Trends in drug resistance mutations in antiretroviral-naïve intravenous drug users of Rio de Janeiro

DNA sequencing of a pol gene fragment from drug-naive injecting drug users samples obtained at two time points of the Brazilian AIDS epidemic (Pre-HAART era: 1994 to early 1997, n = 27; post-HAART era: 1999-2001, n = 38) was undertaken to assess HIV-1 antiretroviral drug resistance mutations and subtyping profiles. Genotypic analysis revealed the presence of PR primary L90M, D30N, M46I, and V82A mutations in 7.9% of the post-HAART group, and a high frequency of secondary mutations (84.2%). Nucleoside RT-associated mutations were observed in 13.2%. In the pre-HAART group, a higher frequency of RT mutations was observed (22.2%) and no PR primary mutations were found, in agreement with the introduction of protease inhibitors (PIs) in therapy during the same period. The identification of 7.9% of drug-naive injecting drug users already bearing RT/PR primary resistance mutations in the post-HAART era group constitutes a major concern in terms of dissemination of drug resistant viruses. The resistance mutations profile of the individuals may reflect the context of antiretroviral treatment in Brazil at the sample collection periods (1994-1997 and 1999-2001). In spite of the differences observed in the drug resistance profiles, similar frequencies of subtype B (63.0 vs. 73.7%), F (22.2 vs. 10.5%), and recombinant B/F (14.8 vs. 15.8%) viruses were found, respectively, in the pre- and post-HAART groups.     

High rates of transmitted drug resistance among newly-diagnosed antiretroviral naïve HIV patients in Northern Greece,data from 2009–2011

We conducted a retrospective study on the prevalence and correlates of transmitted drug resistance among newly-diagnosed antiretroviral naive human immunodeficiency virus (HIV) patients in Northern Greece, during the period 2009–11. Transmitted drug resistance was documented in 21.8% of patients enrolled, affecting approximately 40% of subtype A HIV-1-infected individuals. Overcoming challenges due to the ongoing financial crisis, effective preventive measures should be implemented to control further dissemination of resistant HIV strains.     

Prevalence of anaemia and immunological markers among ghanaian HAART-naïve HIV-patients and those on HAART

Background

Highly active antiretroviral therapy (HAART) for people living with HIV/AIDS (PLWHA) has been generally accepted as the gold standard for the management of HIV patients but conflicting reports about the ability of HAART to improve upon the quality of life of HIV patients has cast doubts over the efficacy and the need for therapy.

Objective

This study was conducted to assess the efficacy and ability of HAART to resolve immunological and haematological abnormalities in HIV infected patients, existent sex variations in immunological and haematological parameters and CD4 predictive ability of the study parameters.

Methods

A total of 442 PLWHA consisting of 166 patients on HAART (28 males and 138 females) and 276 HAART-naïve patients (76 males and 200 females) were recruited for this study. Complete haemogram, immunological analysis (CD4 & CD3) and weight were measured for all the patients.

Results

HAART patients were older and heavier than their naïve counterparts. The incidence of anaemia (Hb less or equal to 10.5 (63%) and PCV < 30% (37.6%)) and lymphopoenia (16.7%) in HAART-naïve patients was significantly higher compared to their counterparts on HAART (46%, 15.2% and 5.3%) respectively. 70% of HAART-naïve females had anaemia in comparison to 44% in HAART-naïve males (P = 0.0001). The likelihood of developing microcytic hypochromic anaemia in HAART-naïve patients was 5 times more compared to those on HAART (P = 0.0002). Total lymphocyte count, haemoglobin, lymphocyte count and weight were significant predictors of CD4 counts and TLC values between 1.0 – 2.0 k µL⁻¹ was a significant predictor of CD4 <200 cells mm⁻³.

Conclusion

HAART has the capability of reducing the incidence of anaemia and lymphopoenia which are associated with disease progression and death in HIV infected patients. Total lymphocyte count, haemoglobin and weight could also serve as useful predictive tools in the management and monitoring of HIV infected patients in resource limited settings.     

The emergence of HIV-1 primary drug resistance genotypes among treatment-naïve men who have sex with men in high-prevalence areas in China

The prevalence of HIV-1 infection in men who have sex with men (MSM) in China has drastically increased, and circulating strains may have acquired transmitted drug resistance (TDR). We determined TDR genotypes among antiretroviral therapy (ART)-naïve MSM in 19 provinces/cities where HIV-1 prevalence among MSM is high, and found an overall 4.9 % TDR rate. Although protease inhibitors (PI) were not in the first-line antiretroviral drug list provided through the National ART Program, 70.4 % of the detected TDR belongs to this category. Our findings confirm the urgent need for TDR surveillance in order to optimize treatment effects of the National ART Program.     

Incidence and risk factors of antiretroviral treatment failure in treatment-naïve HIV-infected patients at Chiang Mai University Hospital, Thailand

Background

HAART has significantly reduced AIDS-related morbidity in children. However, limited evidence is available from developing countries regarding patterns of opportunistic illnesses. We describe these events and their associated factors in children with AIDS in Brazil.

Methods

This study is based on two representative retrospective multi-center cohorts including a total 1,859 children with AIDS, infected via mother-to-child transmission (MTCT), between 1983-2002. Opportunistic illnesses were described and analyzed over time. The association of demographic, clinical and operational data with the occurrence of opportunistic diseases was assessed.

Results

In total, 1,218 (65.5%) had at least one event of an opportunistic disease. Variables significantly associated with occurrence of these events included: region of residence (OR 2.68-11.33, as compared to the Northern region), age < 1 year at diagnosis (OR 2.56, 95% CI 1.81-3.61, p < 0.001), and non-performance of MTCT prevention measures (OR 1.58, 95% CI 1.21-2.07, p < 0.001). Protective factors included year of HIV diagnosis in the HAART era (OR 0.34, 95% CI 0.15-0.76, p = 0.009) and ART use (OR 0.58, 95% CI 0.44-0.77, p < 0.001). In both periods bacterial infections represented the most common opportunistic events (58.6 vs. 34.7%; p < 0.001), followed by Pneumocystis jirovecii pneumonia (21.9 vs. 13.2%; p < 0.001), and bacterial meningitis/sepsis (16.8 vs. 7.4%; p < 0.001).

Conclusions

Despite the significant reduction in recent years, opportunistic illnesses are still common in Brazilian children with AIDS in the HAART era, especially bacterial diseases. The data reinforce the need for scaling up prevention of MTCT, early diagnosis of infection, and improvement of comprehensive pediatric care.     

Prevalence and impact of hepatitis B and C virus co-infections in antiretroviral treatment naïve patients with HIV infection at a major treatment center in Ghana

Data on the effects of the presence of hepatitis B virus (HBV) and hepatitis C virus (HCV) in patients co‐infected with these viruses and HIV in West Africa are conflicting and little information is available in Ghana. A cohort of 138 treatment naïve individuals infected with HIV was screened for HBV and HCV serologic markers; HBsAg positive patients were tested for HBeAg, anti‐HBe, and anti‐HBc IgM. The viral load of HIV‐1 in the plasma was determined in 81 patients. Eighteen of the 138 patients (13%) and 5 (3.6%) had HBsAg and anti‐HCV, respectively. None of the patients had anti‐HBc IgM, but 10 (55.6%) and 8 (44.4%) of the 18 patients who were HBsAg positive had HBeAg and anti‐HBe, respectively. In patients with measurement of CD4⁺ undertaken within 1 month (n = 83), CD4⁺ count was significantly lower in patients with HBeAg (median [IQR], 81 [22–144]) as compared to those with anti‐HBe (median [IQR], 210 [197–222]) (P = 0.002, CI: ?96.46 to 51.21). However, those with HIV mono‐infection had similar CD4⁺ counts (median [IQR], 57 [14–159]) compared to those with HBeAg (P = 1.0, CI: ?71.75 to 73.66). Similar results were obtained if CD4⁺ count was measured within 2 months prior to initiation of HAART (n = 119). Generally, HBV and anti‐HCV did not affect CD4⁺ and viral loads of HIV‐1 in plasma but patients with HIV and HBV co‐infection who had HBeAg had more severe immune suppression as compared to those with anti‐HBe. This may have implication for initiating HAART in HBV endemic areas. J. Med. Virol. 84:6–10, 2011. © 2011 Wiley Periodicals, Inc.     

Characterization of drug resistance mutations in naïve and ART-treated patients infected with HIV-1 in Yaounde, Cameroon

Currently the prevalence of HIV‐1 infection in Cameroon is 5.1%, CRF02_AG subtype is responsible for about 50% of infections. Since an HIV‐1 drug resistance test is not yet available widely, accurate data on the prevalence of resistant viral strains are missing. The objective of this study was to determine HIV‐1 genetic diversity and to characterize HIV‐1 mutations conferring drug resistance among antiretroviral therapy (ART)‐naïve and ART‐treated patients. A cohort of 239 patients infected with HIV were followed‐up between January 2007 and July 2010 in Cameroon. Two hundred and sixteen plasma samples were sequenced for phylogenetic analysis and identification of drug resistance mutations in the HIV‐1 pol region. A significant genetic diversity was found: Seven pure subtypes (A1, A3, D, F1, F2, G, H), nine circulating recombinant forms (CRFs: 01_AE, 02_AG, 06cpx, 09cpx, 11cpx, 13cpx, 16cpx, 18cpx, 37cpx) and one new unique recombinant form (URF) (G/F2). The rate of transmitted drug resistance (TDR) in naïve patients was 8.2% (4/49). Around 80% of patients failing a first‐line ART harbored a virus with at least one resistance mutation to two antiretroviral (ARV) classes, and 36% of those failing a second‐line regimen carried a virus with at least one resistant mutation to three ARV classes. The high level of drug resistance observed in the cohort is alarming because this occurred as a result of only few years of treatment. Adherence to therapy, adequate education of physicians, and the appropriate use of genotypic resistance assay are critical points of intervention for the improvement of patient care. J. Med. Virol. 84:721–727, 2012. © 2012 Wiley Periodicals, Inc.