INTRODUCTION
Increased access to HIV treatment has saved millions of lives and reduced HIV transmissions.1–3 4 5
Botswana is in the midst of a generalized HIV epidemic with an estimated 24.3% of the adult population (15–49 years) living with HIV.6 7,8 8 9,10
High HIV incidence and prevalence among young women remains a hallmark of the HIV-1C epidemic in sub-Saharan Africa.11–13 14 15,16 17 18,19
Early and durable suppression of viral replication evident by undetectable levels of HIV-1 RNA should be the ultimate goal of public health interventions. The population level of viral suppression is depicted by the third “90” of the UNAIDS goals,5
In this study, we focused on PLHIV in 30 communities in Botswana and performed the following analyses: assessed attainment of the “90-90-90” UNAIDS goals5
METHODS
Ethical Approval
The study was approved by the Botswana Health Research and Development Committee (Institutional Review Board of the Botswana Ministry of Health and Wellness) and the US Centers for Disease Control and Prevention Institutional Review Board. All participants provided written informed consent (or assent with guardian permission, in the case of persons at least 16 but less than 18 years of age).
Study Participants
The Botswana Combination Prevention Project (BCPP; also known as the “Ya Tsie” study) is an ongoing pair-matched, cluster-randomized clinical trial in which 15 community pairs were randomized 1:1 to test whether a combination HIV prevention intervention package is able to reduce cumulative 3-year HIV incidence on a population level, as compared to the enhanced national standard of care. Targeted communities were matched in pairs by size, health services, population age structure, and geographic location. The baseline household survey (BHS) enrolled a random, population-based sample of approximately 20% of 16–64-year-old residents between October 2013 and November 2015. The approach to selecting and enrolling the 20% random sample has been previously described.8
During the household visits, eligible residents were asked to sign written informed consent form to participate; to complete an individual questionnaire with sociodemographic and HIV-related information, including history of their HIV testing, ART status, and patterns of sexual behavior; and to donate a blood sample for a rapid HIV test (if no documentation on a previous HIV-positive test was available). Newly diagnosed and ART-naive PLHIV were offered point-of-care CD4 testing, and were asked to donate about 10 mL of blood for HIV-1 RNA testing and viral genotyping (venous blood was collected by phlebotomy in households). PLHIV in the control communities were referred to the Botswana national ART program (free-of-charge treatment for all adults with CD4 ≤ 350 cells per microliter or WHO stage III/IV at the time of the initial survey in 2013–2015). PLHIV in the intervention communities were referred to local government clinic to receive a package of interventions according to the study protocol. Services for pregnant women were focused on identification of HIV-infected pregnant women and strengthening their linkage to care, initiation of treatment, and retention on ART after delivery. HIV retesting during the third trimester was enhanced for pregnant women with a previous HIV-negative test. Participants in the BHS received a BWP 20 (approximately US $2) cellular-telephone prepaid voucher.
HIV Testing
Participants who self-reported HIV-positive status and provided documentation, such as written test results or ART prescription, were not retested for HIV. All other participants were offered counseling and testing for HIV. HIV testing was performed in the household using Botswana HIV Testing guidelines,20
HIV-1 RNA Testing
Venous blood was collected by phlebotomy in households during the baseline survey and was processed in a mobile clinic within 4 hours from sampling. HIV-1 RNA was quantified in all PLHIV enrolled. The completeness of HIV-1 RNA testing was 99.7%. HIV-1 RNA load was quantified by Abbott m2000sp/Abbott m2000rt (Abbott Laboratories, Wiesbaden, Germany) at the Botswana-Harvard HIV Reference Laboratory, which is accredited by the South African National Accreditation System (SANAS) for HIV-1 viral load testing (ISO 17025) and participates in Rush University's Virology Quality Assurance program. HIV-1 RNA load >400 copies per milliliter was considered detectable.
Statistical Analyses
To assess coverage by the UNAIDS “90-90-90” targets5 8 https://links.lww.com/QAI/B161
The first “90” is defined as documented previous knowledge of HIV-positive status. The second and the third 90s were expressed with 2 denominators each. For the proportion of participants on ART, we used either all PLHIV or only previously diagnosed HIV-positive participants (the second UNAIDS target5 5
Modified Poisson generalized estimating equations (with robust standard errors to account for within-community clustering) were used to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) for the following binary outcomes: HIV infection status, previous knowledge of HIV-positive status, documented receipt of ART, and undetectable HIV-1 RNA load (≤400 copies per milliliter). Estimated HIV prevalence and 95% CI according to age (16–29 years vs. 30–64 years) and sex were calculated by fitting an intercept-only logistic regression model with generalized estimating equations accounting for clustering by community. All analyses were conducted using SAS software version 9.4 (SAS Institute, Cary, NC) and R version 3.3.1.21
RESULTS
We recently reported on Botswana's achievement of high rates of HIV testing, treatment coverage, and virologic suppression overall.8 5 Fig. 1A ; see Table 1, Supplemental Digital Content, https://links.lww.com/QAI/B161 Fig. 1A ). The proportion of diagnosed young adults on ART with undetectable HIV-1 RNA (third 90) was 90%, which is also lower than among older adults (97%; Fig. 1A ). Among all PLHIV, the proportion of young adults on ART was 49% vs. 77% in older adults. Similarly, the proportion of virologically suppressed young adults was 44% among all PLHIV vs. 75% in older adults (Fig. 1A ).
FIGURE 1.: Proportions of PLHIV meeting the UNAIDS 90-90-90 targets, on ART, and
virologically suppressed , overall by age and by sex in Botswana. Study participants were sampled in 20% of households in 30 Botswana communities. See Table 1, Supplemental Digital Content,
https://links.lww.com/QAI/B161 for the number of participants in each group. A, General population (total, both sexes) is shown as the darkest gray bar. Young adults (16–29 years old) are shown as medium-tone gray bar. Older adults (30–64 years old) are presented as the lightest gray bar. B, Men. The darkest gray bars indicate men of any age (16–64 years old). Medium-tone gray bars show young men (16–29 years old). The lightest gray bars delineate older men (30–64 years old). C, Women. The darkest gray bars indicate women of any age (16–64 years old). Medium-tone gray bars show young women (16–29 years old). The lightest gray bars delineate older women (30–64 years old).
Compared with older men, fewer young men knew about their positive HIV status (45% vs. 81%; first 90); they were less likely to be on ART (32% vs. 73%; proportion of all men living with HIV who are on ART), and were less likely to have undetectable HIV-1 RNA (24% vs. 71%; proportion of all men living with HIV who are virologically suppressed ; Fig. 1B ). A similar pattern was found among young women (Fig. 1C ). As compared to older women, a smaller proportion of young women were aware of their HIV infection (70% vs. 89%); young women were less likely to be receiving ART (52% vs. 79% among all women living with HIV), and fewer of them had undetectable HIV-1 RNA (48% vs. 77% among all women living with HIV; Fig. 1C ).
Compared with older adults (30–64 years old), young HIV-infected adults were significantly less likely to have undetectable HIV-1 RNA (PR: 0.65; 95% CI: 0.59 to 0.70; P < 0.0001), including both men (PR: 0.43; 95% CI: 0.34 to 0.56; P < 0.0001) and women (PR: 0.67; 95% CI: 0.62 to 0.74; P < 0.0001). Among a subset of PLHIV receiving ART, young adults also were less likely to have undetectable HIV-1 RNA load than older adults (PR: 0.93; 95% CI: 0.90 to 0.95; P = <0.0001).
Reducing the age cut-off from 30 to 25 years resulted in similar proportions across all comparisons. Compared with older adults (25–64 years old), young HIV-infected adults were significantly less likely to have undetectable HIV-1 RNA (PR: 0.59; 95% CI: 0.52 to 0.68; P < 0.0001), including both men (PR: 0.41; 95% CI: 0.26 to 0.65; P < 0.0001) and women (PR: 0.62; 95% CI: 0.53 to 0.73; P < 0.0001). Among a subset of PLHIV receiving ART, young adults also were less likely to have undetectable HIV-1 RNA load than older adults (PR: 0.87; 95% CI: 0.82 to 0.92; P = <0.0001).
HIV Prevalence
We found a substantial sex gap in HIV prevalence across 30 villages in Botswana. Among men aged 16–64 years, 21% (95% CI: 19% to 23%) were HIV-infected. Among women of the same age, 33% (95% CI: 30% to 35%) were infected (P < 0.0001).
Figure 2A demonstrates HIV prevalence by age group (see Table 2, Supplemental Digital Content, https://links.lww.com/QAI/B161
FIGURE 2.: A, HIV prevalence among adults tested in 30 Botswana communities stratified by age and sex. B, Proportion of individuals aware of their positive HIV status stratified by age and sex. Women are represented by circles; men are represented by triangles. Dashed line in (B) denotes the first 90 in the UNAIDS targets.
5 See Table 2, Supplemental Digital Content,
https://links.lww.com/QAI/B161 for the number of participants in each group.
Knowledge of HIV-Positive Status
Knowledge of HIV-positive status by age group (Fig. 2B ) was similar to the HIV prevalence graph (Fig. 2A ). In women aged 16–24 years, awareness of positive HIV status was approximately 60% and gradually increased with age (Fig. 2B ). Knowledge of HIV-positive status was particularly low (below 50%) among men aged 20–29 years. Young PLHIV were less likely to be aware of their positive HIV status compared with older adults (PR: 0.76; 95% CI: 0.71 to 0.80; P < 0.0001).
PLHIV Receiving ART
Stratified by age and sex, the distribution of individuals on ART revealed that younger age was associated with not receiving ART (Figs. 3A, B ; see Table 2, Supplemental Digital Content, https://links.lww.com/QAI/B161 P < 0.0001).
FIGURE 3.: A, Proportion of all PLHIV receiving ART in 30 Botswana communities stratified by age and sex. Dashed line denotes the 81% target (0.90 × 0.90) among PLHIV. B, Proportion of previously diagnosed participants living with HIV currently on ART. Women are represented by circles; men are represented by triangles. Dashed line denotes the second 90 in the UNAIDS targets.
5 See Table 2, Supplemental Digital Content,
https://links.lww.com/QAI/B161 for the number of participants in each group.
The proportions of HIV-infected individuals receiving ART gradually increased with age (Fig. 3A ). Among HIV-positive men older than 50 years, ≥84% were receiving ART. About 50% of young women living with HIV were receiving ART. By contrast, at least 76% of women older than 35 years were on ART.
Figure 3B is restricted to PLHIV who tested HIV-positive in the past and already knew about their positive HIV status at the time of household visit. Young PLHIV were significantly less likely to be on ART compared with older adults (PR 0.84; 95% CI: 0.79 to 0.89; P < 0.0001). A comparison of Figures 3A, B highlights that once diagnosed and initiated ART, there are no sex differences in those who remain on ART.
PLHIV With HIV-1 RNA Load ≤400 Copies Per Milliliter
Younger age was associated with having detectable HIV-1 RNA (Fig. 4A ; see Table 2, Supplemental Digital Content, https://links.lww.com/QAI/B161 virologically suppressed women gradually increased across young age groups and plateaued in the range of 81%–86% after 35 years of age (decreasing to 77% in the age group 60–64 years).
FIGURE 4.: A, Proportion of all PLHIV with undetectable HIV-1 RNA load (≤400 copies per milliliter) in 30 Botswana communities stratified by age and sex. Dashed line denotes the 73% target (0.90 × 0.90 × 0.90) among PLHIV. B, Proportion of PLHIV with undetectable HIV-1 RNA load among participants who were diagnosed previously and were receiving ART at the time of household visit. Women are represented by circles; men are represented by triangles. Dashed line denotes the third 90 in the UNAIDS targets.
5 See Table 2, Supplemental Digital Content,
https://links.lww.com/QAI/B161 for the number of participants in each group.
Young PLHIV were significantly less likely to have undetectable HIV-1 RNA load (PR: 0.57; 95% CI: 0.52 to 0.63; P < 0.0001). Young men were less likely to have undetectable HIV-1 RNA compared with older men (PR: 0.37; 95% CI: 0.29 to 0.48; P < 0.0001).
Figure 4B shows the proportion of PLHIV with undetectable HIV-1 RNA load among those who were previously diagnosed and receiving ART. Remarkably, all individuals in the oldest age groups had undetectable HIV-1 RNA load. Within the subset of previously diagnosed individuals receiving ART, young adults were less likely to have undetectable HIV-1 RNA load than older adults (PR: 0.93; 95% CI: 0.90 to 0.95; P < 0.0001).
We found a subset of young HIV-infected adults (7 men and 29 women) who reported no use of ART, but had undetectable HIV-1 RNA, and therefore fell out of the care continuum scheme because they were not included in the second 90. Accounting for these virologically suppressed individuals effectively increased the proportion of young PLHIV with undetectable HIV-1 RNA to 51%.
DISCUSSION
This study highlights that despite the overall success of the national ART program among the general population in Botswana,8
Importantly, elevated prevalence of viremia in young adults does not seem to be primarily related to poorer ART adherence or retention. Young adults on ART were 7% less likely to have achieved virologic suppression than older individuals, suggesting lower adherence or retention. However, the predominant contributor to lack of virologic suppression among young adults was lack of knowledge that they had HIV and decreased use of ART among those aware that they had HIV infection. Some other factors could also contribute to the elevated levels of HIV-1 RNA in young adults.
The observation of increased viremia prevalence among young adults can likely be attributed in part to ART guidelines at the time of the survey. At the time of the survey, HIV-infected people with CD4 count below 350, or with other indications for treatment, were eligible for ART.22 23 24–29 30 31,32
In addition, reaching men is crucial for ultimate control of the HIV epidemic in Southern Africa. To improve access to diagnosis and linkage to care, men-friendly environments including men peer campaigners and men-targeted HIV services are needed.33 34
It is well known that PLHIV need to take ART to reach virologic suppression. However, virologic suppression among ART-naive PLHIV (eg, “elite,” or viremic controllers) has been reported previously.35–39 40,41 virologically suppressed young adults to 51%. Although this estimate is not technically the third 90 of the UNAIDS targets,5
The study has limitations. The study results could be influenced by CD4-driven initiation of ART at the time of the survey because this approach could disproportionately affect young HIV-infected adults more likely to have shorter duration of HIV infection. Using overall knowledge of HIV-status, we analyzed prevalence of viral suppression. However, if a person does not know they are HIV-infected or has not been referred for treatment, viral suppression is unlikely. Although we highlight that detectable levels of HIV-1 RNA are more prevalent in young adults, merely testing those who are not aware of their HIV status may not be sufficient in achieving community viral suppression. The behaviors and beliefs of young adults in our cohort who were unaware of their HIV status may differ from those young adults aware of their HIV-positive status who pursued treatment. Therefore, programmatic public health strategies must evaluate and monitor the care cascade with a focus on identifying predictors of failure to best customize programming efforts for those least likely to achieve viral suppression and most likely to transmit virus.
The study demonstrates low coverage toward UNAIDS goals among young adults in Botswana, which is a health problem for young PLHIV and a challenge for overall HIV epidemic control. Young adults in Botswana may be contributing disproportionately to HIV-transmission networks. The study results suggest that targeted interventions should be tailored to improve HIV testing, linkage to care, and treatment coverage among young adults, and young men, in particular. Research on the dynamics of HIV transmission networks among young adults could inform more effective prevention programs.
ACKNOWLEDGMENTS
The authors are grateful to all participants of the BCPP study in Botswana and community leaders across the country. They thank the BCPP study field team for their dedication and outstanding outreach work. They thank the Botswana Ministry of Health for collaboration. They thank Tumalano Sekoto and Jesse Rizutko for superior IRB-related support. They thank Lendsey Melton for excellent editorial assistance.
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