Establishing diagnostic cut-off criteria for the COBAS AmpliPrep/COBAS TaqMan HIV-1 Qualitative test through validation against the Amplicor DNA test v1.5 for infant diagnosis using dried blood spots

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Registry: Unusual HIV transmission in children under the age of 10 years [3]

LetterThe original publication is available at http://www.samj.org.za[No abstract available]Publisher’s versio

Antiretroviral therapy in children with tuberculosis: Progress toward defining the issues

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Antiretroviral resistance patterns and factors associated with resistance in adult patients failing NNRTI-based regimens in the western cape, South Africa

Antiretroviral drug resistance in patients failing non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line combination antiretroviral treatment (ART) is influenced by: regimen choice, HIV-1 subtype, detection of and response to therapy failure. In order to describe resistance patterns by genotypic testing, at the time of first-line ART failure and to describe associations with having M184I/V, K65R, three or more thymidine analog mutations (TAMs) and etravirine (ETV) resistance, the prevalence of antiretroviral drug resistance associated mutations in a cross-sectional study, at two South African public health clinic settings, at the time of virologic failure (HIV-1 RNA load >400copies/ml) are described. Also reported are associations of therapy choice, prolonged virologic failure, and concurrent HIV viral load and CD4 count with the presence of M184I/V, TAMs, K65R, and resistance to ETV. Of 167 adult patients with virologic failure on first-line ART, 28 (17%) had no resistance, 137 (82%) had NNRTI resistance, 101 (60%) M184I/V, 20 (12%) TAMs, of which 4 had 3 or more TAMs, and 7 (4%) had K65R, of which 6 were on D4T and one on AZT. A prolonged estimated period of failure was associated with having ≥3 TAMs. Patients treated with nevirapine (NVP) were more likely to have ETV resistance than those treated with efavirenz (EFV). Major protease inhibitor mutations were not detected. A delayed response to ART failure may risk accumulation of TAMs in patients on an NNRTI-based regimen. The use of NVP rather than EFV was associated with ETV resistance. © 2011 Wiley-Liss, Inc..Articl

Protease inhibitor resistance in South African children with virologic failure

Background: In South Africa, first-line antiretroviral therapy for children younger than 3 years of age combines a protease inhibitor (PI) with 2 nucleoside reverse transcription inhibitors. In our study, some pediatric patients received ritonavir (RTV) as single PI (RTV-sPI) and others ritonavir-boosted lopinavir (LPV/r), which has a higher resistance barrier. We explored antiretroviral resistance mutations in pediatric patients failing PI-based antiretroviral therapy and the predictors of major PI resistance mutations (MPIRM) in these patients. MATERIALS AND Methods: We studied pediatric HIV patients at Tygerberg Academic Hospital experiencing virologic failure on a PI regimen. Mixed-effects linear-and mixed-effect logistic regression modeling, were used to explore predictors of MPIRM. Results: MPIRM were found in 12 of 17 patients exposed to RTV-sPI compared with 1 of 13 patients treated with LPV/r. Exposure to RTV-sPI was significantly associated with MPIRM, with both exposure time and estimated failing time on RTV-sPI being significant positive predictors of MPIRM. Neither CD4 count, viral load, age at first visit nor receiving rifampin predicted MPIRM. Conclusions: RTV-sPI in infants and children poses a significant risk of MPIRM which is dependent on the exposure time and time failing while receiving the regimen. © 2009 by Lippincott Williams & Wilkins.Articl

Zidovudine with nevirapine for the prevention of HIV mother-to-child transmission reduces nevirapine resistance in mothers from the Western Cape, South Africa

In the Western Cape province of South Africa, an intensified regimen for the prevention-of-mother-to-child-transmission-of-HIV consisting of zidovudine (AZT) from 34 weeks of pregnancy plus single dose (sd) nevirapine (NVP) during labor was instituted in 2004. The newborn baby receives a single dose of NVP and AZT for 7 days. Similar strategies in Thailand and Africa have been shown to be more effective in reducing transmission than NVP alone. The use of sd NVP only for the prevention-of-mother-to-child-transmission-of-HIV has a high risk of inducing resistance (25-69%) with an average of 35.7% by a recent meta-analysis and has been shown to adversely affect non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy when initiated within 6 months. In this study the prevalence of resistance to NVP and AZT in mothers who had received the intensified regimen was measured. Specimens collected from mothers were genotyped by in-house PCR and sequencing. In specimens obtained within 60 days of delivery, acquired NVP resistance mutations were detected in 13 of 76 patients (17.1%, 95% confidence interval: 8.7-25.6%), which appears to be lower than in studies with sd NVP alone (37.5%, 95% confidence interval: 23.0-50.6%). © 2008 Wiley-Liss, Inc.Articl

HIV treatment adherence, drug resistance, virologic failure: Evolving concepts

Poor adherence to combined antiretroviral therapy (cART) has been shown to be a major determinant of virologic failure, emergence of drug resistant virus, disease progression, hospitalizations, mortality, and health care costs. While high adherence levels can be achieved in both resource-rich and resource-limited settings following initiation of cART, long-term adherence remains a challenge regardless of available resources. Barriers to optimal adherence may originate from individual (biological, socio-cultural, behavioral), pharmacological, and societal factors. Although patients and providers should continuously strive for maximum adherence to cART, there is accumulating evidence that each class of antiretroviral therapy has specific adherence-drug resistance relationship characteristics allowing certain regimens more flexibility than others. There is not a universally accepted measure for cART adherence, since each method has distinct advantages and disadvantages including cost, complexity, accuracy, precision, intrusiveness and bias. Development of a real-time cART adherence monitoring tool will enable the development of novel, pre-emptive adherence-improving strategies. The application of these strategies may ultimately prove to be the most cost-effective method to reduce morbidity and mortality for the individual and decrease the likelihood of HIV transmission and emergence of resistance in the community. © 2011 Bentham Science Publishers Ltd.Articl

Deep sequencing reveals minor protease resistance mutations in patients failing a protease inhibitor regimen.

ArticleStandard genotypic antiretroviral resistance testing, performed by bulk sequencing, does not readily detect variants that comprise 500 copies/ml) of a first-line nonnucleoside reverse transcriptase inhibitor-based regimen, with at least the M184V mutation (lamivudine resistance), and second-line failure of a lopinavir/ritonavir (LPV/r)-based regimen. An amplicon-sequencing approach on the Roche 454 system was used. Six patients with viral loads of >90,000 copies/ml and one patient with a viral load of 520 copies/ml were included. Mutations not detectable by bulk sequencing during first- and second-line failure were detected by deep sequencing during second-line failure. Low-frequency variants (>0.5% of the sequence population) harboring major protease inhibitor resistance mutations were found in 5 of 7 patients despite poor adherence to the LPV/r-based regimen. In patients with intermittent adherence to a boosted PI regimen, deep sequencing may detect minority PI-resistant variants, which likely represent early events in resistance selection. In patients with poor or intermittent adherence, there may be low evolutionary impetus for such variants to reach fixation, explaining the low prevalence of PI resistance

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

The past 2 years, during which waves of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants swept the globe, have starkly highlighted health disparities across nations. Tegally et al. show how the coordinated efforts of talented African scientists have in a short time made great contributions to pandemic surveillance and data gathering. Their efforts and initiatives have provided early warning that has likely benefited wealthier countries more than their own. Genomic surveillance identified the emergence of the highly transmissible Beta and Omicron variants and now the appearance of Omicron sublineages in Africa. However, it is imperative that technology transfer for diagnostics and vaccines, as well the logistic wherewithal to produce and deploy them, match the data-gathering effort