Use Of Antiretroviral Drugs Research Articles

Adverse Neuropsychiatric Events and Recreational Use of Efavirenz and Other HIV-1 Antiretroviral Drugs.

Efavirenz is a highly effective HIV-1 antiretroviral; however, it is also frequently associated with neuropsychiatric adverse events (NPAE) that include abnormal dreams, sleep disturbances, nervousness, anxiety, depression, and dizziness. The incidence of NPAEs upon initiation of treatment with efavirenz-containing medications is high, exceeding 50% in most studies. Although the NPAEs tend to decrease after the first month in many patients, they persist for long periods of time in others. Efavirenz-based treatment is generally well-tolerated in children, although some experience persistent concentration problems, as well as sleep disturbances, psychotic reactions, and seizures. In an effort to link basic with clinical research, parameters associated with efavirenz brain exposure are discussed, and factors that increase efavirenz levels are explored in depth as they are expected to contribute to NPAE risk. These include the role of modifiable and nonmodifiable risk factors such as diet, weight, and drug-drug interactions and sex, age, and ethnicity/pharmacogenetics. In addition to NPAEs, this review explores what is known about antiretroviral (ARV) drugs being used for recreational purposes. Although multiple ARV drugs are covered, special attention is devoted to efavirenz given that the majority of reports of NPAEs and illicit use of ARV drugs concern efavirenz. The evolving molecular mechanistic basis of NPAEs and abuse of efavirenz point to a complex and polymodal receptor pharmacology. Animal studies to date primarily point to a serotonergic mechanism of action. Recently emerging associations between HIV-associated neurocognitive disorder and efavirenz use, and possible contributions of the mitochondrial-immune-inflammatory-redox cascade are explored in the context of the signaling mechanisms that appear to be involved.

Antiretroviral therapy interruptions: impact on HIV treatment and transmission.

IntroductionSuccessful management of pediatric and adult human immunodeficiency virus (HIV) disease includes lifelong administration of antiretroviral therapy (ART). The need for the continuous use of antiretroviral drugs throughout the life course poses a challenge to children, adolescents, and adults living with HIV and their caregivers. Historically, treatment interruptions have been viewed as a negative therapeutic strategy. Recently, however, treatment interruptions or treatment reduction strategies have become a focus of investigations as innovative approaches to the long-term management of HIV disease. Current challenges with treatment interruptions include identifying an appropriate timeframe for length of interruptions and identifying HIV patient populations in whom the treatment interruption can be successful.ObjectiveIn this review, we aimed at summarizing recent studies of planned and unplanned treatment interruptions in children and adults living with HIV.Materials and methodsWe searched two databases (PubMed and Cochrane Controlled Trials Register) using keywords (HIV OR AIDS OR acquired immunodeficiency syndrome OR HIV-1 OR antiretroviral) AND (treatment interruption OR planned interruption OR therapeutic interruption OR unplanned interruption), for published randomized and nonrandomized clinical trials and observational cohort studies in children and adults (from birth to 99 years of age) in global settings covering a period from 2012 to 2018. In this review, only the studies that contained pediatric and adolescent populations with baseline immunological, virological, and clinical characteristics and outcomes after treatment interruption were included.ResultsA total of 174 eligible citations from the two databases were identified. We identified 10 prospective treatment interruption studies on children (five studies) and adults (five studies) during 2012–2018 with a total of 863 pediatric and 273 adult subjects. Collectively, recent studies on children and adults with HIV infection suggest that treatment interruptions with proper monitoring can be successful by instituting well-defined immunological and virological parameters or thresholds such as CD4 count, CD4%, and HIV RNA viral load that identify low-risk populations with treatment failure. In addition to standard virological and immunological outcome measurements, selected biomarkers that help detect early immune activation may also be useful in the monitoring of treatment interruption.ConclusionTreatment interruptions in adult and especially pediatric patients with well-controlled HIV disease may provide an alternative opportunity to optimize long-term HIV management by minimizing drug-associated toxicity and improving long-term adherence and quality of life.

14-Formyl-15-aryloxy/methoxymatrine and 14-Aryloxymethylidenyl-matrine Derivatives as Anti-HIV-1 Agents.

The human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) has always been a global health threat and leading cause of deaths. However, due to the emergence of drug-resistant HIV, an inevitable consequence of increasing use of antiretroviral drugs posed a major threat to antiretroviral therapy success. The discovery of anti-HIV-1 agents will be used for the effective treatment of HIV/AIDS. In continuation of our program aimed to discover anti-HIV-1 agents, twelve matrine derivatives, such as 14-formyl-15-aryloxy/methoxymatrines (3a-j) and 14-aryloxymethylidenylmatrines (3k,l), were semi-prepared from matrine, and evaluated against HIV-1 IIIB replication in acutely infected C8166 cells in vitro. Among them, compound 3j showed the most potent anti-HIV-1 activity with EC50 and therapeutic index (TI) values of 1.79 µg/mL, and 98.2, respectively. It has been demonstrated that the positions of methyl on the phenyl ring and 14- formylmatrine-15-oxy on the naphthyl ring were very important for the activity. It will lay the foundation for further structural modification and application of matrines as HIV-1 inhibitors.

A study of the monitoring of the adverse drug reactions caused by antiretroviral drugs

Introduction: Human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) is a disease of the human immune system. The drugs used in the treatment of HIV/AIDS are known to cause adverse effects, therefore this study was carried out for the monitoring and evaluation of adverse drug reactions (ADRs) caused by the use of antiretroviral drugs in patients of HIV/AIDS. Methods: A prospective, observational, cross sectional study was done in Andaman & Nicobar Islands institute of medical sciences, to monitor ADRs caused by Antiretroviral therapy (ART) over a period of 10 months in 120 patients of HIV/AIDS. Out of 120 patients, 84 had ADR’s. The data collected was filled in the spontaneous ADR reporting forms and Causality assessment was done using the WHO-UMC and Naranjo scale, seriousness was considered as per the ADR reporting form. Results: The study shows that out of 84 patients with ADR’s, 52 patients (61.9%) reported at least one ADR. 68 ADR’s (80.9%) were attributed to the tenofovir + lamivudine + efavirenz regimen. Most of the ADRs were from the system organ class of neurological disorders as 55 patients (65.4%) and 16 patients (19%) were having gastrointestinal ADR’s (19.44%) followed by Cutaneous ADR’s in 5 patients (5.9%). Causality assessment by WHO-UMC scale revealed most of the reactions as ‘possible’ (99.2%) while Naranjo scale assessed most of them as ‘probable’ (69.8%). Conclusion: Antiretroviral drugs have a huge potential for causing ADRs specially neurological and gastrointestinal. Active Pharmacovigilance is vital in recognizing such reactions to ensure timely management and optimal therapeutic outcomes.

FAKTOR-FAKTOR YANG MEMPENGARUHI KEPATUHAN MINUM OBAT ANTIRETROVIRAL DI KELOMPOK DUKUNGAN SEBAYA SEHATI MADIUN (FACTORS AFFECTING ADHERANCE OF TAKING ANTIRETROVIRAL DRUGS IN SEBAYA SEHATI GROUPS MADIUN)

Provision of antiretroviral therapy dramatically decrease the mortality and morbidity of people with HIV / AIDS. Antiretroviral therapy was reduced the rate of HIV transmission in the community, reduced morbidity and mortality associated with HIV, improved the quality of life of , restored and maintained immune function, suppressed viral replication maximally and on continuously. purpose of the research is for knowing was to determine the factors that influence adherence to the use of antiretroviral drugs in HIV / AIDS patients.The type of research is observational analytic with cross sectional approach. The sampling technique used was total sampling of 46 respondents. Data collection using questionnaire through interview. Data analysis was done bivariate and multivariate. The results showed that the factors that influence the adherence of taking ARV drugs among others. The results showed that factors affecting ARV drug adherence were ARV therapy guidelines (p = 0,000, OR = 24.0; 95% CI = 7,9-12,4), coexistent disease characteristics (p = 0.001; OR = 6.66, 95% CI = 1.6-22.2), and family support (p = 0.001; OR = 4.4; 95% CI = 1.3-12.4). This study demonstrates the importance of health counseling to improve adherence to antiretroviral drugs

Hematological Related Disorders and Transfusion of HIV Patients on Highly Active Antiretroviral Therapy (HAART) in the South West Region of Cameroon: Hematological Monitory Parameters for HIV Follow-Up

Background: Hematological abnormalities are probably the commonest complications with Human Immuno-deficiency Virus (HIV). Some antiretroviral (ARV) drugs have been documented to have cytopenic effects, in particular when used as a mono-therapy. The use of antiretroviral drugs could positively or negatively affect these parameters, depending on the choice of combination used. Records of transfusion associated with HIV patients during treatment in Cameroon are scarce. Hematological profile is supposed to be properly monitored during treatment with respect to other associated risk factors like duration on Anti-Retroviral Therapy (ART) and adherence to ART, to improve on the care of the patients and prevent further complications like transfusion. Method: A hospital-based descriptive cross-sectional study was conducted from January 2015 to May 2015. A total of 285 HIV-1/AIDS adult patients on Highly Active Antiretroviral Therapy (HAART) for at least 6 months were enrolled in this study. Participants were grouped into four based on, duration on HAART; Group one (6 months-1 year), Group two (>1 year-3 years), Group three (>3 years-5 years) and Group four (>5 years). Venous blood was collected and analysed using an automated hematology analyzer (Hematology analyzer Sysmex KX-21) for the following parameters: hemoglobin, number of platelets, total white blood cells and differential in HIV-1 patients. Results: Of the 285 patients studied, 167 (58.6%) were anemic, among which 52 (18.2%) were from group one; 113 (39.7%) had eosinophilia, among which 33 (11.6%) were from group one; 83 (29.1%) were neutropenic, among which 25 (8.8%) were from group four; 57 (20%) had leucopenia, among which 16 (5.6%) were both from group one and three; 40 (14%) had thrombocytopenia, among which 14 (4.9%) were from group three; 15 (5.3%) had thrombocytosis, among which 6 (2.1%) were from group two; 4 (1.4%) had leukocytosis, among which 2 (0.7%) were from group four; and 3 (1.1%) were neutrophilic. There was a significant statistic difference in hematological disorder among treatment groups (groups one, three and four) only for anemia P<0.05. Among the 285 patients, 22 (7.7%) had been transfused either one or more times during HAART. The prevalence of transfusion with respect to treatment groups were 8 (11%) from group two, followed by 5 (7%) from groups one and three, and lastly 4 (6%) from group four, with a statistically significant association between gender (P<0.001), age (P<0.020) and HAART regimen (P<0.001) with transfusion. Conclusion: There were significant prevalence of anemia, eosinophilia, neutropenia, leucopenia and thrombocytopenia in HIV-1 patients on HAART in the south west region of Cameroon. A close monitoring of hematology abnormalities of these patients on HAART is advised. The transfusion rate after initiation of HAART is common in the south west region of Cameroon, and it is significantly associated with HAART regimen, age and gender.

Time to overcome pretreatment HIV drug resistance

Time to overcome pretreatment HIV drug resistance

From policy to practice: exploring the implementation of antiretroviral therapy access and retention policies between 2013 and 2016 in six sub-Saharan African countries

BackgroundUnderstanding the implementation of 2013 World Health Organization (WHO) consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection at the facility level provides important lessons for the roll-out of future HIV policies.MethodsA national policy review was conducted in six sub-Saharan African countries to map the inclusion of the 2013 WHO HIV treatment recommendations. Twenty indicators of policy adoption were selected to measure ART access (n = 12) and retention (n = 8). Two sequential cross-sectional surveys were conducted in facilities between 2013/2015 (round 1) and 2015/2016 (round 2) from ten health and demographic surveillance sites in Kenya, Malawi, South Africa, Tanzania, Uganda and Zimbabwe. Using standardised questionnaires, facility managers were interviewed. Descriptive analyses were used to assess the change in the proportion of facilities that implemented these policy indicators between rounds.ResultsAlthough, expansion of ART access was explicitly stated in all countries’ policies, most lacked policies that enhanced retention. Overall, 145 facilities were included in both rounds. The proportion of facilities that initiated ART at CD4 counts of 500 or less cells/μL increased between round 1 and 2 from 12 to 68%, and facilities initiating patients on 2013 WHO recommended ART regimen increased from 42 to 87%. There were no changes in the proportion of facilities reporting stock-outs of first-line ART in the past year (18 to 11%) nor in the provision of three-month supply of ART (43 to 38%). None of the facilities provided community-based ART delivery.ConclusionThe increase in ART initiation CD4 threshold in most countries, and substantial improvements made in the provision of WHO recommended first-line ART regimens demonstrates that rapid adoption of WHO recommendations is possible. However, improved logistics and resources and/or changes in policy are required to further minimise ART stock-outs and allow lay cadres to dispense ART in the community. Increased efforts are needed to offer longer durations between clinic visits, a strategy purported to improve retention. These changes will be important as countries move to implement the revised 2015 WHO guidelines to initiate all HIV positive people onto ART regardless of their immune status.

CNS penetration of ART in HIV-infected children.

Paediatric data on CNS penetration of antiretroviral drugs are scarce. To evaluate CNS penetration of antiretroviral drugs in HIV-infected children and explore associations with neurocognitive function. Antiretroviral drug levels were measured in paired CSF and blood samples of clinically stable HIV-infected children between 8 and 18 years old on long-term combined ART. Plasma drug concentrations were corrected for protein binding. We evaluated CNS penetration using CSF/plasma ratios and compared CSF concentrations with the IC50 as a surrogate marker for effectiveness. Blood-brain barrier permeability was assessed for possible confounding. Associations with neurocognitive function were explored using linear regression analysis. Median CSF/plasma ratios (IQR) were: lopinavir 0.059 (0.024-0.157, n = 7), efavirenz 0.681 (0.555-0.819, n = 12), tenofovir 0.021 (0.020-0.024, n = 4), lamivudine 0.464 (0.331-0.607, n = 17), emtricitabine 0.365 (0.343-0.435, n = 3), nevirapine 1.203 (n = 1), zidovudine 0.718 (0.711-1.227, n = 5) and abacavir 1.344 (0.670-2.450, n = 10). CSF concentrations were below the IC50 for tenofovir (100%), emtricitabine (100%), abacavir (50%) and zidovudine (17%). Lamivudine, lopinavir, efavirenz and nevirapine concentrations were all above the IC50. All participants were virologically suppressed in blood and CSF. CSF drug concentrations were not associated with blood-brain barrier permeability or neurocognitive function. We showed adequate CSF concentrations of lamivudine, lopinavir, efavirenz and nevirapine, and potential suboptimal CSF concentrations of tenofovir, abacavir and emtricitabine in long-term treated HIV-infected children. None the less, the use of combined antiretroviral drugs led to adequate viral suppression.

Effects of antiretroviral treatment and nadir CD4 count in progression to cardiovascular events and related comorbidities in a HIV Brazilian cohort: a multi-stage approach

ABSTRACTThe use of highly active antiretroviral therapy has resulted in changes of comorbidity profile in people living with HIV (PLHIV), increasing non-AIDS-related events. The occurrence of cardiovascular events is greater in PLHIV, but the mechanism responsible for it is still controversial. This article aimed to investigate factors associated with the progression to cardiovascular events in PLHIV using HAART. A 15-years cohort study with 1135 PLHIV was conducted in Rio de Janeiro-Brazil. Clinical progression was stratified in five states: No comorbidities (s1), arterial hypertension (s2), lipid abnormalities (s3), hypertension and lipid abnormalities (s4) and major cardiovascular events (stroke, coronary artery disease, thrombosis or death) (s5). Semi-Markov models evaluated the effects of cardiovascular traditional factors, treatment and clinical covariates on transitions between these states. Hazard Ratios (HR) and 95% confidence intervals (CI) were provided. In addition to traditional factors (age, sex, educational level and skin color), the development of one comorbidity (lipid abnormalities or hypertension) increased in patients with low nadir CD4 (<50 cells/mm3), (HR = 1.59, CI 1.11–2.28 and 1.36, CI 1.11–1.66, respectively). The risk to experience a second comorbidity (s3→s4) increased 75% with low nadir CD4. Age was the only factor that increased the risk of major cardiovascular events once having lipid abnormalities with or without hypertension (s3,s4→s5). The prolonged use of certain antiretroviral drugs (abacavir, didanosine, ritonavir, lopinavir, amprenavir and fosamprenavir) increased the risk of direct transition (s1→s5) to major cardiovascular events (HR = 5.29, CI 1.16–24.05). This analysis suggests that prolonged use of certain antiretroviral drugs led directly to major cardiovascular events, while low nadir CD4 only affected the occurrence of lipid abnormalities and hypertension. Management strategies, including rational use of complex exams (such as, computed-tomography angiography), statins and antihypertensives, should be developed based on the distinct roles of antiretroviral use and of HIV infection itself on the progression to cardiovascular events.

Central nervous system-penetrating antiretrovirals impair energetic reserve in striatal nerve terminals.

The use of antiretroviral (ARV) drugs with central nervous system (CNS) penetration effectiveness (CPE) may be useful in the treatment of HIV-associated neurocognitive disorder (HAND) as well as targeting a CNS reservoir in strategies to achieve a functional cure for HIV. However, increased cognitive deficits are linked to at least one of these drugs (efavirenz). As mitochondrial dysfunction has been found with a number of ARVs, and as such can affect neuronal function, the objective of this study was to assess the effects of ARV with high CPE for toxicological profiles on presynaptic nerve terminal energy metabolism. This subcellular region is especially vulnerable in that a constant supply of ATP is required for the proper maintenance of neurotransmitter release and uptake supporting proper neuronal function. We evaluated the effects of acute treatment with ten different high CPE ARVs from five different drug classes on rat cortical and striatal nerve terminal bioenergetic function. While cortical nerve terminal bioenergetics were not altered, striatal nerve terminals exposed to efavirenz, nevirapine, abacavir, emtricitabine, zidovudine, darunavir, lopinavir, raltegravir, or maraviroc (but not indinavir) exhibit reduced mitochondrial spare respiratory capacity (SRC). Further examination of efavirenz and maraviroc revealed a concentration-dependent impairment of striatal nerve terminal maximal mitochondrial respiration and SRC as well as a reduction of intraterminal ATP levels. Depletion of ATP at the synapse may underlie its dysfunction and contribute to neuronal dysfunction in treated HIV infection.

IDENTIFICATION OF ANTIRETROVIRAL MUTATION IN PROTEASE AND REVERSE TRANCRIPTASE INHIBITOR IN HUMAN IMMUNODEFICIENCY VIRUS-1 OF HIV/AIDS PATIENTS IN MIMIKA REGENCY, PAPUA

Treatment with RT Inhibitors has been used as first line program in Mimika. Regular use of antiretroviral drugs can lower the amount of the virus, but after that HIV can become resistant to the drugs given. Viral resistance to the drugs can occur because of a mutation. If the resistance-associated mutations occur in the DNA of the virus, then the ARV provided will no longer be effective. The aim of this study was to identify the presence of resistance-associated mutations in DNA fragment that encodes the protease and reverse transcriptase. This study used cross sectional design with 84 subjects who had received antiretroviral for &gt; 6 months. The study was conducted in Mitra Masyarakat Mimika Hospital. Laboratory process included extraction, RT-PCR, electrophoresis and sequencing. Data analysis used resistance interpretation algorithms in HIV Database. Results showed that 1 subject who did not receive protease therapy was identified as having minor mutation L10V, 1 subjects receiving NRTI inhibitors had mutation M184V motive and 1 subjects with M41L motive and 1 subjects who received NNRTI inhibitor therapy identified as having mutated Y181C and V108I motive. In conclusion, mutant HIV-1 related to ARV resistance has been identified in two subjects who had received antiretroviral therapy in Mitra Masyarakat Mimika Hospital.

Antiviral Functions of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific IgG Antibodies: Effects of Antiretroviral Therapy and Implications for Therapeutic HIV-1 Vaccine Design.

Contemporary antiretroviral therapy (ART) is effective and tolerable for long periods of time but cannot eradicate human immunodeficiency virus type 1 (HIV-1) infection by either elimination of viral reservoirs or enhancement of HIV-1-specific immune responses. Boosting “protective” HIV-1-specific immune responses by active or passive immunization will therefore be necessary to control or eradicate HIV-1 infection and is currently the topic of intense investigation. Recently reported studies conducted in HIV patients and non-human primate (NHP) models of HIV-1 infection suggest that HIV-1-specific IgG antibody responses may contribute to the control of HIV-1 infection. However, production of IgG antibodies with virus neutralizing activity by vaccination remains problematic and while vaccine-induced natural killer cell-activating IgG antibodies have been shown to prevent the acquisition of HIV-1 infection, they may not be sufficient to control or eradicate established HIV-1 infection. It is, therefore, important to consider other functional characteristics of IgG antibody responses. IgG antibodies to viruses also mediate opsonophagocytic antibody responses against virions and capsids that enhance the function of phagocytic cells playing critical roles in antiviral immune responses, particularly conventional dendritic cells and plasmacytoid dendritic cells. Emerging evidence suggests that these antibody functions might contribute to the control of HIV-1 infection. In addition, IgG antibodies contribute to the intracellular degradation of viruses via binding to the cytosolic fragment crystallizable (Fc) receptor tripartite motif containing-21 (TRIM21). The functional activity of an IgG antibody response is influenced by the IgG subclass content, which affects binding to antigens and to Fcγ receptors on phagocytic cells and to TRIM21. The IgG subclass content and avidity of IgG antibodies is determined by germinal center (GC) reactions in follicles of lymphoid tissue. As HIV-1 infects cells in GCs and induces GC dysfunction, which may persist during ART, strategies for boosting HIV-1-specific IgG antibody responses should include early commencement of ART and possibly the use of particular antiretroviral drugs to optimize drug levels in lymphoid follicles. Finally, enhancing particular functions of HIV-1-specific IgG antibody responses by using adjuvants or cytokines to modulate the IgG subclass content of the antibody response might be investigated in NHP models of HIV-1 infection and during trials of therapeutic vaccines in HIV patients.

Adaptive HIV-1 evolutionary trajectories are constrained by protein stability.

Despite the use of combination antiretroviral drugs for the treatment of HIV-1 infection, the emergence of drug resistance remains a problem. Resistance may be conferred either by a single mutation or a concerted set of mutations. The involvement of multiple mutations can arise due to interactions between sites in the amino acid sequence as a consequence of the need to maintain protein structure. To better understand the nature of such epistatic interactions, we reconstructed the ancestral sequences of HIV-1’s Pol protein, and traced the evolutionary trajectories leading to mutations associated with drug resistance. Using contemporary and ancestral sequences we modelled the effects of mutations (i.e. amino acid replacements) on protein structure to understand the functional effects of residue changes. Although the majority of resistance-associated sequences tend to destabilise the protein structure, we find there is a general tendency for protein stability to decrease across HIV-1’s evolutionary history. That a similar pattern is observed in the non-drug resistance lineages indicates that non-resistant mutations, for example, associated with escape from the immune response, also impacts on protein stability. Maintenance of optimal protein structure therefore represents a major constraining factor to the evolution of HIV-1.

An overview of the molecular and epidemiological features of HIV-1 infection in two major cities of Bahia state, Brazil.

BACKGROUND The high mutation rate of the human immunodeficiency virus (HIV) has created a public health challenge because the use of antiretroviral drugs can generate selective pressure that drives resistance in these viruses.OBJECTIVE The aim of this work was to characterise the molecular and epidemiological profile of HIV in Bahia, Brazil.METHODS DNA sequences from regions of HIV gag, pol, and env genes were obtained from previous studies performed in this area between 2002 and 2012. Their genotype and drug-resistance mutations were identified using bioinformatics tools. Clinical and epidemiological data were analysed.FINDINGS Among 263 individuals (46.4% male), 97.5% were asymptomatic and 49.1% were receiving treatment. Most of the individuals were 31 to 40 years old (36.9%) and infected through heterosexual contact (40.7%). The predominant genotype was B (68.1%) followed by BF recombinants (18.6%). Among the individuals infected with either F or BF genotypes, 68.4% were women and 76.8% were infected through heterosexual transmission. The prevalence of associated mutations conferring antiretroviral resistance was 14.2%, with 3.8% of all mutations conferring resistance to protease inhibitors, 9.43% to nucleoside reverse transcriptase inhibitors, and 8.5% to non-nucleoside reverse transcriptase inhibitors. Drug resistance was higher in individuals receiving treatment (26.1%) than in the drug-naïve (4.3%) individuals.MAIN CONCLUSIONS This study will contribute to the understanding and monitoring of HIV epidemic in this Brazilian region.

Living and dying to be counted: What we know about the epidemiology of the global adolescent HIV epidemic.

Introduction: With increasing survival of vertically HIV‐infected children and ongoing new horizontal HIV infections, the population of adolescents (age 10–19 years) living with HIV is increasing. This review aims to describe the epidemiology of the adolescent HIV epidemic and the ability of national monitoring systems to measure outcomes in HIV‐infected adolescents through the adolescent transition to adulthood. Methods: Differences in global trends between younger (age 10–14 years) and older (age 15–19 years) adolescents in key epidemic indicators are interrogated using 2016 UNAIDS estimates. National population‐based survey data in the 15 highest adolescent HIV burden countries are evaluated and examples of national case‐based surveillance systems described. Finally, we consider the potential impact of adolescent‐specific recommendations in the 2016 WHO Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection. Discussion: UNAIDS estimates indicate the population of adolescents living with HIV is increasing, new HIV infections in older adolescents are declining, and while AIDS‐related deaths are beginning to decline in younger adolescents, they are still increasing in older adolescents. National population‐based surveys provide valuable estimates of HIV prevalence in older adolescents and recent surveys include data on younger adolescents. Only a few countries have nationwide electronic case‐based HIV surveillance, with the ability to provide population‐level data on key HIV outcomes in the diagnosed population living with HIV. However, in the 15 highest adolescent HIV burden countries, there are no systems tracking adolescent transition to adulthood or healthcare transition. The strength of the 2016 WHO adolescent‐specific recommendations on antiretroviral therapy and provision of HIV services to adolescents was hampered by the lack of evidence specific to this age group. Conclusions: Progress is being made in national surveillance and global monitoring systems to specifically identify trends in adolescents living with HIV. However, HIV programmes responsive to the evolving HIV prevention and treatment needs of adolescents can be facilitated further by: data disaggregation to younger and older adolescents and mode of HIV infection where feasible; implementation of tools to achieve expanded national case‐based surveillance; streamlining consent/assent procedures in younger adolescents and consensus on indicators of adolescent healthcare transition and transition to adulthood.

Long-Acting Antiretrovirals: Where Are We now?

Current HIV treatment options require daily use of combination antiretroviral drugs. Many persons living with HIV experience treatment fatigue and suboptimal adherence as a result. Long-acting antiretroviral drugs are being developed to expand options for HIV treatment. Here, we review the agents in development, and evaluate data from recent clinical trials. In addition, we anticipate challenges to successful widespread use of long-acting antiretrovirals. Parenteral nanosuspensions of cabotegravir and rilpivirine, and dapivirine vaginal ring are the farthest in clinical development. Long-acting modalities in earlier development stages employ drug-loaded implants, microparticles, or targeted mutagenesis, among other innovations. Long-acting antiretroviral drugs promise new options for HIV prevention and treatment, and ways to address poor adherence and treatment fatigue. Further studies will identify the long-acting agents or combinations that are suitable for routine use. Creative solutions will be needed for anticipated implementation challenges.

Underlying mechanisms of HIV-1 latency.

Similarly to other retroviruses, HIV-1 integrates its genome into the cellular chromosome. Expression of viral genes from the integrated viral DNA could then be regulated by the host genome. If the infected cell suppresses viral gene expression, the virus will undergo latency. The latently infected cells cannot be detected or cleared by the immune system since they do not express viral antigens. These cells remain undetected for several years, even under antiretroviral treatments. The silenced HIV-1 DNA could be reactivated under certain conditions. Despite the efficient use of antiretroviral drugs, HIV-1 latently infected cells remain the major obstacles to a permanent cure. In this review, we discuss the cellular and molecular mechanisms through which HIV-1 establishes latency.

Tenofovir prodrugs: similar but not the same

Thanks to combination antiretroviral therapy, HIV infection is now often a chronic illness, and patients have near-normal life expectancy. Current treatment combinations suppress viral load below the detection limit in most patients and once-daily dosing is now the norm. In the absence of a cure, however, patients need lifelong treatment to prevent viral rebound and progression to AIDS. This situation has led to an increased effort to reduce the long-term toxicity of combination antiretroviral therapy. Tenofovir disoproxil fumarate, in combination with emtricitabine, is one of the most frequently used antiretrovirals. 1 WHOConsolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. World Health Organization, Geneva2016 Google Scholar , 2 European AIDS Clinical Society (EACS)European Guidelines for Treatment of HIV Positive Adults in Europe. Version 8.0. http://www.eacsociety.org/files/guidelines_8.1-english.pdfDate: 2015 Google Scholar Switching from efavirenz, emtricitabine, and tenofovir disoproxil fumarate to tenofovir alafenamide coformulated with rilpivirine and emtricitabine in virally suppressed adults with HIV-1 infection: a randomised, double-blind, multicentre, phase 3b, non-inferiority studySwitching to rilpivirine, emtricitabine, and tenofovir alafenamide from efavirenz, emtricitabine, and tenofovir disoproxil fumarate was non-inferior in maintaining viral suppression and was well tolerated at 48 weeks. These findings support guidelines recommending tenofovir alafenamide-based regimens, including coformulation with rilpivirine and emtricitabine, as initial and ongoing treatment for HIV-1 infection. Full-Text PDF Switching from tenofovir disoproxil fumarate to tenofovir alafenamide coformulated with rilpivirine and emtricitabine in virally suppressed adults with HIV-1 infection: a randomised, double-blind, multicentre, phase 3b, non-inferiority studySwitching to rilpivirine, emtricitabine, and tenofovir alafenamide was non-inferior to continuing rilpivirine, emtricitabine, tenofovir disoproxil fumarate in maintaining viral suppression and was well tolerated at 48 weeks. These findings support guidelines recommending tenofovir alafenamide-based regimens, including coformulation with rilpivirine and emtricitabine, as initial and ongoing treatment for HIV-1 infection. Full-Text PDF

Cardiovascular disease in women with HIV-1 infection

Cardiovascular disease is a leading cause of death in women, nevertheless it is often underestimated in female patients without overt risk factors. The chronic infection by Human Immunodeficiency Virus (HIV) is clearly associated, along with the use of certain antiretroviral drugs and traditional risk factors, with an increased risk of cardiovascular diseases. The aim of this manuscript is to review the epidemiology, risk factors, pathogenesis, diagnostic approach, primary and secondary prevention strategies of cardiovascular disease in HIV-negative and HIV-positive female subjects. The ultimate goal is to promote knowledge and development of specific and appropriate clinical interventions and guidelines in this group of high-risk patients, mostly in view of the expected growth of ageing females with HIV.