Prevalence of reverse transcriptase and protease mutations associated with antiretroviral drug resistance among drug-naïve HIV-1 infected pregnant women in Kagera and Kilimanjaro regions, Tanzania

<p>Abstract</p> <p>Background</p> <p>Access to antiretroviral drugs for HIV-1 infection has increased in sub-Saharan Africa (SSA) during the past few years. Mutations in the HIV-1 genome are often associated with treatment failure as indicated by viral replication and elevated levels of virus in the blood. Mutations conferring resistance to antiretroviral drugs are based on comparing gene sequences with corresponding consensus sequences of HIV-1 subtype B that represents only 10% of the AIDS pandemic. The HIV pandemic in SSA is characterized by high viral genetic diversity. Before antiretroviral drugs become more widely available, it is important to characterize baseline naturally occurring genetic mutations and polymorphisms associated with antiretroviral drug resistance among circulating HIV-1 subtypes.</p> <p>Methods</p> <p>The prevalence of mutations associated with antiretroviral drug resistance in protease (PR) and reverse transcriptase (RT) regions among antiretroviral treatment-naïve HIV-1 infected pregnant women was investigated in Bukoba (Kagera) and Moshi (Kilimanjaro) municipalities, Tanzania, between September and December 2005. The HIV-1 <it>pol </it>gene was amplified using primers recognizing conserved viral sequences and sequenced employing BigDye chemistry from 100 HIV-1 seropositive treatment-naïve pregnant women and 61 HIV-1 seropositive women who had received a single dose of Nevirapine (sdNVP). Positions 1–350 of the RT and 1–99 of the PR genes were analyzed for mutations based on the Stanford University HIV Drug Resistance Database.</p> <p>Results</p> <p>HIV-1 subtypes A, C, D, CRF10_CD and Unique Recombinant Forms (URF) were detected. Primary mutations associated with NRTI and NNRTI resistance were detected among 3% and 4% of treatment-naïve strains, respectively. Primary mutations associated with NRTI and NNRTI resistance were detected in 1.6% and 11.5% of women who had received sdNVP, respectively. None of the primary mutations associated with PI resistance was found. Polymorphisms detected in RT and PR sequences were mainly mutations that are found in the consensus sequences of non-B subtypes</p> <p>Conclusion</p> <p>Based on the WHO HIV Drug Resistance Research Network Threshold of less than 5%, the baseline prevalence of primary mutations among treatment-naïve HIV-1 infected pregnant women in Kagera and Kilimanjaro regions was low. The significance of HIV-1 subtype B polymorphic positions with respect to antiretroviral resistance identified among the prevalent HIV-1 subtypes is unknown. More studies addressing the correlation between polymorphic mutations, antiretroviral resistance and clinical outcome are warranted in regions where non-B subtypes are prevalent.</p

HIV-1 drug mutations in children from northern Tanzania

Objectives: In resource-limited settings, it is a challenge to get quality clinical specimens due to poor infrastructure for their collection, transportation, processing and storage. Using dried blood spots (DBS) might be an alternative to plasma for HIV-1 drug resistance testing in this setting. The objectives of this study were to determine mutations associated with antiretroviral resistance among children 400 copies/mL. Results: Genotypic resistance mutations were detected in 13 of 46 children (28%). HIV-1 genotypes were A1 (n = 27), C (n = 10), A/D (n = 4), D (n = 3) and CRF10_CD (n = 2). The median age was 12 weeks (IQR 6–28). The mean log10 viral load was 3.87 copies/mL (SD 0.995). All major mutations were detected in the reverse transcriptase gene and none in the protease gene region. The most frequent mutations were Y181C (n = 8) and K103N (n = 4), conferring resistance to non-nucleoside reverse transcriptase inhibitors. Conclusions: One-third of infants newly diagnosed with HIV in northern Tanzania harboured major drug resistance mutations to currently used antiretroviral regimens. These mutations were detected from DBS collected from the field and stored at room temperature. Surveillance of drug resistance among this population in resource-limited settings is warranted

HIV-1 drug mutations in children from northern Tanzania

Objectives: In resource-limited settings, it is a challenge to get quality clinical specimens due to poor infrastructure for their collection, transportation, processing and storage. Using dried blood spots (DBS) might be an alternative to plasma for HIV-1 drug resistance testing in this setting. The objectives of this study were to determine mutations associated with antiretroviral resistance among children 400 copies/mL. Results: Genotypic resistance mutations were detected in 13 of 46 children (28%). HIV-1 genotypes were A1 (n = 27), C (n = 10), A/D (n = 4), D (n = 3) and CRF10_CD (n = 2). The median age was 12 weeks (IQR 6–28). The mean log10 viral load was 3.87 copies/mL (SD 0.995). All major mutations were detected in the reverse transcriptase gene and none in the protease gene region. The most frequent mutations were Y181C (n = 8) and K103N (n = 4), conferring resistance to non-nucleoside reverse transcriptase inhibitors. Conclusions: One-third of infants newly diagnosed with HIV in northern Tanzania harboured major drug resistance mutations to currently used antiretroviral regimens. These mutations were detected from DBS collected from the field and stored at room temperature. Surveillance of drug resistance among this population in resource-limited settings is warranted

Deciphering the Complex Distribution of Human Immunodeficiency Virus Type 1 Subtypes among Different Cohorts in Northern Tanzania.

Increased understanding of the genetic diversity of HIV-1 is challenging but important in the development of an effective vaccine. We aimed to describe the distribution of HIV-1 subtypes in northern Tanzania among women enrolled in studies preparing for HIV-1 prevention trials (hospitality facility-worker cohorts), and among men and women in an open cohort demographic surveillance system (Kisesa cohort). The polymerase encompassing partial reverse transcriptase was sequenced and phylogenetic analysis performed and subtype determined. Questionnaires documented demographic data. We examined factors associated with subtype using multinomial logistic regression, adjusted for study, age, and sex. Among 140 individuals (125 women and 15 men), subtype A1 predominated (54, 39%), followed by C (46, 33%), D (25, 18%) and unique recombinant forms (URFs) (15, 11%). There was weak evidence to suggest different subtype frequencies by study (for example, 18% URFs in the Kisesa cohort versus 5-9% in the hospitality facility-worker cohorts; adjusted relative-risk ratio (aRR) = 2.35 [95% CI 0.59,9.32]; global p = 0.09). Compared to men, women were less likely to have subtype D versus A (aRR = 0.12 [95% CI 0.02,0.76]; global p = 0.05). There was a trend to suggest lower relative risk of subtype D compared to A with older age (aRR = 0.44 [95% CI 0.23,0.85] per 10 years; global p = 0.05). We observed multiple subtypes, confirming the complex genetic diversity of HIV-1 strains circulating in northern Tanzania, and found some differences between cohorts and by age and sex. This has important implications for vaccine design and development, providing opportunity to determine vaccine efficacy in diverse HIV-1 strains

Co-occurrence of bacteria and viruses and serotype distribution of Streptococcus pneumoniae in the nasopharynx of Tanzanian children below 2 years of age following introduction of the PCV13

IntroductionPneumococcal conjugate vaccines have reduced severe disease attributed to vaccine-type pneumococci in children. However, the effect is dependent on serotype distribution in the population and disease development may be influenced by co-occurrence of viral and bacterial pathogens in the nasopharynx.MethodsFollowing introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in Tanzania we performed repeated cross-sectional surveys, including 775 children below 2 years of age attending primary healthcare centers. All children were sampled from nasopharynx and pneumococci were detected by single-target PCR. Pneumococcal serotypes/groups and presence of viruses and other bacteria were determined by two multiplex PCR assays.ResultsThe prevalence of PCV13 vaccine-type pneumococci decreased by 50%, but residual vaccine-types were still detected in 21% of the children 2 years after PCV13 introduction. An increase in the non-vaccine-type 15 BC was observed. Pneumococci were often co-occurring with Haemophilus influenzae, and detection of rhino/enterovirus was associated with higher pneumococcal load.DiscussionWe conclude that presence of residual vaccine-type and emerging non-vaccine-type pneumococci in Tanzanian children demand continued pneumococcal surveillance. High co-occurrence of viral and bacterial pathogens may contribute to the disease burden and indicate the need of multiple public health interventions to improve child health in Tanzania

HIV-1 Subtypes and treatment outcome among adults on Antiretroviral therapy at tertiary hospital in Moshi, Tanzania

Background: Human Immunodeficiency virus (HIV) is characterized by great genetic diversity due to its high mutations that occur during replication. Its infection also characterized by high rates of viral turnover and extensive viral diversity. This diverse has implication on disease progression, diagnostic strategies, vaccine development as well as treatment response to antiretroviral drugs.Methods: 63 HIV positive adults infected by different HIV-1 Subtypes at Kilimanjaro Christian Medical Centre (KCMC) in Moshi, Tanzania were studied. HIV-1 Subtypes were characterized using peptide ELISA representing HIV-1 subtypes A, B, C, D and E derived from consensus gp 120 V3 sequences. The CD4+T-lymphocyte cell counts were measured at baseline, six and twelve months using FACS Calliber (Becton Dickinson, San Jose, CA, USA).Results: HIV-1 Subtype A was the most prevalent (47.62%), followed by Subtype C (36.51%) and Subtype D (15.87%). Subtype D showed higher immunological and clinical failures as compared to subtype A and C with Hazard Ratio (H.R, 5.6) and 95% CI=1.3-5.2, P=0.02). After adjustment for sex, baseline CD4+ T Lymphocyte and clinical stage, the association remained the same.Conclusions: HIV-1 A was the most predominant followed by C and D was less predominant. HIV-1 D showed rapid progression of diseases with poor treatment outcomes relative to others subtypes. Keywords: HIV-1 diversity, immunological failure, ELISA, Peptides and immunodominant regio

Prevalence of reverse transcriptase and protease mutations associated with antiretroviral drug resistance among drug-naïve HIV-1 infected pregnant women in Kagera and Kilimanjaro regions, Tanzania-0

Ce O ANT70 was used as out-group for phylogenetic analysis.<p><b>Copyright information:</b></p><p>Taken from "Prevalence of reverse transcriptase and protease mutations associated with antiretroviral drug resistance among drug-naïve HIV-1 infected pregnant women in Kagera and Kilimanjaro regions, Tanzania"</p><p>http://www.aidsrestherapy.com/content/5/1/13</p><p>AIDS Research and Therapy 2008;5():13-13.</p><p>Published online 21 Jun 2008</p><p>PMCID:PMC2443165.</p><p></p

Prevalence of reverse transcriptase and protease mutations associated with antiretroviral drug resistance among drug-naïve HIV-1 infected pregnant women in Kagera and Kilimanjaro regions, Tanzania-1

Ce O ANT70 was used as out-group for phylogenetic analysis.<p><b>Copyright information:</b></p><p>Taken from "Prevalence of reverse transcriptase and protease mutations associated with antiretroviral drug resistance among drug-naïve HIV-1 infected pregnant women in Kagera and Kilimanjaro regions, Tanzania"</p><p>http://www.aidsrestherapy.com/content/5/1/13</p><p>AIDS Research and Therapy 2008;5():13-13.</p><p>Published online 21 Jun 2008</p><p>PMCID:PMC2443165.</p><p></p