Inferring HIV-1 transmission networks and sources of epidemic spread in Africa with deep-sequence phylogenetic analysis

To prevent new infections with human immunodeficiency virus type 1 (HIV-1) in sub-Saharan Africa, UNAIDS recommends targeting interventions to populations that are at high risk of acquiring and passing on the virus. Yet it is often unclear who and where these ‘source’ populations are. Here we demonstrate how viral deep-sequencing can be used to reconstruct HIV-1 transmission networks and to infer the direction of transmission in these networks. We are able to deep-sequence virus from a large population-based sample of infected individuals in Rakai District, Uganda, reconstruct partial transmission networks, and infer the direction of transmission within them at an estimated error rate of 16.3% [8.8–28.3%]. With this error rate, deep-sequence phylogenetics cannot be used against individuals in legal contexts, but is sufficiently low for population-level inferences into the sources of epidemic spread. The technique presents new opportunities for characterizing source populations and for targeting of HIV-1 prevention interventions in Africa

An analysis of survivorship care strategies in national cancer control plans in Africa

PURPOSE: In 2017, the World Health Organization urged member states to develop and implement national cancer control plans (NCCPs) and to anticipate and promote cancer survivor follow-up care, which is a critical yet often overlooked component of NCCPs. This study aims to examine the inclusion of cancer survivorship-related strategies and objectives in NCCPs of African countries. METHODS: Independent reviewers extracted strategies, objectives, and associated indicators related to survivorship care from 21 current or recently expired NCCPs in African countries. Building on a similar analysis of the US state cancer control plans, reviewers categorized these strategies according to an adapted version of the ten recommendations for comprehensive survivorship care detailed in the 2006 National Academy of Medicine report. RESULTS: A total of 202 survivorship-related strategies were identified, with all NCCPs including between 1 and 23 references to survivorship. Eighty-three (41%) strategies were linked to measurable indicators, and 128 (63%) of the survivorship-related strategies were explicitly focused on palliative care. The most frequent domains referenced were models of coordinated care (65 strategies), healthcare professional capacity (45), and developing and utilizing evidence-based guidelines (23). The least-referenced domains were survivorship care plans (4) and adequate and affordable health insurance (0). CONCLUSIONS: The results of this study indicate that survivorship objectives and strategies should extend beyond palliative care to encompass all aspects of survivorship and should include indicators to measure progress. IMPLICATIONS FOR CANCER SURVIVORS: Stakeholders can use this baseline analysis to identify and address gaps in survivorship care at the national policy level

Direct provision versus facility collection of HIV self-tests among female sex workers in Uganda: A cluster-randomized controlled health systems trial

Background: HIV self-testing allows HIV testing at any place and time and without health workers. HIV self-testing may thus be particularly useful for female sex workers (FSWs), who should test frequently but face stigma and financial and time barriers when accessing healthcare facilities. Methods and findings We conducted a cluster-randomized controlled health systems trial among FSWs in Kampala, Uganda, to measure the effect of 2 HIV self-testing delivery models on HIV testing and linkage to care outcomes. FSW peer educator groups (1 peer educator and 8 participants) were randomized to either (1) direct provision of HIV self-tests, (2) provision of coupons for free collection of HIV self-tests in a healthcare facility, or (3) standard of care HIV testing. We randomized 960 participants in 120 peer educator groups from October 18, 2016, to November 16, 2016. Participants’ median age was 28 years (IQR 24–32). Our prespecified primary outcomes were self-report of any HIV testing at 1 month and at 4 months; our prespecified secondary outcomes were self-report of HIV self-test use, seeking HIV-related medical care and ART initiation. In addition, we analyzed 2 secondary outcomes that were not prespecified: self-report of repeat HIV testing—to understand the intervention effects on frequent testing—and self-reported facility-based testing—to quantify substitution effects. Participants in the direct provision arm were significantly more likely to have tested for HIV than those in the standard of care arm, both at 1 month (risk ratio [RR] 1.33, 95% CI 1.17–1.51, p < 0.001) and at 4 months (RR 1.14, 95% CI 1.07–1.22, p < 0.001). Participants in the direct provision arm were also significantly more likely to have tested for HIV than those in the facility collection arm, both at 1 month (RR 1.18, 95% CI 1.07–1.31, p = 0.001) and at 4 months (RR 1.03, 95% CI 1.01–1.05, p = 0.02). At 1 month, fewer participants in the intervention arms had sought medical care for HIV than in the standard of care arm, but these differences were not significant and were reduced in magnitude at 4 months. There were no statistically significant differences in ART initiation across study arms. At 4 months, participants in the direct provision arm were significantly more likely to have tested twice for HIV than those in the standard of care arm (RR 1.51, 95% CI 1.29–1.77, p < 0.001) and those in the facility collection arm (RR 1.22, 95% CI 1.08–1.37, p = 0.001). Participants in the HIV self-testing arms almost completely replaced facility-based testing with self-testing. Two adverse events related to HIV self-testing were reported: interpersonal violence and mental distress. Study limitations included self-reported outcomes and limited generalizability beyond FSWs in similar settings. Conclusions: In this study, HIV self-testing appeared to be safe and increased recent and repeat HIV testing among FSWs. We found that direct provision of HIV self-tests was significantly more effective in increasing HIV testing among FSWs than passively offering HIV self-tests for collection in healthcare facilities. HIV self-testing could play an important role in supporting HIV interventions that require frequent HIV testing, such as HIV treatment as prevention, behavior change for transmission reduction, and pre-exposure prophylaxis. Trial registration ClinicalTrials.gov NCT0284640

Primary and secondary study outcomes at 1 month and 4 months.

<p>Primary and secondary study outcomes at 1 month and 4 months.</p

Time line of study interventions and assessments (conducted by research assistants, in blue).

<p>Participants were randomized in groups of 1 peer educator and 8 FSWs. The text following the subscripts below describe details about each peer educator visit: ^<b>1</b>Research assistants gave all participants a referral card for free HIV testing and a study contact card. The referral card could be used at 10 private healthcare facilities participating in this study. The study contact card included a toll-free hotline number, which participants could call for information about linkage to care, to report potential adverse events, or to ask questions related to HIV self-testing (intervention arms only). ²The peer educators gave all participants condoms. In the direct provision arm, the peer educators additionally gave the participants oral HIV self-tests; in the facility collection arm, participants received coupons, which they could exchange for an HIV self-test at the participating healthcare facilities. ³The peer educators gave all participants condoms.</p

Participant recruitment, eligibility, randomization, and follow-up.

<p>CONSORT flow diagram. HIVST, HIV self-test; <i>n</i>, number; <i>k</i>, clusters; LTFU, loss to follow-up; mo, month.</p

Participant baseline descriptive characteristics.

<p>Participant baseline descriptive characteristics.</p

Primary and secondary study outcomes at 1 month and 4 months.

<p>Primary and secondary study outcomes at 1 month and 4 months.</p

Effect size estimates for impact of HIV self-testing on facility-based HIV testing.

<p>All outcomes since study start. Facility-based testing included private and public healthcare facilities. Comparisons between study arms: direct provision versus standard-of-care (dark blue), facility collection versus standard-of-care (light blue), direct provision versus facility collection (gray).</p

Implementation activities reported by participants at 4 months.

<p>Implementation activities reported by participants at 4 months.</p