Background Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. Methods In nine countries, we...

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Prevention of HIV-1 Infection with Early Antiretroviral Therapy

Prospective Cohort Study

Secret History: Return of the Black Death Channel 4, 7-8pm In 1348 the Black Death swept through London, killing people within days of the appearance of their first symptoms. Exactly how many died, and why, has long been a mystery. This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale. And they ask, what might be coming next?

Medscape

Background Antiretroviral preexposure prophylaxis is a promising approach for preventing human immunodeficiency virus type 1 (HIV-1) infection in heterosexual populations. Methods We conducted a randomized trial of oral antiretroviral therapy for use as preexposure prophylaxis among HIV-1–serodiscordant heterosexual couples from Kenya and Uganda. The HIV-1–seronegative partner in each couple was randomly assigned to one of three study regimens — once-daily tenofovir (TDF), combination tenofovir–emtricitabine (TDF–FTC), or matching placebo — and followed monthly for up to 36 months. At enrollment, the HIV-1–seropositive partners were not eligible for antiretroviral therapy, according to national guidelines. All couples received standard HIV-1 treatment and prevention services. Results We enrolled 4758 couples, of whom 4747 were followed: 1584 randomly assigned to TDF, 1579 to TDF–FTC, and 1584 to placebo. For 62% of the couples followed, the HIV-1–seronegative partner was male. Among HIV-1–seropositive par...

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Antiretroviral prophylaxis for HIV prevention in heterosexual men and women.

https://www.commed.vcu.edu/Chronic_Disease/2012/cochranrvwrschbias.pdf

The Cochrane Collaboration's tool for assessing risk of bias in randomised trials

The World Health Organization (WHO) issued the first evidence-based treatment guidelines for cryptococcal meningitis in December 2011. Although its incidence has decreased with increased access to antiretroviral therapy, cryptococcal meningitis remains a major cause of death in people with HIV/AIDS, with over 500 000 deaths every year in sub-Saharan Africa. It is a leading cause of death in the Medecins sans Frontieres (MSF) HIV/AIDS programmes in Africa.

Responding to the evidence for improved treatment for cryptococcal meningitis in resource-limited settings : correspondence

Background Global HIV treatment programs have sought to lengthen the interval between clinical encounters for people living with HIV (PLWH) who are established on antiretroviral treatment (ART) to reduce the burden of seeking care and to decongest health facilities. The overall effect of reduced visit frequency on HIV treatment outcomes is however unknown. We conducted a systematic review and meta-analysis to evaluate the effect of implementation strategies that reduce the frequency of clinical appointments and ART refills for PLWH established on ART. Methods and findings We searched databases between 1 January 2010 and 9 November 2021 to identify randomized controlled trials (RCTs) and observational studies that compared reduced (6- to 12-monthly) clinical consultation or ART refill appointment frequency to 3- to 6-monthly appointments for patients established on ART. We assessed methodological quality and real-world relevance, and used Mantel–Haenszel methods to generate pooled risk ratios (RRs) with 95% confidence intervals for retention, viral suppression, and mortality. We evaluated heterogeneity quantitatively and qualitatively, and overall evidence certainty using GRADE. Searches yielded 3,955 records, resulting in 10 studies (6 RCTs, 3 observational studies, and 1 study contributing observational and RCT data) representing 15 intervention arms with 33,599 adults (≥16 years) in 8 sub-Saharan African countries. Reduced frequency clinical consultations occurred at health facilities, while reduced frequency ART refills were delivered through facility or community pharmacies and adherence groups. Studies were highly pragmatic, except for some study settings and resources used in RCTs. Among studies comparing reduced clinical consultation frequency (6- or 12-monthly) to 3-monthly consultations, there appeared to be no difference in retention (RR 1.01, 95% CI 0.97–1.04, p = 0.682, 8 studies, low certainty), and this finding was consistent across 6- and 12-monthly consultation intervals and delivery strategies. Viral suppression effect estimates were markedly influenced by under-ascertainment of viral load outcomes in intervention arms, resulting in inconclusive evidence. There was similarly insufficient evidence to draw conclusions on mortality (RR 1.12, 95% CI 0.75–1.66, p = 0.592, 6 studies, very low certainty). For ART refill frequency, there appeared to be little to no difference in retention (RR 1.01, 95% CI 0.98–1.06, p = 0.473, 4 RCTs, moderate certainty) or mortality (RR 1.45, 95% CI 0.63–3.35, p = 0.382, 4 RCTs, low certainty) between 6-monthly and 3-monthly visits. Similar to the analysis for clinical consultations, although viral suppression appeared to be better in 3-monthly arms, effect estimates were markedly influence by under-ascertainment of viral load outcomes in intervention arms, resulting in overall inclusive evidence. This systematic review was limited by the small number of studies available to compare 12- versus 6-monthly clinical consultations, insufficient data to compare implementation strategies, and lack of evidence for children, key populations, and low- and middle-income countries outside of sub-Saharan Africa. Conclusions Based on this synthesis, extending clinical consultation intervals to 6 or 12 months and ART dispensing intervals to 6 months appears to result in similar retention to 3-month intervals, with less robust conclusions for viral suppression and mortality. Future research should ensure complete viral load outcome ascertainment, as well as explore mechanisms of effect, outcomes in other populations, and optimum delivery and monitoring strategies to ensure widespread applicability of reduced frequency visits across settings.

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Evaluation of HIV treatment outcomes with reduced frequency of clinical encounters and antiretroviral treatment refills: A systematic review and meta-analysis

Tuberculosis (TB) remains a leading cause of human immunodeficiency virus (HIV) associated mortality and morbidity among both adults and children worldwide,1,2 with an estimated 390 000 deaths from HIV-associated TB in 2014.3 Recent systematic reviews have found that TB is the most common cause of death in hospitalised adults and children living with HIV,4 and is responsible for 40% of causes of death confirmed by autopsy among people living with HIV.5 Preventing, diagnosing and treating TB in HIV-positive individuals remains an urgent public health priority. The provision of integrated TB and HIV services at the same place and time for people living with HIV is one of the key recommendations for HIV-associated TB.6 Integration can be achieved in different ways, including partial or full integration or co-location of services using either TB or HIV as an entry point.7

This issue of Public Health Action provides a before–after evaluation of the impact of integrating of TB and HIV activities across 12 ‘one-stop’ services in two districts of Rwanda.8 Key activities included providing HIV counselling and testing in TB clinics, providing antiretroviral therapy in the TB clinic for the duration of TB treatment, screening all HIV patients for TB and contact tracing for TB patients via home-based visits. HIV testing, cotrimoxazole prophylaxis and initiation of antiretroviral therapy (ART) all increased after implementation of the service in both districts. Qualitative research indicated high levels of client and health provider satisfaction. Other indicators were unchanged.

There are limitations to the study. Sources of bias include the fact that data were assessed retrospectively, and less than half of facilities in the two districts were assessed. In particular, it is unclear how these facilities and districts were chosen, and the reported outcomes may not be representative of other sites. Nevertheless, operational research reports such as this are valuable in providing programme managers with an insight into what can be achieved in programmatic settings, in contrast to the carefully controlled and well-resourced context of a randomised trial.9

For Rwanda, this study provides some direction for action to further reduce HIV-associated TB mortality. The findings suggest that further improvements can be made in initiating ART in TB patients (only 71% initiated in Kicukiro district) and to improve outcomes of TB treatment, in particular to reduce the relatively high mortality (11–15%), which is likely multifactorial and deserving of further investigation. Delayed diagnosis, late initiation of treatment, suboptimal adherence to treatment, and type of TB disease (pulmonary or extrapulmonary) can all contribute to increased mortality in co-infected patients. Furthermore, the provision of isoniazid preventive therapy (IPT) = is not widely practised and reported in Rwanda, and this also requires urgent attention.

Finally, there are other components to successful integration of HIV and TB care that are important to implement and monitor. Future studies reporting on the outcomes of integrated TB and HIV services are encouraged to report on the additional components, including earlier and prompt TB diagnosis, provision of IPT, and HIV testing and TB screening among family members of people living with HIV,6 all of which remain major challenges in the implementation of TB-HIV collaborative activities.10

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Service integration to reduce HIV-associated TB mortality

Lack of funding and global investment are denying patients evidence based interventions

With the growth of global health schools and programmes at most universities in developed counties and the interest in neglected tropical diseases, it should follow that common medical conditions in developing settings are being researched.1 However, this is not so for scorpion stings, snake bites, and other animal envenomations. In the linked randomised clinical trial (doi:10.1136/bmj.c7136), Bawaskar and Bawaskar compare the effectiveness of scorpion antivenom plus or minus prazosin for the treatment of scorpion stings.2 The trial is a reminder that global health researchers often neglect conditions that matter to large impoverished communities⇓.



ephotocorp/Alamy

Of around 1500 species of scorpions worldwide, around 30 are potentially dangerous to humans.3 About 1.2 million scorpion stings occur worldwide each year, of which roughly 3250 are fatal. The incidence and severity vary geographically, with reported incidence among the general population …

Research into scorpion stings.

Mahar Ghandi and Rajiv Khanna’s recent review of cytomegalovirus infection highlights the important burden of this disease in immunocompromised individuals. In Thailand where ophthalmological changes due to cytomegalovirus have been observed in a third of HIV-infected patients management of cytomegalovirus retinitis poses a considerable challenge. Treatment of opportunistic infections is an integral part of HIV management. Local production of generic HIV medicines in Thailand is making treatment more affordable. For example 4 years ago treatment of cryptococcal meningitis was out of reach for most because fluconazole cost US$13 a day. Generic production reduced the cost to 30 cents a day and this treatment is now universally available. Ideally treatment of cytomegalovirus retinitis requires both intravenous therapy and intravitreal ganciclovir injections both of which are costly and impractical. Intravitreal injections require referral to an ophthalmologist at provincial level although in practice few ophthalmologists provide this service. Long-term intravenous therapy is difficult to administer. (excerpt)

Nathan Ford

Papers

Responding to the evidence for improved treatment for cryptococcal meningitis in resource-limited settings : correspondence

Evaluation of HIV treatment outcomes with reduced frequency of clinical encounters and antiretroviral treatment refills: A systematic review and meta-analysis

Service integration to reduce HIV-associated TB mortality

Research into scorpion stings.

HIV and cytomegalovirus in Thailand