Risk Factors for Measles in HIV-infected Children and Adolescents in Botswana.

We conducted a matched case-control study of 566 HIV-infected children in Botswana during a 2009-2010 measles outbreak to identify the risk factors for measles. Children in the oldest age quartile (≥13.1 years) were 4-fold more likely to acquire measles than those in the youngest quartile (<7.1 years). HIV-infected older children and adolescents may benefit from additional measles vaccination.

Airborne outreach: building HIV capacity and strengthening health care systems in rural Botswana.

There is a paucity of research demonstrating how HIV-funded services in Africa have improved equity and access to non-HIV services for both HIV-infected and uninfected patients. In this short communication, we describe the impact of an airborne outreach program to provide HIV services to high-HIV burden health facilities in rural Botswana. The analysis demonstrates how this HIV-funded program enhanced access to essential subspecialist services at several rural health facilities across Botswana.

Protease genotypes in patients failing protease inhibitor-based antiretroviral therapy at a pediatric center in Botswana.

With increasing use of protease inhibitors (PI) in Botswana, a large proportion of HIV-infected children are now exposed to PI-based regimens. There is limited protease genotype data from African children and adolescents who have failed PI-based antiretroviral therapy. We describe a cohort of pediatric HIV-infected patients experiencing virologic failure at time of second-line or salvage PI-based regimens and analyze associated PI mutations.

Early outcomes of darunavir- and/or raltegravir-based antiretroviral therapy in children with multidrug-resistant HIV at a pediatric center in Botswana.

BACKGROUND: Data on the use of ritonavir-boosted darunavir (DRV/r) and/or raltegravir (RAL) in resource-limited settings are rare and there is currently no published data regarding their use among African children. Botswana has recently made DRV/r and RAL available for patients failing second-line antiretroviral therapy (ART). METHODS: Retrospective chart review of 4 multidrug-resistant pediatric patients on DRV/r- and/or RAL-based regimens. Viral load, CD4 count, adherence by pill count, and World Health Organization (WHO) clinical stage prior to and after switch to DRV/r- and/or RAL-based regimen were assessed. Antiretroviral therapy history, duration of virologic failure, and time to viral suppression were also noted. Genotypic resistance assays reviewed for mutations present prior to switch. RESULTS: All patients achieved viral suppression, showed improved/stable CD4 counts, and obtained or maintained WHO clinical treatment stage I, even after long-standing virologic/immunologic failure. CONCLUSIONS: Well tolerated by and effective in our patients, DRV/r and RAL provide potentially lifesaving ART options for children and adolescents in resource-limited settings failing ART due to ritonavir-boosted lopinavir (LPV/r) resistance.

Evaluation of the effectiveness of an outreach clinical mentoring programme in support of paediatric HIV care scale-up in Botswana.

Clinical mentoring by providers skilled in HIV management has been identified as a cornerstone of scaling-up antiretroviral treatment in Africa, particularly in settings where expertise is limited. However, little data exist on its effectiveness and impact on improving the quality-of-care and clinical outcomes, especially for HIV-infected children. Since 2008, the Botswana-Baylor Children's Clinical Centre of Excellence (COE) has operated an outreach mentoring programme at clinical sites around Botswana. This study is a retrospective review of 374 paediatric charts at four outreach mentoring sites (Mochudi, Phutadikobo, Molepolole and Thamaga) evaluating the effectiveness of the programme as reflected in a number of clinically-relevant areas. Charts from one visit prior to initiation of mentoring and from one visit after approximately one year of mentoring were assessed for statistically-significant differences (p<0.05) in the documentation of clinically-relevant indicators. Mochudi showed notable improvements in all indicators analysed, with particular improvements in documentation of pill count, viral load (VL) results, correct laboratory monitoring and correct antiretroviral therapy (ART) dosing (p<0.0001, p<0.0001, p<0.0001 and p<0.0001, respectively). Broad and substantial improvements were also seen in Molepolole, with the most improvement in disclosure documentation of all four sites. At Thamaga, improvements were restricted to CD4 documentation (p<0.001), recent VL and documented pill count (p<0.05 and p<0.05, respectively). Phuthadikobo showed the least amount of improvement across indicators, with only VL documentation and correct ART dosing showing statistically-significant improvements (p<0.05 and p<0.0001, respectively). These findings suggest that clinical mentoring may assist improvements in a number of important areas, including ART dosing and monitoring; adherence assessment and assurance; and disclosure. Clinical mentoring may be a valuable tool in scale-up of quality paediatric HIV care-and-treatment outside specialised centres. Further study will help refine approaches to clinical mentoring, including assuring mentoring translates into improved clinical outcomes for HIV-infected children.

Assessing the Impact of Airborne Outreach to Build Clinical Capacity in Rural Botswana.

There is a paucity of research demonstrating how best to address inequalities in health and access to specialist care faced by rural disadvantaged populations in high HIV-prevalent settings in Sub Saharan Africa. Delivering equitable and cost-effective specialist clinical services in many parts of Africa is challenging, given human resource shortages, poor transport infrastructure and competing health priorities. In this report we describe how an airborne outreach program to provide HIV services to high HIV burden health facilities in rural Botswana has been an important catalyst for improving specialist service delivery across the spectrum of clinical care. The success of Botswana's airborne program is a consequence of many country-specific determinants as well as external funding support. We argue that lessons learned from the experience in Botswana are normative for other African settings. Specialist medical airborne outreach to rural hospitals can improve access to and quality of care, when part of a multifaceted, multidisciplinary intervention. Furthermore, we demonstrate how an HIV funded program can be a vehicle for enhanced access to essential sub-specialist clinicians in rural Botswana.

Reverse transcriptase genotypes in pediatric patients failing initial antiretroviral therapy in Gaborone, Botswana.

BACKGROUND: Limited data are available on patterns of resistance mutations in pediatric patients in southern Africa, where HIV-1 subtype C (HIV-1C) predominates. METHODS: Retrospective chart review of pediatric patients. Nucleoside reverse transcriptase inhibitor (NRTI)- and nonnucleoside reverse transcriptase inhibitor (NNRTI)-associated resistance mutations quantified from population-based sequencing genotypic resistance assay results taken at time of first-line antiretroviral therapy (ART) failure (first-line ART = stavudine [d4T] or zidovudine [ZDV] + lamivudine [3TC] + nevirapine [NVP] or efavirenz [EFV]). RESULTS: Total number of patients with resistance assays analyzed is 45. Nucleoside reverse transcriptase inhibitor-associated mutation frequencies noted were M184V (n = 41; 91.1%); thymidine analogue mutations (TAMs; n = 20; 44.4%); >1 TAM (n = 9; 20%); TAM-2 pathway (n = 10; 22.2%); TAM-1 pathway (n = 7; 15.6%); TAM-1 and TAM-2 pathways (n = 3; 6.7%); K65R (n = 2; 4.4%); Q151M (n = 1; 2.2%); and L74V (n = 0; 0%). Nonnucleoside reverse transcriptase inhibitor-associated mutation frequencies noted were associated with notable resistance to either/both NVP and EFV (n = 40; 88.9%); K103N (n = 15; 33.3%); ≥1 mutations associated with etravirine (ETR) failure (K101E, Y181C, and G190A; n =20; 44.4%); and ≥2 notable NNRTI mutations (n = 12; 26.7%). CONCLUSIONS: In this cohort, low-genetic barrier mutations were common, as were TAMs, including more than 1 TAM. Mutations compromising nonthymidine analogue backbones were rare, suggesting that it is likely that children who fail first-line NRTI backbones containing d4T or ZDV/3TC would still respond to abacavir (ABC), didanosine (ddI), and, for adolescents, tenofovir (TDF). Our data support the empiric continuation of 3TC in second-line regimens.