Introduction: HIV in South Africa
An estimated 6.8 million people were living with HIV and AIDS in South Africa as of 2014 the highest number of people in any country.[UNAIDS 2014] In the same year, 140,000 South Africans died of AIDS-related causes. HIV prevalence is 19% among those 15-49 years of age but varies by region.[UNAIDS 2014; ZA HIV Prevalence Survey 2012] In KwaZulu-Natal, the region with the highest prevalence, approximately 15.8% of persons are living with HIV.[UNAIDS ZA Progress Report 2012] At the lower end of the scale is the Western Cape, with an HIV prevalence rate of 3.8%.
Although HIV prevalence among individuals aged 15-49 years in South Africa remains at approximately 19%, the absolute number of persons living with HIV and AIDS is increasing by approximately 100,000 each year.[UNAIDS ZA Progress Report 2012] This is due to the number of annual new infections exceeding annual AIDS-related deaths; that is, antiretroviral treatment (ART) is prolonging the lives of persons living with HIV so that the population size of HIV-infected persons is increasing each year. There was a substantial decrease in AIDS-related mortality in the last half of the most recent decade, with the annual number of AIDS deaths reduced from approximately 257,000 in 2005 to approximately 140,000 in 2014.[UNAIDS 2014] This was largely due to the expansion of the ART programme.
Current challenges in HIV treatment in South Africa include
- Pregnant women continue to present with HIV at a prevalence of approximately of 30%.[ZA NDOH Antenatal Sentinel Survey 2012] However, there are areas of higher prevalence where rates are 40% or higher as well as areas where rates are lower than 20%. Informal periurban and perirural areas, including communities with new industrial and mining developments, are particularly prone to rapid increases in incidence and prevalence, particularly among young, poor women who have not completed secondary school. There is a high rate of teenage pregnancy in poor areas with inadequate school health services including sexual and reproductive health programmes. HIV testing, contraception, and barrier methods are not accessible through schools at this time despite some schools having 10% of the female secondary school learners becoming pregnant each year.[Panday 2009]
- The prevalence of HIV is lower in men (eg, 4 times lower in men 20-24 years of age than among women in the same age group)[UNAIDS ZA Progress Report 2012] until their later 20s when prevalence in both sexes reaches similar levels in those communities with stable populations. Said in another way, HIV rates in women reflect the rates of men on average 5 years older.[ZA HIV Prevalence Survey 2012] Other factors that will continue to promote the spread of HIV include the recent downturn in the economy and high unemployment that exacerbates food insecurity and access to basic services like health, welfare, and electricity. The overall situation is worsened by a rapidly growing population younger than 15 years of age adding pressure to a dysfunctional educational system with few prospects for ongoing learning for matriculants.
- Neglected key populations that affected by the HIV epidemic are poor young women, men who have sex with men, transgender persons, out-of-school youth, sex workers and their clients, those who abuse drugs and alcohol, seronegative partners in serodiscordant couples, migrants, and refugees.[UNAIDS ZA Progress Report 2012; ZA Natl Strategic Plan; WHO Key Populations 2014] Persons from these populations continue to present with high HIV prevalence, but there are no systematic routinised seroprevalence surveys undertaken to guide planning of intervention programmes. Support for these populations remains fragmented and poorly coordinated with mainstream services. Access to HIV treatment and prevention services remains elusive and challenging for these populations.
- Testing for HIV is now readily available and obtainable from all primary healthcare facilities as well as in the private sector from general practitioners, pharmacies, and for-profit and not-for-profit nongovernment organisations. The tests used are not standardised, and they have varying sensitivity and specificity rates; therefore, quality control is difficult to maintain.
- Linked to the ongoing burden of HIV is the ongoing tuberculosis (TB) epidemic. South Africa has one of the highest incidences of TB in the world, with more than 400,000 new cases registered in 2013.[WHO TB Report 2014] The rates of multidrug and extensively drug resistant TB are continuing to increase as the burden of new cases makes follow-up of defaulters particularly challenging. Early HIV treatment reduces the rate of TB infection,[Dheda 2004] and high levels of adherence to ART and TB treatment will ensure the reduction of resistant TB.
- South Africa continues to show trends toward a more unequal society, leading the world in the income differential between the rich and the poor. This divided society results in limited access to critical services for the poor and the uninsured. At present, 83% of HIV-infected persons receives care through public health services, and 17% of the population accesses private health coverage.[Gray 2011] The National Health Insurance plan[ZA National Health Ins] that is expected to roll out during the next few years may help address these inequalities through ensuring adequate healthcare for all through innovative ways of bringing the private and public health sectors to share the burden of care.
HIV Treatment Recommendations in South Africa
Treatment guidelines have continued to change since antiretroviral therapy (ART) was first suggested for the management of HIV in 1996. In the beginning, early treatment was recommended, but the toxicity related to components of the early regimens suggested that a more conservative approach was prudent. Several cohort studies have confirmed that earlier treatment reduces morbidity and mortality.[Kitahata 2009; Sterne 2009; May 2007] In addition, the START[INSIGHT 2015] and TEMPRANO ANRS 1236[TEMPRANO 2015] randomised trials have demonstrated a significant individual clinical benefit from starting ART immediately in patients with CD4+ cell counts > 500 cells/mm³ rather than deferring until a certain lower CD4+ threshold or clinical indication was met. In addition, HPTN-052, demonstrated significantly reduced sexual transmission with early antiretroviral therapy.[Cohen 2011] As such, US, European, and World Health Organisation (WHO) HIV treatment guidelines recommend treatment soon after diagnosis, regardless of CD4+ cell count.[DHHS ART; Günthard 2014; WHO ART 2015] This recommendation has been recently echoed in private sector treatment in South Africa with new guidelines issued by the Southern Africa HIV Clinicians Society (Management Guidelines).[ZA HIV Clin Soc Update 2015] These recommendations are practical when there is a wide range of antiretroviral agents available. For adults with HIV infection treated in the public sector where options may be limited, the current South Africa National Department of Health ART guidelines recommend treatment for (Management Guidelines)[ZA NDOH HIV Tx 2015]:
- All HIV-positive patients with CD4+ cell counts ≤ 500 cells/mm3, regardless of WHO clinical stage
- Patients with CD4+ cell counts ≤ 350 cells/mm3 or WHO clinical stage 3 or 4 should be prioritised
- All HIV-positive patients with WHO clinical stage III or IV disease, regardless of CD4+ cell count
- All HIV-positive patients with active tuberculosis (TB) disease (both drug resistant and drug sensitive, including extrapulmonary), regardless of CD4+ cell count
- Pregnant and breast-feeding women who are HIV positive
- Patients with known hepatitis B virus coinfection
In general, ART should be initiated as soon as the patient is ready and within 2 weeks after the most recent CD4+ cell count. There are certain specific cases, however, where ART should be hastened or delayed.
All HIV-infected pregnant or breast-feeding women should initiate lifelong ART, regardless of CD4+ cell count, preferably on the same day as diagnosis, unless active TB is present or there is a contraindication to the recommended first-line regimen. Timing of ART in TB-coinfected patients depends on CD4+ cell count. In those with CD4+ cell count < 50 cells/mm3, ART should be initiated within 2 weeks of TB treatment, as soon as the patient’s symptoms are improving and TB treatment is tolerated. For those with CD4+ cell counts > 50 cells/mm3, ART should be initiated 2-8 weeks after starting TB treatment. For those with cryptococcal or TB meningitis, ART should be deferred for 4-6 weeks. Certain patients with advanced HIV disease should be started on ART within 7 days (“fast tracked”): those with CD4+ cell counts ≤ 200 cells/mm3 and those with HIV stage 4 disease, even if the CD4+ cell count is not available.
There are limited numbers of drugs available for first- and second-line treatment in the public sector in South Africa. Third-line ART is available only at specialised public-sector HIV clinics that have adequate donor funding or for those with adequate health insurance in the private sector. It is limited to patients who have documented resistance to the PIs they are currently receiving.
The 2015 guidelines from the South African National Department of Health recommend a fixed-dose combination regimen of tenofovir/emtricitabine/efavirenz for all adult patients weighing more than 40 kg initiating first-line ART, including women who are pregnant or breastfeeding and patients with other comorbidities (eg, diabetes, hypertension, respiratory disease such as TB, hepatitis B), unless there is a contraindication to efavirenz. If less than 40 kg, the regimen is abacavir/lamivudine plus efavirenz. If it is not possible to include efavirenz in the regimen (either because of neurologic toxicity, psychiatric comorbidity, or work requirements), nevirapine or lopinavir/ritonavir should be substituted. In addition, all patients receiving a stavudine-based regimen should be switched to tenofovir. The 2015 guidelines recommend that no patient should remain on a stavudine-based regimen, even if that regimen is well tolerated. In addition, a position paper issued by the South African National Department of Health indicates that whenever possible, lamivudine should not be prescribed as a single tablet but rather as part of a fixed-dose combination: either abacavir/lamivudine or tenofovir/emtricitabine in the case of first-line regimens (where emtricitabine is substituted for lamivudine).[ZA NDOH FDCs]
- South Africa has made great strides in the public sector in reducing the rate of vertical transmission from mother to child to 2.7%, and some provinces have achieved transmission rates of < 2% using the standard government treatment protocols.[ZA PMTCT Interventions] This is due to HIV testing and antiretroviral treatment of all pregnant women (and their infants) with ART triple therapy.[ZA NDOH HIV Tx 2015] However, a small but significant number of pregnant women seroconvert later in pregnancy or during lactation. For that reason, 3% of women who were thought to be HIV negative gave birth to HIV-positive children.[Dinh 2015] It is critical that all HIV-negative pregnant women or those who are breastfeeding be tested regularly (suggested every 3 months throughout pregnancy, at labour/delivery, at the 6-week Expanded Programmme on Immunisation visit and every 3 months throughout breast-feeding)[ZA NDOH HIV Tx 2015] so that ART can be initiated to prevent transmission. (One of the authors of this chapter has reported that his centre has increased frequency of HIV counselling and testing to monthly and has decreased rate of mother-to-child transmission by 75% Ashraf Grimwood, personal communication). The testing of partners of pregnant women continues to remain a challenge, and those untested continue to present a risk of HIV transmission to these women. Getting these men tested early is a priority, and early couple counselling, testing, and treatment be made available (Management Guidelines).[WHO ART 2013]
- Adolescents continue to present unique challenges for the transmission and management of HIV. Nondisclosure (of their own infection) to adolescents may result in adherence difficulties, lack of trust in parents or caregivers, and possible transmission if the patient becomes sexually active. Adolescents can provide informed consent for testing at 12 years of age, but their specific needs must be addressed to ensure maximum adherence to therapy.[ZA NDOH HIV Tx 2015] Their needs are perhaps best met in the public sector, where the presence of many other adolescent patients can facilitate the formation of peer support groups.
- The following groups of adolescents are considered to be most at risk for HIV[ZA NDOH HIV Tx 2015]:
- Adolescent females who are poor and food insecure and engage in transactional sex to survive
- Adolescents who are sexually active
- Adolescents who become pregnant
- Adolescents who inject drugs
- Transgender adolescents, both male and female
- Adolescents affected by AIDS (orphans and children of chronically ill caregivers)
- Adolescent clients of sex workers and the partners of these clients
- HIV-negative partners in serodiscordant couples
- Noncommunicable diseases such as hypertension, diabetes, and obesity are some of the 4 main health challenges facing South Africans. Management of these diseases forms part of the Negotiated Service Development Agreement[ZA NSDA] between the president of South Africa and the minister of health. These diseases will play a larger role in the ongoing management of chronic HIV as the population of South Africa ages. Healthcare workers have to be prepared for this eventuality.