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Characteristics and outcomes of individuals enrolled for HIV care in a rural clinic
in Coastal Kenya
Hassan, A.S.
Publication date
2014
Link to publication
Citation for published version (APA):
Hassan, A. S. (2014). Characteristics and outcomes of individuals enrolled for HIV care in a
rural clinic in Coastal Kenya.
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9
DISCUSSION
It is three decades since the first reported case of HIV/AIDS. Despite the unprecedented global response in terms of drug development and the establishment of national programmes, HIV/ AIDS remains a global public health concern, with an estimated 34 million people living with the disease by the end of 2011. Almost all (97%) of cases live in low and middle income countries [1]. In Kenya, an estimated 1.2 million people were living with the infection at the end of 2012 [2]. HIV services in the Kenyan public health sector were rolled out in 2003, followed by a scale up testing and antiretroviral therapy (ART) in 2006. Despite the roll out and scale up of HIV testing and ART services, the continuum of HIV care, especially from rural Kenya, remains less well described.
We set up a longitudinal surveillance at the HIV clinic located within the Kilifi District Hospital, a rural secondary level public health facility in Coastal Kenya, to describe the characteristics and outcomes of individuals enrolling for HIV care. Newly diagnosed individuals enrolling for care were consented and followed up over time to describe their characteristics and identify gaps in the continuum of HIV care in this setting. Routine sociodemographic, clinical and laboratory data were collected at every individual clinic visit. In addition, remnant blood samples from routine clinic diagnostics were captured and archived for follow-up studies. Studies included in this thesis were carried out from data and samples collected from this surveillance.
PART 1: Characteristics of individuals enrolling for HIV Care
Data from our surveillance suggests that majority (more than two-thirds) of adults enrolling for HIV care were women. These data may be a good reflection of the disproportionate distribution of HIV by gender, with women being more affected by the epidemic than men. Indeed, the prevalence of HIV infection among women in Kenya is higher (6.9%) compared to men (4.4%) [2]. The physiological make up of the female genital tract makes women more vulnerable to acquisition of HIV infection than men.
The mean age at enrolment into HIV care in our setting was reported at around 35 years, with men being older compared to women. Unlike in men, women are picked earlier on because of the existence of various women-targeted interventions including the preven-tion of mother to child transmission (PMTCT) programs, in which all pregnant women are counseled and tested for HIV infection. When ill, men are also less likely to seek health care than women, which may be attributed to their perceptions of masculinity and poor health seeking behavior [3, 4]. This may also explain why women are diagnosed with HIV infection earlier on compared to men.
158 Chapter 9
Encouragingly, the mean body mass index (BMI) and cd4 T-cell count at enrolment into HIV care were around 21 kg/m2 and 450 cells/μL respectively, suggesting relatively normal
nutri-tion and immune funcnutri-tioning at enrolment into HIV care in this setting.
HIV-1 subtype B is most common in Europe and America while subtypes A and D are widespread in sub-Saharan Africa (sSA). It is postulated that HIV-1 subtype A and D were introduced into East Africa after 1950 and spread during the 1970’s [5]. We carried out a study to describe the subtype diversity of HIV-1 infections among individuals enrolled for care in our setting (Chapter 3). Of the 153 samples that were sequenced and analyzed, around 59% were subtype A1, 9% subtype D and 8% subtype C. However, considerable complexity was also observed, with 27% of the samples being complex intersubtype recombinants. Results from phylogeographic analyses showed that most of the subtypes A1 originated in Kenya, while many of the other strains had widely dispersed origins, including some from West Africa.
Our findings are consistent with data from other Kenyan studies reporting predominance of HIV-1 subtype A1 followed by subtype D [6-9]. In addition though, we also report high levels of complex intersubtype and novel recombinants. Given the extensive transport links from Kilifi (by road) and Mombasa (through global shipping and airline linkages), we postulate increasing diversity with multiple introductions of many subtypes and much recombination in this setting.. This may be exacerbated by the flourishing sex work among the high-risk population in coastal Kenya, especially given that up to 83% of men who have sex with men (MSM) report bisexual behavior in this setting [10]. In addition, there is some evidence sug-gesting HIV-1 transmission links between MSM and heterosexuals in Kenya [11], sugsug-gesting transmission possibilities between these populations leading to an increase in complex and novel recombinants. Not only do increasing recombinants pose a major challenge towards anti-HIV vaccine design, their effect on disease progression and acquisition of drug resistance is yet unclear, though there is some evidence to suggest a reduced risk of transmitted drug resistance (TDR) among individuals infected with intersubtype recombinants when compared to those infected with a pure subtype [12].
HIV-1 TDR has been shown to compromise the effectiveness of antiretroviral therapy [13-15]. Emergence of HIV-1 TDR therefore threatens the success of ART programme in sSA. High levels of TDR have been reported in resource rich countries [16-19]. In sub-Saharan Africa, low levels of <5% TDR have been previously reported [20-27]. However, recent studies sug-gest an increase in transmitted drug resistance in sSA [12, 28-31]. Importantly, a study carried out in Mombasa, a region barely 50 km away from our setting, and using the WHO threshold survey approach [21], reported a high prevalence of 13.2% [32].
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We analyzed samples from 182 ART naïve HIV infected adults enrolling for HIV care to determine the prevalence of HIV-1 TDR from our rural HIV clinic in Coastal Kenya (Chapter
4). Two TDR mutations to nucleoside reverse transcriptase inhibitors (n=1) in a 16 year old
female participant and a protease inhibitor (n=1) in a 23 year old female participant were observed, giving an overall TDR prevalence of 1.1%. While recent data from other settings, including those from Mombasa, report moderate to high levels of TDR, data from our setting suggests low levels of TDR.
The high levels of TDR in other settings compared to our setting maybe the compounding effect of several factors, including longer availability of ART or higher ART coverage or a combination of both. Indeed, in our setting, provision of ART in the public health sector started less than a decade ago, making our population relatively ART naïve, compared to other sub-Saharan settings. The rural nature of our setting also implies less developed infra-structure hence low ART coverage, which may explain the low TDR prevalence observed in individuals enrolling for care in this setting.
PART 2: Outcomes of Individuals prior to ART Initiation
HIV infected individuals are enrolled and put on life-long care and treatment. In our setting, the mean cd4 T-cell count at enrolment is around 450 cells/μL, suggesting that a substantial proportion were not eligible for ART at enrolment into care. While a lot of studies have been done to describe outcomes of HIV-infected individuals initiated ART [33, 34], a paucity of data on pre-ART outcomes exists. A better understanding of pre-ART outcomes is critical in designing interventions aimed at improving long term care and timely ART initiation. We recruited 530 HIV infected ART ineligible individuals enrolling for care and followed them up over a period of 6 months to describe their rate and predictors of loss to follow up (LTFU) from HIV care (Chapter 5). Of those followed up, approximately a third (33.6%) were LTFU within 6 months of enrolment into care, with more than a half of these (53.9%) enrolling for care but not retruning for follow up within the next 6 months. Further distance from the clinic and single marital status at time of enrolment were independent predictors of time to LTFU. Although services are offered free of charge, indirect costs, including distance travelled for care, reduce accessibility for HIV services. HIV-related stigma and disclosure may also contribute to the high rate of loss to follow up among participants of single marital status. Importantly advanced HIV disease as measured by cd4 T-cell count, WHO clinical staging and body mass index (BMI) did not predict pre-ART LTFU. Studies in individuals on ART report low cd4 T-cell count, advanced WHO clinical staging and low BMI as independent predictors of LTFU [35-39] and have been attributed to non-reported death secondary to advanced HIV infection at ART initiation.
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LTFU in children born to HIV infected mothers (HIV exposed infants), is equally important, especially in light of the strategy towards elimination of mother to child transmission of HIV infection [40]. Many HIV infected infants die from HIV-related causes without knowing their HIV status, or receiving HIV care. We retrospectively followed up 213 infants born to HIV infected mothers to determine uptake and constraints of the early infant diagnosis (EID) process for detection of HIV infection and to describe LTFU of these infants from HIV care
(Chapter 6). Approximately two-thirds (68%) infants enrolled for HIV care after 2 months of
age, which is against the nationally recommended age of 6 weeks. In addition, around two thirds (65%) were LTFU before the recommended 18 months age, with almost half (43%) being LTFU within two months of enrolment into care. Our data therefore suggests that majority of our HIV-exposed infants did not get HIV PCR done at 6 weeks as recommended by the Kenyan national guidelines, did not benefit from early cotrimoxazole and postnatal PMTCT interventions and were therefore at increased risk of postnatal HIV acquisition and early HIV-related mortality.
Without PMTCT interventions, the risk of HIV transmission before or during birth is 15-25%, while breastfeeding increases this risk by 5–20% (ref). In addition, without access to cotri-moxazole prophylaxis and antiretroviral therapy, about a third of HIV infected infants die by one year, and a half by two years of age [41]. Majority of HIV-exposed infants in our setting present late for care and are LTFU immediately thereafter, implying that they do not benefit from postnatal PMTCT intervention and a confirmatory HIV test. Given the high risk of HIV transmission from breastfeeding exposure, our data suggests that a substantial proportion of these infants may have acquired HIV infection but did not know their status. Maternal factors associated with infant LTFU were younger maternal age and maternal LTFU from care. Improving adult retention may therefore also contribute to improved early infant diagnosis and infant retention in HIV care.
PART 3: Outcomes of Individuals following ART Initiation
In our setting, the median age of individuals at ART initiation was estimated at 36 years. The median CD4 T-cell count was around 142 cells/μL, with 40% of these being severely immunocompromised i.e. CD4 T-cell count of <100 cells/μL. Similarly, their median BMI was around 19 Kg/m2, with 40% of these having moderate to severe malnutrition (BMI <18.5
Kg/m2). Men were more likely to be older and more immunocompromised at ART initiation
compared to women. These data are suggestive of late ART initiation in our setting, with men being more affected than women. This may be explained by the fact that men visit public health facilities much less frequently than women do [42, 43] and are therefore less likely to be identified, HIV tested and enrolled for care, which may be mostly attributed to the ‘masculinity’ phenomenon [3]. The availability of facility-based infrastructure and support that largely targets women, e.g. PMTCT interventions, may also play a contributing role to
9
the earlier identification of women for care and treatment initiation. Late ART initiation has been reported to contribute to poor outcomes, including early attrition (LTFU and death) from ART care.
We followed up 928 HIV infected individuals initiated on ART over a period of two years to describe their incidence and predictors of time to attrition from ART care in our clinic
(Chapter 7). Of those followed up, a third (33.2%) were either LTFU or reported dead,
with more than a half of these occurring within six months of treatment initiation. Male gender, younger age, severe malnutrition and severe immunosupression were independent predictors of time to attrition. Of interest is the equally high attrition rate observed in indi-viduals with CD4 T-cell counts of >350 cells/μL at ART initiation. Our findings are consistent with those from other sub-Saharan settings reporting male gender, younger age and severe immunosupression as predictors of time to attrition [35, 37-39]. Whilst ART scale up and treatment coverage in Kenya has been impressive, with reported ART coverage of 81% in adults by 2012 [44], high attrition remains a major challenge for the success of ART program in this setting. Advanced HIV disease at time of ART initiation strongly contributes to high initial or early attrition, while weak ART support systems after treatment initiation contributes to subsequent or late attrition.
Late attrition from ART care may also be a consummation of treatment failure following acquisition of antiretroviral drug resistance. Emerging HIV drug resistance and subsequent treatment failure threatens to reverse the gains made by the scale up of ART in sSA. However, due to cost implications, virological monitoring and HIV drug resistance testing is currently not routinely recommended in resource constrained settings. Instead, the World Health Organization (WHO) recommend use of clinical and immunological criteria to monitor treatment failure and drug resistance [45]. These criteria have been demonstrated to be poor correlates of treatment failure and drug resistance, leading to missed opportunities or unnecessary medication switches [46-50], which not only increase treatment costs, but also limit future treatment options.
We cross sectionally sampled 232 individuals on ART over a median duration of 14 months to determine the prevalence and correlates of HIV-1 virologic failure and acquired drug resistance in our setting (Chapter 8). Of those sampled, a quarter (25%) had virologic failure. Around half (53%) of those with virologic failure had acquired at least one drug resistance mutation. Younger age and unsatisfactory adherence were strong correlates of virologic failure and acquired drug resistance. High viral load was also correlated with presence of at least one drug resistance mutation. The most prevalent resistance mutations were observed within the reverse transcriptase at codon positions M184 and K103, conferring high level resistance to Nucleoside Reverse Transcriptase Inhibitors and Non-Nucleoside Reverse Transcriptase
Inhibi-162 Chapter 9
tors respectively. These results are consistent with findings from systematic reviews of studies on virological efficacy and drug resistance from resource limited settings, reporting 24% VF and 11% ADR at more than twelve months of follow-up [51, 52].
When adherence is optimal, virological suppression is achieved. However, poor adherence results to insufficient virological suppression which fosters emergence of resistance muta-tions. This explains the role of poor adherence on virologic treatment failure and emergence of resistance mutations in our setting. On the other hand, younger individuals, or the youth, face a complex myriad of challenges including their rebellious nature, peer related stigma, disclosure, sexual and other reproductive health issues [53], which may indirectly contribute to poor adherence, hence acquisition of drug resistance mutations and subsequent virologic treatment failure leading to immunosuppression, emergence of opportunistic diseases and death.
Future Perspectives
The aim of this thesis was to describe the characteristics and outcomes of individuals enroll-ing for HIV care in a rural HIV clinic in Coastal Kenya. Our data suggests that women are disproportionately affected by the HIV epidemic compared to men in this setting. Most HIV interventions have hence justifiably targeted women. As a result, more women are diag-nosed, enrolled for HIV care and started on ART much earlier, compared to men. As a result, men have poorer HIV outcomes, compared to the women. Interventions, including outreach programs and home based counseling and testing strategies, are therefore warranted to engage, identify and link HIV infected men to early care in this setting.
The high HIV-1 diversity observed in our setting is of interest. Anti-HIV/AIDS vaccines should be designed and developed in consideration to the increasing complexity of HIV-1 subtypes in this setting. In addition, studies should be done to assess the role of increasing recombi-nant subtypes on onward HIV-1 transmission, strain pathogenecity, disease progression and acquisition of drug resistance.
With time and as programs scale up antiretroviral coverage, the emergence of transmitted HIV drug resistance is inevitable. These data therefore warrant continued surveillance of TDR in our setting. The stringent eligibility criteria as recommended by the WHO truncated sampling approach for surveillance of TDR [21] made it technically challenging to achieve the pre-determined sample size of at least 47 persons, especially in areas of low HIV prevalence. It is also emerging that even within a small geographic region, substantial variations in the extent and profiles of transmitted drug resistance may occur, posing challenges in interpreta-tion and recommendainterpreta-tion for nainterpreta-tional policy. These challenges underscore the limitainterpreta-tions of the previous WHO truncated sampling method and probably justifies the current WHO
9
recommended, nationally representative survey approach. The Kenyan National HIV/AIDS program should therefore prioritize the assessment of TDR in all their national HIV/AIDS surveys. An alternative strategy for national surveillance of TDR, especially in regions with low HIV/AIDS prevalence, is the use of ART naive individuals enrolling for HIV care and prior to ART initiation. However, reversion of mutations should be acknowledged in the latter approach.
After enrolment, retention in care remains a major challenge in HIV programs. In our setting, we postulate that a substantial proportion of individuals enroll for HIV care while they are still healthy and immunocompetent, but drop out of care thereafter due to minimal sup-port, monitoring and the possible perception of being relatively healthy, only to present later with very advanced disease necessitating ART initiation, with poor outcomes. Interventions aimed at strengthening pre-ART care are therefore warranted to improve pre-ART retention, slow HIV disease progression and improve timely ART initiation. In addition to cotrimoxazole prophylaxis, the standard pre-ART package of care may include a structured framework of psychosocial support, isoniazid preventive therapy and nutritional support in the form of food programmes (which is currently mostly restricted to individuals on ART). These interven-tions may not only serve as an incentive for follow up, but also have the potential to slow down disease progression, treat intercurrent infections and enable timely ART initiation. Late presentation and poor retention in care for infants born to HIV- infected mothers also remains a major challenge in the prevention of postnatal mother to child transmission and early HIV diagnosis in our setting. To achieve the recent global move towards elimination of mother to child transmission of HIV/AIDS [40], interventions aimed at early presentation for care and improving retention through the Early Infant Diagnosis (EID) process for HIV exposed infants are warranted. To this effect, integration of EID services within postnatal and Maternal and Child Health (MCH) care has since been implemented in Kenya, albeit with minimal support. Peer support programs for HIV infected pregnant mothers may play a critical role in ensuring early presentation of infants for care and improved retention. Aggres-sive defaulter tracing for exposed infants is also necessary to account for all infants born to HIV-infected mothers for possible and timely interventions.
While individuals enroll for HIV care when they are still relatively well, a good proportion of individuals initiating ART are severely immunocompromised, confirming our hypothesis above, and contributing to the high rates of early attrition from ART care observed in our setting. Practical and sustainable interventions are warranted to decrease attrition from ART care in this setting. In the short term after ART initiation, biological interventions including therapeutic food supplementation and more potent efficacious regimens should be consid-ered to mitigate early attrition through mortality in the most immunocompromised
individu-164 Chapter 9
als. In the long term, social support systems addressing stigma and facilitating disclosure, especially among the youth and young adults, are needed to offset late attrition and improve on treatment outcomes in this population. More studies are also needed to clearly delin-eate the relationship between high baseline CD4 T-cell count and attrition from ART care, especially in the context of treatment as prevention strategies. In addition, programs should be cognizant of the potential challenges that may face treatment as prevention strategies, including emergence and spread of HIV drug resistance and the resultant treatment failure. In our setting, high levels of virologic treatment failure and acquired drug resistance muta-tions were observed among individuals with unsatisfactory adherence and in the younger adults/youths. Implementation of youth friendly support networks may play a critical role in addressing the complex challenges facing HIV-infected youth in our setting. To address un-satisfactory adherence, our data warrants prioritization of strengthened adherence support and close monitoring through direct observation therapy among individuals with virologic treatment failure before regimen switches. The immuno-virological dissociation observed confirms the need for scale up of affordable point of care viral load tests for monitoring treat-ment failure. Targeted HIV drug resistance testing should also be considered in individuals with confirmed virologic failure to prevent unnecessary/premature switches and to provide guidance on the most susceptible alternative regimen.
Conclusion
In conclusion, this thesis provides data describing the characteristics of individuals enroll-ing for HIV care and identifies important gaps in continuum of care and treatment at a rural HIV clinic in Coastal Kenya. The data from this thesis suggests that characteristics and outcomes of Individuals enrolled for HIV care in this setting is largely comparable to those from HIV programs in other parts of Kenya and sSA. Potential challenges facing this rural HIV clinic include increasing complexity in the diversification of circulating HIV strains and the emergence of HIV-1 drug resistance mutations among ART naïve individuals. Of concern is the finding that individuals enrol for care when they are relatively healthy but then only start ART when they are severely immunocompromised, followed with poor outcomes, including high attrition, acquisition of drug resistance and treatment failure. Continued surveillance activities are therefore needed to understand the evolving nature of the epidemic in this setting with an aim of identifying potential interventions aimed at improving outcomes. Practical and sustainable multifaceted interventions aimed at improving timely ART initiation and treatment outcomes are also warranted in this rural HIV clinic in Coastal Kenya.
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