Risk Factors for First-line Antiretroviral Treatment Failure in HIV-1 Infected Children Attending Jos University Teaching Hospital, Jos, North Central Nigeria.

Aim: To determine risk factors for first-line antiretroviral treatment failure in HIV-1 infected children attending Jos University Teaching Hospital, Jos. Study Design: Retrospective cohort study. Place and Duration of Study: Paediatric HIV clinic at the Jos University Teaching Hospital, Jos, between February 2006 and December 2010. Methodology: Data on demographic, clinical and laboratory variables for 580 HIV-1 infected children aged 2 months to 15 years on antiretroviral therapy (ART) were analysed. A comparison of the data on children with and without treatment failure was made. Variables associated with treatment failure in a univariate analysis were then fit in a multivariate logistic model to determine the factors that were associated with treatment failure. Results: The rate of treatment failure among the children was 18.8%. Previous antiretroviral drugs (ARV) exposure for treatment, not receiving cotrimoxazole prophylaxis before commencement of ART and having severe immune suppression at HIV diagnosis were the factors independently associated with treatment failure. Children with previous ARV exposure for treatment were 4 times more likely to fail treatment compared to those without previous exposure (AOR=4.20 (1.93-9.15); p <0.001). Children who did not receive cotrimoxazole prophylaxis were twice more likely to develop treatment failure compared to those who did (AOR=2.26 (1.06-4.79); p=0.03) and children with severe immune suppression at HIV diagnosis were twice more likely to develop treatment failure compared to those without severe immune suppression (AOR=2.34 (1.47-3.72); p<0.001). Conclusion: HIV-infected children with previous ARV exposure for treatment and severe immune suppression should be monitored closely and given frequent adherence counseling to minimize the risk of treatment failure. Cotrimoxazole prophylaxis should be encouraged in HIV-infected children while they await commencement of ART, which may improve ART adherence and thus reduce the risk of treatment failure.

High Frequency of Non-B Human Immunodeficiency Virus Type 1 (HIV-1) Subtype Specific Mutations at the Protease Gene among Treatment-naive HIV-1 Infected Individuals in Jos, Nigeria.

Aims: To determine the prevalence of non-B HIV-1 subtype specific mutations in the protease gene among antiretroviral drug-naive individuals in Jos, Nigeria. Study Design: This was a cross-sectional study in which randomly selected blood samples of HIV-1 positive anti-retroviral drug-naïve individuals were used for genotyping assay. Place and Duration of Study: The study was conducted at the adult HIV clinic of the AIDS Prevention Initiative in Nigeria (APIN) programme, Jos University Teaching Hospital (JUTH), Jos, Nigeria between October 2010 and April 2011. Methodology: Of the one hundred and five plasma samples, 100 samples were successfully reverse transcribed and amplified by nested PCR. The amplicons were directly sequenced on an automated ABI genetic analyzer using BigDye Terminator Cycle Sequencing Kit. Subtyping and phylogenetic analyses were performed using the REGA subtyping tool version 2.0 and MEGA 5.0 software. Both the Stanford HIV database algorithm and IAS-USA 2013 drug resistance update were used for interpretation of drug sensitivity. Results: The proportion of the non-B HIV-1 subtypes were as follows: CRF02_AG (48%), G (41%), CRF06_cpx (6%), A (5%). Q58E, a major drug resistance mutation to PI, occurred as a low prevalence mutation in subtype G. The most common mutations observed among the subtypes were I13V, K14R, K20I, M36I, R41K, H69K, V82I and L89M. Conclusion: A non-uniform distribution of non-B HIV-1 subtypes were observed in Jos, Nigeria, with CRF02_AG and G predominating among the antiretroviral drug-naive individuals. Among the different subtypes in circulation, there was a high prevalence of minor mutations and natural polymorphisms associated with the protease gene. Such mutations define the subtype diversity which may impact on virulence and drug ‘responses’, thus further studies are needed to evaluate the clinical implications of these mutations.

Association of HIV-induced immunosuppression and clinical malaria in Nigerian adults

Abstract Despite the growing body of evidence on the interaction between HIV and malaria in sub-Saharan Africa, there is a dearth of data on clinical malaria in HIV-infected patients in Nigeria. We determined the burden of clinical malaria in HIVinfected adult Nigerians and further investigated the association between their immunological status and the rates of clinical malaria. Ninety seven antiretroviral treatment-naïve HIV-infected adults were enrolled in a cross-sectional study from August to December, 2009. The participants had a complete clinical evaluation, thick and thin blood films for malaria parasites and CD4 cell count quantification. Clinical malaria was defined as having fever (temperature ≥ 37.5oC or history of fever within 48 hours) and a malaria parasite density above the median value obtained for subjects with co-existing fever and parasitaemia. Clinical malaria was diagnosed in 10 out of 97 patients (10.3%). Lower CD4 cell counts were associated with increasing rates of clinical malaria which was 0% at CD4 cell count of ≥ 500, 2.6% at 200-499 and 30% at <200 cells/µL (χ2 = 18.3, p = 0.0001). This association remained significant after controlling for other factors in a multivariate analysis (AOR=22.98, 95% C.I: 2.62-20.14, p= 0.005). An inverse relationship between CD4 cell count and parasite density was demonstrated (regression co-efficient = -0.001, p = 0.0002). More aggressive malaria control measures are highly needed in severely immunosuppressed HIV-infected patients