Age at antiretroviral therapy initiation predicts immune recovery, death, and loss to follow-up among HIV-infected adults in urban Zambia

AIDS Res Hum Retroviruses. 2014 Jul 6. [Epub ahead of print] 24998881

Vinikoor MJ, Joseph J, Mwale J, Marx MA, Mulenga L, Stringer JS, Eron JJ, Chi B


We analyzed the association of age at antiretroviral therapy (ART) initiation with CD4+ T-cell count recovery, death, and loss to follow-up (LTFU) among HIV-infected adults in Zambia.


We compared baseline characteristics of patients by sex and age at ART initiation (categorized as 16-29 years, 30-39 years, 40-49 years, 50-59 years, 60 years and older (P for trend<0.001). We used the medication possession ratio to assess adherence and analysis of covariance to measure the adjusted change in CD4+ T-cell count during ART. Using Cox proportional hazard regression, we examined the association of age with death and LTFU. In a secondary analysis, we repeated models with age as a continuous variable.


Among 92,130 HIV-infected adults who initiated ART, the median age was 34 years and 6,281 (6.8%) were aged ≥50 years. Compared with 16-29 year-olds, 40-49 year-olds (-46 cells/mm3), 50-59 year olds (-53 cells/mm3), and 60+ year-olds (-60 cells/mm3) had reduced CD4+ T-cell gains during ART. The adjusted hazard ratio (AHR) for death was increased for individuals aged ≥40 years (AHR 1.25 for 40-49 year-olds, 1.56 for 50-59 year-olds, and 2.97 for 60+ year-olds). Adherence and retention in care were poorest among 16-29 year-olds but similar in other groups. As a continuous variable, a 5-year increase in age predicted reduced CD4+ T-cell count recovery and increased risk of death.


Increased age at ART initiation was associated with poorer clinical outcomes, while age <30 years was associated with higher likelihood of being lost to follow-up. HIV treatment guidelines should consider age-specific recommendations.

Clinical Performance of Digital Cervicography and Cytology for Cervical Cancer Screening in HIV-infected Women in Lusaka, Zambia

J Acquir Immune Defic Syndr. 2014 Jun 24. [Epub ahead of print] 24977474

Bateman AC, Parham GP, Sahasrabuddhe VV, Mwanahamuntu MH, Kapambwe S, Katundu K, Nkole T, Mulundika J, Pfaendler KS, Hicks ML, Shibemba A, Vermund SH, Stringer JS, Chibwesha CJ.



While there is a growing literature on the clinical performance of VIA in HIV-infected women, to our knowledge none have studied VIA enhanced by digital cervicography. We estimated clinical performance of cervicography and cytology to detect cervical intraepithelial neoplasia grade 2 or worse. Sensitivity and specificity of cervicography were 84% (95% confidence interval [CI]: 72%-91%) and 58% (95%CI: 52%-64%). At the high-grade squamous intraepithelial lesion or worse cutoff for cytology, sensitivity and specificity were 61% (95%CI: 48%-72%) and 58% (95%CI: 52%-64%). In our study, cervicography appears to be as good as cytology in HIV-infected women.


Derivation of a tuberculosis screening rule for sub-Saharan African prisons.

Int J Tuberc Lung Dis. 2014 Jul;18(7):774-80. doi: 10.5588/ijtld.13.0732.

Harris JB, Siyambango M, Levitan EB, Maggard KRHatwiinda S, Foster EM, Chamot E, Kaunda K, Chileshe C, Krüüner AHenostroza G, Reid SE.



To derive screening rules for tuberculosis (TB) using data collected during a prison-wide TB and human immunodeficiency virus (HIV) screening program.


We derived rules with two methodologies: logistic regression and classification and regression trees (C&RT). We evaluated the performance of the derived rules as well as existing World Health Organization (WHO) screening recommendations in our cohort of inmates, as measured by sensitivity, specificity, and positive and negative predictive values.


The C&RT-derived rule recommended diagnostic testing of all inmates who were underweight (defined as body mass index [BMI] < 18.5 kg/m(2)] or HIV-infected; the C&RT-derived rule had 60% sensitivity and 71% specificity. The logistic regression-derived rule recommended diagnostic testing of inmates who were underweight, HIV-infected or had chest pain; the logistic regression-derived rule had 74% sensitivity and 57% specificity. Two of the WHO recommendations had sensitivities that were similar to our logistic regression rule but had poorer specificities, resulting in a greater testing burden.


Low BMI and HIV infection were the most robust predictors of TB in our inmates; chest pain was additionally retained in one model. BMI and HIV should be further evaluated as the basis for TB screening rules for inmates, with modification as needed to improve the performance of the rules.

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Health systems implications of the 2013 WHO consolidated antiretroviral guidelines and strategies for successful implementation

AIDS. 2014 Mar;28 Suppl 2:S231-9. doi: 10.1097/QAD.0000000000000250.

Holmes C, Pillay Y, Mwango A, Perriens J, Ball A, Barreneche O, Wignall S, Hirnschall G, Doherty MC.


To successfully implement the 2013 WHO consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection at country level, the implications for national and regional health systems need to be considered and addressed. The guidelines target the entire continuum of care for the HIV-infected individual, and in some cases, their partners, and those with unknown status. The guidelines include not only a more inclusive treatment initiation threshold of CD4+ T-cell count of 500 cells/μl or less for adults and adolescents, treatment for life for pregnant and breastfeeding women (or treatment for the duration of pregnancy and breastfeeding regardless of CD4+ T-cell count), treatment regardless of CD4+ T-cell count for children under 5 years of age, discordant couples, those co-infected with either tuberculosis (TB) or severe hepatitis B virus (HBV), and diversification of effective strategies to reach those with unknown status through couples testing and community-based testing.

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Application of Balanced Scorecard in the Evaluation of a Complex Health System Intervention: 12 Months Post Intervention Findings from the BHOMA Intervention: A Cluster Randomised Trial in Zambia


Introduction:In many low income countries, the delivery of quality health services is hampered by health system-wide barriers which are often interlinked, however empirical evidence on how to assess the level and scope of these barriers is scarce. A balanced scorecard is a tool that allows for wider analysis of domains that are deemed important in achieving the overall vision of the health system. We present the quantitative results of the 12 months follow-up study applying the balanced scorecard approach in the BHOMA intervention with the aim of demonstrating the utility of the balanced scorecard in evaluating multiple building blocks in a trial setting.
Methods: The BHOMA is a cluster randomised trial that aims to strengthen the health system in three rural districts in Zambia. The intervention aims to improve clinical care quality by implementing practical tools that establish clear clinical care standards through intensive clinic implementations. This paper reports the findings of the follow-up health facility survey that was conducted after 12 months of intervention implementation. Comparisons were made between those facilities in the intervention and control sites. STATA version 12 was used for analysis.
Results:The study found significant mean differences between intervention(I) and control (C) sites in the following domains: Training domain (Mean I:C; 87.5.vs 61.1, mean difference 23.3, p = 0.031), adult clinical observation domain (mean I:C; 73.3 vs.58.0, mean difference 10.9, p = 0.02 ) and health information domain (mean I:C; 63.6 vs.56.1, mean difference 6.8, p = 0.01. There was no gender differences in adult service satisfaction. Governance and motivation scores did not differ between control and intervention sites.
Conclusion:This study demonstrates the utility of the balanced scorecard in assessing multiple elements of the health system. Using system wide approaches and triangulating data collection methods seems to be key to successful evaluation of such complex health intervention.

Authors: Wilbroad Mutale, Jeffrey Stringer, Namwinga Chintu, Roma Chilengi, Margaret Tembo Mwanamwenge, Nkatya Kasese, Dina Balabanova, Neil Spicer, James Lewis, Helen Ayles.

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Short communication: Late refills during the first year of antiretroviral therapy predict mortality and program failure among HIV-infected adults in urban Zambia


We evaluated the association of the number of late antiretroviral therapy (ART) refills with patient outcomes in a large public-sector human immunodeficiency virus treatment program in Lusaka, Zambia. Using pharmacy data routinely collected during 2004-2010, we calculated the number of late refills during the initial year of ART. We used multivariable Cox proportional hazard regression to examine the association between the number of late refills and death or program failure (i.e., death, loss to follow-up, or program withdrawal) >12 months after ART initiation, with and without stratification by the medication possession ratio (MPR) during the initial year of ART. Of 53,015 adults who received ART for ≥12 months (median follow-up duration, 86.1 months; interquartile range, 53.2-128.2 months), 26,847 (50.6%) had 0 late refills, 16,762 (31.6%) had 1, 6,505 (12.3%) had 2, and 2,901 (5.5%) had ≥3. Kaplan-Meier analysis revealed that ≥3 late refills was associated with a greater mortality risk than 1 and 2 late refills (p<0.001, by the log-rank test). The mortality risk was greater for patients with 2 late refills [adjusted hazard ratio (HR), 1.17; 95% confidence interval (CI), 0.99-1.38] or ≥3 late refills (adjusted HR, 1.51; 95% CI, 1.23-1.87), compared with that for patients with 0-1 late refills. Program failure was associated with ≥2 late refills. An MPR of <80% was associated with similar increases in mortality risk across late-refill strata. Monitoring late refills during the initial period of ART may help resource- and time-constrained clinics identify patients at risk for program failure.

Authors: Vinikoor MJ, Schuttner L, Moyo C, Li M, Musonda P, Hachaambwa LM, Stringer JS, Chi BH.

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Single genome amplification of proviral HIV-1 DNA from dried blood spot specimens collected during early infant screening programs in Lusaka, Zambia


The ability to evaluate individual HIV-1 virions from the quasispecies of vertically infected infants was evaluated in a field setting at the Centre for Infectious Disease Research in Zambia. Infant heel-prick blood specimens were spotted onto dried blood spot (DBS) filter paper cards at government health clinics. Nucleic acid was extracted and used as a template for HIV-1 proviral DNA detection by a commercial Amplicor HIV-1 PCR test (Roche, version 1.5). On samples that tested positive by commercial diagnostic assay, amplification of DNA was performed using an in-house assay of the 5′ and 3′ region of the HIV-1 genome. Additionally, fragments covering 1200 nucleotides within pol (full length protease and partial reverse transcriptase) and 1400 nucleotides within env (variable 1-variable 5 region) were further analyzed by single genome amplification (SGA). In summary, we have demonstrated an in-house assay for amplifying the 5′ and 3′ proviral HIV-1 DNA as well as pol and env proviral DNA fragments from DBS cards collected and analyzed entirely in Zambia. In conclusion, this study shows the feasibility of utilizing DBS cards to amplify the whole proviral HIV-1 genome as well as perform SGA on key HIV-1 genes.

Seu L, Mwape I, Guffey MB

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