Strategic Plan For HIV Group

STRATEGIC PLAN HIV WORK PACKAGE

Introduction

Combined Antiretroviral Therapy (cART) has become widely available in SSA. However, the recommended frequent clinic visits and the increasing number of HIV infected people enrolled into cART programs, combined with the shortage of health-care personnel and stagnant funding for HIV pose considerable challenges. The long waiting time at the clinics and insufficient time for care and counselling leads to attrition from care. A review from 2015 estimated that the average 36-month retention rate in Africa was as low as 65%. Furthermore, poor adherence leads to treatment failure, increased transmission and resistance development. Treatment of people harbouring drug resistant HIV virus require use of significantly more expensive second-line drugs.

Until 2015, eligibility for cART was determined by the level of immune-system destruction (measured by  CD4 cell counts) or by diagnosis of specific opportunistic infections (OI). Now  the WHO recommends that all people infected with HIV should receive cART as soon as possible after diagnosis. Furthermore, in 2014 UNAIDS set the ambitious worldwide target of 90-90-90, whereby by 2020 90% of HIV infected people will know their HIV status, 90% of these will be on cART, and 90% (i.e. 72% if HIV infected people) will have viral suppression. In 2016 only an estimated 53% of the world’s people living with HIV were accessing cART. Therefore, improving both the efficiency and increasing the cost-effectiveness of the cART programs are paramount to increasing their capacity to sustinably accommodate the increasing number of patients while continuing to deliver appropriate care and monitoring.

Ways of optimizing the use of existing personnel resources to promote retention in care and adherence while finding ways to improve monitoring of treatment effect must be sought.

The most recent guideline published in 2017 recommends differentiated care whereby patients on cART are grouped into unstable and stable patients. This guideline recommends a variety of new initiatives to make the monitoring strategy for the individual patient more targeted.  The guideline has not yet been implemented in Kilimanjaro region and the impact thus remains to be seen.

One of the groups that pose a particular challenge with regard to retention are HIV infected new mothers: studies show that these women remain in care until their babies have been HIV tested, and subsequently a large proportion are lost to follow up (LTFU).

The gold standard of treatment monitoring is the measurement of blood HIV RNA , also termed viral load (VL). Both the WHO and the Tanzanian national treatment guidelines recommend VL treatment monitoring and define viral suppression as having VL <1,000 cp/ml. The current assay used in Tanzania is costly and due to the complexity of the technologies, infrastructure and trained personnel requirement, it is only implemented at 4 centralized zonal laboratories. Preliminary studies during BSU II indicate a long turn around time (TAT) for VL results. Studies carried out by the CDC in 2016 have shown a mean VL TAT of 34 days in Tanzania. VL TAT exceeding 14 days has been associated with an increased risk of LTFU and having a missing or unknown VL with an even greater risk of LTFU. Data from 2016 have shown that only 9% of patients on cART in Tanzania had ever had a VL measurement. Therefore, implementation of point-of-care VL platforms at the clinic, that can provide same-day results, may have a significant impact on patient retention.

The SAMBA HIV-1 Semi-Q Test is a nucleic acid-based amplification assay developed for VL monitoring in resource-constrained settings. It is semi-quantitative and distinguishes between a VL >/< 1,000 cp/ml. It was initially developed for use on the SAMBA I system for laboratory use and has since been further developed for use on the fully automated SAMBA II system for true point-of-care use in remote clinical settings. With a processing time of only 90 minutes the clinician and patient are provided with an immediate assessment of treatment effect and can take appropriate action based on gold-standard criteria. SAMBA II has been tested on samples from several SSA countries and found to have excellent sensitivity and specificity compared to currently used laboratory platforms.

Identification of alternative explanations including resistance development and pharmacogenetics factors leading to fast metabolism of cART drugs leading to sub-therapeutic drug concentrations must be monitored and ruled out. Some studies have reported that more than 95% of the study participants reported that they took their medication regularly and this was proved by measuring not only the concentration of the parent drug efavirenz but also its major primary metabolite, 8-hydroxyefavirenz concentrations. And the decrease in efavirenz concentration was accompanied by an increase in 8-hydroxyefavirenz, indicating elevations in efavirenz metabolism. This has been reported previously to have a significant correlation between plasma efavirenz concentration and efavirenz metabolic ratio defined as the efavirenz/8-hydroxyefvaurenz ratio. Therefore the decrease in efavirenz plasma concentration was attributed to auto-induction but not due to lack of adherence. The extent of the decline in efavirenz plasma concentrations and metabolic ratios over time due to efavirenz autoinduction was more prominent in Tanzanian than Ethiopian. The variations in efavirenz plasma exposure may result in varying clinical treatment outcomes among HIV-1 infected patients on cART.

The broad objective of the HIV group:

Optimization of monitoring of patients on antiretroviral therapy.

OBJECTIVES

Ph.D. project

Broad Objective

To assess the impact and challenges of the Differentiated HIV and AIDS service delivery model at Kilimanjaro Christian Medical Centre (KCMC), Mawenzi Regional Referral Hospital (MRRH), St. Joseph District Designated Hospital (SDDH), Majengo(MHC) and Padua(PHC) Health Centres.

Specific Objectives

Primary outcome:

  1. To determine retention in care among HIV infected individuals attending CTCs at KCMC, MRRH, SDDH, MHC and PHC before and after the implementation of Differentiated HIV and AIDS service delivery model

Secondary outcomes

  1. To determine viral load suppression through the collection of routinely measured VL according to national guidelines among HIV infected individuals attending CTCs at KCMC, MRRH, SDDH, MHC and PHC before and after the implementation of Differentiated HIV and AIDS service delivery model.
  2. To determine the time elapsed between the registered time of diagnosis and treatment initiation, among newly diagnosed HIV infected individuals attending CTCs at KCMC, MRRH, SDDH, MHC and PHC before and after the implementation of Differentiated HIV and AIDS service delivery model.
  3. To assess the health care workers’ perception of the burden of HIV and AIDS service delivery before training, after training and after implementation of Differentiated HIV and AIDS service delivery model in CTCs at KCMC, MRRH, SDDH, MHC, and PHC.
  4. To assess the patients’ perception of HIV and AIDS service delivery before and after implementation of Differentiated HIV and AIDS service delivery model in CTCs at KCMC, MRRH, SDDH, MHC, and PHC.
  5. To determine the rate and barriers to partner notification, testing and linkage to care among newly diagnosed HIV infected patients attending CTCs and antenatal clinics (ANCs) at KCMC, MRRH, SDDH, MHC, and PHC.
  6. To determine the viral load suppression and retention in care following partner notification, testing and linkage to care among newly diagnosed HIV infected patients attending CTCs and antenatal clinics (ANCs) at KCMC, MRRH, SDDH, MHC, and PHC.

SAMBA study

Primary objective

To assess the performance of the SAMBA semi-Q point of care viral load test in HIV-1 infected adults compared to gold standard COBAS® TaqMan® before ART initiation and during treatment in Moshi, Municipal.

 Secondary objective

To assess the performance of the SAMBA test concerning HIV-1 subtypes among patients on ARVs and treatment naïve in Moshi, Municipal. (This will not be done as part of this study however, samples will be stored for this purpose and applications for a grant for this part have been initiated).

Further planned studies

Qualitative study

Zero stigmas and discrimination

Conducting HIV and AIDS interventions focusing on reducing Stigma

  • HIV infected mothers group study
  • Strengthening and establishment of PLHIV support groups
    • HIV infected mothers group study
  • Linking PLHIV with other services including legal and financial services
    • HIV infected mothers group study
  • Capacity building of HIV and AIDS service providers of quality HIV and AIDS-related services without stigma and discrimination
    • HIV infected mothers group study

Pharmacogenetic differences in cART metabolism

A possible explanation for treatment failure despite high self-reported adherence?

Assessment of the feasibility of the establishment of pharmacogenetic analyses to identify causes for treatment failure in adherent patients

Assessment of point of care resistance assays

SAMBA assay – Assessment of the feasibility of the establishment of resistance analyses among patients initiated and failing treatment.