Antiretroviral-naive Patients Research Articles

Cabotegravir: its potential for antiretroviral therapy and preexposure prophylaxis.

Analyzing the evidence for the strand transfer integrase inhibitor cabotegravir (CAB; GSK744, GSK1265744), its properties and differences from other compounds in the class, as well as reviewing the preclinical and clinical evidence for its potential in antretroviral therapy and medical HIV prevention. CAB has been investigated both as an oral and an injectable compound. Recent results show that it has promising properties with regards to its potential for parenteral maintenance therapy in combination with other compounds in HIV-infected patients currently suppressed on oral agents, as well as in preexposure prophylaxis. The strand transfer integrase inhibitor CAB is currently being investigated as an intramuscular preparation with a long half-life allowing for four to eight-weekly injection intervals, and as an oral preparation. The latter is currently only used in trials for achieving an undetectable viral load in antiretroviral-naive patients, assessing tolerability, and covering phases of suboptimal exposure to the parenteral preparation. Phase 2 trials of a dual regimen of CAB and rilpivirine have demonstrated promising virological activity in oral as well as in parenteral therapy, which are currently investigated in phase three trials. Moreover, CAB protected macaques from experimental simian/human immunodeficiency virus infection and showed promising tolerability in the first trial in humans for preexposure prophylaxis of HIV infection. CAB might, therefore, provide the basis of the new treatment paradigm of parenteral treatment and prevention of HIV infection.

Tenofovir and emtricitabine resistance among antiretroviral-naive patients in the Canadian Observational Cohort Collaboration: implications for PrEP.

The real-world effectiveness of pre-exposure prophylaxis (PrEP) may be influenced by circulating HIV strains resistant to either tenofovir or emtricitabine. Yet, few studies have examined rates of resistance to these drugs in clinical settings. We conducted a retrospective cohort study of antiretroviral-naive participants in the Canadian Observational Cohort collaboration who initiated antiretroviral therapy between 2006 and 2014. In separate analyses, we determined the prevalence of pretherapy resistance and cumulative incidence of follow-up resistance to tenofovir and emtricitabine. We used multivariable proportional hazards models to examine associations between baseline variables and the development of resistance. We studied 6,622 antiretroviral-naive participants initiating therapy, of whom 5,428 (82.0%) had a baseline resistance test. Baseline resistance to tenofovir and emtricitabine was observed in 83 (1.5%) and 21 (0.4%) patients, respectively. Among patients without baseline resistance, the cumulative incidence of resistance to tenofovir and emtricitabine 5 years following treatment initiation was 0.0070 (95% CI 0.0046, 0.0095) and 0.033 (95% CI 0.028, 0.038), respectively. Following multivariable analysis, a baseline viral load ≥100,000 copies/ml was associated with emergence of tenofovir (hazard ratio [HR] 2.88; 95% CI 1.35, 6.15) and emtricitabine (HR 2.27; 95% CI 1.64, 3.15) resistance. Initiating an integrase inhibitor-based regimen and CD4+ T-cell count below 200 cells/mm3 were also associated with resistance to each drug. We observed a low prevalence of baseline resistance and a low incidence of emergence of resistance to tenofovir and emtricitabine among antiretroviral-naive patients in routine clinical care.

Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics of Efavirenz 400 mg Once Daily During Pregnancy and Post-Partum

A clinical trial showed that efavirenz 400 mg once daily (EFV400) is as effective as the standard adult dose. World Health Organization recommends EFV400 as an alternative first-line agent, but data are lacking in the third trimester of pregnancy (TT). We investigated the pharmacokinetics, efficacy, and CYP2B6 pharmacogenetics in HIV-infected women (WLWH) on EFV400 during TT and post-partum (PP). An open-label 2-center study (United Kingdom, Uganda) was conducted in WLWH receiving antiretroviral regimens containing efavirenz 600 mg, who had their efavirenz dose reduced to EFV400. Weekly therapeutic drug monitoring (TDM), steady-state pharmacokinetic profiles (TT and PP), safety, virological efficacy, and CYP2B6 polymorphisms at positions 516 (C > T) and 938 (T > C) were evaluated. Twenty-five WLWH of African origin were enrolled. All had viral loads <50 copies/mL at baseline, which were maintained throughout the study. No infant was HIV infected. No WLWH were withdrawn due to low EFV400 TDM results. Geometric mean ratios (TT/PP; 90% confidence interval) for EFV400 maximum observed plasma concentration, area under the curve, and plasma concentration measured 24 hours after the observed dose were 0.97 (.85-1.10), 0.87 (.76-.99), and 0.77 (.65-.91), respectively. Five of 25 WLWH were slow metabolizers. Although EFV400 pharmacokinetic parameters were slightly lower for TT compared with PP values, efavirenz concentrations exceeded cutoff levels established by the study and those measured in antiretroviral-naive patients receiving EFV400 in ENCORE1. All subjects maintained a viral load <50 copies/mL, suggesting that EFV400 can be used in pregnant WLWH.

Minority resistant variants are also present in HIV-2-infected antiretroviral-naive patients.

To assess the prevalence of minority resistant variants (MRV) and X4-tropic minority variants in ART-naive HIV-2-infected patients. ART-naive HIV-2-infected patients with detectable plasma viral load (>100 copies/mL) included in the ANRS HIV-2 CO5 Cohort were assessed. We performed ultra-deep sequencing (UDS) of protease, RT, integrase and gp105 regions. Only mutations in the HIV-2 ANRS list >1% were considered. HIV-2 tropism was assessed by V3 loop region UDS, and each read was interpreted with determinants of CXCR4-coreceptor use. Among the 47 patients assessed, three displayed plasma viruses with a resistance-associated mutation (RAM) above the 20% detection threshold, all in RT, resulting in a prevalence of transmitted drug resistance for NRTI of 7.9% (95% CI 0.0%-16.5%). No RAM above the 20% detection threshold was found in protease or integrase. At the 1% detection threshold the transmitted drug resistance prevalence was 9.8% (95% CI 0.6%-19.0%), 13.2% (95% CI 3.5%-22.9%) and 4.5% (95% CI 0%-17.5%) for PI, NRTI and integrase inhibitors. The most prevalent MRV was the PI RAM I50V detected in three samples. Tropism analysis showed that 21% of patients (4 of 19) exhibited X4-tropic viruses: two in majority proportion and two in minority proportions (1.5% and 1.9%). In this first study assessing the prevalence of MRV in HIV-2 infection among ART-naive patients, we observed a 2-3-fold higher prevalence of RAM when a 1% detection threshold of mutations was used compared with a 20% threshold. Similarly, the proportion of patients with X4-tropic viruses was twice as high when UDS was used.

Phenotypic analysis of HIV-1 E157Q integrase polymorphism and impact on virological outcome in patients initiating an integrase inhibitor-based regimen.

To assess the phenotypic susceptibility of the E157Q polymorphism in HIV-1 integrase (IN) and the virological outcome of patients infected with E157Q-mutated virus initiating an IN inhibitor (INI)-based regimen. This was a multicentre study assessing IN sequences from INI-naive patients among 17 French HIV clinical centres. E157Q site-directed mutants in pNL4.3 and pCRF02_AG contexts were assessed in a recombinant phenotypic assay. Prevalence of the E157Q polymorphism was 2.7% among 8528 IN sequences from INI-naive patients and its distribution was 1.7%, 5.6% and 2.2% in B, CRF02_AG and various non-B subtypes, respectively. Thirty-nine INI-naive patients with E157Q-mutated virus initiated an INI-based regimen. Among them, 15 had a viral load (VL) <50 copies/mL at initiation and virological suppression was maintained during the first year of follow-up in all but two exhibiting a viral blip. Twenty-four patients had a VL > 50 copies/mL at the time of INI-based regimen initiation. Among them eight were receiving a first-line regimen and the only two patients who did not reach VL < 50 copies/mL at week 24 were receiving elvitegravir. The 16 remaining patients were ART experienced in virological failure with drug-resistant viruses displaying several virological outcomes independently of the genotypic susceptibility score. Phenotypic analyses showed a fold change in EC50 of 0.6, 0.9 and 1.9 for raltegravir, dolutegravir and elvitegravir, respectively, in a subtype B context, and 1.1, 1.9 and 2.4 for raltegravir, dolutegravir and elvitegravir, respectively, in a CRF02_AG context. Assessment of virological response in 39 patients initiating an INI-based regimen with E157Q-mutated virus, in combination with phenotypic analysis, suggests that particular attention should be paid to antiretroviral-naive patients and dolutegravir should be preferentially used in these patients.

Seroprevalence and Risk Factors of Syphilis Infection among Antiretroviral Therapy Naive HIV Patients at the Cape Coast Teaching Hospital, Ghana

Diagnosis of sexually transmitted infections is very important considering the spread of HIV and the extensive use of highly active antiretroviral therapy worldwide. This will assist in planning of treatment schedule in controlling these infections. The study therefore aimed at determining the prevalence of syphilis in HIV positive antiretroviral therapy naive patients in Cape Coast and the associated risk factors involved in infection. A cross-sectional study was carried out using initial HIV rapid and confirmation tests, and then Venereal Disease Research Laboratory test with the Ultra Rapid Test Kits for syphilis. Demographic data, risky sexual behaviours capable of co-transmission of both HIV and Syphilis, were also collected through the use of questionnaires. In all, 150 HIV positive antiretroviral naive subjects were studied and 15 (10%) were positive for VDRL test, with females (6.00%) and males (4.00%), who were mainly within the age group of 20 - 39 years. A significant number of males (p = 0.019) and females (p = 0.015) participants were not smoking with a fewer number of the females (p = 0.002) having multiple sexual partners. Also a smaller number of those who were infected with the bacteria (p = 0.004) did not support the control of sexually transmitted infection (p = 0.022). The result showed that co-infection of Syphilis in HIV positive antiretroviral therapy naive patients persists in the Cape Coast Metropolis, which is an indication of prominence of STIs that require further study on a larger scale to ascertain the extent of co-infection and to formulate policy for treatment to help minimize the rate of infection.

Prevalence of chronic kidney disease among antiretroviral naïve human immunodeficiency virus-infected patients

Background: Chronic kidney disease (CKD) is one of the important complications of human immunodeficiency virus (HIV) infection. The prevalence of CKD in HIV-infected Nigerians at presentation is currently unknown. Materials and Methods: This was a comparative study of 400 antiretroviral drug naive HIV-infected patients attending the HIV clinic of a teaching hospital in North Central Nigeria and 140 apparently healthy individuals. CKD was defined as estimated glomerular filtration rate (eGFR)

Nevirapine- versus Efavirenz-based antiretroviral therapy regimens in antiretroviral-naive patients with HIV and Tuberculosis infections in India: a multi-centre study

BackgroundAccording to World Health Organization (WHO) guidelines, which have also been adopted by the National AIDS Control Organization (NACO), India, Efavirenz-based Anti-Retroviral Therapy (ART) is better in Human-Immunodeficiency-Virus (HIV)-infected patients who are also being treated with Rifampicin-based Anti-Tuberculous Therapy (ATT). However, Efavirenz is much more expensive. We hypothesize that Nevirapine is a cheaper alternative that possesses equal efficacy as Efavirenz in HIV-Tuberculosis (TB) co-infected patients.MethodsA parallel open-label randomized clinical trial was conducted at All India Institute of Medical Sciences (AIIMS), New Delhi and National AIDS Research Institute (NARI), Pune. Those who were ART-naïve and co-infected with TB were randomized to receive either Nevirapine (Group 1)- or Efavirenz (Group 2)-based ART along with Rifampicin-based ATT. ATT was begun first in ART-naïve patients according to the NACO guidelines, with a median of 27 days between ATT and ART in both groups. The primary endpoint was a composite unfavourable outcome (death and/or ART failure) at 96 weeks, and the secondary outcome was successful TB treatment at 48 weeks.ResultsA total of 284 patients (mean age 36.7 ± 8.1 years) were randomized in a 1:1 ratio to receive either Nevirapine (n = 144)- or Efavirenz (n = 140)-based ART after a median ATT-ART gap of 27 days. The median CD4 count was 105 cells/μl, with a median viral load of 820,200 copies/μl and no significant difference between the groups. Composite unfavourable outcomes were reported in 49 patients in the Nevirapine group and 51 patients in the Efavirenz group (35.3% vs. 36.9%; hazard ratio, 0.95, 95% confidence interval (CI), 0.63,1.43, adjusted). There was no difference in successful TB treatment outcome between the groups (71.5% vs. 65.6%, 95% CI -3.8,17.9, adjusted). The results were similar, showing no difference between the groups in the two centres of the study after adjusting for disease stage.ConclusionsComposite unfavourable outcome in HIV-TB co-infected patients who were ART-naïve showed no statistically significant difference in the Nevirapine or Efavirenz groups.. Therefore, Nevirapine-based ART is a reasonable alternative to Efavirenz in resource-limited settings. However, multi-centric studies with larger sample sizes are required to confirm these findings.Trial registrationNCT01805258 (Retrospectively registered on March 6, 2013) Date of registration: March 2013.

Impact of protease inhibitors on circulating PCSK9 levels in HIV-infected antiretroviral-naive patients from an ongoing prospective cohort.

The study aims to assess the association between proprotein convertase subtilisin/kexin type 9 (PCSK9), a major regulator of LDL cholesterol (LDL-C) homeostasis, and HIV-related dyslipidaemia in a cohort of HIV-positive (HIV+) patients under protease inhibitors. Plasma PCSK9 levels were measured in 103 HIV+ patients before and after initiating protease inhibitor-based antiretroviral therapy (ART), and in 90 HIV-negative controls matched for age and sex. PCSK9 was measured by ELISA. HIV+ patients who were not virologically suppressed at follow-up or were on lipid-lowering therapy were excluded. In HIV+ (median age 36 years; 77.7% men), PCSK9 levels did not increase after protease inhibitor exposure (median 14 months) (279.5 ng/ml before, 289.6 ng/ml after; P = 0.49) and were significantly elevated versus controls at all timepoints (adjusted P value before and after: <0.05). After protease inhibitor initiation, total cholesterol, LDL-C and HDL cholesterol levels increased, but LDL-C remained lower versus controls. At baseline, PCSK9 levels were positively associated with immunodeficiency and the severity of HIV disease [HIV-1 viral load (P = 0.01), CD4 T-cell count <200/μl, P = 0.002], stage C HIV disease (P = 0.0002). In protease inhibitor-treated patients, PCSK9 levels were no longer associated with HIV-related factors but with total cholesterol (P = 0.0006), LDL-C (P = 0.01), HDL cholesterol (P = 0.01), triglycerides (P = 0.05) and glycaemia (P = 0.006). PSCK9 levels are elevated in HIV+ patients. In ART-naive patients, the relationship between PCSK9 levels and infection severity suggests an effect of HIV disease. After initiating protease inhibitor-containing ART in virologically suppressed patients, PCSK9 levels were associated with dyslipidaemia similar to controls.

Gender Differences in Outcomes of Antiretroviral Treatment Among HIV-Infected Patients in China: A Retrospective Cohort Study, 2010-2015.

Women now account for about half of all people living with HIV worldwide, but researchers lack clear information and large population-based study about gender differences in treatment outcomes. A nationwide retrospective observational cohort study with data from the China National Free Antiretroviral Treatment Program was performed. Antiretroviral-naive patients older than 18 years initiating standard antiretroviral therapy between January 1, 2010, and December 31, 2011, were included and followed up to December 31, 2015. We used modified Poisson regression models to estimate the impact of gender on virological suppression and retention in treatment, and Kaplan-Meier analysis and Cox proportional hazard models to evaluate gender difference in mortality. Sixty-eight thousand six hundred forty-six patients [46,083 (67.1%) men and 22,563 (32.9%) women] with HIV met eligibility criteria. Women were significantly more likely to achieve virological suppression than men both at 12 months [adjusted relative risk (aRR) 1.02, 95% confidence interval (CI): 1.01 to 1.03, P < 0.001] and 48 months (aRR 1.01, 95% CI: 1.00 to 1.02, P = 0.005) after initiating antiretroviral treatment. Women were also more likely to remain in treatment at 12 months (aRR 1.02, 95% CI: 1.01 to 1.02, P < 0.001) and 48 months (aRR 1.04, 95% CI: 1.03 to 1.05, P < 0.001), although the difference became insignificant in alive patients. All-cause mortality was lower in women than in men (2.34 vs. 4.03 deaths/100PY, adjusted hazard ratio 0.72, 95% CI: 0.67 to 0.77, P < 0.001). In China, women are more likely to achieve virological suppression, remain in treatment, and have a significantly lower risk of death than men. Future studies could take both biological and sociobehavioral factors into analysis to clarify the influence factors.

Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection.

Long-acting rilpivirine is a candidate for preexposure prophylaxis (PrEP) for prevention of HIV-1 infection. However, rilpivirine resistance mutations at reverse transcriptase codon 138 (E138X) occur naturally in a minority of HIV-1-infected persons; in particular those expressing human leukocyte antigen (HLA)-B18 where reverse transcriptase-E138X arises as an immune escape mutation. We investigate the global prevalence, B18-linkage and replicative cost of reverse transcriptase-E138X and its regional implications for rilpivirine PrEP. We analyzed linked reverse transcriptase-E138X/HLA data from 7772 antiretroviral-naive patients from 16 cohorts spanning five continents and five HIV-1 subtypes, alongside unlinked global reverse transcriptase-E138X and HLA frequencies from public databases. E138X-containing HIV-1 variants were assessed for in-vitro replication as a surrogate of mutation stability following transmission. Reverse transcriptase-E138X variants, where the most common were rilpivirine resistance-associated mutations E138A/G/K, were significantly enriched in HLA-B18-positive individuals globally (P = 3.5 × 10) and in all HIV-1 subtypes except A. Reverse transcriptase-E138X and B18 frequencies correlated positively in 16 cohorts with linked HIV/HLA genotypes (Spearman's R = 0.75; P = 7.6 × 10) and in unlinked HIV/HLA data from 43 countries (Spearman's R = 0.34, P = 0.02). Notably, reverse transcriptase-E138X frequencies approached (or exceeded) 10% in key epidemic regions (e.g. sub-Saharan Africa, Southeastern Europe) where B18 is more common. This, along with the observation that reverse transcriptase-E138X variants do not confer in-vitro replicative costs, supports their persistence, and ongoing accumulation in circulation over time. Results illustrate the potential for a natural immune-driven HIV-1 polymorphism to compromise antiretroviral-based prevention, particularly in key epidemic regions. Regional reverse transcriptase-E138X surveillance should be undertaken before use of rilpivirine PrEP.

A Prospective Study of Antiretroviral Therapy Naive Patients in Tertiary Care Hospital, Maharashtra

A Prospective Study of Antiretroviral Therapy Naive Patients in Tertiary Care Hospital, Maharashtra

State of the Art of Dual Therapy in 2015

Dual therapy refers to combinations of two antiretroviral drugs applied in different clinical settings; they are considered and studied due to possibly reduced drug toxicities. In antiretroviral-naive patients, dual combinations have lower virologic efficacy than standard therapy; the sole efficacious regimen is lamivudine plus lopinavir/ritonavir. Due to a higher possibility of virologic failure, these regimens are generally not allowed in this clinical setting. In antiretroviral-experienced patients, dual regimens are examined in studies with a small sample size, centered on clinical practice, and should be ritonavir-boosted protease inhibitor-based. These combinations have a good virological efficacy; combinations with the integrase inhibitor raltegravir have small sample size and demonstrated efficacy only with etravirine. Virological aspects involving dual therapy should always consider genetic barriers, particularly in simplification strategies, and ritonavir-boosted protease inhibitors are mandatory. As far as immunological aspects are concerned, nucleoside reverse transcriptase inhibitor-sparing regimens have some encouraging data, probably due to the bone marrow toxicity of this class. Combinations with maraviroc were effective in reducing inflammation, but data about immunological recovery are conflicting. The choice of regimen should focus on specific class toxicity since dual regimens are studied in particular for improving safety and tolerability. This review will analyze different dual regimens in the clinical setting, with a peculiar focus on ameliorating toxicities and improving quality of life.

Simplifying HAART: the Role of Two-Drug Therapy

Since 1996, triple-drug combinations consisting of two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) plus either a ritonavir-boosted protease inhibitor, a non-nucleoside reverse transcriptase inhibitor or recently, an integrase inhibitor have been considered the standard of care for treatment of HIV-infected individuals. As patients’ life expectancy has increased, an increasing rate of comorbidities has been reported. Cumulative toxicity and cost have become an important concern motivating new research exploring alternative antiretroviral treatment strategies. In different clinical trials, NRTI-sparing regimens have been explored in order to preserve effectiveness while reducing toxicity and potential costs. However, to date, class-sparing regimens have shown lower effectiveness than standard triple-drug therapy regimens in antiretroviral-naive patients. On the other hand, the use of dual therapy without certain nucleosides, such as tenofovir or zidovudine, was explored in the GARDEL trial consisting of the use of ritonavir-boosted lopinavir and lamivudine. This is the only large trial showing non-inferiority of dual therapy at 48 and 96 weeks compared to triple therapy. The improved potency, tolerability and durability, and fewer reported toxicities, of newer drugs with a higher resistance barrier paved the way for the evaluation of other class-sparing strategies, including monotherapy and dual therapies that are being applied as initial therapy or as a switch strategy in patients virologically suppressed on triple-drug regimens. The aim of the dual strategy is to achieve and maintain viral suppression, improve immunologic recovery, minimize short- and long-term adverse effects, and thereby improve adherence and potentially reduce costs.

Depression and HIV: Epidemiological and clinical aspects at the Bamako University Hospital (Mali).

Depression plays an important role in clinical worsening, morbidity and mortality related to HIV/AIDS. To describe the epidemiological and clinical aspects of depressive disorders in people with HIV in Mali. This prospective study took place in the department of psychiatry and infectious diseases at the Bamako University Hospital from July 2004 through October, 2005 and included all HIV-positive antiretroviral-naive patients with depression, diagnosed according to ICD-10 criteria. The study included 84HIV-positive patients with a depressive disorder; our total population of HIV-positive patients was 316during the study period, for a prevalence rate of 26.7% in this population. The mean age of these depressed patients was 36.7 ± 8.5years (range: 20-57); 63.1% were women, 47.7% had not attended or at least not completed primary school; 66.6% were married, and 92.9% lived in urban areas. Sad mood, anxiety, and refusal to eat were reported by 27.7%, 10.9%, and 9.1%, respectively, as a reason for consultation. Depression was associated with an anxiety disorder in 33 (39.3%) and a delusional disorder in 14 (16.7%). Severe depression was associated with low BMI and at a CD4 count <200cells/mm3. Depression was found at a high frequency in our study. Its detection, operational research about it, and improved management are recommended to improve the health of people living with HIV.

Prevalence and associated factors of thrombocytopenia among human immunodeficiency virus-infected patients at a tertiary care hospital in İzmir, Turkey.

The aim of this study was to determine the prevalence and associated factors of thrombocytopenia in human immunodeficiency virus (HIV)-infected patients. A cross-sectional study was conducted in a tertiary care hospital in İzmir, Turkey. All HIV-infected patients admitted to the Department of Infectious Diseases and Clinical Microbiology between 2006 and 2011 were recruited. Patients with thrombocytopenia at any time point were defined as the case group and the remaining patients were defined as the control group. The frequency of thrombocytopenia was 35.8%. Thrombocytopenia was more frequent in patients with acquired immune deficiency syndrome (AIDS) than in patients without AIDS (P < 0.05) and in antiretroviral-naive patients than in patients on combination antiretroviral therapy (cART) or those who had ever used cART in the past (P < 0.05). Additionally, rates of tuberculosis infection, prophylactic use of trimethoprim-sulfamethoxazole (TMP/SMX), and being anti-HCV seropositive at any time point were higher in patients with thrombocytopenia than in the control group (P < 0.05), and the case group had lower CD4+ T lymphocytes at first admission (P < 0.05). The main finding was the clear association between thrombocytopenia and advanced and uncontrolled HIV infection. Tuberculosis and HCV coinfections were also identified as associated factors for thrombocytopenia.

Risk Factors of Nevirapine Hypersensitivity Reaction among Human Immunodeficiency Virus-1 Infected Treatment Naïve Patients at Korle-Bu Teaching Hospital

Objective: Ghana like most African countries, still carry the communicable disease burden. The introduction of antiretroviral drugs in Ghana has improved survival rates amongst HIV patients. According to the National Guidelines for antiretroviral treatment in Ghana, administration of nevirapine, a frontline antiretroviral drug leads to hypersensitivity reactions in some patients. This study examines the clinical risk factors and specific genotypic alleles associated with nevirapine hypersensitivity reactions. Methods: Seventy (70) antiretroviral naive HIV patients, initiating nevirapine-based HAART therapy were enrolled in this cohort study and monitored clinically over a period of 24 weeks from July 2013 through to June 2014. Blood samples were evaluated for aminotransferase activity and DNA genotyped for specific ABCB1 and CYP2B6 markers. Results: Eleven (15.7%) patients were identified as cases and 59 (84.3%) patients classed as comparisons out of the study population at the end of the 24 week-monitoring periods. Eight out of the observed cases were categorized as nevirapine hypersensitivity rash and 4 as hepatotoxicity. The concentration of AST was much higher in the cases (119.44 ± 155.86) compared to the comparisons group (68.80 ± 42.65), p=0.056. The Concentration of ALT was also higher in the cases (136.44 ± 165.99) compared to the control (56.72 ± 33.02) p=0.003. The CYP2B6 516 G>T, variant allele frequency observed in the study was 62 (44.3%). However, there was no variant allele detected for the three SNPs in ABCB1 gene genotyped. Conclusion: The observed NVP HSR outcome suggests an adverse reaction among the cohort of HIV-1 infected patients within the Ghanaian population studied. The effect of this outcome although not statistically significant, might be clinically traced to non-adherence to medication and hospitalization of patients which seem to be a major factor to treatment failure in resource-limited countries.

Involvement of the Genetic Diversity of HIV-1 in the Virological Treatment Failure of First Line Antiretroviral in Kinshasa

Background: Genetic diversity of human immunodeficiency virus affects the treatment and the emergence of resistance. Some subtypes would develop resistance more frequently than others. The aim of this study is to determine the rate of virological treatment failure and the involvement of genetic diversity and different mutations in this failure in Kinshasa. Methods: Of the 153 Antiretroviral-naive patients who were included in the cohort, 138 patients have been received for the appointment of the 6th month. Clinical parameters were recorded on individual patient charts. The determination of Viral Load (VL) was done at the Laboratory of Molecular Biology. Clinical and biological parameters of the 6th month were compared with those taken at baseline of the cohort to determine the evolution of patients under treatment. Results: At the consultation of the 6th month, 138 patients (90.2%) had returned out of the 153 included. Eighty-one (58.7%) patients were women and 57 (41.3%) men. The age of patients is between 18 and 65 with an average of 37 years. Ten deaths (6.5%) and 5 (3.3%) lost have been reported. One hundred twenty-five patients (90.5%) were in clinical stage 3 and 13 (9.5%) in clinical stage 4. The median CD4 T cells is 560 cells mm3. The median VLs of patients was 0.90 log10 RNA copies/ml. Of the 34 patients in virological failure, 8 (23.5%) are minimal failure, 23 (67.7%) in moderate failure and 3 (8.8%) in severe failure. According to the Pearson’s test, VLs at 6th months were highly correlated with that of inclusion, with V75 and K70 mutations for NRTIs, with V108 mutation for NNRTI well as the virological failure of treatment. Conclusion: Our results confirmed the hypothesis that high Viral Load at the start of the treatment is a poor prognosis for the development of therapy. Transmitted mutations are involved in treatment failure.

Identifications of drug resistance mutations among antiretroviral treatment naive HIV-1 patients in Peninsular Malaysia.

To determine drug resistance mutations and the HIV-1 subtypes among antiretroviral treatment naive HIV-1 patients in Peninsular Malaysia. A total of 45 samples from four hospitals that provide HIV viral load services were subjected to the amplification of the protease and two third of reverse transcriptase regions of the pol gene by RT-PCR and Sanger sequencing. Drug resistance mutation (DRM) interpretation reports the presence of mutations related to protease inhibitors (PIs), Nucleoside reverse-transcriptase inhibitors (NRTI) and Non-nucleoside reverse-transcriptase inhibitors (NNRTI) based on analysis using Stanford HIV database program. DRMs were identified in 35% of patients, among which 46.7% of them showed minor resistance to protease inhibitor with A71V and L10l were the commonest DRMs detected. About 21.4% and 50.0% of patients had mutations to NRTIs and NNRTIs, respectively. CRF01_AE was found to be the predominant HIV-1 subtype. These findings have served as an initial crucial data in determining the prevalence of transmitted HIV-1 drug resistance for the country. However, more samples from various parts of the country need to be accumulated and analyzed to provide overall HIV-1 drug resistance in the country.

Differences in the integrase and reverse transcriptase transmitted resistance patterns in Northern Poland

IntroductionWith the widespread introduction of the integrase (In) inhibitors into clinical practice, transmission of drug resistance to this class of antiretroviral medications may expand. The aim of this study was to analyze the recent patterns of In resistance in treatment naive individuals in Northern Poland and its association with transmitted protease (PR) and reverse transcriptase (RT) mutations. MethodsStudy included 172 PR, RT and InI sequences from antiretroviral treatment naive HIV-1 infected patients linked to care in Northern Poland from 2010 to 2015. Drug resistance was interpreted based on the WHO surveillance and IAS-USA mutation lists. For phylogeny maximum likelihood and Bayesian Monte Carlo Markov Chain analyses were used. ResultsOverall rate of transmitted drug resistance was 12.21%. Nucleoside reverse transcriptase inhibitor (NRTI) resistance associated substitutions were found in 11.05% of cases and non-nucleoside reverse transcriptase inhibitor resistance variants in 1.16%. In multivariate models transmitted resistance strongly associated with subtype D infections [66.67% compared to the 3.84% for subtype B (p=0.001)]. No transmission of major protease or integrase mutations were observed. Polymorphisms associated with resistance against integrase inhibitor, mostly E157Q, were found in 21.5% sequences and associated with female (31.91% vs. 15.2% for male, p=0.01), injection drug use (84.21% compared to 22.08% for heterosexual and 1.39% for men-who-have-sex-with-men transmissions, p<0.0001) as well as hepatitis C coinfection [63.64% for positive, versus 8.57% for HCV antibody negative, p<0.0001]. Clusters of nucleoside reverse transcriptase mutations in subtype D and integrase E157Q variants in subtype B were observed. ConclusionsTransmitted drug resistance frequency was high in subtype D but limited to clustered NRTI mutations, being infrequent among subtype B infected cases. Despite lack of major integrase resistance in treatment naive patients, variants potentially affecting susceptibility to this class were common, which indicates the potential need for extended surveillance in the near future.