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1.  Mortality among pulmonary tuberculosis and HIV-1 co-infected Nigerian children being treated for pulmonary tuberculosis and on antiretroviral therapy: a retrospective cohort study 
Germs  2016;6(4):139-150.
Background
Mortality data, including the risk factors for mortality in HIV-infected children with pulmonary TB (PTB) being treated for PTB and who are on antiretroviral therapy (ART), are scarce in Nigeria. We determined the mortality rate and risk factors for mortality among such children, at the pediatric HIV clinic of the Jos University Teaching Hospital (JUTH) in Jos, Nigeria.
Methods
We performed a retrospective cohort study on 260 PTB-HIV-1 co-infected children, aged 2 months to 13 years, being treated for PTB and on ART from July 2005 to March 2013. The mortality rate and associated risk factors were determined using multivariate Cox proportional hazards modelling.
Results
The mortality rate for the study cohort was 1.4 per 100 child-years of follow-up. Median follow-up time was 5.2 years (IQR, 3.5-6.0 years) with total study time being 1159 child-years. The median age of those who died was lower than that of survivors, 1.9 years (IQR, 0.6-3.6 years) versus 3.8 years (IQR, 1.8-6.0 years), p=0.005). The majority of the deaths occurred in males (13, 81.2%), those <5 years of age (14, 87.4%) and those who had severe immunosuppression (11, 68.8%). Risk factors for death were age (with the risk of dying decreasing by 25% for every 1 year increase in age, adjusted hazard ratio (AHR)=0.75 [0.58-0.98], p=0.032), male gender (AHR=3.80 [1.07-13.5], p=0.039) and severe immunosuppression (AHR=3.35 [1.16-9.66], p=0.025).
Conclusion
In our clinic setting, mortality among our PTB-HIV co-infected children being treated for PTB and on ART was low. However, those presenting with severe immunosuppression and who are males and very young, should be monitored more closely during follow-up in order to further reduce mortality.
doi:10.11599/germs.2016.1099
PMCID: PMC5187755  PMID: 28053917
mortality; HIV-1; pulmonary TB; co-infection; severe immunosuppression; children
2.  Prevalence of and risk factors for pulmonary tuberculosis among newly diagnosed HIV-1 infected Nigerian children 
Germs  2016;6(1):21-28.
Introduction
Studies on the prevalence of and risk factors for tuberculosis (TB) among newly diagnosed human immunodeficiency virus (HIV)-infected children in sub-Saharan Africa are scarce and in Nigeria there is paucity of reported data. We determined the prevalence of and risk factors for pulmonary TB (PTB) in newly diagnosed (treatment-naïve) HIV-1 infected children at the pediatric HIV clinic of the Jos University Teaching Hospital (JUTH) in Nigeria.
Methods
We performed a retrospective analysis of 876 children, aged 2 months – 13 years, diagnosed with HIV-1 infection between July 2005 and December 2012, of which 286 were diagnosed with PTB at presentation after TB screening. The study site was the AIDS Prevention Initiative in Nigeria (APIN)-supported Pediatric HIV clinic at JUTH, Jos. A multivariate forward logistic regression modelling was used to identify risk factors for PTB-HIV co-infection.
Results
The prevalence of PTB-HIV co-infection was 32% (286/876). Severe immunosuppression (SI) and World Health Organization (WHO) HIV clinical stage 3/4 were identified as independent risk factors for PTB-HIV co-infection in HIV infected children. The odds of PTB-HIV co-infection was increased two-fold in HIV-infected children with WHO clinical stage 3/4 compared to those with stage 1/2 (adjusted odds ratio (AOR) 1.76 [1.31-2.37], p<0.001) and 1.5-fold in children with SI compared to those without SI (AOR 1.52 [1.12-2.06], p=0.007).
Conclusion
In our setting, the burden of PTB was high among newly diagnosed HIV-infected children, and late WHO HIV clinical stage and severe immunosuppression were associated with PTB-HIV co-infection. Therefore there is a clear need to improve strategies for early diagnosis of both HIV and PTB to optimize clinical outcomes.
doi:10.11599/germs.2016.1085
PMCID: PMC4788778  PMID: 27019829
HIV-1; PTB; co-infection; severe immunosuppression; WHO HIV clinical stage; children
3.  Predictors of impaired renal function among HIV infected patients commencing highly active antiretroviral therapy in Jos, Nigeria 
Background:
Kidney disease is a common complication of human immunodeficiency virus (HIV) infection even in the era of antiretroviral therapy, with kidney function being abnormal in up to 30% of HIV-infected patients. We determined the predictors of impaired renal function in HIV-infected adults initiating highly active antiretroviral therapy (HAART) in Nigeria.
Materials and Methods:
This was a retrospective study among HIV-1 infected patients attending the antiretroviral clinic at the Jos University Teaching Hospital (JUTH), between November 2005 and November 2007. Data were analysed for age, gender, weight, WHO clinical stage, CD4 count, HIV-1 RNA viral load, HBsAg and anti-HCV antibody status. Estimated glomerular filtration rate (eGFR) was calculated using the Cockcroft-Gault equation. Statistical analysis was done using Epi Info 3.5.1.
Results:
Data for 491 (294 females and 197 males) eligible patients were abstracted. The mean age of this population was 38.8±8.87 years. One hundred and seventeen patients (23.8%; 95% CI, 20.2-27.9%) had a reduced eGFR (defined as <60 mL/min), with more females than males (28.6% vs. 16.8%; P=0.02) having reduced eGFR. Age and female sex were found to have significant associations with reduced eGFR. Adjusted odds ratios were 1.07 (95% CI, 1.04, 1.10) and 1.96 (95% CI, 1.23, 3.12) for age and female sex, respectively.
Conclusions:
Older age and female sex are independently associated with a higher likelihood of having lower eGFRs at initiation of HAART among our study population. We recommend assessment of renal function of HIV-infected patients prior to initiation of HAART to guide the choice and dosing of antiretroviral drugs.
doi:10.4103/0300-1652.86133
PMCID: PMC3213750  PMID: 22083208
Highly active antiretroviral therapy; human immunodeficiency virus; predictors; renal function; serum creatinine
4.  Superior Effectiveness of Zidovudine Compared With Tenofovir When Combined With Nevirapine-based Antiretroviral Therapy in a Large Nigerian Cohort 
While tenofovir-containing antiretroviral therapy is generally considered superior to zidovudine, our analysis demonstrates a higher rate of virologic failure when tenofovir, as compared with zidovudine, was combined with nevirapine-based first-line antiretroviral therapy in a Nigerian human immunodeficiency virus treatment program.
Background. Despite sparse efficacy data, tenofovir–emtricitabine or tenofovir–lamivudine plus nevirapine is used in many resource-constrained settings.
Methods. This retrospective cohort study included patients initiating nevirapine-based antiretroviral therapy (ART) with either tenofovir–emtricitabine or lamivudine (tenofovir group) or zidovudine–lamivudine (zidovudine group). Clinical, virologic, and immunologic evaluations were performed at baseline and every 6 months. Virologic failure was defined as 2 consecutive human immunodeficiency virus (HIV)-RNA values >1000 copies/mL. Patients were included from ART initiation until time of failure, regimen switch, discontinuation, or last HIV-RNA measurement. Cox proportional hazards regression was used to model factors influencing time to failure. Bias due to dependent censoring was investigated via inverse probability weighted pooled logistic regression.
Results. A total of 5547 patients were evaluated; 1484 (26.8%) were in the tenofovir group and 4063 (73.2%) were in the zidovudine group. In the adjusted model, tenofovir regimen (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.21–1.79) and higher baseline log10 HIV-RNA (HR, 1.15; 95% CI, 1.03–1.28) were associated with virologic failure. Higher baseline log10 CD4+ cell count (HR, 0.50; 95% CI, .40–.63) and increasing age (HR, 0.98; 95% CI, .97–.99) decreased the risk of virologic failure. Inverse probability weighting results were consistent with the primary analysis.
Conclusions. Compared with zidovudine–lamivudine, the use of tenofovir–lamivudine or emtricitabine in combination with nevirapine was a strong predictor of virologic failure in our cohort, which was not explained by other risk factors or criteria for regimen selection.
doi:10.1093/cid/civ928
PMCID: PMC4725384  PMID: 26561532
zidovudine; tenofovir; nevirapine; virologic failure; antiretroviral therapy
5.  HIV Associated Chronic Obstructive Pulmonary Disease in Nigeria 
Objective
To determine the prevalence and risk factors for chronic obstructive pulmonary disease (COPD) among HIV-infected adults in Nigeria.
Design
Cross-sectional study.
Methods
HIV-infected adults aged ≥ 30 years with no acute ailments accessing care at the antiretroviral therapy clinic of Jos University Teaching Hospital were enrolled consecutively. Participants were interviewed to obtain pertinent demographic and clinical information, including exposure to risk factors for COPD. Post-bronchodilator spirometry was carried out. HIV related information was retrieved from the clinic medical records. COPD case-definition was based on the Global Initiative for Obstructive Lung Disease (GOLD) criteria using post-bronchodilator FEV1/FVC <0.7. COPD prevalence was also calculated using the lower limit of normal for FEV1/FVC criteria (LLN) from the European Respiratory Society normative equation. Factors associated with COPD were determined using logistic regression models
Results
Study population comprised 356 HIV infected adults with mean age of 44.5 (standard deviation, 7.1) years and 59% were female. The mean time elapsed since HIV diagnosis was 7.0 (SD, 2.6) years and 97.5% of the respondents were on stable ART with virologic suppression present in 67.2%. Prevalence of COPD were 15.4% (95% confidence interval [CI] 11.7-19.2), 12.07% (95% CI 8.67-15.48), 22.19% (95% CI 18.16-26.83) using GOLD, ERS LLN and GLI LLN diagnostic criteria respectively. In multivariate analyses adjusting for gender, exposure to cigarette smoke or biomass, history of pulmonary tuberculosis, use of antiretroviral therapy, current CD4 T-cell count and HIV RNA, only age > 50 years was independently associated with COPD with OR 3.4; 95% CI 1.42-8.17 when compared to ages 30-40 years.
Conclusion
HIV-associated COPD is common in our population of HIV patients.
doi:10.4172/2155-6113.1000453
PMCID: PMC4521629  PMID: 26236557
COPD; Lung disease; Spirometry; HIV; Nigeria; Africa
6.  Hepatitis B Co-Infection is Associated with Poorer Survival of HIV-Infected Patients on Highly Active Antiretroviral Therapy in West Africa 
Background
Hepatitis B has been reported to be high in HIV-infected African populations. However, the impact of this co-infection on the survival of HIV-infected Africans on long-term highly active antiretroviral therapy (HAART) remains poorly characterised. We investigated the impact of HBV/HIV co-infection on survival of HIV infected patients undergoing antiretroviral therapy in a West African population.
Methods
This was a clinic-based cohort study of HIV-infected adults enrolled in Nigeria, West Africa. Study subjects (9,758) were screened for hepatitis B and hepatitis C at HAART initiation. Kaplan-Meier survival and Cox proportional hazards models were used to estimate probability of survival and to identify predictors of mortality respectively, based on hepatitis B surface antigen status. All patients had signed an informed written consent before enrolment into the study; and we additionally obtained permission for secondary use of data from the Harvard institutional review board.
Results
Patients were followed up for a median of 41 months (interquartile range: 30–62 months) during which, 181 (1.9%) patients died. Most of the deaths; 143 (79.0%) occurred prior to availability of Tenofovir. Among those that were on antiretroviral therapy, hepatitis B co-infected patients experienced a significantly lower survival than HIV mono-infected patients at 74 months of follow up (94% vs. 97%; p=0.0097). Generally, hepatitis B co-infection: HBsAg-positive/HIV-positive (Hazards Rate [HR]; 1.5: 95% CI 1.09–2.11), co-morbid tuberculosis (HR; 2.2: 95% CI 1.57–2.96) and male gender (HR; 1.5: 95% CI 1.08–2.00) were significantly predictive of mortality. Categorising the patients based on use of Tenofovir, HBV infection failed to become a predictor of mortality among those on Tenofovir-containing HAART.
Conclusions
HBsAg-positive status was associated with reduced survival and was an independent predictor of mortality in this African HIV cohort on HAART. However, Tenofovir annulled the impact of HBV on mortality of HIV patients in the present study cohort.
doi:10.4172/2155-6113.S3-006
PMCID: PMC4199237  PMID: 25328814
Mortality; Hepatitis B surface antigen; HIV; CD4; HAART; Survival; Africa
7.  Treatment Outcomes in a Decentralized Antiretroviral Therapy Program: A Comparison of Two Levels of Care in North Central Nigeria 
AIDS Research and Treatment  2014;2014:560623.
Background. Decentralization of antiretroviral therapy (ART) services is a key strategy to achieving universal access to treatment for people living with HIV/AIDS. Our objective was to assess clinical and laboratory outcomes within a decentralized program in Nigeria. Methods. Using a tiered hub-and-spoke model to decentralize services, a tertiary hospital scaled down services to 13 secondary-level hospitals using national and program guidelines. We obtained sociodemographic, clinical, and immunovirologic data on previously antiretroviral drug naïve patients aged ≥15 years that received HAART for at least 6 months and compared treatment outcomes between the prime and satellite sites. Results. Out of 7,747 patients, 3729 (48.1%) were enrolled at the satellites while on HAART, prime site patients achieved better immune reconstitution based on CD4+ cell counts at 12 (P < 0.001) and 24 weeks (P < 0.001) with similar responses at 48 weeks (P = 0.11) and higher rates of viral suppression (<400 c/mL) at 12 (P < 0.001) and 48 weeks (P = 0.03), but similar responses at 24 weeks (P = 0.21). Mortality was 2.3% versus 5.0% (P < 0.001) at prime and satellite sites, while transfer rate was 8.7% versus 5.5% (P = 0.001) at prime and satellites. Conclusion. ART decentralization is feasible in resource-limited settings, but efforts have to be intensified to maintain good quality of care.
doi:10.1155/2014/560623
PMCID: PMC4083764  PMID: 25028610
8.  Pharmaceutical care outcomes in an outpatient human immunodeficiency virus treatment center in Jos, Nigeria 
Rationale:
Pharmacotherapy for patients infected with human immunodeficiency virus (HIV) is complex and increases the potential for drug therapy problems (DTPs). We described the frequency and type of DTPs in a Nigerian cohort of HIV infected patients on antiretroviral therapy (ART), as well as the changes in HIV clinical outcomes after pharmacists’ intervention.
Methods:
A prospective 1-year descriptive study was conducted from July 2010 to June 2011, at the adult HIV clinic of Jos University Teaching Hospital, Nigeria. DTPs and the associated pharmacist-initiated interventions were documented. Chi-square and Wilcoxon signed ranks test was used as appropriate, to compare the main outcome measures of pre- and post-intervention levels of viral load and CD+ cell count.
Results:
A total of 64,839 prescriptions were dispensed to 9320 patients. Interventions were documented for 85 unique patients (incidence of 1.31 interventions/1000 prescriptions), of which 62 (73%) and 3 (3.5%) were on first- and second-line ART, respectively, while 20 (23.5%) were yet to commence ART. Reasons for pharmacist intervention included failure to initiate therapy for HIV or hepatitis B infection; therapeutic failure (25.9%); and drug toxicity (24.7%). After intervention, the percentage of patients with HIV ribonucleic acid level <400 copies/mL rose from 29.4% to 67.1% (P < 0.001), while median (interquartile range) CD4+ cell count increased from 200 (123–351) to 361 (221–470) cells/mm3 (P < 0.001).
Conclusion:
Pharmacist intervention resulted in clinically significant improvements in patients HIV virological and immunological outcomes. This highlights an important role for the pharmacist in the treatment and care of HIV-infected patients, in a multidisciplinary team.
doi:10.4103/0976-0105.139727
PMCID: PMC4160720  PMID: 25278667
Antiretroviral therapy; drug therapy problem; pharmacist intervention
9.  Toward an Understanding of Disengagement from HIV Treatment and Care in Sub-Saharan Africa: A Qualitative Study 
PLoS Medicine  2013;10(1):e1001369.
Norma Ware and colleagues conducted a large qualitative study among patients in HIV treatment programs in sub-Saharan Africa to investigate reasons for missed visits and provide an explanation for disengagement from care.
Background
The rollout of antiretroviral therapy in sub-Saharan Africa has brought lifesaving treatment to millions of HIV-infected individuals. Treatment is lifelong, however, and to continue to benefit, patients must remain in care. Despite this, systematic investigations of retention have repeatedly documented high rates of loss to follow-up from HIV treatment programs. This paper introduces an explanation for missed clinic visits and subsequent disengagement among patients enrolled in HIV treatment and care programs in Africa.
Methods and Findings
Eight-hundred-ninety patients enrolled in HIV treatment programs in Jos, Nigeria; Dar es Salaam, Tanzania; and Mbarara, Uganda who had extended absences from care were tracked for qualitative research interviews. Two-hundred-eighty-seven were located, and 91 took part in the study. Interview data were inductively analyzed to identify reasons for missed visits and to assemble them into a broader explanation of how missed visits may develop into disengagement. Findings reveal unintentional and intentional reasons for missing, along with reluctance to return to care following an absence. Disengagement is interpreted as a process through which missed visits and ensuing reluctance to return over time erode patients' subjective sense of connectedness to care.
Conclusions
Missed visits are inevitable over a lifelong course of HIV care. Efforts to prevent missed clinic visits combined with moves to minimize barriers to re-entry into care are more likely than either approach alone to keep missed visits from turning into long-term disengagement.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The human immunodeficiency virus (HIV) infects cells of the immune system, destroying or impairing their function. As the infection progresses, the immune system becomes weaker, and the affected person becomes more susceptible to life-threatening infections. Over the past three decades, 25 million people have died from HIV, and according to the World Health Organization, in 2011, there were roughly 34.2 million people living with HIV, over 60% of whom lived in sub-Saharan Africa. Although HIV cannot be cured, the virus can be suppressed by combination antiretroviral therapy (ART) consisting of three or more antiretroviral drugs. ART controls viral replication and strengthens the immune system, allowing the affected person to fight off infections. With ART, HIV can be managed as a chronic disease: people living with HIV can live healthy lives as long as they take antiretroviral drugs regularly for the rest of their lives.
Why Was This Study Done?
Unfortunately, poor retention in HIV programs is a huge problem: a large proportion—30%–60% in some settings in sub-Saharan Africa—of people starting ART, are lost to follow-up and stop taking treatment. Few studies have looked in depth at the reasons why people with HIV in sub-Saharan Africa miss clinic appointments or even stop coming altogether. So in this study in Tanzania, Uganda, and Nigeria, the researchers did a qualitative analysis from the patients' perspective on the reasons for missing clinic visits. Qualitative research can use information-gathering techniques, such as open-ended interviews, to develop an in-depth understanding of human behavior and the reasons behind such behavior.
What Did the Researchers Do and Find?
The researchers indentified people to interview by using “tracking lists” from HIV/AIDS care clinics in the three countries—patient tracking by clinical trackers is increasingly used as a way to contact patients who have missed clinic appointments. The researchers included people in the study who had been tracked and contacted by clinic trackers, had been absent from the clinic for three months or more, and gave consent to be re-contacted by the researchers. The researchers interviewed participants, using their local language, on several topics, including their experiences of care at the clinic and of tracking, and the circumstances of missed appointments. The detailed accounts were transcribed, and then the researchers categorized the reasons for missing appointments into intentional and unintentional reasons.
Eight-hundred-ninety patients in the three countries were tracked during the study period, but only 287 were located, of whom 91 participated in the study. Of the 91 participants, 76 were being prescribed ART, and 15 had not started treatment. The main unintentional reason for missing clinic visits was a conflicting demand on the patients' time, which was often unexpected and for complex reasons, such as caring for a dying relative, going to a funeral, or traveling to work. These reasons were often transient and changed over time. Intentional reasons were often related to dissatisfaction with the care received at the clinic, especially “the harsh treatment” they received from health workers, which typically referred to behavior perceived by patients to be rude. For example, participants reported being spoken to “roughly” or feeling that the clinic staff “didn't care.” Such behavior made patients feel hurt, humiliated, and angry, and reluctant to return to the clinic. The researchers found that, overall, disengagement from care appeared to be a process through which missed visits and subsequent reluctance to return over time eroded patients' sense of connectedness to care.
What Do These Findings Mean?
Absences from care will be inevitable over a lifetime course of treatment for HIV/AIDS. These findings indicate that absences may be unintentional as well as intentional, and that the reasons are complex and can change over time. Initial reasons for missing may disappear, leaving patients free, but reluctant, to return to care. Reasons for reluctance include shame at having been absent and the anticipation of a negative response to return from care providers. Patient education for ART initiation in sub-Saharan Africa often includes stern warnings about the lifelong commitment beginning ART represents. Paradoxically, educational efforts intended to maximize the benefits of ART for patients may be driving some away from care. Therefore, efforts to prevent missed clinic visits coupled with strategies to minimize any obstacles to coming back to care are necessary to keep patients' missed visits from turning into long-term disengagement from treatment.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001369.
This study is further discussed in a PLOS Medicine Perspective by Edward Mills
The World Health Organization has the latest data on access to ART
The US National Institute of Allergy and Infectious Diseases has more information on types of ART, and also on adherence to treatment
The US Centers for Disease Control and Prevention has some information about interventions to help improve adherence
doi:10.1371/journal.pmed.1001369
PMCID: PMC3541407  PMID: 23341753
10.  Association of HIV-Induced Immunosuppression and Clinical Malaria in Nigerian Adults 
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 HIV-infected 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 ≥ 37.5°C 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.
PMCID: PMC3578644  PMID: 23878715
HIV; Immunosuppression; Clinical malaria; Adults

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