V, M36I, H69K, and L89M were observed more frequently in CRF_01 AE. By multivariate analysis, the factors "HIV-1 subtype B" and "low pretreated CD4+ cell count" were associated with a higher rate of DRAMs. HIV-1 DRAMs, especially to NNRTIs, are emerging in a middle-income country after widespread use of NNRTI-based ART. HIV genotypic assays before ART initiation in patients with chronic HIV-1 infection should be considered.

Rosuvastatina e ciprofibrato no tratamento da dislipidemia em pacientes com HIV

Dyslipidemia secondary to highly active antiretroviral therapy in patients with HIV is associated with a significant increase in cardiovascular morbidity and mortality due to atherosclerotic disease, requiring, thus, immediate and effective treatment. To demonstrate the effectiveness and safety of rosuvastatin and ciprofibrate in the treatment of dyslipidemia associated with highly active antiretroviral therapy in patients with HIV. Three hundred and forty-six patients with dyslipidemia underwent pharmacological treatment as follows: 200 patients with hypertriglyceridemia received ciprofibrate (Group I); 79 patients with hypercholesterolemia received rosuvastatin (Group II); and 67 patients with mixed dyslipidemia received ciprofibrate associated with rosuvastatin (Group III). The lipid profile was assessed before and after the lipid-lowering treatment, and the Wilcoxon test was used for statistical comparison. Liver transaminases and creatine phosphokinase were measured to assess liver and muscle toxicity. The serum concentrations of triglycerides and total cholesterol were significantly lower than those obtained before the lipid-lowering treatment in the three experimental groups (p < 0.002). A significant increase in HDL-cholesterol was observed in Groups I and III (p < 0.002). In Groups I and II, LDL-cholesterol was significantly lower (p < 0.001). None of the patients experienced elevations in transaminases or creatine phosphokinase to significantly toxic levels. The results of this study show that ciprofibrate and rosuvastatin or a combination of both can be considered an effective, safe and well-tolerated lipid-lowering treatment for patients with AIDS on highly active antiretroviral therapy.

Importance of Identification of Complications of Antiretroviral Therapy in Patients With Multiorgan Dysfunction Syndrome

Importance of Identification of Complications of Antiretroviral Therapy in Patients With Multiorgan Dysfunction Syndrome