What Works

Provision and Access
Adherence and Support
Staying Healthy and Reducing Transmission

Antiretroviral therapy has transformed HIV to a chronic - though still incurable - virus requiring ongoing therapy and strict adherence to treatment. For the most part, virally suppressed people living with HIV today have no difference in life expectancy than demographically similar HIV-negative individuals (Sabin, 2013 cited in Justice and Falutz, 2014; Maman et al. 2012a).

This section does not provide clinical guidance, which is available from WHO, but rather a public health perspective on what works for women to access treatment, adhere to antiretroviral therapy and to reduce transmission and stay healthy.While no documented cases of a true cure exist (Dieffenbach and Fauci, 2011), "investigators and scientists seek to completely eradicate HIV infections (called by some a sterilizing cure) or allow patients to interrupt antiretroviral therapy (ART) without the risk of viral rebound (known as a functional cure)" (Margolis, 2014: 1069). Unfortunately, an HIV cure that is broadly applicable has yet to be found (Colasanti et al., 2014). While progress has been achieved, "the global response will clearly have to be sustained for at least several decades" (Piot and Quinn, 2013: 2216). 

The benefits of HAART are widely known to increase life expectancy, quality of life and the ability to work and perform daily activities for people living with HIV (Antiretroviral Therapy Cohort Collaboration, 2008; Beard et al., 2009; Iwuji et al., 2011; Rosen et al., 2010; Jahn et al., 2008; Stover et al., 2008). A woman in Tanzania noted that the scale up of treatment in her country reduced the stigma surrounding HIV: "I see that... I am not the only one. Now it is the whole of Tanzania" (Roura et al., 2009: 4).

Treatment Programming Must Continue to be Scaled Up

Access to ART has been steadily increasing. By the end of 2013, more than 11.7 million people were on ART in low and middle-income countries, representing about one-third of those living with HIV (Stover et al., 2014). However, 22 million people who need it are still not accessing ART (UNAIDS, 2014a). Reductions in HIV funding threaten to interrupt treatment provision. Interrupted or episodic treatment increases individuals’ risk for drug resistance, disease progression and death (SMART Study Group, 2006; Kaufmann et al., 2011).

The benefits of ART are widely known to increase life expectancy, quality of life and the ability to work and perform daily activities for people living with HIV (Antiretroviral Therapy Cohort Collaboration, 2008). Accelerating treatment access for adults with young children can reduce the numbers of orphans, and improve pediatric survival and social wellbeing. [See also Orphans and Vulnerable Children] Furthermore, many studies have shown that providing ART is cost-effective (Bor et al., 2012; Koenig et al., 2011; Walensky et al., 2011; Iwuji et al., 2011). Conversely, "failure to scale up ART…would mean a sizable reduction in national economic activity, many fewer healthcare workers and teachers and worse educational outcomes for today’s generation of children, in addition to the humanitarian impact of increased mortality" (Holmes et al., 2010a: 177). A recent analysis by the Global Fund found that economic returns on AIDS treatment, through improved worker productivity and by averting future costs to care for children orphaned by the epidemic may equal or outweigh the costs of treatment (GFTAM, 2010 cited in AIDS2031 Consortium, 2010). 

WHO’s 2013 ART guidelines were designed to increase the potential number of people eligible for ART to 28.6 million by calling for treatment initiation when a patient’s CD4 count falls below 500 cells/µl rather than the earlier standard of 350 (WHO, 2014a). WHO modeling shows that the incremental cost of moving ART initiation criterion from CD4 counts of under 350 to under 500 is "relatively small," (WHO, 2013: 97) but people needing treatment could increase by 25% (WHO, 2013: 97). Scaling up access to ARVs as per WHO 2013 guidelines would cost US$350 per quality life year gained, "well below the cost-effectiveness threshold recommended by the Commission on Macroeconomics and Health" (Stover et al., 2014: S228).

Several modeling studies have been carried out estimating the cost-effectiveness of expanding ART initiation and found that doing so could result in highly cost-effective interventions with improved survival rates and reduced transmission. A study in South Africa found with estimates at 5 and 40 years (for the year 2050), expanding ART initiation guidelines to those with CD4 counts less than 350 cells/µl, those with counts of less than 500 cells/µl and all CD4 levels result in cost savings in the long run as compared to the current regimen (at the time of the study) of ART initiation at 200 cells/µl. With each increasing level of CD4 initiation, there is a corresponding decrease in mortality and in transmission rates (Granich et al., 2012).

Mathematical models used to evaluate the health outcomes, cost, and cost-effectiveness of different adult ART eligibility criteria in South Africa, Zambia, India, and Vietnam found that expanding treatment coverage to adults with CD4 counts at or below 500 cells/µl in a generalized epidemic was cost-effective and that expanding treatment to key affected populations with CD4 counts at or below 500 cells/µl in concentrated epidemics was cost-effective (Eaton et al., 2014; Eaton et al., 2013). A modeling study in Mozambique demonstrated that point-of-care CD4 testing could improve treatment outcomes through nearly one year of additional life expectancy, and be cost-effective compared to lab-based CD4 testing, provided linkages to care were improved (Hyle et al., 2014).

Yet, some question how much effort should focus on increasing access to treatment for people whose CD4 counts are over 350 when access to treatment for individuals under 350 is still not universal (Anglemyer et al., 2013). In fact, a review of 379,865 patients from seventeen low- and middle-income countries found that median CD4 counts increased in lower income countries between 2000 and 2009 but still remained under 200 (Avila et al., 2014). If guidelines reduce the opportunities for people with low CD4 counts to initiate treatment, this could increase inequities and mortality at a population level (Cohen et al., 2013). Experts have argued that finding, treating and retaining people with high viral loads or low CD4 counts should be the priority rather than treating healthy people (Bassett and Brudney, 2013). Given the results of the START study that showed that early initiation of ART (above CD4 counts of 500) had beneficial health effects, as well as the study results of HPTN 052 that showed that early treatment reduced HIV transmission, how to scale up universal access to testing and treatment in a way that respects human rights, choice, and the ability of people living with HIV to decide when they are ready to adhere to treatment for life remains a global challenge.

Women Have Particular Treatment Needs and Risks

Women constitute a higher proportion of those receiving ART than men; likely due to greater interactions with the health care system for pregnancy and child-related care. For all low- and middle-income countries, women make up 51% of those eligible for care but make up 59% of those receiving ART (WHO et al., 2013). However, while more women than men have accessed treatment globally, structural factors and traditional gender norms can jeopardize women’s adherence, retention in care and their ability to prevent acquisition (if HIV-negative) or reduce transmission (if HIV-positive). [See Strengthening the Enabling Environment] 

While many treatment strategies have been evaluated as a whole, very little sex-disaggregated data or analyses have been published in 30 years of the epidemic to evaluate what works in treatment for women, especially when separating out data for pregnant women. Other issues such as cardiovascular disease, osteoporosis and drug resistance have important implications for women living with HIV. For example, HIV, even for those on ART and virally suppressed, is an independent risk factor for cardiovascular disease (Freiberg et al., 2013; Islam et al., 2012 cited in So-Armah and Freiberg, 2014) and young African women living with HIV seem to be at particular risk. In an analysis of a group of 741 women under age 35 with advanced HIV disease from seven countries in Sub-Saharan Africa, nearly all women had no signs of cardiovascular disease when they initiated ART. However, after 144 weeks of follow up after ART initiation, increases in all cardiovascular risk factors were seen (Shaffer et al., 2014). A cross-sectional study in Malawi showed that cardiovascular risk factors – including insufficient fruit and vegetable diet, high blood pressure, weight gain, increased cholesterol levels, and low physical activity – were all common among long-term ART patients (Muronya et al., 2011). Some studies have shown that women are also at higher risk of osteoporosis, which is more common among those living with HIV (Mallon, 2014). Even though women have higher CD4 cell counts than men following HIV seroconversion, when men and women have the same level of viral loads, progression to AIDS is faster in women (Addo and Altfeld, 2014). Little is known about long-term outcomes among people living with HIV in lower- and middle-income countries with regard to how ART affects cardiovascular and pulmonary diseases (Bloomfield et al., 2014). 

Following ART initiation, some studies have found different side effects for women than for men suggesting the need for "sex specific approaches to ART" (Addo and Altfeld, 2014: S91). Though the 2013 WHO guidelines do not include monitoring recommendations for disaggregation of data by sex, only distinguishing between pregnant and breastfeeding women and other adults (WHO, 2013), UNAIDS now recommends core indicators that include disaggregation by sex and age for percentage of adults currently receiving ART and percentage of adults with HIV known to be on treatment 12 months after initiation of ART (UNAIDS, 2014a). The Global Fund to Fight AIDS, Tuberculosis and Malaria also now requires sex- and age-disaggregated data. Such disaggregation can illuminate potential discrepancies in ART outcomes for women and men.

Drug resistance is a risk for everyone. However, in a review of outcomes comparing nevirapine and efavirenz among 114,391 patients, nevirapine-based ARVs were significantly more likely to lead to resistance and virologic failure. Yet, overall, more women have been placed on nevirapine, as until recently efavirenz was contraindicated during pregnancy. "This analysis found that the [treatment] benefit of efavirenz over nevirapine was especially highlighted in resource-limited settings when compared to resource-rich settings" (Pillay et al., 2013: para 34). Single dose nevirapine was used for many years as the mainstay of antiretroviral therapy for pregnant women to reduce vertical transmission without assessing the impact of single dose nevirapine on the mother’s future treatment options. [See Antenatal Care - Treatment] 

"…We are more than mothers…" (Dilmitis, 2014: 5)

Women may be at greater risk for becoming drug resistant themselves or transmitting drug resistant strains due to the temporary use of antiretrovirals to reduce perinatal transmission. Further evaluation is needed to understand these risks. While it is clear that those who go on ARV therapy for their own treatment needs should not interrupt treatment (Fauci, 2009a; SMART Study Group, 2006), treatment interruption for women who are on HAART simply to prevent perinatal transmission rather than for their own health needs is currently being evaluated under the PROMISE study. "The risk for maternal health of stopping…maternal triple ARV prophylaxis after breastfeeding cessation is unknown" (WHO, 2010i: 47) – especially if a woman living with HIV has multiple pregnancies. WHO recommendations for Option B+, i.e., lifelong treatment for pregnant women, may reduce stopping and re-starting ART which can carry increased risk for women’s mortality and morbidity. [See Antenatal Care - Treatment] Women living with HIV globally have had mixed opinions around Option B+, and have raised concerned about possible human rights violations and the lack of choice in when to start treatment (for their own health), lack of community-based support, and health system challenges that need to be addressed for Option B+ to work effectively (Hsieh et al., 2014).

Successful and promising strategies for treatment can be further broken down into the following sections: provision and access; adherence and support; and staying healthy and reducing transmission. Many of these strategies can be applied to both men and women in gender–responsive ways.