Translating evidence into policy in low-income countries: lessons from co-trimoxazole preventive therapy

In the April 2010 issue of this journal, Date et al. expressed concern over the slow scale-up in low-income settings of two therapies for the prevention of opportunistic infections in people living with the human immunodeficiency virus: co-trimoxazole prophylaxis and isoniazid preventive therapy. This short paper discusses the important ways in which policy analysis can be of use in understanding and explaining how and why certain evidence makes its way into policy and practice and what local factors influence this process. Key lessons about policy development are drawn from the research evidence on co-trimoxazole prophylaxis, as such lessons may prove helpful to those who seek to influence the development of national policy on isoniazid preventive therapy and other treatments. Researchers are encouraged to disseminate their findings in a manner that is clear, but they must also pay attention to how structural, institutional and political factors shape policy development and implementation. Doing so will help them to understand and address the concerns raised by Date et al. and other experts. Mainstreaming policy analysis approaches that explain how local factors shape the uptake of research evidence can provide an additional tool for researchers who feel frustrated because their research findings have not made their way into policy and practice.     

Medical eligibility,contraceptive choice,and intrauterine device acceptance among HIV-infected women receiving antiretroviral therapy in Lilongwe,Malawi

Objective

To determine medical eligibility for contraceptive use, contraceptive preference, and acceptance of a copper intrauterine device (IUD) among a cohort of HIV-infected women receiving antiretroviral therapy (ART).

Methods

All HIV-infected women who received ART and sought contraceptive services at the Lighthouse clinic, an integrated HIV/ART clinic in Lilongwe, Malawi, between August and December 2010 were invited to participate in a structured interview. Eligibility and preference for the following contraceptive methods were assessed: combined hormonal contraceptives, progestogen-only pills, copper IUD, injectable depot medroxyprogesterone acetate (DMPA), and contraceptive implants.

Results

The final sample included 281 women; five were pregnant. The remaining 276 women were eligible for at least three contraceptive methods, with 242 (87.7%) eligible for all five methods evaluated. After counseling, 163 (58.0%) selected DMPA and 98 (34.9%) selected an IUD as their preferred contraceptive method. Regardless of their method of choice, 222 (79.0%) women agreed to have an IUD placed on the same day.

Conclusion

Most methods of contraception are safe for use by HIV-infected women. Approximately 80% of the women were willing to receive an IUD. Efforts must be made to increase education about, and access to, long-acting reversible methods that may be acceptable and appropriate contraceptive options for HIV-infected women.     

Diagnosis of antiretroviral therapy failure in Malawi: poor performance of clinical and immunological WHO criteria

Objectives  In antiretroviral therapy (ART) scale-up programmes in sub-Saharan Africa viral load monitoring is not recommended. We wanted to study the impact of only using clinical and immunological monitoring on the diagnosis of virological ART failure under routine circumstances.
Methods  Clinicians in two urban ART clinics in Malawi used clinical and immunological monitoring to identify adult patients for switching to second-line ART. If patients met clinical and/or immunological failure criteria of WHO guidelines and had a viral load <400 copies/ml there was misclassification of virological ART failure.
Results  Between January 2006 and July 2007, we identified 155 patients with WHO criteria for immunological and/or clinical failure. Virological ART failure had been misclassified in 66 (43%) patients. Misclassification was significantly higher in patients meeting clinical failure criteria (57%) than in those with immunological criteria (30%). On multivariate analysis, misclassification was associated with being on ART <2 years [OR = 7.42 (2.63, 20.95)] and CD4 > 200 cells/μl [OR = 5.03 (2.05, 12.34)]. Active tuberculosis and Kaposi's sarcoma were the most common conditions causing misclassification of virological ART failure.
Conclusion  Misclassification of virological ART failure occurs frequently using WHO clinical and immunological criteria of ART failure for poor settings. A viral load test confirming virological ART failure is therefore advised to avoid unnecessary switching to second-line regimens.     

Associations of chemokine receptor polymorphisms With HIV-1 mother-to-child transmission in sub-Saharan Africa: possible modulation of genetic effects by antiretrovirals

BACKGROUND: HIV-1 mother-to-child transmission (MTCT) remains an important route of infection in sub-Saharan Africa. METHODS: Genetic variants in CCR5 promoter, CCR2, CX3CR1, and Stromal cell-derived factor-1 (SDF-1) genes were determined in 980 infants from sub-Saharan Africa using real-time polymerase chain reaction to determine association with MTCT. RESULTS: In antiretroviral-naive mother-infant pairs (n = 637), CCR5 promoter polymorphisms at positions 59029: A allele vs. G/G [odds ratio (OR): 1.61, 95% confidence interval (CI): 1.04 to 2.48; P = 0.032] and 59356: T allele vs. C/C (OR: 0.63, 95% CI: 0.41 to 0.96; P = 0.033) and CCR2-180: G allele vs. A/A (OR: 3.32, 95% CI: 1.13 to 9.73; P = 0.029) were associated with risk of MTCT. Treatment of HIV-1-infected mothers and infants with single-dose nevirapine or perinatal zidovudine altered but did not eliminate the association of genetic variants with MTCT. CONCLUSIONS: CCR5 promoter, CCR2, and CX3CR1 polymorphisms were associated with risk of MTCT likely through their role as an HIV-1 coreceptor or by modulating the early immune response. Host genetics may continue to alter MTCT when short-course interventions that only partially suppress virus are used. These findings will need to be confirmed in validation cohorts with a large number of infected infants.     

Cost-effectiveness analysis of establishing a distance-education programme for health personnel in Swaziland

There is a growing conviction among policy-makers that the availability of adequate numbers of well-trained and motivated human resources is a key determinant of health system' s capacity to achieve their health, responsiveness and fairness-improving goals. The objective of this study was to estimate the cost, effectiveness and incremental cost-effectiveness ratios of various distance-education strategies for the health sector in Swaziland; and recommend the most cost-effective option. The distance-education strategies evaluated included: Mobile library services (MLS); micro-resources centers WITHOUT video conferencing in five health centers and four regional hospitals (MRC-VC); micro-resources centers WITH video conferencing in five health centers and four regional hospitals (MRC+VC); centralized resource center WITHOUT video conferencing (CRC-VC); centralized resource center WITH video conferencing (CRC+VC); and status quo (SQ). The incremental cost-effectiveness ratio for MLS was Emalangeni (E) 41,846; MRC-VC was E42,696; MRC+VC was E45,569; CRC-VC was E43,578; CRC+VC was E40,827; the latter being the most cost-effective distance-education strategy. According to policy-makers, this study served to clarify the various distance-education strategies, their costs and their benefits/effectiveness. There is a need for developing in Africa a culture of basing policy and management decisions of such kind on systematic analyses. Of course, economic evaluation will, at most, be a guide to policy- and decision-making, and thus, the onus of decision-making will always be on policy-makers and health-care managers.     

Mortality among HIV-1- and human herpesvirus type 8-affected mother-infant pairs in Zambia

OBJECTIVE: To determine the respective trends in mortality of Zambian mother-infant pairs based on maternal infection with HIV-1 and human herpesvirus type 8 (HHV-8). METHODS: A prospective cohort study was done on Zambian mother-infant pairs, stratified by maternal serologic status and followed from 6 weeks postdelivery for 48 months. Statistical analysis of the differences in the calculated mortality rates among the four groups was done using Stata 7.0. Kaplan-Meier analysis and Cox proportional hazard models were used to measure subject survival time. RESULTS: Between September 1998 and March 2002, a total of 1,425 mother-infant pairs were enrolled. The crude mortality rate among children born to dually infected mothers was approximately 9 times higher (245.90 deaths per 1,000 live births) when compared with the death ratio of children born to seronegative mothers (24.63 deaths per 1,000 live births). The incidence rate for death was 0.34/1,000 in infants of co-infected mothers in comparison with 0.32/1,000 among HIV-1-infected mothers, 0.0336/1,000 among uninfected mothers, and 0.0403/1,000 among HHV-8-infected mothers (chi(2) = 154.56; P < 0.01). Infants of co-infected mothers had a comparable risk of death in comparison with infants infected with HIV-1 alone [hazard ratio, 9.91 [95% confidence interval (95% CI), 5.08-19.37] for co-infected versus 9.26 [95% CI, 4.75-18.07] for HIV-1-infected alone]. Infants of mothers infected only with HHV-8 also had comparable survival in comparison with uninfected infants (hazard ratio, 1.21; 95% CI, 0.56-2.61). CONCLUSION: Infants born to mothers dually infected with both HIV-1 and HHV-8 have comparable survival with infants exposed to HIV-1 alone. Infants born to mothers infected only with HHV-8 have comparable survival with uninfected infants.     

HIV epidemic trend and antiretroviral treatment need in Karonga District, Malawi

We describe the development of the HIV epidemic in Karonga District, Malawi over 22 years using data from population surveys and community samples. These data are used to estimate the trend in HIV prevalence, incidence and need for antiretroviral treatment (ART) using a simple mathematical model. HIV prevalence rose quickly in the late 1980s and early 1990s, stabilizing at around 12% in the mid-1990s. Estimated annual HIV incidence rose quickly, peaking in the early 1990s at 2.2% among males and 3.1% among females, and then levelled off at 1.3% among males and 1.1% among females by the late 1990s. Assuming a 2-year eligibility period, both our model and the UNAIDS models predicted 2.1% of adults were in need of ART in 2005. This prediction was sensitive to the assumed eligibility period, ranging from 1.6% to 2.6% if the eligibility period was instead assumed to be 1.5 or 2.5 years, respectively.