The Imperative for Family Planning in ART in Africa

Commentary by James D. Shelton, USAID and Dr. E. Anne Peterson
Published in The Lancet
November 27, 2004 - Vol 364

A massive and extremely ambitious initiative is underway to provide antiretroviral therapy to millions of patients with HIV in the developing world, especially Africa, very quickly.¹ Recognizing the need for simplicity in such resource-poor settings, WHO guidance calls for one of four first-line tripletherapy alternatives—each with two nucleoside reverse-transcriptase inhibitors (NRTIs) and one non-nucleoside reverse-transcriptase inhibitor (NNRTI).²

In addition to supplying antiretrovirals in mass amounts, major challenges include: identifying willing patients at the later stages of HIV infection, when antiretroviral therapy is appropriate; overcoming AIDS-related stigma; ensuring adherence to the regimens; and providing sustained care and follow-up. In the middle of efforts to provide antiretrovirals rapidly on such a grand scale, important needs such as family planning risk being overlooked. However, ensuring that contraception is available to women on antiretrovirals is crucial—not only for the well-being of women and children, but also as a potent instrument to combat AIDS.

In Africa, HIV is mostly transmitted heterosexually and women are somewhat more likely to be infected than men. Although women of reproductive age make up about 20% of the population, they are 53% of the HIV-infected population.³ Therefore, as the provision of antiretroviral drugs advances, we must pay heed to important problems facing women.

Need for contraception is high in Africa. Similar to people everywhere, couples in Africa deal with the issue of whether and when to have children. Effective contraception provides major health benefits for women by preventing pregnancy-related morbidity and mortality and for children by allowing their parents to space births. Contraception also provides various social and economic benefits.⁴ About 20-25% of women are exposed to the risk of unintended pregnancy, but are not using contraception.⁵ Therefore, providing accessible high-quality services for family planning is a major public-health priority in Africa that demands further attention.

Yet HIV-infected women may well have an even greater need for contraception. In addition to the general demand women have for family planning, women with advanced HIV have extraordinary life stresses that can make the additional burden of an unwanted pregnancy even more onerous. Some women receiving antiretroviral therapy will want to get pregnant, perhaps partly because the therapy makes them feel better and provides hope for long-term survival. However, limited evidence suggests that desire for contraception in HIV-positive women might be high.⁶ Thus it is humane to make contraception readily available to women with HIV infection. Also, beyond this direct benefit, there are other compelling reasons to make contraception available.

First, antiretrovirals have potential to harm fetuses in utero. Taking any drug during pregnancy raises concerns about the drug’s effects on the fetus. For women with advanced HIV disease who are already pregnant, the known benefits of antiretroviral therapy outweigh any health concerns. But for women with such advanced disease who do not want to become pregnant, the imperative for available contraception is compelling. Importantly, one of the two choices for an NNRTI—efavirenz—is considered a potentially potent teratogen. WHO guidelines state “Efavirenz should be avoided . . . because of its potential for teratogenicity” and remains an appropriate drug when “effective contraception can be assured.”² Efavirenz is important because in some (but not all) studies it performed better than the alternative, nevirapine.⁷ Also, efavirenz is recommended in patients with tuberculosis, and nevirapine use might be compromised in the future because of increasing drug resistance.⁸ Availability of contraception could allow access to a wider range of antiretrovirals.

Similarly, the other class of antiretrovirals—the NRTIs, which represent two of three drugs in recommended firstline triple therapy—are also a concern to the fetus because of mitochondrial toxicity. NRTIs truncate mitochondrial DNA synthesis, which leads to a loss of mitochondrial energy-producing capacity, and results in side-effects, such as cardiovascular and skeletal myopathy, neuropathy, liver toxicity, and lactic acidosis.⁹ Although most infants exposed to NRTIs during pregnancy show no clinical signs of compromise, exposures have been associated with mitochondrial dysfunction in a small number of children¹⁰ and observable molecular mitochondrial damage in lymphocytes has been reported for at least 2 years.¹¹ Beyond the mitochondrial concerns, studies in animals and some human data show that NRTIs also affect nuclear DNA, raising theoretical concerns about genotoxicity and potential long-term carcinogenesis.¹¹

Next, contraception can prevent maternal-to-child transmission of HIV by preventing unwanted pregnancy. Short-term antiretroviral therapy, especially nevirapine, is used to prevent mother-to-child transmission during pregnancy. Similarly, triple therapy should effectively prevent mother-to-child transmission during pregnancy; except sometimes, for example, when women discontinue therapy or therapy fails. Women are generally placed on antiretrovirals when they are in the late stages of infection. Should therapy fail, risk of transmission from mother to child could be high. Moreover, even if vertical transmission is prevented, a woman might be concerned that an additional child could be orphaned if her therapy fails. Preventing unwanted pregnancy in the first place avoids these problems.

Health effects that are more subtle in the developed world loom larger in the developing world. Studies in the developing world usually find an increased rate of low birthweight for babies of HIV-positive women and limited evidence of increases in other adverse events, such as low Apgar scores and even infant death.^12,13 Triple-therapy taken throughout pregnancy should mitigate such negative effects, but less so if the drugs are taken suboptimally. Antiretrovirals might also have negative effects on birth outcomes. For example, the European Collaborative Study found an association between combination-antiretroviral therapy and increased prematurity.¹⁴ However, an analysis of cohorts in the USA did not find an effect of antiretroviral therapy on prematurity or low birthweight, although there was a suggestion of increased very low birthweight with protease inhibitors.¹⁵

Already about half of maternal deaths occur in African women,¹⁶ many of whom have poor nutrition, poor maternal care, and other diseases. HIV seems to increase both maternal mortality and morbidity in the developing world.¹⁷ In part, this is exacerbated by co-infections such as malaria, which carries a higher toll in HIV-positive women during pregnancy because of HIV-impaired immunity.¹⁸

Fortunately, pregnancy does not seem to hasten HIV progression.¹⁹ However, even in the best circumstances, pregnancy causes biological stress in women, and the effects of antiretrovirals might compound those of pregnancy. For example, antiretrovirals can cause anaemia and insulin resistance, ^2,20 which also tend to worsen in pregnancy. When health is already compromised, such effects could be formidable.

There are also programmatic advantages gained from linking family planning and antiretroviral-drug services. Current guidance recognizes that reaching out to potential recipients of antiretroviral therapy in resource-poor settings requires various existing entry points, such as maternal-child health services, including family planning.²¹ Indeed, some of the priority countries for antiretroviral therapy, such as South Africa, Botswana, and Kenya, have relatively successful family planning programmes. Such entry points might provide antiretrovirals directly or serve as a conduit to other treatment sites. Thus antiretroviral therapy and other services are destined to become intimate partners. An entry point that provides a robust range of services (such as family planning or other maternal and child health services) is more attractive to potential patients for antiretroviral therapy and can help overcome the stigma related to AIDS—one of the major constraints to recruitment of patients for antiretroviral therapy. Providing more than one service can also support drug adherence and follow-up. Finally, removing the potential for unwanted pregnancy should allow women to focus more on their antiretroviral regimens and the other demands related to HIV disease.

There are compelling human, medical, social, and programmatic reasons to make high-quality, highly accessible, effective, and voluntary contraception available to women on antiretroviral drugs in Africa. It is morally imperative and programmatically pragmatic. As programmes scale-up to the challenge of providing antiretrovirals, they should be designed to strengthen family planning and other integral and vital health services from the beginning. At USAID we have begun serious efforts to make contraception available to women on antiretroviral drugs. We call on providers and other partners in international health to do the same.

We declare that we have no conflict of interest. Our views do not necessarily reflect those of USAID.

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