Malaria prevention in HIV-positive pregnant women

Three or more doses of SP (sulfadoxine-pyrimethamine) may have advantages over standard two doses for malaria prevention in HIV-positive pregnant women, but further research is needed

Why are drugs for preventing malaria in HIV-positive pregnant women important?

  • In Sub-Saharan Africa, 55% of those living with HIV are women of reproductive age. Malaria is common in this region, and HIV increases the severity of malaria in pregnant women. Malaria also contributes significantly to low birthweight, premature delivery, stillbirth, and spontaneous abortion. Each year, 25 to 30 million pregnancies in the Sub-Saharan region are at high risk of these consequences of malaria.

Do they work?

  • Sulfadoxine-pyrimethamine (SP) and chloroquine are the safest and most readily available and affordable drugs for the prevention of malaria in pregnancy in most African countries. However, these drugs are becoming less effective in many African countries due to drug resistance.
  • SP and other drugs like amodiaquine and artemisinin derivatives are being assessed for prevention and treatment of malaria in pregnancy. However, the overall impact of these drugs has to be assessed for HIV-positive pregnant women.
  • Three or more doses of SP may have some advantages over the standard two doses in HIV-positive pregnant women in their first or second pregnancies, but larger trials are needed to confirm an effect on patient important outcomes.
  • For HIV-positive women in their third or higher pregnancy, there is insufficient evidence to reach a conclusion on the benefit of monthly SP compared to the standard two doses.

Equity - Do they work in the disadvantaged?

  •  Of the two trials included in the review, one was conducted in a low income country (Malawi) and the other was conducted in a lower-middle-income country (Zambia), both in Sub-Saharan Africa. Around 60% of clinical cases of malaria, and over 90% of malaria-related deaths occur in Sub-Saharan Africa, a region of predominantly low and lower-middle-income countries. Both malaria and HIV/AIDS are associated with poverty and share similar determinants of vulnerability to infection, many of which are present in Sub-Saharan Africa, and target the same vulnerable populations in this region. Effective prevention of malaria in HIV-positive pregnant women can help improve survival and well-being amongst this disadvantaged group.  The quality of the evidence in the two trials was evaluated as low to very low, demonstrating the need for further research.

Intervention delivery

  • The two trials included in the review compared monthly SP treatment during pregnancy to the WHO-recommended 2-dose SP treatment in the second and third trimesters of pregnancy.
  • Intervention doses: three or more directly observed SP doses (25 mg/kg sulphadoxine and 1.25 mg/kg pyrimethamine) during the second and third trimester; first dose at enrollment and then monthly until delivery.
  • Control doses: two directly observed SP doses (25 mg/kg sulphadoxine and 1.25 mg/kg pyrimethamine); first dose at enrollment and second dose in the third trimester.

Population and setting

  • HIV-positive pregnant women in geographical locations where malaria is common
  • The first trial was limited to HIV-positive women of any age having their first or second pregnancies
  • The second trial included HIV-positive women 18 years or older having their first to third or higher pregnancies
  • Patients who had previously had a bad reaction to sulfa-containing drug were excluded

Summary of Findings (SOF) Tables: Monthly SP during pregnancy compared to two-doses for HIV +ve women in their first or second pregnancy

Patient population: HIV-positive pregnant women

Settings: Malawi, a low-income country, and Zambia, a lower-middle-income country

Intervention: Monthly sulfadoxine-pyrimethamine (SP)

Comparison: Standard 2-dose SP

Outcomes

Anticipated absolute effects

Risk Ratio
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Risk with standard regimen - 2 doses (Control)

Risk difference with monthly regimen - 3 or more doses (95% CI)

Maternal parasitaemia (at delivery)

22 per 100

5 per 100 (3 to 10)


RR 0.25 (0.14 - 0.43)


  463 (2 studies)


Low 1,2

Placental parasitaemia (at delivery)

14 per 1000

5 per 100 (3 to 10)

RR 0.38 (0.21 - 0.7)

459 (2 studies)

Low 1,2

Maternal anaemia (Hb < 11g/dL at delivery)

66 per 1000

61 per 100 (47 to 79)

RR 0.93 (0.72 - 1.2)

447 (2 studies)

Low 1,2

Low birth weight (< 2.5 kg)

20 per 100

16 per 100 (11 to 25)

R.R. 0.8 (0.52 - 1.23)

469 (2 studies)

Low 1,2

Neonatal mortality

8 per 100

2 per 100 (1 to 8)

R.R. 0.29 (0.08 - 1.05)

253 (1 study)

Very low 1,3

RR = Risk Ratio; CI = Confidence Interval

  1. Downgraded by 1 under risk of bias: both studies had a high proportion of missing outcomes which sensitivity analysis indicates could induce clinically relevant bias.
  2. Downgraded by 1 for imprecision: larger trials would be necessary to have full confdence in this result.
  3. Downgraded by 2 for imprecision: the number of neonatal deaths was very low, and the single trial underpowered to detect an effect on mortality. In addition, one study which did not separate women into primigravidae, secundigravidae and multigravidae found a trend towards higher neonatal mortality with monthly SP.

Relevance of the review for disadvantaged communities

Findings

Interpretation

Equity – Which of the PROGRESS groups examined

 

The first trial included in the review was conducted in a low income country (Malawi) and the second trial was conducted in a lower-middle-income country (Zambia), both in Sub-Saharan Africa.

 

 

Around 60% of clinical cases of malaria, and over 90% of malaria-related deaths occur in Sub-Saharan Africa, a region of predominantly low and lower-middle-income countries. Both malaria and HIV-AIDS are associated with poverty and share similar determinants of vulnerability to infection, many of which are present in Sub-Saharan Africa, and target the same vulnerable populations in this region. HIV increases the severity of malaria in pregnant women. Effective prevention of malaria in HIV-positive pregnant women can help improve survival and well-being amongst this marginalized group. The results of this study are likely applicable to HIV-positive pregnant women in other areas with malaria transmission such as Asia and Latin America. 

The Malawi trial was conducted in a rural setting and the Zambia trial was conducted in an urban setting. No other information on PROGRESS groups is provided.

Compared to previous studies and to the Malawi trial, the intensity of malaria transmission in the Zambia trial was lower, due perhaps to the urban location coupled with expansion of insecticide-treated bed nets and indoor spraying with pesticides. Different malaria transmission dynamics in rural and urban settings highlight challenges in formulating a single policy to prevent malaria during pregnancy that can be widely applied in Sub-Saharan Africa, without unintentionally widening the health equity gap between the most and the least disagvantaged.

Equity Applicability

 

Co-trimoxazole is often prescribed to prevent infection in HIV-positive pregnant women, but cannot be administered concurrently with SP.

The review authors note that one study suggests that daily co-trimoxarole may be more effective than SP at reducing malaria in HIV-positive pregnant women, but this needs to be tested by additional research.

The review summarized findings based on studies in which the level of organization may be higher than that outside the research setting.

Factors to consider when assessing whether intervention effects are transferable to your local setting include:

  • the financial and organizational resources available to provide the intervention (GPs, nurses, pharmacists, medication).

Cost-equity

 

The studies included in the review did not report on the cost-equity of providing two-dose or monthly SP to HIV-infected pregnant women.

Policymakers should examine the costs associated with the medication, personnel to provide it, follow up with pregnant women taking the medication, and should include a strategy to ensure the most disadvantaged women are able to benefit from the intervention (e.g. provide transportation vouchers to get to the hospital, provide subsidized/free medication, etc.).

Monitoring & Evaluation for PROGRESS Groups

 

More research is needed regarding drugs for prevention and treatment of malaria in HIV-positive pregnant women.

 

Three or more doses of SP may have some advantages over the standard two doses in HIV-positive pregnant women in their first or second pregnancies, but larger trials are needed to confirm an effect on patient important outcomes. The quality of the evidence in the two trials was evaluated as low to very low, demonstrating the need for further research. Results were inconclusive for third or higher pregnancies, and accordingly, more research is needed for this sub-population. Chloroquine and SP are becoming less effective in many African countries due to drug resistance. Cotrimoxarole may be an alternative for HIV-positive pregnant women, but additional research is needed.

 

 Comments on this summary? Please contact Jennifer Petkovic.

This summary was prepared by Karen Moore.